Brain Tumors - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

RAIN UMORS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N...

Author: Health Publica Icon Health Publications

110 downloads 634 Views 6MB Size Report

This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!

Report copyright / DMCA form

DOWNLOAD PDF

RAIN UMORS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Brain Tumors: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83799-6 1. Brain Tumors-Popular works. I. Title.

iii

Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

iv

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on brain tumors. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

v

About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

vi

About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON BRAIN TUMORS ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Brain Tumors................................................................................ 5 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 68 CHAPTER 2. NUTRITION AND BRAIN TUMORS ............................................................................. 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Brain Tumors............................................................................. 115 Federal Resources on Nutrition ................................................................................................. 122 Additional Web Resources ......................................................................................................... 123 CHAPTER 3. ALTERNATIVE MEDICINE AND BRAIN TUMORS ....................................................... 125 Overview.................................................................................................................................... 125 National Center for Complementary and Alternative Medicine................................................ 125 Additional Web Resources ......................................................................................................... 132 General References ..................................................................................................................... 134 CHAPTER 4. DISSERTATIONS ON BRAIN TUMORS ......................................................................... 135 Overview.................................................................................................................................... 135 Dissertations on Brain Tumors.................................................................................................. 135 Keeping Current ........................................................................................................................ 136 CHAPTER 5. CLINICAL TRIALS AND BRAIN TUMORS ................................................................... 137 Overview.................................................................................................................................... 137 Recent Trials on Brain Tumors.................................................................................................. 137 Keeping Current on Clinical Trials ........................................................................................... 159 CHAPTER 6. PATENTS ON BRAIN TUMORS ................................................................................... 161 Overview.................................................................................................................................... 161 Patents on Brain Tumors........................................................................................................... 161 Patent Applications on Brain Tumors ....................................................................................... 187 Keeping Current ........................................................................................................................ 199 CHAPTER 7. BOOKS ON BRAIN TUMORS ....................................................................................... 201 Overview.................................................................................................................................... 201 Book Summaries: Federal Agencies............................................................................................ 201 Book Summaries: Online Booksellers......................................................................................... 203 The National Library of Medicine Book Index ........................................................................... 207 Chapters on Brain Tumors......................................................................................................... 209 CHAPTER 8. MULTIMEDIA ON BRAIN TUMORS ............................................................................ 213 Overview.................................................................................................................................... 213 Video Recordings ....................................................................................................................... 213 Bibliography: Multimedia on Brain Tumors ............................................................................. 214 CHAPTER 9. PERIODICALS AND NEWS ON BRAIN TUMORS ......................................................... 215 Overview.................................................................................................................................... 215 News Services and Press Releases.............................................................................................. 215 Academic Periodicals covering Brain Tumors ........................................................................... 220 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 221 Overview.................................................................................................................................... 221 U.S. Pharmacopeia..................................................................................................................... 221 Commercial Databases ............................................................................................................... 222 Researching Orphan Drugs ....................................................................................................... 222 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 227 Overview.................................................................................................................................... 227

viii Contents

NIH Guidelines.......................................................................................................................... 227 NIH Databases........................................................................................................................... 229 Other Commercial Databases..................................................................................................... 232 The Genome Project and Brain Tumors..................................................................................... 232 APPENDIX B. PATIENT RESOURCES ............................................................................................... 237 Overview.................................................................................................................................... 237 Patient Guideline Sources.......................................................................................................... 237 Associations and Brain Tumors................................................................................................. 256 Finding Associations.................................................................................................................. 260 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 263 Overview.................................................................................................................................... 263 Preparation................................................................................................................................. 263 Finding a Local Medical Library................................................................................................ 263 Medical Libraries in the U.S. and Canada ................................................................................. 263 ONLINE GLOSSARIES................................................................................................................ 269 Online Dictionary Directories ................................................................................................... 269 BRAIN TUMORS DICTIONARY............................................................................................... 271 INDEX .............................................................................................................................................. 363

1

FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with brain tumors is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about brain tumors, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to brain tumors, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on brain tumors. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to brain tumors, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on brain tumors. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

3

CHAPTER 1. STUDIES ON BRAIN TUMORS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on brain tumors.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and brain tumors, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “brain tumors” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Food fright Source: Women's Sports and Fitness. p. 132-5. November/December 1999. Summary: A recent mass e-mail links NutraSweet to brain tumors and multiple sclerosis. As we feast on fake sugars and fats, Billings asks, should we fear for our health? Artificial sugars and fats now flavor so many foods, it's hard to avoid them. This article contains a guide to what you're really eating.

•

Alzheimer's Disease and Dementing Disorders Source: Physical Medicine and Rehabilitation: State of the Art Reviews. 4(1): 9-17. February 1990.

4

Brain Tumors

Summary: Dementia is a major cause of disability in the elderly. Alzheimer's disease and multiple brain infarctions account for more than 80 percent of patents with dementia. The rest suffer from other disorders such as Pick's disease, Parkinson's disease, Creutzfeldt-Jakob disease, Huntington's chorea, multisystem atrophy, and progressive supranuclear palsy. Other causes of dementia are potentially reversible, such as subdural hematoma, brain tumors, or normal pressure hydrocephalus. Subacute and chronic infections of the central nervous system (CNS) can also cause dementia, such as syphilis, AIDS, and cryptococcal meningitis. Factors extrinsic to the CNS may cause dementia, which is often preventable, arrestable, or reversible. Examples include drug intoxication, liver disease, thyroid disorders, high or low blood sugar, and thiamine deficiency. Lastly, mental depression in the elderly can sometimes mimic dementia. The etiology of Alzheimer's disease remains unknown, although evidence suggests a genetic factor. Experimental treatment of Alzheimer's disease with cholinergic agents has met with limited success. Reversible disorders must be ruled out prior to the diagnosis of Alzheimer's dementia in the elderly patient. 42 references. •

Differential Diagnosis of Dementia, Delirium and Depression: Implications for Drug Therapy Source: Drugs and Aging. 5(6): 431-445. December 1994. Summary: This article discusses the differential diagnosis, evaluation, and treatment options for dementia, delirium, and depression. It presents the clinical features and causes of each disorder and the neuropsychological and laboratory tests used in diagnosis. Comprehensive clinical evaluation is necessary because these disorders are not mutually exclusive. Furthermore, physical diagnoses, such as chronic obstructive lung disease, congestive heart failure, stroke, and endocrine disorders are frequently associated with depressive symptoms. Laboratory testing is required to exclude concurrent metabolic, endocrine and infectious disorders, and drug effects. Imaging studies should be obtained selectively in patients with signs and symptoms, such as focal neurological findings and gait disturbances, which are suggestive of structural lesions: stroke, subdural hematoma, normal pressure hydrocephalus, and brain tumors. Appropriate management involving pharmacological and nonpharmacological measures could result in significant improvement in most patients with these syndromes. In delirious patients the underlying illness may be treated concomitantly with the use of psychotropics, if necessary. Although no current medications have been shown to have a significant effect on the functional status of patients with the two most common causes of dementia, Alzheimer's disease (AD) and multi-infarct dementia, the management of concomitant illness in these patients may result in improved function for as long as a year. Tacrine (Cognex) improves cognitive function slightly in selected patients with AD over short periods. Finally, the treatment of depression with medications or electroconvulsive therapy may result in significant reductions in mortality and morbidity. 4 tables, 43 references. (AA-M).

•

What You Need to Know About Organ Donation Source: Patient Care. 32(7): 94, 97-98, 100. April 15, 1998. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This article gives primary care physicians an update on organ donation, including current information on donor cards, mandated choice, presumed consent, brain death, and cadaver donor protocols. The author first encourages readers to have

Studies

5

all their patients discuss organ donation with their family members, as this is the most important part of the process. The author then notes who organ donors usually are (most cadaveric donors were in good health but died suddenly from fatal neurologic injuries, primary central nervous system events, cerebrovascular accidents, subarachnoid hemorrhage, brain tumors or injuries, accidents, drug overdose, smoke inhalation, suicide, or cardiac arrest). Living donors can donate bone marrow, a kidney, and portions of the lungs, liver, and pancreas. Most living-donor solid organ and bone marrow transplants are performed on a relative of the donor. While many more people need transplants than there are organs available, efforts at increasing the donor pool have not yet equalized supply and demand. The mandated choice proposal currently being debated would require competent adults to decide whether they wish to donate organs when they die. People would have to register their choice in a database when they obtain a driver's license or file a tax return. The question of whether mandated choice and presumed consent violate personal freedom or the right to privacy is controversial. The guidelines issued by the National Kidney Foundation about communication between donor families and transplant recipients are also discussed. These guidelines are based on the belief that donor families and recipients have the right to choose whether they want to communicate with each other. Confidentiality is ensured for those who decline to communicate, and those who want contact are first provided with written information. Other topics covered include payment for organ donation, reasons people don't want to donate or sign a donor card, cadaveric donors, and hospital protocols for organ donation. 1 table. 3 references. •

Potentially Reversible Dementia: A Review Source: Australian and New Zealand Journal of Psychiatry. 25(4): 506-518. December 1991. Summary: This journal article reviews potentially reversible dementia with respect to their diagnosis, causes, and outcomes and compares them to irreversible dementias such as Alzheimer's disease and to other causes of chronic mental impairment. The review examines a number of kinds of cognitive impairment, including normal pressure hydrocephalus, hypothyroidism, hyperthyroidism, subdural hematoma, brain tumors, vitamin B12 deficiency, folate deficiency, neurosyphilis, alcoholic dementia, drug toxicity, other organic disorders, and psychiatric disorders. The authors conclude that the concept of a potentially reversible dementia is not supported. Generally, cognitive impairments that are reversible, such as those caused by drug toxicity or depression, are not forms of dementia. Few cases of dementia recover. When the diagnosis of dementia is established, only mild subcortical impairments of short duration are likely to improve. Nonetheless, cases of well-established dementia should have a thorough clinical examination as dual pathology often exists, and all cases require psychosocial management.

Federally Funded Research on Brain Tumors The U.S. Government supports a variety of research studies relating to brain tumors. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration

6

Brain Tumors

database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to brain tumors. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore brain tumors. The following is typical of the type of information found when searching the CRISP database for brain tumors: •

Project Title: AGT DEPLETION FOR THERAPY OF CNS TUMORS Principal Investigator & Institution: Quinn, Jennifer A.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: The prognosis of patients with malignant glioma remains dismal, with conventional treatment with surgery, radiotherapy and alkylnitrosourea-based chemotherapy failing to cure all patients with glioblastoma multiforme and the majority of patients with anaplastic astrocytoma. This failure is due almost exclusively to de novo or acquired resistance to chemotherapy with subsequent tumor growth and patient death. The nitrosoureas and methylators such as procarbazine were originally chosen for treatment of central nervous system tumors on the basis of favorable physiochemical properties such as lipophilicity as well as activity against L1210 leukemia cells growing intracranially in mice. Nevertheless, despite moderate sensitivity to malignant glioma to BCNU or lomustine, the nitrosoureas have not dramatically altered survival for patients with malignant brain tumors. This situation presumably reflects de novo or acquired intrinsic cellular resistance rather than restricted delivery to the intracranial site. The major mechanism of resistance to alkylnitrosourea and methylator therapy is the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT). AGT removes chlorethylation or methylation damage from the O6-position of guanine prior to cell injury and death. The high incidence of AGT activity in human central nervous system tumors, as well as the inverse relationship between procarbazine activity and alkyltransferase levels in human brain tumor xenografts, supported a role for this protein in mediating resistance to nitrosoureas in patients with CNS tumors and provided an approach for reversal of drug resistance. Furthermore three recent clinical trials have suggested that AGT levels in patients receiving BCNU therapy correlate with outcome. The hypothesis of this proposal are 1) AGT plays a critical role in mediating resistance of malignant glioma to nitrosoureas and methylators and 2) O6benzylguanine (O6-BG) mediated reduction of glioma AGT levels can enhance nitrosourea (BCNU) and methylator (temozolomide) treatment of these tumors. The specific aims of this proposal are 1) to further define the toxicity of BCNU + O6- BG and temozolomide + O6-BG respectively, in the treatment of adults with malignant glioma; 2) to define the activity and subsequently efficacy of BCNU +06-BG and temozolomide and O6-BG respectively, in the treatment of adults with malignant glioma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

(FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies

•

7

Project Title: ANNEXIN II & PLASMIN MEDIATED HIGH GRADE GLIOMA INVASION Principal Investigator & Institution: Acharya, Suchitra S.; Pediatrics; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (Applicant's Description): Malignant primary brain tumors, especially gliomas, are characterized by a propensity to invade surrounding brain structures resulting in a high rate of local recurrence and a dismal clinical outcome. The invasion process is a complex cascade of events. A l though multiple mechanisms may be involved, it appears that focal proteolytic activity is needed for extracellular matrix (ECM) remodeling and s u bsequent invasion. The plasminogen-plasmin system directly or, by activating matrix metalloproteinases (MMPs) has been implicated in the proteolytic remodeling of ECM. Annexin II (Ann II), a newly identified endothelial cell surface protein, is a co-receptor for plasminogen (PLG) and its activator, tissue plasminogen activator (t-PA). Ann II increases the catalytic efficiency of plasmin generation up to 60-fold over baseline in a purified protein system. We have employed C6 rat glioma cells, a well-defined in vitro model of human high grade glioma to study the potential role of Ann II in plasmin - mediated invasion. Preliminary in vitro data suggest that C6 cells abundantly express annexin II (Ann II), enhance plasmin generation in functional studies and mediate t-PA-dependent migration of C6 cells through both collagen and laminin matrices. Also, the invading edges of high grade human gliomas show strong positive staining for Ann II in the tumor cells. Based upon these preliminary data, this project will test the hypothesis that Ann II plays a role in plasmin - mediated high grade glioma invasion. The research will focus on defining the role of Ann II in vitro using invasion and matrix degradation assays, radiolabeled binding assays, specific functional assays and substrate zymography. Also, the hypothesis will be tested in an in vivo system with stereotactic injection of C6/lac Z cells into Fischer rat brains to produce tumors and to inhibit invasion with anti-Ann II antibodies and anti-sense Ann II constructs. Human brain tumor sections will be studied immunohistochemically for Ann II, t-PA expression and plasmin activity. By understanding mechanisms of invasion, it may be possible to devise novel therapeutic approaches to brain tumors specifically targeted to limit Ann II - mediated invasion. These studies could also have far reaching implications for the diagnosis and treatment of other locally invasive and metastatic tumors in a wide variety of settings. The principal investigator for this application is a board certified pediatrician, who during the process of training in pediatric hematology/oncology has spent 2 years in a vascular biology laboratory under the direction of Dr. Katherine A. Hajjar. The proposed plan will continue under her supervision at Weill Medical College of Cornell University. Her lab is part of a Specialized Center for Thrombosis Research and a Program Project in Vascular Biology, and is well equipped to carry out the investigations. Apart from weekly lab meetings to discuss individual projects, weekly research seminars and journal clubs provide an opportunity to meet with other investigators at the medical college and exposure to new ideas. Dr. Hajjar is also very accessible for individual weekly meetings when the need arises. T h i s environment will provide excellent training for a developing physician-researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: APPROACHES TO BRAIN TUMOR THERAPY Principal Investigator & Institution: Brem, Steven; Professor; Neurology; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620

8

Brain Tumors

Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-DEC-2002 Summary: (Applicant's Description) The long-term objective is the development of innovative approaches at the Moffitt Cancer Center to improve the and quality of life of adult with primary malignant tumors of the central nervous system (CNS) - by the initiation, co analysis, and reporting of Phase I/II clinical trials focused on promising molecular biologic strategies within the organizational framework of the NABTT, "New Approaches to Brain Tumor Therapy", CNS cancer consortium. A major research thrust at the Moffit" Cancer Center is in place, in three areas l i nked to neuro-oncology, to develop technologies and discover novel cytostatic and cytotoxic agents suitable for Phase I/II clinical testing: 1) Drug Discovery, evaluating i) antagonists of angiogenesis and invasiveness; ii) inhibitors of ras-mediated signal transduction pathways, eg., farnesyl transferase; iii) topoisomerase inhibitors, and iv) inhibitors of multidrug resistance; 2) Neuro-imaging, developing MRI technology for therapeutic trials in neuro-oncology; and 3) Genetic and Immunological Therapies, inhibition of t u m o r growth using immune modulators and antibody-based approaches. Specifically, the Brain Tumor Research Laboratory will continue to develop angiogenesis inhibitors: two Phase II protocols using penicillamine for malignant gliomas are under review at the NABTT Central Office. Candidate molecules for Phase I/II protocols include i) angiogenesis antagonists: captopril, platelet- factor four and inhibitors of urokinase plasminogen activator; ii) signal transduction Inhibitors; iii) a benzamide-derivative chemosensitizer to counter multiple drug resistance; iv) cytokines (eg., IL-12), and v) targeted antibodies. The Neurooncology Program at the Moffitt Cancer Center will build on its track record of patient accrual, transnational research, protocol development, and provide the CNS Consortium: (1) 20 to 30 patients per year with primary brain tumors; (2) an expert multidisciplinary clinical team; (3) extensive clinical and laboratory resources for Interactive collaborations with other NABTT centers; (4) grant-supported brain tumor biology and pharmacology research, including a NCI-sponsored National Cooperative Drug Discovery Group; (5) expertise in oncology, pharmacology, new drug development, Phase I and II c l i nical trials; (6) state-of-the-art radiation therapy; stereotactic radiosurgery; - computer-driven, navigational neurosurgery; and advanced MR neuroimaging; (7) expertise in biostatistics, protocol development, data management, and the coordination of multi-institutional studies; (8) an established Brain Tumor Bank with correlative studies of glioma biomarkers; and (9) Phase II protocols submitted to NABTT Central Office for anti-angiogenesis and other novel approaches to brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASSESSMENT OF HYPOXIA IN MALIGNANT GLIOMAS USING EF5 Principal Investigator & Institution: Evans, Sydney M.; Associate Professor; Radiation Oncology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 04-JUN-2001; Project End 31-MAY-2003 Summary: (Provided by applicant) It has been known since the 1950s that hypoxic tumor cells require up to 3 times the radiation dose compared to aerobic cells for equal toxicity. Because the total radiation dose administered is limited by the tolerance of normal adjacent tissues, the search for approaches to overcome the "hypoxia problem" has dominated radiation biology research for the last half century. One of the major limitations to attacking this problem has been the inability to identify and quantitate the presence of hypoxic cells in individual patients. In the last decade, the availability of the Eppendorf needle electrode technology has allowed data to be obtained on tumor tissue oxygenation in patients. Such studies have demonstrated hypoxia to negatively

Studies

9

influence outcome in cervix, sarcomas and head and neck cancers. There is also substantial evidence that hypoxia exists and is biologically relevant in malignant brain tumors. The overall goal of our clinical hypoxia program is to determine whether the presence, levels and patterns of EF5 binding are important in the prognosis and therapy response of cancer patients. Our interests include patients with sarcomas, head and neck squamous cancer, cervix cancer and now, patients with brain tumors. In the studies proposed herein, we will study EF5 binding in patients with de novo supratentorial malignant gliomas (SMG). Concurrent studies in the same patient group using the Eppendorf needle electrode will serve as a bridge to previously published work. We will determine the relationship between EF5 binding and clinical outcome in patients with glioblastoma multiforme (GBM) versus non-GBM histologies. To better understand the pathophysiology of MG, we will study the presence and levels of various additional biomarkers. These studies are the necessary preliminary studies towards non-invasive studies of hypoxia in brain tumors. These non-invasive studies will be based on Positron Emission Tomographic (PET) imaging of 18F-EF5 followed by hypoxia-specific treatment interventions. 18F-EF5 has been synthesized and studied in animal tumors by our group. The necessary additional pre-clinical studies and applications for permits for these PET studies are ongoing at the University of Pennsylvania (PENN). We project that we will be able to institute clinical EF5 PET studies at PENN in patients with brain tumors in approximately 2 years, corresponding to the time that much of the data from the studies proposed herein will mature. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN NEOPLASMS, LEUKEMIA & PETROCHEMAL EXPOSURES Principal Investigator & Institution: Christiani, David C.; Professor; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2005 Summary: (Adapted from the Applicant's Abstract): Brain tumors and leukemia are the most common children and adolescent malignancies in the U.S. Adequate information on the role of inherited genetic susceptibility and environmental exposures in the development of neoplasms in children and adolescents is lacking. In Taiwan, four large petrochemical industries are located in Kaohsiung metropolitan area. These facilities are proximal to residential areas because of the high population density in the region. Data have shown that the concentrations of ambient polycyclic aromatic hydrocarbons (PAH) and volatile organic compounds (VOC) around the petrochemical industries are at least 10 and 2 times, respectively, higher than those in U.S. industrialized communities. Our preliminary case-control study in Kaohsiung metropolitan showed that young residents (< 30 yr) living within 3 kilometers (km) of the vicinity of petrochemical industries have a 6.0 fold increase in brain neoplasms and a 2.9 fold increase in leukemia. The purpose of this proposal is to examine the association of exposure to air contaminants (PAH & VOC) emitted from the petrochemical industries, specific genetic polymorphisms (P4501A1 (MspI & exon 7) and GSTMI & Tl) from study subjects and their parents, and the risks of brain tumors and leukemia among children and youths in metropolitan Kaohsiung. Our hypothesis is that there is an increase risk of brain tumors and leukemia in patients with higher cumulative exposure to these hazards, and that heritable polymorphisms in several genes modify this association. In addition to an independent association of environmental and genetic factors with brain neoplasm and leukemia, we hypothesize that there is greater risk associated with the presence of combined environmental exposure and the high risk genotype. We also assess the role

10

Brain Tumors

of the parental genetic polymorphisms in the development of cancer in their sibling. This proposed study uses an environmental molecular epidemiologic approach, utilizing prospective enrollment of a cohort of brain tumor and leukemia subjects and a population-based case-control design. This proposal is responsive to the recommendation of the National Research Council that risk assessment and public health policy pay special attention to the protection of children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN TUMOR THERAPEUTIC EFFICACY BY QUANTITATIVE MR Principal Investigator & Institution: Ross, Brian D.; Dir of Clinical Lab; Radiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 05-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Among the causes of death due to cancer, brain tumors are ranked second in the pediatric age group and fourth in middle-aged man and malignant gliomas are uniformly fatal with only 50 percent of patients surviving one year from initial diagnosis. These stark statistics underscore the urgent need for improved therapies along with capabilities that would provide for early therapeutic assessment of efficacy in these patients. A sensitive and early predictor of therapeutic outcome for patients would provide for improved care and the opportunity to individualize and adjust the treatment to each patient. The central hypothesis of this project is that the effectiveness of therapeutic interventions can be determined prior to tumor shrinkage using quantitative MR diffusion, perfusion and 1H spectroscopic methods. Both animal and human brain tumors will be evaluated using MR following therapeutic intervention including chemotherapy, radiation, gene, nanoparticles and antiangiogenic therapies. This research program will provide new mechanistic insights into: The use of MRI/S for the early detection of brain tumor response to therapy and the effects of neovascularization on therapy (Project 1); The sensitivity and resolution of MRI/S for the detection of therapeutic transgene delivery, function and therapeutic efficacy in brain tumors (Project 2); The capability of using NanoPlatforms for the delivery of image contrast agents and potentially therapeutic drugs to brain tumors (Project 3); and The predictiveness of MRI for the early assessment of human brain tumor response to therapy (Project 4). This research plan is an outgrowth of the progress made with previous NCI support. Four interactive projects and four cores are proposed. The Administrative Core A provides administrative support along with internal and external review for all projects. The Animal MR Imaging Core B provides the necessary MRI/S services for Projects 1-3. The Digital Image Processing Core C provides a centralized and high-throughput capability for the digital post processing of all acquired MR data for all projects (Projects 1-4). The Biostatistical Core D provides statistical support to all projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: BRAIN SPECTROSCOPY

TUMOR/TUMOR

MARGIN

ID

BY

OPTICAL

Principal Investigator & Institution: Mahadevan-Jasen, Anita; Assistant Professor; Biomedical Engineering; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2005

Studies

11

Summary: (Verbatim Adapted from Applicant's Abstract): Research has shown removing maximum amount of tumor with minimal sacrifice to normal tissues is the key to improving the survival rate of brain tumors. Thus, there is a greater need for an intra-operative tool, which effectively detects tumor margins in real time and provides a sub-millimeter spatial resolution for guidance of tumor resection. Optical spectroscopy can provide such a tool as it has the advantage of providing automated, real-time, nonintrusive diagnosis with high sensitivity and spatial resolution. Fluorescence and diffuse reflectance spectra were acquired from normal and various types of tumor brain tissues in vitro of about 20 patients. Based on the spectral differences, diagnostic algorithms developed showed that fluorescence could differentiate normal white and gray matter from primary tumors with 97 percent sensitivity. Fluorescence alone was insufficient in separating normal brain tissues from secondary tumors; combining diffuse reflectance with fluorescence yielded 97 percent sensitivity for this discrimination. Following the success of these studies, a pilot study of 21 patients was successfully performed. Preliminary in vivo results showed that tumor margin tissues can be differentiated from normal tissues with a sensitivity and specificity of 83 percent and 85 percent respectively using fluorescence and diffuse reflectance spectra. In this proposal, we plan to develop autofluorescence in combination with diffuse reflectance spectroscopy for intraoperative brain tumor and tumor margin detection in real-time to guide tumor resection. To achieve this goal, the following specific aims are proposed; (1) Characterize tissue fluorescence and diffuse reflectance signatures of brain tissues in vivo. (2) Develop diagnostic algorithms that separate normal and tumor tissues from tumor margins. (3) Study the basis of observed differences in the spectral characteristics using microspectroscopy, cyto-chemical analysis, and modeling. (4) Conduct retrospective and prospective evaluation of the algorithms developed to obtain estimates of their performance. (5) Assess the feasibility of using optical spectroscopy during stereotactic procedures and verify the performance capability of this technique for brain tumor demarcation. (6) Develop (a) software interface to implement and automate data acquisition and diagnosis that provides real-time feedback to the surgeon for therapy guidance and (b) next-generation clinical spectroscopic system to reduce the scale but not the accuracy of the spectroscopic system. This research will have tremendous impact on the future of tumor resection as upon the successful development of the proposed research, this can be translated to the application of other organ systems such as prostate and ovary. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL BIOLOGY OF ASIC2 IN GLIOMA Principal Investigator & Institution: Benos, Dale J.; Professor & Chair; Physiology and Biophysics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 06-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Gliomas are primary brain tumors that arise from differentiated glial cells through a poorly understood process of malignant transformation. Brain tumors display a complex biology because of their remarkable degree of antigenic heterogeneity, variable mutations in their genome, and their propensity for invasion into normal brain tissue. In studying gliomas obtained from patients that were diagnosed with tumors of varying degrees of malignancy, we observed the expression of a voltage-independent, amiloride-inhibitable, inward Na+ conductance that was not present in normal human glial cells or in low-grade tumors. We hypothesize that high-grade glioma cells show functional up-regulation of this characteristic Na + conductance. Glioma cell migration, cell proliferation, and cell

12

Brain Tumors

volume regulation are all compromised if this conductance pathway is blocked with amiloride or by a peptide isolated from a spider venom. Thus, the channel membrane proteins that underlie this conductance are potentially unique, therapeutic targets. The research proposed in this application has one objective of characterizing thoroughly the ability of one subunit (ASIC2) of this amiloride-sensitive Na+ conductance pathway to traffic through the cellular biosynthetic pathway. In addition, we hypothesize that this same subunit (ASIC2) is transcriptionally regulated. Thus, in malignant brain tumors, ASIC2 either is not expressed or is retained intracellularly. There are two Specific Aims: 1) to test the hypothesis that lack of plasma membrane expression of ASIC2 in a subset of high-grade tumor cells is a consequence of endoplasmic reticulum retention due to channel misfolding; and 2) to test the hypothesis that in the majority of high-grade gliomas ASIC2 gene expression is transcriptionally regulated by factors specific to the brain tumor microenvironment. We anticipate that this work will provide new fundamental insights into the molecular mechanisms involved in the regulation of amiloride-sensitive Na + channels in brain tumors. Moreover, this work will provide important clues as to the role of these channels in the pathogenesis and life cycle of glioma cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL TYPE-SPECIFIC VIRAL TRANSLATION IN THE CNS Principal Investigator & Institution: Gromeier, Matthias; Molecular Genetics and Microbiology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 21-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The aim of this project is to elucidate the mechanism of cell type-specific viral translation in the central nervous system (CNS). A cis-acting genetic element located within the 5' non-translated region of picornaviruses, the internal ribosomal entry site (IRES), was found to confer specificity for cells of neuronal origin. We have developed a novel approach to treat malignant tumors of the CNS based on the principles of IRES-mediated cell type-specific translation. This strategy uses picornaviruses engineered to contain IRES elements with cell type-specific deficits in neuronal cells. These chimeric viruses exhibit excellent growth and lytic potential in cancerous cells derived from malignant brain tumors. Pre-clinical studies in non-human primates demonstrated neuronal IRES repression to render these agents safe to be used in patients. We plan to identify the molecular mechanisms of cell type-specific IRES function by mapping the genetic loci important for tissue specificity. Furthermore, the identification of eukaryotic trans-acting factors in permissive tumor cells or resistant neurons is expected to shed light on selective IRES activity in neoplastic cells. We will attempt to determine the stage of neuronal differentiation that correlates with neuronal IRES repression. Unraveling of the molecular mechanism of cell type-specific IRES function may lead to the development of novel gene expression systems with exclusive targeting to cancer cells in the CNS. Malignant tumors of the CNS are resistant to all currently available treatment modalities. Conditional replication mediated by IRES selectivity of recombinant oncolytic picornaviruses is the first example of tumor targeting at the level of translational control. This principle has shown great promise in pre-clinical studies in experimental animals and in primary explant cultures of human CNS tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

13

Project Title: CHILDRENS NATIONAL MEDICAL CENTER Principal Investigator & Institution: Packer, Roger J.; Children's Research Institute Washington, D.C., Dc 20010 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: As a member of the Pediatric Brain Tumor Clinical Trials Consortium, the CNMC Neuro-Oncology Program proposes to develop, facilitate, and participate in innovative hypothesis-driven, technically challenging, clinical research designed to improve the survival and quality of life of children with primary central nervous system tumors. It is anticipated that these investigations will include, but will not be limited to: the use of novel chemotherapeutic agents; means to overcome the blood-brain barrier, immunotherapeutic approaches; modifications of radiation therapy; and new neurobiologic approaches, such as gene therapy, maturation agents, and antiangiogenesis agents. The CNMC Neuro-Oncology Program plans on participating in research investigations which will improve the means to diagnose and characterize childhood brain tumors and to develop and participate in carefully monitored innovative diagnostic and therapeutic studies which will lead to future Phase III studies for children with such tumors. Over the past five years, the CNMC Neuro-Oncology Program has evaluated and managed 442 children (new to the institution) with primary central nervous system tumors and has entered over 189 children on Phase I, Phase II, and Phase III clinical investigations. Investigations have been done over this period of time, in concert with private industry and working groups, evaluating novel approaches such as gene therapy, immunotherapy, and approaches to overcome the blood-brain barrier; as well as evaluations of new chemotherapeutic agents, intensification of chemotherapy, and means to increase the efficacy of radiotherapy. The CNMC NeuroOncology Program has a well-developed multidisciplinary clinical core which includes a weekly neuro-oncology clinic, a quarterly groupwide neuro- oncology planning meeting, and a regional referral system. The program has a well-designed data management system, and an established system for specimen accrual. State-of-the-art neuroradiologic, neuropathologic, neurosurgical and radiation-oncologic facilities are available. In addition, innovative neurobiologic investigations in childhood brain tumors have been successfully completed and are underway at CNMC. The welldeveloped program structure, expertise of the CNMC Neuro-Oncology Program, proven commitment to performance of clinical trials, and available facilities should ensure the ability of the CNMC Neuro-Oncology Program to effectively participate in the proposed Pediatric Brain Tumor Clinical Consortium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CLINICAL RESEARCH IN NEURO-ONCOLOGY Principal Investigator & Institution: Patchell, Roy A.; Chief of Neuro-Oncology; Surgery; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: Dr. Roy A. Patchell's entire medical career has been devoted to patient oriented clinical Neuro-Oncology research. He completed a residency in Neurology at Johns Hopkins and a fellowship in clinical Neuro Oncology at Memorial Sloan-Kettering Cancer Center. He then came to the University of Kentucky and ha developed a comprehensive clinical Neuro-Oncology research program. This has involved the development of numerous clinical trials investigating the treatment of metastatic and primary brain tumors. On all of these studies, Dr. Patchell has been the principal investigator. He has had continuous extramural funding since 1986 and continuous RO1

14

Brain Tumors

NIH funding since 1988 and has a currently funded RO1 grant. All of his RO1 funding has been for clinical Neuro-Oncology trials. In addition to past and currently ongoing clinical trials assessing the effects of commonly available therapies for cancers of the nervous system, Dr. Patchell has invented an implantable, refillable, sustained-release device for the delivery of intratumoral chemotherapy for primary brain tumors. This device is currently being used in several phase I and phase II trials designed by Dr. Patchell, and one study has become a national trial under the auspices of the Radiation Therapy Oncology Group (RTOG). Dr. Patchell is continuing to collaborate with basic scientists at the University of Kentucky to investigate further uses of the device, including use with non-conventional agents such as anti-angiogenesis factors, biological response modifiers, radiation cell sensitizers, and other compounds. Dr. Patchell has a strong record of actively mentoring budding clinical investigators including residents, fellows, and junior faculty members at the University of Kentucky. In 1995, he established a Neuro-Oncology Fellowship Training Program and is currently training Neuro-Oncology Fellows. Dr. Patchell's careers goals include obtaining additional external funding so that he can expand the Neuro-Oncology Fellowship training program and continue to devote the majority of his time to mentoring his NeuroOncology Fellows and to developing new treatments for primary and metastatic brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTENT BASED NEURO IMAGE CLASSIFICATION Principal Investigator & Institution: Sinha, Usha; Assistant Professor; Radiological Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The goal of this proposal is the automated classification of imaging studies of patients with tumors. As the role of imaging becomes increasingly important in medical care, effective methods for storing and retrieving key images will become critical. Image classification and subsequent summarization proffers a method to compress imaging studies by selecting only pertinent image slices that objectively document a patient's condition, while preserving the full integrity of the original data; as such, its applications include multimedia electronic medical records, telemedicine, and teaching files. This proposal details an innovative method to accomplish image classification based on principal component analysis. A training set of images classified by experts will be used to generate a basis set of images that captures the variance among the images. The projection on this basis set of images, called eigenimages, is used as an image index for classification and retrieval. Two key aspects critical to the success of accurate image classification are described: normalization of both image spatial and intensity properties. A modification to this methodology is also proposed to handle images with small abnormalities: image sub-regions that are 'abnormal' are located by searching the query image for the region that best matches a training set of sub-images of 'abnormal regions'. The target domain for the proposal is MR imaging studies of patients with brain tumors; in future work, this research will be extended to cover other neurological conditions, imaging modalities, and anatomical regions. Technical evaluation will be performed by comparing the automated methods with that of experts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

15

Project Title: DNA ADDUCTS FORMED DURING BRAIN TUMOR THERAPY Principal Investigator & Institution: Bodell, William J.; Neurological Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2002 Summary: Each year there are approximately 50,000 newly diagnosed brain tumors. Chemotherapy is established to be important in the treatment of newly diagnosed and recurrent brain tumors. Laboratory based studies have established that DNA alkylation plays a key role in the initiation of cellular death by chemotherapeutic agents. In order to achieve a better understanding of this process in brain tumor therapy; we propose to measure the formation of DNA abducts in intracerebral (ic.) Tumors treated with alkylating chemotherapeutic agents currently being evaluated for the treatment of brain tumors. To achieve this goal we propose to Aim 1. Optimize a dissociation enhanced lanthanide fluoroimmunoassay (DELFIA) method fo the quantitatation of O6 methyldeoxguanosine (O6 -MedG). The levels of N7 -methyldeoxguanosine (N7 - MeG) will be determined by electrochemical detection. We will measure the levels of O6 MedG and N7 -MeG formed in U-87MG cells grown as ic. Tumors in athymic rats treated with temozolamide (TMZ). In these tumors, we will investigate the relationships between levels of O6 -MedG and N7-MeG formed and route of administration, treatment dose and agent and number of treatments. The levels of these alkylation products formed in the ic. tumors will be compared with the levels formed in the contralateral hemisphere and in normal tissues. These methodologies will provide ea unique approach for preclinical analysis of alkytating chemotherapeutic agents in treatment of brain tumors. Aim 2. We will develop a poly clonal antiserum to the dGdC crosslink (1- [N3-2'deoxycytidly], 2-[N1-2; -DEOXYGUANOSYL]-Ethane) formed by BCNU. Using this antiserum, we will optimize a DELFIA method for the quantitation of the dG-dC crosslink. Aim 3 Investigate the formation of the dG-dC crosslink, O6-(2hydroxy ethyl) deoxyguanosine (O6- HOEtdG) and N7 - (2-hydroxy ethyl) deoxyguanosine N7-HOEtG. Athymic rats bearing U-87MG ic. Tumors will be treated with either BCNU SarCNU or mitozolamide. The formation of dG-dC crosslink, O6HOEtdG and N7-HOEtG will be quantitated. We will examine the relationships between levels of these alkylation products and treatment agent, dose and. Number of treatment. These studies will be the first to investigate the formation of BCNU derived DNA abducts in a ic. Brain tumor model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ENDPOINT ANALYSES OF ANTI-INTEGRIN THERAPY FOR GLIOMAS Principal Investigator & Institution: Nabors, Louis B.; Neurology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Anti-integrin therapies that target specific mechanisms of tumor neovascularization and invasion present difficult problems in assessing their relative efficacy. Since the anti-angiogenesis effect may result in a significantly delayed or clinically inapparent anti-tumor effect when compared with that seen in therapies that target tumor cells directly, the most appropriate methods to assess an anti-angiogenesis effect need to be identified and validated. In patients with malignant brain tumors, it is procedurally high-risk, infeasible and unethical to obtain routine multiple tissue biopsies on a longitudinal basis to verify, at histopathological, cellular and molecular levels, that tumor vasculature is being appropriately targeted and

16

Brain Tumors

adversely affected. The overall objective of this project will be to evaluate the capacity of several different non-invasive mechanisms and assays to correlate changes in vascularization of recurrent malignant gliomas in patients who will be treated with a novel anti-angiogenic drug, cyclic RGD (EMD121974). Our hypothesis is that specific non-invasive methodologies can be used to visualize and quantify the responses of tumor vasculature to an anti-angiogenesis therapy that focuses on a specific molecular target on activated endothelial cells. Under the auspices of the New Approaches to Brain Tumor Therapy (NABTT) consortium, we will conduct a dose-escalating Phase 1 Clinical Trial of EMD121974 (IND #59,073) using a novel anti-integrin drug supplied by CTEP. We propose to (1) determine the ability of dynamic contrast susceptibility (DCS) MR imaging to assess and quantify neovascularization responses to EMD121974 therapy at specific time points during the course of therapy; (2) perform specific in vitro assays on patient biofluids (blood, csf, urine, etc.) at these imaging timepoints that will assess antiangiogenic activity against endothelial cell function required for neovascularization (proliferation, migration, apoptosis) or glioma cells for invasion; and, (3) explore the utility of a labeled, targeted nanoparticle to quantify tumor and tumor-vascular burden in a mouse brain tumor model. Data from these studies will be critically important in developing, refining and validating non-invasive methodologies for timely assessment of specific anti-angiogenic therapies for malignant brain tumors in patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENHANCED DRUG DELIVERY TO METASTATIC BRAIN TUMORS Principal Investigator & Institution: Black, Keith L.; Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Brain capillary endothelium and its contiguous cells, pericytes and astrocytes, are the structural and functional components of the bloodbrain barrier (BBB). Microvessels supplying brain tumors retain characteristics of the BBB, forming a blood-tumor barrier (BTB). While adequate delivery of drugs occurs to systemic tumors, the BTB limits delivery of antineoplastic agents to metastatic brain tumors. Drugs such as Herceptin, which is effective in treating metastatic tumors outside the brain have a high failure rate within the brain due to inadequate delivery across the BTB. The incidence of metastatic brain tumors is ten-fold higher than primary brain tumors. We have demonstrated that calcium-sensitive potassium (KCa) channel agonists selectively increase drug delivery across the BTB, and have postulated the biochemical mechanisms of this selective BTB permeability increase. We also have preliminary data suggesting that ATP-sensitive potassium (KATP) channel agonists selectively increase BTB permeability independent of KCa channels. These novel observations allow for a pharmacological mechanism for selectively increasing drug delivery across the BTB. This proposal will (a) further understand the mechanisms of KCa, and KATP channel activation in increasing BTB permeability and (b) optimize delivery of effective concentrations of drugs to metastatic breast and lung tumors in rats and humans via potassium channel-based mechanisms. We build on our data showing the ability of KCa channel agonists to selectively increase drug delivery across the BTB in rat glioma models and preliminary evidence suggesting that the BTB permeability increase may relate to over expression of KCa channels on glioma cells and tumor capillary endothelium. In this grant we will investigate 5 specific aims. Aim 1: To determine whether KCa and KATP channels are over expressed in metastatic brain tumor microvessels and tumor cells and whether increased expression correlates with increased permeability induced by KCa and KATP agonists. To test whether tumor cells

Studies

17

can induce over expression of KCa or KATP channels on brain endothelial cells. Aim 2: To test by quantitative electron microscopy whether the mechanism of KATP channel agonist-induced BTB permeability increase is due to increased endothelial vesicular transport or opening of tight junctions. To test whether increased vesicle formation is correlated with changes in endothelial and tumor cell membrane potential. Aim 3: To investigate whether KCa and KATP channel agonists increase delivery of therapeutic monoclonal antibodies and chemotherapeutic drugs across the BTB into metastatic human breast and lung cancer in nude rats/mice. Aim 4: In nude rats/mice harboring metastatic breast and lung tumors we will investigate whether increased drug delivery across the BTB using KCa or KATP agonists results in inhibition of tumor growth, and whether survival is increased. Aim 5: The ability of a KATP channel agonist, minoxidil, to increase delivery of an anti-tumor drug to patients with brain tumors will be determined by LC-MS-MS in resected tumor tissues. This grant is responsive to the recent Brain Tumor PRG recommendation in 2001 to support studies to improve delivery of drugs across the BBB, particularly for metastatic brain tumors. Overall, these studies will further delineate the role of KCa and KATP channel activation as a mechanism for selective delivery of anti-cancer agents across the BTB and could potentially result in improved control of disease in patients with metastatic brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION OF ASTROCYTOMAS WITH HRMAS 1HMR SPECTROSCOPY Principal Investigator & Institution: Cheng, Leo L.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 15-FEB-1999; Project End 31-JAN-2004 Summary: Astrocytomas, the most common type of brain tumors, are primarily diagnosed by the histopathological evaluation of cellular morphological changes in biopsy samples. In addition to changes in cell morphology, tumors also display altered cellular biochemistry. Tumor metabolic alterations may provide valuable information for clinical grading, biology-based prognosis, and therapeutic monitoring of astrocytomas. Conventional ex vivo 1HMRS has been used to study tumor samples; however, it is hampered by the need for the often destructive chemical extraction of tissue. We propose to evaluate the diagnostic potential of the newly developed highresolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy (1HMRS) on intact specimens of human astrocytomas. We plan to quantify HRMAS metabolites and measure histopathological features on the same tumor specimens, to select tumor metabolic markers, and to establish biochemical databases for astrocytoma diagnosis and prognosis. Our specific aims are: 1) To quantify metabolic concentrations with HRMAS 1HMRS in different regions of normal human brain; 2) To quantify metabolic alterations in newly diagnosed, adult supratentorial, diffuse fibrillary astrocytomas, and to use these measures to identify and define HRMAS 1HMRS markers able to type and grade these tumors; 3) To evaluate the capability of HRMAS spectroscopic markers in predicting the histological grade of adult cerebral hemisphere astrocytomas; and 4) To evaluate the usefulness of HRMAS metabolic markers as independent indicators of tumor behavior and predictors of 2 year survival for patients with glioblastoma multiforme (GBM). If successful, our study will establish astrocytoma HRMAS metabolic databases and objective parameters to serve as an adjunct modality for predicting tumor development, progression and patient outcome. We expect that current diagnostic sensitivity and specificity will be improved by utilizing HRMAS

18

Brain Tumors

1HMRS tumor markers. The results from this study will also further current understanding of tumor neurobiology and provide new linkages among fields such as clinical pathology, clinical radiology, tumor biology and molecular genetics. Astrocytoma metabolic markers obtained from this study will have important implications on the future development of magnetic resonance spectroscopic imaging (MRSI) and localized in vivo MR spectroscopy for non-invasive diagnosis and therapeutic monitoring of these neoplasms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPLORING GENE-ENVIRONMENT FACTORS IN CHILD BRAIN TUMORS Principal Investigator & Institution: Mueller, Beth A.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The causes of childhood brain tumors (CBT) are largely unknown. Environmental exposures are thought to play a role due to the vulnerability of fetal and early childhood brain to environmental toxins. This project would improve our limited understanding of the relationships of environmental and genetic factors in CBT occurrence by providing necessary preliminary data about the frequency of selected polymorphisms in CBT cases and controls, and demonstrating the feasibility of measuring polymorphisms in dried blood spots (DBS) from newborn screening archives for population-based epidemiologic studies of CBT, thus positioning us for larger CBT studies examining genes and environment. We have an opportunity to gain this information efficiently and economically, as specimens and exposure data already have been obtained. We propose to measure polymorphisms for genes which code for enzymes that metabolize chemicals potentially related to CBT occurrence, in DBS collected from 66 CBT cases and 237 controls. We will compare polymorphisms for the following genes: 1) Cytochrome P-450 (CYP) 2E1 and CYP 2D6, coding Phase I enzymes that activate nitrosamines and other chemicals into cancer-causing intermediates; 2) Glutathione S-transferase (GST) (GSTP1, GSTT1, and GSTM1), which code for Phase II enzymes that detoxify organochlorine pesticides, nitrosoureas, CYPactivated nitrosamines, polycyclic aromatic hydrocarbons (PAH); 3) Microsomal epoxide hydrolase, relevant to activation of PAHs into cancer-causing intermediates; 4) Paraoxonase (PON1), potentially important in detoxifying metabolites of the common organophosphate (OP) insecticides chlorpyrifos and diazinon. To the extent possible with these data, we will describe polymorphisms within histologic categories and by age at diagnosis, and examine their relationship with relevant environmental exposures among a subset of subjects with exposure data for the prenatal and early childhood periods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GENE EXPRESSION BASED CLASSIFICATION OF GLIAL TUMORS Principal Investigator & Institution: Nelson, Stanley F.; Research Scientist; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JAN-2005 Summary: (Applicant's Description) Astrocytic brain tumors are among the most lethal and morbid tumors of adults, often occurring during the prime of life. The current system of diagnosis and classification of brain tumors is partially predictive of

Studies

19

outcomes, and remains based primarily upon morphologic criteria. Although recent work has shown a number of genetic differences which are critical in the oncogenesis and progression of astrocytic tumors, there is insufficient data to develop a molecular classification system. The availability of cDNA clones, large amounts of sequence, data and the technology for cDNA arrays provides a platform for the large scale analysis of gene expression in astrocytoma. We propose to identify a set of genes that will allow the molecular characterization of brain tumors by using cDNA microarray technology. Using a flexible microarray format will enable us to easily alter the arrayed genes whose expression patterns are most informative allowing us to create cost-effective glial tumorrelated reagents. It is our central hypothesis that a much more detailed analysis of the genes that are expressed in astrocytomas will provide a more precise prognostic ability, subgroup patients for optimal treatment, and help identify appropriate therapeutic targets, subgroups patients for optimal treatment 1)To determine the optimal means of sampling low grade astrocytomas, anaplastic astrocytomas, and glioblastoma multiformes, to determine the degree of molecular heterogeneity within astrocytic tumors, to determine whether the heterogeneity is greater between tumors than within an individual tumor at each gene, and to determine the level of variance of each gene on the microarray. 2)To determine the gene expression profiles of 120 excisional glioma and meningioma brain tumor biopsies to develop a reclassification of the tumors based on gene expression profiles. 3)To develop a set of genes with prognostic importance in low grade astrocytomas. 4)To validate the importance of the genes from specific aims 2 and 3 in the prognosis of low grade astrocytomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE THERAPY FOR BRAIN TUMORS Principal Investigator & Institution: Hochberg, Fred H.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 15-AUG-1996; Project End 31-JUL-2005 Summary: Malignant gliomas represent the single most costly and morbid neoplasm per capita. The prognosis for patients with these tumors has been largely unchanged by advances in surgery, radiation therapy and drug design. Our proposal provides an integrated effort to translate to clinical human trials laboratory advances in the design of herpes virus (HSV) vectors for the delivery of drug-enhancing genes to tumor cells. These effects build on achievements including over 35 publications over the past 2.5 years, the conduct of a human retroviral "gene-marking trial" and the design of three human therapeutic trials Four Projects and four Cores are united , in collaboration with GMP vector facilities, as a resource for the brain-tumor Consortium (NABTT) to provide gene therapies of glioblastomas. Our studies explore vascular and migratory cell delivery systems (Project 4- Breakfield) of herpes virus and herpes-based amplicon vector systems. Studies are designed to provide high titers of HSV vector containing enzymes and herpes-based amplicon vector systems. Studies are designed to provide high titers of HSV vector containing enzymes which separately and in synergy activate pro-drugs including cyclophosphamide and irinotecan. Initial toxicity studies in Aoutus and Scientific Advisory meetings have resulted in the addition of two new scientific aims: We will track the delivery of vector, transgene and delivery cells using novel radiolabels in rodents and we will evaluate the Cytotoxic T Lymphocyte response to novel tumor antigens B-gal and OVA as distinguished from herpes vectors. In Aoutus and Human Trials we will distinguish from herpes vectors. In Aoutus and Human trials we will examine the local CTL responses that follow herpes vector transduction into brain. Human and in-vitro drug studies will be supported by for manufacture of

20

Brain Tumors

polymeric pro-drug systems, and analysis and modeling for single and multiple activated drugs. All studies will be supported by histologic and immunohistochemical evaluations of gene expression and changes in tumor and surrounding brain, as well as the molecular characterization of tumors. Our program defines a rational and scientific means to evaluate and expand the potential of gen therapy for brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE THERAPY TARGETING HYPOXIC GLIOMA CELLS Principal Investigator & Institution: Deen, Dennis F.; Berthold and Belle N. Guggenhime Profess; Neurological Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: Radiation is a primary treatment modality for patients with malignant gliomas, and in most patients radiation therapy is clearly beneficial. However, the overall outcome of therapy for these patients is dismal, and most patients with glioblastoma multiforme (GBM) die within a year of diagnosis. The presence of hypoxic cells in brain tumors is a major obstacle for radiation therapy, because these cells are notoriously resistant to radiation-induced damage. Therefore, we propose to devise a gene therapy approach for killing hypoxic brain tumor cells during the course of radiation therapy. The DNA construct to be delivered to the tumor cells contains hypoxia-responsive elements (HREs) in the enhancer region of the promoter and a suicide gene. Under hypoxic conditions, the transcriptional complex hypoxia inducible factor-1 (HIF- 1) builds up in cells and binds to HREs. This, in turn, activates the adjacent promoter and causes expression of the downstream suicide gene that kills the cell. This project has 2 goals. The first is to investigate how several cellular or intratumoral characteristics impact on this gene therapy strategy. The second is to investigate whether the gene therapy enhances the radiation response of the tumor cells. We propose 4 specific aims to accomplish these goals. 1) investigate the relationship between HIF-1 and oxygenation status in brain tumor and normal brain; 2) evaluate suicide genes under low pH and in noncycling brain tumor cells; 3) reveal and investigate any bystander effect (BE) produced by specific suicide genes under hypoxic conditions; 4) determine whether expression of suicide genes in hypoxic and oxic cells enhances their response to radiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GENETICALLY ENGINEERED VIRUSES FOR BRAIN TUMOR THERAPY Principal Investigator & Institution: Martuza, Robert L.; Chief of Neurosurgery; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-MAY-1994; Project End 31-MAR-2007 Summary: (provided by applicant): We have developed genetically engineered herpes simplex virus-1 (HSV-1) vectors that can selectively and efficiently infect and kill brain tumor cells in situ without harming surrounding brain cells and without causing systemic disease. Having taken one such vector into human clinical trial, we set forth testable hypotheses aimed at further understanding and improving this method of brain tumor therapy. In order to increase the efficacy of HSV oncolysis in brain tumor therapy, we hypothesize that: a.) HSV oncolytic therapy can be improved by using a HSV vector in conjunction with commonly used chemotherapeutic agents for brain tumors; b.) The efficacy of herpes vectors for brain tumor therapy can be improved

Studies

21

through the use of a HSV backbone that replicates better in glioma cells while retaining the necessary safety features for clinical trials. In order to better understand and improve the delivery of HSV vectors for brain tumor therapy, we hypothesize that: a.) Some of the efficacy following intravascular or intratumoral HSV tumor therapy may be due to selective injury of tumor vasculature versus normal vasculature; b.) The timing of co-treatment with antiangiogenesis agents may either inhibit or augment the selective injury to tumor vasculature by oncolytic HSV vectors; c.) Prior anti-HSV immunity could alter the efficacy of intravascular delivery of oncolytic HSV but can be modulated with immunosuppressive agents. In order to further improve the anti-tumor immunity induced by HSV tumor therapy, we hypothesize that: a.) Defective HSV vectors expressing immune-modulatory genes will increase the survival of animals harboring intracranial tumors, b.) A recombinant virus can be constructed from an appropriate parent virus that will express a cytokine without down-regulating MHC-I thus enhancing the anti-tumor immune response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESISTANCE

GSH

TRANSFERASE

PI

POLYMORPHISM

AND

DRUG

Principal Investigator & Institution: Ali-Osman, Francis C.; Professor and Head; Experimental Pediatrics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: (Applicant's Abstract) Malignant brain tumors continue to increase in incidence in the US, and currently are the most common solid tumors of childhood and adolescence. Unfortunately, however, brain tumors remain among the most therapeutically intractable of human tumors, and long term survivors are rare among patients with highly anaplastic astrocytomas or glioblastoma multiforme. A major cause of failure of brain tumor therapy, as in most other human cancers, is drug resistance, and much effort has been devoted towards understanding the cellular and molecular mechanisms that underly it. These studies have shown that drug resistance mechanisms often involve the dysregulation of genes, many of which are involved in normal cellular processes, such as metabolism, transport, DNA repair and cell cycle progression. One of the best characterized of these mechanisms is that of GST-pi over-expression. This application is founded on two significant recent findings from the applicant's laboratory related to the GST-pi gene. The first is that in gliomas, GST-pi over-expression is associated with drug resistance, malignant progression and poor patient survival. Secondly, he has made the potentially very important discovery that the human GST-pi gene locus is polymorphic and contains, at least, three allelic GST-pi gene variants. One of these variants, hGSTP1*C, is more frequently present in gliomas than in normal cells/tissues. The applicant has cloned the variant cDNAs and shown the encoded proteins to be structurally and functionally different. These findings are having a significant impact in the field of GST research. The primary goal of this application is to examine the influence of this newly discovered GST-pi genetic polymorphism on drug resistance in human gliomas and to determine whether specific GST-pi genotype/phenotypes are associated with differential therapeutic outcome and in patient survival. The Specific aims are: 1) To determine by molecular dynamic modeling, the differential binding affinities of anticancer agents to the active sites of proteins encoded by GST-pi allelic gene variants and correlate these with the differential abilities of the GST-pi proteins to inactivate anticancer agents; 2) To determine whether different GST-pi gene variants confer different levels of drug resistance to malignant

22

Brain Tumors

glioma cells; 3) To determine whether GST-pi allelotype is related to the level of in vitro drug resistance of gliomas, and with in vivo response to therapy and survival of glioma patients following chemotherapy; and, 4) To determine whether down-regulation of GST-pi gene expression in gliomas that express different GST-pi gene variants will differentially affect drug resistance. The applicant believes that this application is wellfocused and has a significant degree of novelty, with respect to the hypothesis, preliminary data and experimental techniques to be used. He believes the results are likely to make important and critical contributions to understanding the cellular, molecular and genetic mechanisms involved in GST-pi mediated drug resistance in human gliomas that will be applicable to many other human tumor types for which GST-pi over-expression has been shown to be an important determinant of drug resistance and failure of patients to respond to therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HARVARD PEDIATRIC BRAIN TUMOR CENTER Principal Investigator & Institution: Kieran, Mark W.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The Harvard Pediatric Brain Tumor Center will join the Pediatric Brain Tumor Clinical Trials Consortium, endorse its Constitution, participate in committee activities, give absolute priority to Consortium protocols, and collaborate with other Consortium members. Our multi-disciplinary group is committed to: 1) Ensuring that, each year, more than 15 patients with newly diagnosed or recurrent brain tumors are available for Consortium studies; 2) Acting as a resource for the Consortium in those areas where our expertise will assist the Consortium in ensuring its success; our commitment to being a resource will include members from all areas, including our departments of Neurosurgery, Radiation Oncology, Oncology, Neurology, Pathology, Radiology, Gene Therapy and Angiogenesis. 3) Proposing novel studies that meet the Consortium's goals. In that regard, we have already developed three proposals: i) Phase I study of endostatin, an angiogenic inhibitor, in pediatric patients with poor prognosis malignancies; ii) Phase I study of GM3, a novel ganglioside in pediatric patients with malignant brain tumors; iii) a Phase I study of oxaliplatin as a radiation sensitizer in pediatric brain stem gliomas. 4) Developing and expanding a pediatric brain tumor tissue bank. We will cooperate with Consortium partners to develop a new central tissue bank or a virtual tissue bank. On request, we will also make material from the Harvard Brain Tumor Tissue Bank, which currently has over 1500 adult and 200 pediatric samples, available to Consortium members. 5) Continuing to develop our current expertise in several areas, including: anti-angiogenic molecules (Dr. Judah Folkman); biodegradable wafers containing endostatin (Dr. Peter Black); novel gene therapy vectors (Dr. Richard Mulligan); proton beam and stereotactic radiation therapy (Dr. Nancy Tarbell); small molecule signal transduction inhibitors (Dr. Chuck Stiles); Multivoxal high resolution magnetic resonance spectroscopy (Dr. Aria Tzika); and molecular characterization of brain tumors (Dr. David Louis). In summary, we will bring the full thrust of a Comprehensive Cancer Center and the full services of a pediatric center to enhance the Consortium and our mutual missions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

23

Project Title: HUMAN BRAIN PROTEIN MR IMAGING AND SPECTROSCOPY AT 3T Principal Investigator & Institution: Zhou, Jinyuan; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Despite the abundance of proteins inside many cell types, these proteins do not provide intense signals in proton magnetic resonance (MR) spectra, and little has been studied about cellular proteins in vivo or in cells, in particular, there are presently no magnetic resonance imaging (MRI) methods to spatially assess protein content and status in vivo. Yet, most cellular activities are performed by proteins, and various lesions, such as those found in cancer and stroke, may show changes in protein content and amide proton exchange properties, and thus the interpretation of the nature of these proteins is important for earlier detection, better spatial definition, and improved characterization of diseases. We will develop novel MRI and MRS (magnetic resonance spectroscopy) methods for studying mobile cellular proteins and their properties in tissue. We hypothesize that detection sensitivity enhancement through selective saturation transfer via water-exchangeable amide protons of mobile proteins allows spatial assessment of protein content and status in biological tissue via the water signal. The overall goal of this study is to develop a completely new MRI technique, called amide proton transfer (APT) imaging, which opens the possibility of adding intrinsic protein-based contrast to the diagnostic capability of high-field MRI. The clinical use of this type of imaging will first be demonstrated for human brain tumors. Therefore, the specific aims of this application are: (1) To develop new MR spectroscopy methods with a WATERGATE detection scheme and to quantify amide proton content and exchange rates in the human brain on a 3T clinical MRI system. (2) To develop and implement a new single-slice amide proton transfer imaging technique and to quantify amide proton transfer contrast for imaging of brain tumors on a 3T human MRI system. (3) To determine brain tumor boundary and volume using multi-slice amide proton transfer imaging on a 3T human MRI system. APT imaging can be used to study a host of potentially abnormal proteins in cancer, stroke, metabolic disorders, and other diseases. The successful outcome of this application will offer a sensitive and specific modality in the clinical MRI examination of diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HUMAN NEURAL STEM CELLS TARGET GENE THERAPY-BRAIN TUMORS Principal Investigator & Institution: Aboody, Karen S.; Professor; Layton Bioscience, Inc. 709 E Evelyn Ave Sunnyvale, Ca 94086 Timing: Fiscal Year 2001; Project Start 26-JUN-2000; Project End 31-JUL-2003 Summary: Neural stem cells (NSCs) show a remarkable ability to migrate throughout the CNS, intermingle with host cells, and express foreign transgenes following transplantation. Intriguingly, this inherent migratory property of NSCs emulates the migratory pattern of some brain tumors, such as gliomas, characterized by invasive single cell migration. Potentially, the migratory properties of NSCs can be harnessed to disseminate therapeutic genes products to invading brain tumor cells. As the first step toward this goal, results from phase I studies demonstrated that human NSCs displayed significant tumor targeting migratory behavior toward gliomas while stable expressing a reporter gene. Phase II entails genetically modifying NSCs to express an array of

24

Brain Tumors

therapeutic genes, and then assessing their potential to target tumor cells and elicit an anti-tumor response. It is anticipated that genetically modified NSCs will infiltrate the tumor mass, track individual tumor cells, and stably express oncolytic proteins that can destroy the cancerous cells in rodent models. These studies will advance the development of a potentially revolutionary treatment strategy using human NSCs as a novel, efficient delivery vehicle to target therapeutic genes to refractory brain tumors. PROPOSED COMMERCIAL APPLICATIONS: Neural stem cells represent a compelling new technology platform for the treatment of neurological diseases. Their natural migratory capacity provides a powerful vehicle to target therapeutic agents directly to refractory brain tumors. This project will evaluate an array of therapeutic genes to expedite the development of a potentially revolutionary cancer therapy strategy to treat deadly brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPOXIA AS A TARGET FOR THE TREATMENT OF BRAIN TUMORS Principal Investigator & Institution: Van Meir, Erwin G.; Professor; Neurosurgery; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 03-MAY-2001; Project End 31-JAN-2004 Summary: (provided by applicant): Primary brain tumors (mainly malignant gliomas, medulloblastomas and ependymornas) have become the main cause of death from cancer in children and young adults. Hypoxia is a physiological difference between normal and tumor tissue. We propose to exploit this difference to construct a novel type of cancer therapy adenovirus. We will conditionally regulate the replication ability of an adenovirus by placing the adenoviral EIA gene under the control of an exogenous hypoxia-regulated promoter (HYPR-Ad). Since adenoviruses have a cytolytic cycle, the selective replication of adenoviruses within hypoxic tumor cells will lead to oncolysis. Moreover, we will augment the antitumor capability of this oncolytic: virus by having it function as a therapeutic gene delivery vehicle. We will introduce into the HYPR viral vector an expression cassette for the angiogenesis inhibitor thrombospondin-1 (HYPRAAd). The production of this inhibitor by infected hypoxic cells will generate a field effect that should counteract the action of the angiogenic stimulators released by these cells in response to hypoxia. In addition, it should reduce the expansion of noninfected and normoxic tumor cells since they will not be able to recruit new vascular supply. These recombinant adenoviruses will be studied for their ability to infect, replicate, and induce cytolysis of cells derived from pediatric glioma, medulloblastoma and ependymoma under normoxic and hypoxic conditions in vitro. Subsequently, the therapeutic efficacy of these viruses against xenografts of these pediatric brain tumors will be examined, in both subcutaneous and intracerebral models in immunocompromised (nulnu) mice. The tumor therapy approach presented in this proposal is novel in that these viruses can provide direct oncolytic therapy as well as deliver adjuvant gene therapy. Although these viruses have broad applicability to treat ALL cancer types which develop hypoxia, regardless of their tissue of origin and genetic composition, funding of this application will enable us to specifically develop this strategy to treat/cure pediatric brain tumors. The translation of these preclinical studies have the potential to directly benefit human health by improving the survival of children and adults with cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

25

Project Title: IMAGING BRAIN TUMORS WITH FACBC Principal Investigator & Institution: Blasberg, Ronald G.; Professor; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): A frequent question in the management of primary brain tumors in the post-treatment period is whethei a new or expanding brain lesion observed on CT or MR imaging represents recurrent tumor or treatment effects. This is of particular concern in the management of patients with previously treated low grade or anaplastic gliomas. PET imaging can provide "functional" information, in addition to that obtained by MRI, which may be useful in patient management decisions. Amino acid imaging of tumors with positron emission tomography (PET) dates back two decades, and the consensus opinion that is amino acid images provide better information with respect to brain tumor localization than fluorodeoxyglucose (FDG). We propose an initial small series of PET imaging studies that compare a fluorine-18 labeled amino acid analogue, 3-fluoroaminocyclobutane carboxylic acid (3-[18F]FACBC) to carbon-11 labeled [methyl-11c]-l-methionine, the amino acid currently used in most brain tumor imaging studies and considered to be the "gold standard". Compared to [methyl-11c]-L-methionine, [18F]-FACBC provides substantial logistical and cost-effective benefits for brain tumor imaging in a busy nuclear medicine department; this is due to the longer half-life of [18F] (t 1/2=110 min) compared to [11C] (t1/2=20 min). The goals of this proposal are: 1) to obtain sufficient [18F]-FACBC biodistribution and dosimetry data in human subjects that will support the submission of an investigational new drug (IND) application to the Food and Drug Agency (FDA); 2) to show that [18F]-FACBC has equal or better brain tumor imaging characteristics than [methyl-11C]-L-methionine, and has the potential to improve the "early" detection of recurrent or progressive primary brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: IMPROVED MRI CONTRAST AGENTS Principal Investigator & Institution: Hainfeld, James F.; Biophysicist; Nanoprobes, Inc. 95 Horseblock Rd Yaphank, Ny 11980 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): A new class of MRI contrast agents has been discovered and synthesized by Nanoprobes. Initial MRI animal studies showed excellent definition of some types of brain tumors, which were undetectable with the commonly used agent, gadodiamide. Furthermore, initial toxicity studies showed the agents to be non-toxic. One new agent was coupled to antibodies and showed high delivery to antigen on bench tests, indicating hope for development of targeted contrast agents for functional MRI. This project will focus on continued development including chemical synthesis, purification, chemical and magnetic characterization, in vivo animal studies, and antibody targeting of the agents in vivo. PROPOSED COMMERCIAL APPLICATIONS: MRI us a highly useful non-invasive technique. Unfortunately, many brain tumors are poorly detected with the current contrast agents. New agents that give improved imaging of not only brain, but breast, prostate and other cancers would have extensive application. Furthermore, the development of targeted agents could functionally distinguish between benign and malignant tumors and be used to diagnose many other conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

26

Brain Tumors

•

Project Title: INTERACTIONS BETWEEN IMMUNE SYSTEM AND VIRAL ONCOLYSIS Principal Investigator & Institution: Johnson, R. Paul.; Associate Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2002 Summary: The ability of Herpes simplex virus (HSV) vectors to induce selective death of brain tumor cells in vivo may be due to a number of different mechanisms, including direct virus-induced oncolysis, sensitization of the tumor to chemotherapy-induced cell death or induction of immune responses directed against the vector of tumor antigens. At present, little is known about the relative contribution of these different mechanisms of about immune responses, directed against HSV vectors. Cellular immune responses to HSV vectors may augment viral oncolysis; alternatively, they may inhibit oncolysis by limiting replication of the vector. Addressing these issues is critical to the successful development of HSV vectors for gene therapy for brain tumors, since the answers to these questions can result in a modification to either augment of diminish immunogenicity resulting in improved oncolysis. We propose to address this issue through the following set of specific aims: 1. To examine the effect of the host immune response on tumor cell killing in mice using the model glioma GL261; 2. To determine the immune mechanism of tumor cell killing in this model; 3. To characterize CTL responses to HSV mutants following intracerebral injections in Aotus monkeys; and 4. To characterize the specificity of tumor infiltrating lymphocytes (TILs) in recognizing viral mutants and/or tumor in patients affected by malignant glioma. The results from these experiments should shed light on potential beneficial or adverse interactions between the immune system and viral oncolysis and ultimately assist in the development of more effective HSV vectors for the treatment of brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: INTERDISCIPLINARY TUMOR COMPLEXITY MODELING Principal Investigator & Institution: Chiocca, E Antonio.; Professor of Neurosurgery; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): "Interdisciplinary Tumor Complexity Modeling" (2nd RESUBMISSION). In spite of aggressive l therapies, the outcome for patients suffering from highly malignant brain tumors remains uniformly fatal. Responsible for this grim outcome are rapid tumor growth, clonal heterogeneity, acquired treatment resistance and extensive tumor invasion, rendering cytoreductive therapy ineffective. We believe that malignant tumors behave as complex dynamic, adaptive and selforganizing biosystems rather than as unorganized cell masses. If this is true, such malignant tumors also have to be investigated and ultimately targeted as complex: systems. Our work is therefore motivated by the following three hypotheses: (1) malignant brain tumors behave as complex dynamic biosystems; (2) these tumors systems invade according to the principle of "least resistance, most permission and highest attraction "; (3) their spatio-temporal behavior can be studied, simulated and predicted using an interdisciplinary approach combining in vitro and in vivo experiments, human imaging data and computational modeling. To investigate these hypotheses, our specific aims are as follows. Specific AIM 1: We will develop a novel 3D in vitro assay system, suitable of displaying several key-features of multicellular tumor spheroids (MTS) in parallel over a prolonged period of time. The experimental studies using these devices include the microstructural analysis of the extracellular matrix gel-

Studies

27

medium as well as the structural, genetics and functional analysis of the spatio-temporal expansion of the micro-tumor system (i.e., on site proliferation and invasive cell network). We will also study tumor growth, invasion and physiology (blood flow and blood volume) in vivo, using MR-imaging of an orthotopic xenogeneic brain tumor model in athymic rats. Studies follow, which investigate invasive tumor cell dynamics in vivo with and without specifically implanted "attractor" sites. Both, in vitro and in vivo results will generate dynamic, multiscaled multi-modality data sets, which will then be incorporated into the computational models. Specific AIM 2: We will develop a set of related, innovative computational models to simulate brain tumor proliferation, genetic and epigenetic heterogeneity, angiogenesis and most importantly, tissue invasion. Discrete and continuum approaches include a variety of techniques such as cellular automata, Kinetic Monte Carlo (KMC) simulations, agent based modeling, generegulatory net modeling, fractal analysis and coupled reaction-diffusion equations. Once developed, the computational models will drive the experiments and vice versa. Finally, the merged models will be used to predict the course of brain tumor expansion using real human imaging data (retrospective study) and will be further developed into powerful virtual reality platforms for treatment planning and surgical training tools (feasibility study). Based on our convincing preliminary studies paradigm-shifting insights into brain tumor growth, heterogeneity, invasion and angiogenesis can be expected. The presented work is highly innovative and profoundly interdisciplinary as it combines many seemingly disparate disciplines such as cancer research, statistical physics and mechanics, materials science, biomedical engineering and -imaging, computational visualization, mathematical biology, computational and complex systems science. This Bioengineering Research Partnership investigates groundbreaking tumor biology concepts. This work can therefore very well build the basis for the development of novel diagnostic tools, innovative patient specific treatment planning devices and thus, may ultimately lead to more successful therapeutic strategies, capable of changing the grim outcome of the many patients suffering from this devastating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IR-INDUCED APOPTOSIS IN THE DEVELOPING NERVOUS SYSTEM Principal Investigator & Institution: Mckinnon, Peter J.; Associate Member; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2001; Project Start 15-JAN-2001; Project End 31-DEC-2004 Summary: (adapted from applicant's abstract): Brain tumors are second only to leukemia as the most prevalent form of pediatric malignancy. However, unlike leukemia, effective treatments for brain tumors are lacking. Ionizing radiation is one of the more common strategies used to treat brain tumors. While radiation can be effective in killing the tumor, a devastating consequence of this approach is damage to normal tissues, resulting in severe cognitive impairment. It has been estimated that upward of 60 percent of children treated for brain tumors by irradiation develop significant cognitive defects. The damaging effects of radiation upon both tumor and normal tissue are likely to involve apoptosis. The prevention of damage to normal tissue as well as radiosensitizing the tumor would have significant clinical impact. Both scenarios would benefit from a comprehensive understanding of the regulatory components operating during apoptosis. Therefore, a detailed molecular understanding of the apoptotic process will afford the opportunity for therapeutic intervention and the clinical control of these processes. Research described in this proposal will elucidate critical components of the ionizing radiation induced apoptotic pathway in the nervous system, thereby

28

Brain Tumors

facilitating a greater understanding of the molecular interplay involved. Additionally, this research will also provide fundamental information about the role of death regulators in the nervous system. The investigator's preliminary data show that new gene expression is required for IR-induced apoptosis in the developing nervous system. The PI will use cDNA microarray analysis, representational difference analysis and protein interaction analysis to determine which genes are causal in IR-induced damage of the early postnatal nervous system. The PI will subsequently focus the analysis of these genes by selecting those that are regulated in wildtype mice, but not in mice such as Atm or p53-null, with defective IR-induced neural apoptosis. Using a variety of in vitro and in vivo approaches, they will determine the contribution of these IR-induced genes towards apoptosis in the nervous system. Identifying and characterizing the genes involved in cell death will be valuable for rational design of approaches to manipulate these processes clinically. Moreover, as neurodegenerative disease may engage similar apoptotic pathways, the findings from this proposal will be relevant for understanding neuronal death in neurodegenerative disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LOCAL THERAPY OF GLIOMAS USING A NOVEL BCNU FORMULATION Principal Investigator & Institution: Pietronigro, Dennis; Direct Therapeutics, Inc. 460 Seaport Ct, Ste 220 Redwood City, Ca 95063 Timing: Fiscal Year 2003; Project Start 23-MAY-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Brain tumors are the second leading cause of cancer-related deaths in children and fourth in middle-aged man. Malignant gliomas remain uniformly fatal underscoring the urgent need for new, more effective treatments. More effective therapies coupled with improved imaging information would provide important opportunities to improve care and individualize treatments. Results from preclinical studies funded by the Phase I award using a direct injection of BCNU dissolved in ethanol (DTI-015) have revealed significant therapeutic efficacy compared to systemic delivery of BCNU. Moreover, recent results obtained from two clinical Phase I/II trials by Direct Therapeutics, Inc. have generated a great deal of excitement for the use of DTI015 for the treatment of malignant brain tumors. A significant limitation of the DTI-015 formulation is that The toxicity of the absolute ethanol limits the scope of its applicability to solid, small (3-4 cm) well Circumscribed tumors in humans. In an effort to treat larger as well as disseminated, infiltrating malignant gliomas, we propose to investigate the use of alternate drug delivery vehicles, which are proposed to have reduced toxicity and the potential to deliver BCNU over a larger tissue volume. In this Phase II proposal, we will use a rodent glioma model to optimize the BCNU formulation to achieve maximal delivery and therapeutic efficacy. Phase I award results demonstrated a tumoral transient vascular collapse after administration of DTI-015 that may play a significant role in the efficacy of the agent due to the retention of BCNU within the tumor tissue. The ability of alternate vehicles to induce this vascular collapse without toxicity resulting in an improvement in therapeutic efficacy will be investigated. The proposed studies will be facilitated through the use of noninvasive serial magnetic resonance imaging to evaluate the dynamic distribution of the solvent vehicle as well as the therapeutic effectiveness by diffusion weighted MRI. The use of MRI will prove beneficial for subsequent translation of an optimized formulation into clinical trials. Although the present study is focused on the treatment of brain tumors, the successful local treatment of this disease would motivate future clinical trials to other tumor sites including breast, prostate and pancreas.

Studies

29

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MAGNETIC RESONANCE SPECTROSCOPIC NEOPLASM IMAGING Principal Investigator & Institution: Spielman, Daniel M.; Associate Professor; Radiology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 23-JUL-1990; Project End 31-JUL-2004 Summary: The overall goal of this project is the development of proton magnetic resonance spectroscopic imaging (MRSI) techniques and their subsequent application for aiding in the diagnosis and treatment monitoring of patients with tumors. As a noninvasive tool providing unique biochemical information supplemental to conventional imaging, in vivo MRSI has been shown to have a valuable role in the study of cancer. However, significant technical improvements, particularly for the reliable acquisition of volumetric MRSI data from tumors throughout the body, are needed to fully realize the clinical potential of this powerful imaging modality. This proposal is focused on the continued technical development of innovative spectroscopic techniques for the robust and efficient collection, quantification, and display of this information. The techniques will be tested on phantoms, normal volunteers, as well as patients with brain tumors, metastatic neck nodes of squamous cell carcinomas, and breast cancer. In parallel with the continued technical development, we will conduct a focused, wellcontrolled clinical study comparing the abilities of proton MRSI and FDG PET for differentiating radiation necrosis from recurrent glial tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MENTORED DEVELOPMENT AW

PATIENT

ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Sampson, John H.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract): The brain is the most frequent site of crippling and incurable human disease, and malignant primary brain tumors alone are more common than Hodgkin's disease, and cause more deaths than cancer of the bladder or kidney, leukemia, or melanoma. Conventional therapy for malignant brain tumors is ineffective and incapacitating, and represents the most expensive medical therapy per quality- adjusted life-year saved currently provided in the U.S. At the investigators institution, direct injection of (131)I-labeled, operationally-specific, monoclonal antibodies (MAbs) into brain tumor resection cavities delivers extremely high radiation doses to tumor cells around the resection cavity and has produced promising results in Phase II clinical trials. However, these MAbs diffuse only short distances beyond the cavity. Therefore, most of the radiation extending beyond the cavity is not specifically targeted to tumor cells and the radiation dose delivered beyond the cavity declines exponentially from the cavity interface. As a result, tumor cells that are known to infiltrate the brain for significant distances beyond the cavity are subopitimally treated and lethal tumors always recur within 2cm of the radiated resection cavity. Continuous microinfusion is a promising technique that allows homogeneous delivery of even large molecular weight molecules at high concentrations throughout large areas of the brain. Although this technique may enhance the delivery of (131)I-labeled MAbs and other therapeutic agents to diffusely infiltrating malignant brain tumors and reduce recurrence rates, the parameters that govern this technique and its limitations have not been defined. One of the major goals of this proposal is to

30

Brain Tumors

define these parameters. In addition, this proposal is designed to investigate whether targeted radiotherapy might be improved through the use of human chimeric MAbs with increased biostability and the use of high linear energy transfer radioisotopes, such as (211)At, with greater relative biological effectiveness. The hypothesis to be tested in this proposal is that continuous microinfusion will widely deliver operationally tumorspecific MAbs conjugated to (131)I or the alpha-emitter (211)At such that they will be specific and potent therapeutic agents against malignant brain tumors with major reductions in toxicity to normal brain over conventional whole brain radiotherapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC POLYMORPHISMS AND SURVIVAL FROM BRAIN TUMORS Principal Investigator & Institution: Bondy, Melissa L.; Professor; Epidemiology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The outcome for patients with primary malignant brain tumors is poor. Radiotherapy and chemotherapy have improved the outcome, especially in the chemotherapy-sensitive group of tumors such as anaplastic astrocytoma and anaplastic oligodendroglioma. Yet it is not possible to identify the patients who will benefit from such treatments in advance. Inherited variability in metabolism of therapeutic agents is suggested to be responsible, in part for individual differences in response to cancer treatment. Overall purpose of the proposed study is to investigate the role of genetic polymorphisms in the glutathione s-transferase (GST) enzyme family in predicting survival in 305 patients with anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma, treated at the University of Texas MD Anderson Cancer Center between 1994 and 2004. We hypothesize that patients with inherent low GST activity have reduced clearance of reactive agents of chemo- and radiotherapy and are more likely to have a better treatment effect at the tumor site. Further, we predict that individuals with low activity GST genotypes will have increased survival time when compared to those with inherently high GST activity. We will determine the frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in 350 cases by polymerase chain reaction and restriction fragment length polymorphisms. We will review medical records of the 350 patients and abstract information on outcome, treatment and clinically significant adverse events related to radiotherapy and, chemotherapy that required delaying or cessation of treatment. To assess if GST polymorphisms are associated with outcome in patients with primary malignant brain tumor we will perform Kaplan-Meier and Cox proportional hazard analyses. To explore whether metabolic polymorphisms of the GST enzyme family are correlated with occurrence of adverse effects secondary to chemotherapy we will use logistic regression, Kaplan-Meier and Cox proportional hazard analyses. Based on the results of the proposed study, in the future chemotherapy regimens can be tailored according to individual patient's metabolic enzyme profile. Thus, patients who can tolerate higher doses of chemotherapy can be treated more efficiently, suffering from less side effects and potentially may have a better outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MICROBEAM RADIATION THERAPY FOR GLIOMAS Principal Investigator & Institution: Dilmanian, F Avraham.; Scientist; Brookhaven Science Assoc-Brookhaven Lab Brookhaven National Lab Upton, Ny 11973

Studies

31

Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Microbeam Radiation Therapy (MRT) is a novel approach that utilizes parallel, thin (<100 mum wide) planes of synchrotron-generated x-rays (microplanar beams, or microbeams). Single-fraction unidirectional MRT preferentially kills gliomas in experimental animals while sparing normal brain tissue, thus producing a higher therapeutic index (ratio of maximum dose tolerated by normal tissue to the minimum dose ablating the tumor) than conventional broad-beam therapy. We hypothesize that the normal-tissue-sparing of MRT is due to the replacement of lethally injured endothelial cells in the direct paths of the microbeams by their neighboring cells surviving between the beams. This proposal will evaluate the above hypothesis, and examine possible enhancement of the MRT's beneficial effects by a) dose-fractionation, and b) by gadolinium administration. Intracranial CNS-1 rat glioma and the normal rat brain will be used as models. Microbeams' therapeutic index will be compared to that of broad beams. A major consideration in the experimental design of Aim 1, dose-fractionated MRT, is that MRT dose must be fractionated at intervals, 1-3 weeks, long enough to permit (presumably) vascular repair; this limitation exists because the microbeam pattern from the second irradiation may fall between the pattern from the first one, thus interfering with the repair process. Therefore, mechanistic studies to estimate the recovery time of normal brain tissue from MRT will be pursued first to estimate the recovery time. Unidirectional unfractionated (two equal dose fractions, each tentatively half the unfractionated dose) and fractionated MRT, as well as unfractionated broad beams will be studied. The endpoints will include normal-tissue damage and tumor control assessed by MRI, behavioral tests, survival, and histology. Aim 2, Gd-enhance MRT, is motivated by a) the large uptake of Gd by the glioma after injecting the MRI contrast agent, Gadovist, and, b) Monte Carlo simulations of MRT dose distribution demonstrating that the tumor's the radiation leakage between microbeams (the "valley" dose) in the tumor increases three-fold after Gd uptake. Experiments will include unidirectional microbeam and broad-beam irradiations 5 minutes after Gd administration. Optimizing the highly innovative method of MRT from our findings may significantly boost its therapeutic index, leading to a breakthrough in the radiation therapy of brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETICS OF INHERITED NEUROLOGICAL DISEASES Principal Investigator & Institution: Breakefield, Xandra O.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 23-JAN-1987; Project End 31-AUG-2006 Summary: (provided by applicant) The goals of this Neurogenetics Center are to elucidate the molecular etiology and to ameliorate the course of hereditary tumors of the nervous system, in particular in neurofibromatosis type 2 (NF2) and tuberous sclerosis (TSC) This research will provide insight into the etiology of spontaneous neural tumors and mechanisms of growth regulation in the developing nervous system. The focus of the proposed studies is on understanding the genetic basis of functional changes in merlin (NF2), hamartin (TSC1) and tuberin (TSC2) and their role in formation and progression of meningiomas and other brain tumors. Elucidation of the cellular function of these proteins will be facilitated through identification and characterization of interacting proteins. Further, transgenic mouse models of these diseases will be used to understand physiologic changes associated with loss of these tumor suppressor genes and to provide a platform for therapeutic strategies. Project 10 (Gusella)-Molecular

32

Brain Tumors

genetics of meningioma and NF-related disorders: elucidate cellular functions of merlin in growth and adhesion; determine the role of this and other genes in the ontogeny and progression of meningiomas; and identify genes involved in related, hereditary neural tumor syndromes; Project 11 (Ramesh, Ito)-Characterization of TSC proteins hamartin and tuberin: determine whether cortical lesions in TSC patients have loss of heterozygosity at the cellular level; and characterize the role of tuberin in control of cell cycle via elucidation of interacting proteins in mammalian cells and Drosophila; Project 12 (Kwiatkowski)-Murine models of TSC1: mechanisms and therapies: generate and characterize knock-out and conditional transgenic mice for TSC1 in the homozygous and heterozygous states and in different genetic backgrounds; characterize the phenotypic consequences of missense mutations in TSC1; and attempt to arrest cell growth in lesions using vectors. Project 13 (Breakefield, Brown)-Gene therapy for hereditary tumors in experimental models of TSC: evaluate gene delivery in mouse models of liver hemangioma, cortical harmartomas and renal cell carcinoma (TSC2+/-); generate brain lesions in TSC1 conditional knock-out animals by injection of Cre-bearing vectors; and test gene therapy models in vivo with herpes hybrid amplicon vectors and endothelial cell vehicles bearing genes for anti-angiogenic and apoptotic factors. These projects will be supported by Cores for Clinical Services (Sims, MacCollin) and Neuropathology and Tumor Banking (Louis and Stemmer-Rachamimov). Collectively these studies provide a concerted effort towards understanding the neurologic functions of NF2 and TSC genes and treating disease manifestations associated with these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR TARGETING OF EGFR FOR THE TREATMENT OF GLIOMAS Principal Investigator & Institution: Barth, Rolf F.; Pathology; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The overall objective of this translational research project is to develop a two pronged attack against high grade brain tumors, first, by specific molecular targeting of either the epidermal growth factor receptor (EGFR) or a mutant isoform of the receptor, EGFRvIII. However, since there is considerable variability in EGFR expression among malignant gliomas and within individual tumors themselves, this receptor alone cannot be the only target for gliomas in general or for all of the constituent cells of any individual tumor. Therefore, combinations of agents will be required. Accordingly, the second part of this attack will utilize two FDA approved, low molecular weight drugs that have been used clinically for boron neutron capture therapy (BNCT). The first is a boronophenylalanine or BPA, which is preferentially taken up by more metabolically active tumor cells, and the second is a blood-brain barrier permeable drug, sodium borocaptate (BSH). Following administration of the boron delivery agents, BNCT will be initiated at a point in time when there is an optimum tumor to normal brain boron ratio. To carry out these studies, we have developed two rat glioma models from the EGFR (-) F98 parental tumor, which has been transfected with either the gene encoding human "wild type" EGFR or EGFRvIII. The F98EGFR expresses amplified wild type EGFR and the second, F98EGFRVIII, expresses an amplified mutant isoform of the receptor, EGFRvlII, which has a more restricted expression on human malignant gliomas. Each of these receptors is expressed with high density (>105 receptor sites) in the corresponding F98 transfectant. Targeting agents that already have been developed by us include heavily boronated EGF and a boronated

Studies

33

monoclonal antibody, which recognizes EGFRvIII. Since systemic administration of high molecular weight agents has been ineffective in targeting brain tumors, a more efficient approach, convection-enhanced delivery, will be used. The most important question raised by any translational research project is its applicability to future clinical trials. The key question that we will answer is "Can molecular targeting of EGFR (or EGFRvIII), combined with the second generation drugs BPA and BSH, produce a significant improvement in survival following BNCT compared to that which we have obtained with BSH and BPA in combination, using the F98EGFR and F98EGFRVIII glioma models?" Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MRI CONTRAST AGENT METHODS OF ASSESS TUMOR ANGIOGENESIS Principal Investigator & Institution: Schmainda, Kathleen M.; Assistant Professor; Radiology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2003; Project Start 01-MAR-2000; Project End 31-MAR-2007 Summary: (provided by applicant): Patients with brain tumors are in desperate need of new therapies, such as those that inhibit new vessel formation (angiogenesis). Recent clinical testing of angiogenesis inhibitors has accentuated the need for non-invasive measures of tumor vasculature. Therefore, the long-term goal of this first-time competitive renewal application is to develop MRI contrast agent methods that efficiently evaluate the clinical potential of anti-angiogenic therapies. The general hypothesis is that MR contrast-agent methods will provide relevant markers of tumor angiogenesis if the biophysical relationships underlying these methods are well characterized. Excellent progress has been made in this regard, especially considering that the initial 5 year proposal was awarded 3 years of funding. Simulations and experiments, made in a rat brain tumor model, using contrast-agent T1 methods demonstrate that an accurate measurement of tissue blood volume fraction depends profoundly on the choice of imaging sequence and parameters. Studies to characterize the susceptibility-based blood volume measurements have shown that the susceptibility calibration factor is different for tumor and normal brain tissue, a new finding that may be due to the differences in vascular geometry. Treatment of the rat 9L gliosarcoma with the steroid dexamethasone demonstrated a vessel-size selective effect, which may parallel the balance of angiogenic factors. Using a novel GE(gradient-echo)/SE(spinecho) imaging method we demonstrated that dynamic susceptibility contrast (DSC) measures of total and microvascular rCBV (relative cerebral blood volume), along with vessel size information could be obtained from patients with brain tumors. Total rCBV and vessel diameter information ware found to be statistically different between low and high-grade tumors. Discerning this difference depends on the proper consideration of contrast agent extravasation effects. The specific aims are logical and exciting extensions of the initial aims. We will continue to develop and validate the susceptibility contrast methods for measuring blood volume and vessel diameter with i. the development of a novel tumor-specific simulation model and ii. MRI and histology measurements made in a rat 9L gliosarcoma model (Aim 1). The usefulness of these methods to track changes with therapy will be evaluated (Aim 2). Tumor-appropriate methods to measure cerebral blood flow (CBF) will be developed and validated (Aim 3). The optimized CBV, CBF methods will be applied to brain tumor patients and correlated with relevant immunohistochemical markers (Aim 4). Significance: Completion of these studies should move us closer to the ultimate goal of dramatically improving the diagnosis and management of patients with vascular tumors such as

34

Brain Tumors

gliomas. Novelty: A key unique component of the proposed studies is the characterization of the biophysical relationships underlying the proposed methods. This will not only aid in assessing the accuracy of the techniques, but will also help us to exploit the wealth of information that can be derived from such measurements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NABTC MEMBER INSTITUTION GRANT (UCSF PROJECT LEADER) Principal Investigator & Institution: Lieberman, Frank S.; Neurological Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 18-MAR-1994; Project End 31-DEC-2003 Summary: (Applicant's Description) Malignant brain tumors are highly lethal cancers. Despite considerable efforts at improving treatment through advances in neurosurgical technique, neuroimaging, radiotherapy, and chemotherapy, the overall prognosis of patients with malignant brain tumors remains grim. To improve outcome, coordinated clinical research is required to evaluate promising new treatment approaches. Laboratory studies of basic brain tumor biology are needed to develop more effective and better tolerated therapeutic strategies. The North American Brain Tumor Consortium (NABTC) was established four years ago for the broad purpose of stimulating cooperative efforts among multidisciplinary teams of clinical and laboratory researchers to improve treatment for patients with brain tumors. To accomplish the long term goal of developing more effective therapies for patients with brain tumors, we specifically propose to: 1. Share expertise with brain tumor clinicians and researchers in multiple disciplines. 2. Conduct joint Phase I and 11 clinical trials for patients with brain tumors, providing adequate patient populations for their timely completion. 3. Share brain tumor specimens and data that will be useful in the conduct of clinical pharmacologic and correlative laboratory studies. This proposal describes the neuro-oncology activities at the University of Pittsburgh, and reviews the resources available through the University of Pittsburgh Cancer Institute (UPCI), an NCIdesignated Comprehensive Cancer Center, and the University of Pittsburgh Medical Center (UPMC), qualifying it for continuing participation in the North American Brain Tumor Consortium. The Central Operations Office/Coordinating Center for the NABTC will remain at the University of California, San Francisco. The UPCI and UPMC will provide essential support for all NABTC-related trials through such facilities as the General Clinical Research Center, the Clinical Core Facility, and the Tumor Tissue Bank. The University of Pittsburgh will collaborate with other members of the NABTC to rapidly evaluate new treatments by enrolling patients in Phase I and 11 NABTC clinical trials and to develop promising new therapeutic strategies through translational laboratory studies of brain tumor specimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: NABTC--CLINICAL CENTER Principal Investigator & Institution: Yung, W K Alfred.; Professor; Neuro-Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 25-MAR-1994; Project End 31-DEC-2002 Summary: The overall goals of this grant application are to develop innovative Phase I and Phase II trials of new and promising agents of therapeutic approaches for primary malignant CNS tumors, and to provide a carefully maintained database of clinical trial results. MDACC will be part of the National Central Nervous System Consortium (NCNSC) of five clinical centers with the Central Operation Office/Coordinating Center

Studies

35

located at MDACC. Some of the hypotheses, based on our own research interest, that we will test, with respect to specific clinical therapies, are: a) Combination of biological and cytotoxid chemotherapeutic agents that show synergistic activity in cell culture may be active in patients with primary malignant brain tumors. b) Anti-angiogenesis agents will inhibit tumor growth and/or invasion by suppression of new tumor vessel formation. c) Replacement of tumor suppresser gene will modify the malignant phenotype of malignant brain tumors. d) Oncogene encoded proteins, growth factors, angiogenic factors and their receptors that are associated with brain tumors can be potential therapeutic targets for antisense approaches. Based on these hypotheses, our specific aims are to: 1) Treat cerebral gliomas at progression or recurrence with new agents and innovatinve combinations of biological and chemotherapeutic agents in the form of Phase I and Phase II clinical trials. 2) Collaborate with other member clinical centers within the consortium to develop gene therapy trials of viral vectors or antisense approaches transferring knowledge learned in the laboratory to the clinic. 3) Continue laboratory modeling of molecular approaches to replace mutated/deleted tumor suppresser genes as well as to regulate the expression of oncogene encoded protein, growth factor and growth factor receptor targets with the aim of bringing these approaches to clinical trials by the consortium. 4) Maintain a patient data base on all patients with brain tumors including relevant clinical and laboratory data using the Protocol Data Management System (PDMS) software available at the MDACC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROCOGNITIVE PROGNOSIS IN SURVIVORS OF BRAIN TUMORS Principal Investigator & Institution: Farace, Elana; Assistant Professor; Neurological Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 16-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Current neuro-oncology research relies on medical outcome measures such as time to tumor progression and survival. However, clarification of the inter-relationships of variables that make up patients' quality of life (QOL), their trajectory over time, and their prognostic value in brain tumors could prove to be superior for decision-making by patients, families, and clinicians. This career development proposal is designed to enhance the Candidate's clinical research skills in the application of multivariate behavioral research methods to the study of QOL and neurocognition in oncology. The Candidate is a fellowship-trained, research-oriented, clinical neuropsychologist, dedicated to a career in patient-oriented, neuropsychological-oncology outcomes research. Strengths of the applicant include interdisciplinary training, a demonstrated ability to engage in programmatic research, experience in clinical service and teaching, and a commitment to the care of patients with malignant brain tumors. Training plan the training will focus on psychological health-outcomes research methodology, behavioral oncology, and observational training in the practice of neurosurgery. The trainee will receive close supervision from experts in psychology, neurosurgery, neuro-oncology, and health evaluation sciences. Specifically, the Candidate will receive training in 1) behavioral health-outcomes research methodology, 2) psycho-oncology and health psychology, and 3) the clinical content of neuro-oncology. In addition, she will receive further training in research ethics, the formation of research collaborations, research presentations, and scientific writing. Research plan the central tenet of the proposed research is that including neuropsychological variables can improve understanding of patients' QOL, elucidate QOL trajectory to end-of-life, and help predict length of survival in malignant brain

36

Brain Tumors

tumor patient populations. In order to test this proposal, structural equation modeling will be performed to determine inter-relationships of components of QOL, their trajectory over time, and the extent to which QOL predicts patient survival. Environment the University of Virginia, the Department of Neurosurgery, the Cancer Center, and the NeuroOncology Center have outstanding clinical, surgical, and epidemiological resources, and a demonstrated commitment to expanding these assets and supporting the Candidate's research. Results will have implications not only for neuro-oncology, but also for all cancer patients with cognitive impairment, contributing to improved QOL and survivorship for these populations. The ultimate goal is to maximize both survival and QOL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW APPLICATIONS IN BRAIN TUMOR THERAPY Principal Investigator & Institution: Mikkelsen, Tom; Co-Director; Neurological Surgery; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (Applicant's Description) This application represents the Henry Ford Hospital System participation in the CNS consortium entitled, New Applications in Brain Tumor Therapy (NABTT), formed for the purpose of designing and carrying out Phase I and Phase II clinical trials of new agents and approaches in the treatment of primary central nervous system tumors. Henry Ford Hospital and the Midwest Neurooncology Center have a large number of brain tumor patients, a multi-disiplinary neurooncology team, extensive clinical and laboratory resources to apply to these endeavors, NIH funded, peer reviewed research programs to support the development and translation of novel diagnostic and therapeutic approaches in primary brain tumors, NIH funded research programs and neuroimaging research, expertise in biostatistics, cancer epidemiology, and outcomes research, and a national recognized reputation for excellence in clinical care and research. Henry Ford Hospital investigators have been designated to head the therapeutic response and imaging research programs, and Henry Ford Hospital has been designated a NABTT wide correlative biology laboratory site. The Principal Investigator has headed or is heading three consortium therapeutic protocols. Finally, Henry Ford Hospital radiation research group is continuing pre-clinical efficacy and safety testing with gene therapy/radiation synergy trials, to build upon gene marking protocols and development at other centers. Through these efforts, state of the art clinical trials and a research program aimed at generating next generation treatment approaches and protocols [sic]. In this application, Principal Investigator, Dr. Tom Mikkelsen, and his colleagues propose to carry out Phase I and Phase II clinical trials in patients with primary central nervous system tumors, as well as maintaining neuroscience tissue bank to collect relevant materials for further correlative and therapeutic research. Further, this proposal also seeks to develop additional research programs considered to be directly related to clinical applications, as well as understanding processes involved in progression of tumors to higher grade, and assessment of tumor invasion markers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: NEW CONSORTIUM

APPROACHES

TO

BRAIN

TUMOR

THERAPY

CNS

Principal Investigator & Institution: Brem, Henry; Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218

Studies

37

Timing: Fiscal Year 2001; Project Start 21-MAR-1994; Project End 31-DEC-2002 Summary: (Applicant's Description) The long-term objective is to develop innovative approaches at Johns Hopkins to improve the survival and quality of life of adults with primary malignant tumors of the central nervous system (CNS), by the participation and completion of Phase I/II clinical trials within the organizational framework of NABTT, New Approaches to Brain Tumor Therapy. Since the creation of NABTT, Johns Hopkins has been the most active site with the highest accrual to NABTT therapeutic and nontherapeutic trials. We have been the largest source of NABTT protocols. In 1996, 482 brain tumor patients were treated at Hopkins, of which 112 had high grade gliomas. Hopkins has extensive experience in carrying out multi-institutional Phase I and II trials. The Oncology Center, which is a Phase I testing center for the NCI, has an extensive and specialized infrastructure to meet our goals within NABTT. Also, a large research effort in brain tumors is ongoing involving basic laboratories, pharmacology laboratories, and pre-clinical laboratories with the goal of developing more effective treatments for patients. A large number of the laboratories are tied together by two multispecialty groups, the National Cooperative Drug Discovery Group Controlled Release Polymers for Brain Tumors and the Vascular Biology of Brain Tumors Research Center. These research efforts have translated into seven Phase I, II, and III multi-institutional trials which were run by Hopkins investigators and led to the FDA's first approval in 23 years for treatment for malignant brain tumors (Gliadel). The Johns Hopkins Neuro-oncology Program will use its extensive resources and experience to provide the NABTT CNS consortium with: 1) a large n u m b er of adult patients with primary brain tumors, 2) an expert m u ltidisciplinary clinical team, 3) extensive clinical and laboratory resources, 4) a striking number of ongoing high quality, clinically relevant, peer-reviewed and NIHfunded clinical and laboratory brain tumor research projects, 5) nationally recognized expertise in oncology, neurosurgery, p h armacology, new drug development, Phase I and II clinical trials, neuroradiology, and neuropathology, 6) extensive expertise in statistics, data management, coordination of multi-institutional studies, and innovative design of brain tumor clinical trials and 7) an exceptional reputation for excellence in clinical care and research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW CONSORTIUM

APPROACHES

TO

BRAIN

TUMOR

THERAPY

CNS

Principal Investigator & Institution: Grossman, Stuart A.; Professor of Oncology, Medicine and Neur; Oncology Center; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 21-MAR-1994; Project End 31-DEC-2002 Summary: The primary long-term objective of this proposal is to improve the therapeutic outcome for adults with primary brain tumors. This will be accomplished by fostering Phase I and II clinical evaluations of promising new agents, biologic approaches, routes of administration, and trial design in the treatment of primary malignancies of the central nervous system through the continued efforts the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium." This consortium is specifically designed to combine and focus the experience, resources, and capabilities of thirteen outstanding medical institutions (Brown University, Columbia University, Emory University, Henry Ford Hospital, Johns Hopkins University, Massachusetts General Hospital, Moffitt Cancer Center, Northwestern University [Chicago], the University of Alabama, the University of Texas at San Antonio, the University of Pennsylvania, Wake Forest University, and Washington University) to bear on primary

38

Brain Tumors

brain tumors. The participating institutions have (1) a large number of adult patients with primary brain tumors, (2) expert multidisciplinary clinical teams caring for these patients, (3) extensive clinical and laboratory resources, (4) a striking number of ongoing high quality, clinically relevant, peer-reviewed and NIH funded clinical and laboratory brain tumor research projects, (5) nationally recognized expertise in oncology, pharmacology, new drug development, Phase I and II clinical trials, neurosurgery, and neuropathology, (6) extensive expertise in biostatistics, data management, and the coordination of multi-institutional studies, and (7) exceptional reputations for excellence in clinical care and research. The consortium adds to these strengths with a well-defined and smoothly functioning structure, an emphasis on clinical trial design, protocol development, quality control, study monitoring, and data management and analysis. The secondary long-term objective of this proposal is to utilize this consortium to share human brain tumor specimens as well as other clinical and laboratory data to conduct additional research pertaining to (1) the basic biology of primary brain tumors, (2) the neuro-pharmacology of new therapies for primary brain tumors, and (3) improving the care and quality of life of adults with primary brain tumors. This objective will be reached using the strengths of the participating institutions and the NABTT Correlative Biology Research Center, The NABTT Pharmacology Center, and The NABTT Working and Scientific Committees. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW APPROACHES TO BRAIN TUMOR THERAPY--A CNS CONSORTIUM Principal Investigator & Institution: Alavi, Jane B.; Neurology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 23-APR-1998; Project End 31-DEC-2002 Summary: (Applicant's Description) The primary long-term objective of this proposal is to improve the therapeutic outcome for adults with primary brain tumors. This will be accomplished by P h a se 1/11 clinical evaluations of promising new agents, biological a p proaches, and roots of administration in the treatment of primary malignancies of the central nervous system through the establishment of the consortium. This consortium is specifically designed to combine and focus experienced resources and capabilities of thirteen Outstanding medical institutions to bear on primary brain tumors. To meet this objective, the consortium will rely on the special strength and abilities that rest within each participating institution and within the consortium as a whole. The University of Pennsylvania Medical Center has 1) a large number of adult patients with primary brain tumors, 2) expert Mult-disciplinary clinical teams to care for these patients, 3) extensive clinical and laboratory researchers, 4) a striking number of on-going high quality, clinically relevant, peer reviewed and NIH funded clinical and laboratory brain tumor research projects, 5) nationally recognized expertise in Oncology, Pharmacology, new drug development, Phase I/II clinical trials, Neurosurgery, and Neuropathology, 6) extensive statistics, data management, and coordination of multi-institutional studies, and 7) exceptional reputation for excellence in clinical care and research. The consortium adds these strengths with a well defined and smoothly functioning organizational structure, and emphasis on clinical trial design, protocol development, quality control, study monitoring and data management and analysis. The secondary long-term objective of this protocol is to use this consortium to share human brain tumor specimens as well as other clinical and laboratory data to collect additional research pertaining to 1) the basic biology of primary brain tumors, 2) the Neuropharmacology of new therapies for primary brain tumors, and 3) improving the care and quality of life

Studies

39

of adults with primary brain tumors. This objective will be reached using the strengths of the participating institutions and the NABTT correlative biology research center, the NABTT pharmacology center, and the NABTT working in scientific committees. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NORMAL AND NEOPLASTIC GROWTH REGULATION IN THE BRAIN Principal Investigator & Institution: Curran, Tom; Member and Chairman; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: The goal of this program project is to increase understanding of the molecular basis of normal and neoplastic growth in the developing brain. The ultimate objective is to use this knowledge to devise novel strategies for treatment of medulloblastoma, the most common pediatric malignancy of the central nervous system. This objective is being pursued through four interactive projects that investigate the role of different signaling pathways in the growth of the central nervous system and brain tumors supported by an Administrative Core and a Bioinformatics and Microarray Core. In Project 1, T. Curran utilizes a mouse model of medulloblastoma to investigate the role of the Shh/Ptc/Smo pathway in tumorigenesis. This involves the use of pharmacological inhibitors in cell culture and in vivo, a molecular characterization of Gill and comparison of the epigenetic and genetic alterations underlying medulloblastoma by nuclear transplant into oocytes. In Project 2, P. McKinnon investigates the contribution of DNA damage signaling to medulloblastoma formation. This project is based on the characterization of a novel model for medulloblastoma in mice lacking DNA Ligase IV and p53. This analysis will involve comparison of gene expression microarray profiles of the different medullobalstomas in the program. In Project 3, R. Gilbertson is investigating the role of ERBB2 in human medulloblastoma. This involves the characterization of human medulloblastoma cell lines using pharmacological and gene expression microarray approaches. The information will be compared to the data obtained on mouse models and an existing database of human brain tumors. A mouse model will be created in which ERBB2 is expressed in cerebellar granule neurons. In Project 4, S. Baker is studying the role of the Pten signaling pathway in growth regulation in the brain. This includes characterization of the function of downstream effector genes in the cerebellum and the creation of new mutant mouse strains to investigate its contribution to growth, proliferation and tumorigenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: NORTH CENTRAL CANCER TREATMENT GROUP Principal Investigator & Institution: Buckner, Jan C.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-JAN-1982; Project End 31-DEC-2006 Summary: The North Center Cancer Treatment Group (NCCTG) is a multi- disciplinary research organization comprised primarily of community physicians in concert with the Mayo Clinic Cancer Center (an NCI- designated Comprehensive Cancer Center) which serves as its primary Research Base. Its broad, long-term objectives are to 1) develop and test new methods of cancer treatment to improve survival and quality of life for adult patients with malignant disease, 2) provide cancer patients access to state-of-the-art clinical trials in their home community, 3) promote discoveries elucidating the biology

40

Brain Tumors

of cancer through translational research studies And analyses of clinical databases which will lead to improvements in therapy, 4) provide a platform and infrastructure for studies of cancer prevention and symptom management, and 5) provide underserved populations access to NCCTG clinical research protocols. The NCCTG strategy is based on the premises that quality cancer treatment research can be conducted by the community clinic, and that the community clinic provides the ultimate proving ground for applicability of new cancer treatment procedures to the general population. Specific aims are to advance the treatment of patients with gastrointestinal cancer, breast cancer, lung cancer, brain tumors, hematologic malignancies, and select other adult solid tumors; to identify tumor treatment which will lead to better cancer therapy. Methods utilized by the NCCTG to achieve its goals include pilot, phase II, and phase III clinical trials; laboratory correlative studies performed on tissue specimens or blood samples from patients participating in clinical trials,; and analyses of clinical and laboratory databases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL TREATMENT APPROACHES FOR PEDIATRIC BRAIN TUMORS Principal Investigator & Institution: Pollack, Ian F.; Walter Dandy Professor of Neurosurgery; Neurological Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Brain tumors are the leading cause of cancer-related deaths among children. Despite considerable efforts to refine the treatment of these tumors, the overall prognosis of affected patients has improved minimally during the last decade. To improve outcome, coordinated efforts are required to evaluate new treatment approaches in parallel with correlative studies of tumor biology to identify novel therapeutic strategies. Our proposal for inclusion in the Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC) reflects our institutional commitment to contribute to such studies. To accomplish the goal of developing more effective therapies for children with brain tumors, we propose to: 1) share institutional expertise with clinicians and researchers at other consortium centers; 2) design and conduct innovative pilot, phase I, and phase II clinical trials for children with brain tumors, and provide adequate patient populations for their timely completion; and 3) share brain tumor specimens and other data that will be useful in the conduct of clinical, pharmacological, and correlative laboratory and imaging studies. This proposal describes the extensive neuro-oncology activities at the Children s Hospital of Pittsburgh (CHP) and the University of Pittsburgh Medical Center (UPMC). Our group has been at the forefront of applying stereotactic radiosurgical approaches to the treatment of brain tumors and in translating novel preclinical therapeutic strategies to the clinical arena. The broad-based biological and molecular therapeutics efforts for brain tumors reflect the depth of institutional resources within the University of Pittsburgh Cancer Institute (UPCI). Promising approaches that are currently being translated to clinical studies that could be adopted by the Consortium include cytokine-based glioma vaccines and novel signal transduction inhibitors. Innovative imaging modalities for evaluating disease response are provided by institutional PET and MR Research Centers. Our group is also leading multi-institutional molecular marker studies on childhood high-grade gliomas, which could potentially be incorporated in PBTCTC studies. CHP, UPMC, and UPCI will provide essential support for consortium-related clinical trials through such facilities as the General Clinical Research Center, the Tumor Tissue Bank, the Pediatric Brain Tumor

Studies

41

Registry, the Center for Image-Guided Neurosurgery, and the Imaging Core facilities. In addition to the above, our institution is a regional and national referral center for childhood brain tumors, with approximately 80 new or recurrent brain tumor patients per year, and 20 to 25 children who are entered on institutional pilot or cooperative phase I or phase II studies. With these clinical and scientific resources, our institution is well poised to collaborate with other members of the PBTCTC to rapidly evaluate new treatments by enrolling patients in studies of the Consortium and to develop promising new therapeutic strategies through translational laboratory studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC BRAIN TUMOR CLINICAL TRIAL CONSORTIUM Principal Investigator & Institution: Prados, Michael D.; Professor; Neurological Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The University of California San Francisco (UCSF) has a long history of commitment to the treatment of children with brain tumors. Clinical and laboratory investigators in the Brain Tumor Research Center (BTRC) have over 25 years of experience in funded research of the biology and treatment of these diseases. Brain tumors are now the leading cause of cancer-related death in children. Currently available treatment for tumors such as brainstem glioma and malignant astrocytoma will not effectively control tumor growth for many of these children. In other types of brain tumors, treatment may control disease but will cause significant toxicity such as developmental and growth delay. For children who progress following initial therapy, few effective alternatives exist. Substantial gains for these children will only come about by an understanding of the biology of these diverse tumors, and the use of innovative treatment strategies based upon these data. Novel treatment approaches will require the expertise of physicians and researchers at institutions with the unique talents and resources available to employ these technologies. Clinical collaborations will be needed to efficiently conduct phase-I and II studies because of the small numbers of patients seen at various medical centers. UCSF has the physician talent, patient population, treatment and diagnostic resources, and Institutional commitment to collaborate with and achieve the goals of a Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC). We plan to utilize state of the art neuroimaging to diagnosis and monitor children with brain tumors. Advanced neurosurgical navigational techniques will be used for maximal tumor resection. Specialized methods of radiation therapy and unique drug therapy will be available, including but not limited to interstitial brachytherapy, radiosurgery, and experimental chemotherapy and gene therapy. Scientists in the BTRC will continue to use human tumor tissue to study the biology of childhood brain tumors, with the goal to translate this biologic information into newer, non-toxic, disease-specific treatments. UCSF will collaborate with the PBTCTC to achieve its Consortium goals, and contribute to its scientific agenda, taking a leadership role in study concept proposals and biologic studies. The aim of these treatment approaches is to increase disease-free and overall survival in children with brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PEDIATRIC BRAIN TUMOR CLINICAL TRIALS CONSORTIUM Principal Investigator & Institution: Friedman, Henry S.; Professor; Pediatrics; Duke University Durham, Nc 27706

42

Brain Tumors

Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The goals of the Brain Tumor Center at Duke are to foster interaction among a group of basic, translational, and clinical scientists to improve diagnosis and treatment of primary and metastatic brain tumors in adults and children and to train new basic, translational, and clinical investigators to work in Neuro-Oncology. The Brain Tumor Center at Duke (also called the Neuro-Oncology Program) is one of the oldest organ-site cancer programs at Duke and it predates the Cancer Center by a generation. The clinical and basic investigation in neuro- oncology at Duke began in 1937 under the leadership of the late Barnes Woodhall, M.D., first Professor of Neurosurgery at Duke and the second Chancellor of the Medical Center. Subsequent leaders of the Program were Guy L. Odom, M.D., James B. Duke Professor of Neurosurgery, and the late M. Stephen Mahaley, Jr., M.D. Dr. Darell Bigner has led the Program since its formal status as a Cancer Center Program was established more than 15 years ago when Core Grants initiated program status. The Neuro- Oncology Program is composed of 21 senior faculty who hold 23 peer-reviewed grants relative to neuro-oncology from the National Institute of Neurological Diseases and Stroke. The most significant progress in the ability to conduct clinical trials in adult and pediatric brain tumor patients at Duke was administrative reorganization of Clinical Neuro-Oncology to effectively merge surgical and medical care of both pediatric and adult patients. This important reorganization was envisioned and successfully negotiated with Duke Hospital, the relevant Department Chairs, and the Chancellor by the new Director of the Duke Comprehensive Cancer Center, O. Michael Colvin, M.D. First, in 1996, a Division of Pediatric NeuroOncology was created with Dr. Henry S Friedman as Chief with two additional pediatric neuro-oncology faculty. Dr. Friedman was then given appointments in both the Departments of Medicine and Surgery, and he and Dr. Allan Friedman, Chief of Neurosurgery, were made Co-Directors of Clinical Neuro-Oncology at Duke. The offices, data management staff, physician extenders, and medical and pediatric faculty staff were physically consolidated. With this new administrative structure 450 new adult patients, and 100 new pediatric patients were seen in 1997. There were 400 craniotomies for brain tumor performed in 1997, and approximately 600 adults and 400 children with primary brain tumors are being followed in 1998. The specific aims of this proposal are to 1) design innovative clinical trials for children with brain tumors based on in vitro and preclinical in vivo laboratory studies and 2) to conduct these trials with appropriate patient accrual, data management and monitoring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC BRAIN TUMOR CLINICAL TRIALS CONSORTIUM Principal Investigator & Institution: Geyer, J R.; Children's Hospital and Reg Medical Ctr Box 5371, 4800 Sand Point Way Ne, Ms 6D-1 Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Therapeutic advances in pediatric neurooncology over the last two decades have been limited. New clinical research opportunities exist including novel approaches in the areas of cytotoxic drugs, radiation therapy and immunotherapy which require evaluation. No single institution accrues sufficient numbers of children with brain tumors to conduct trials of such new approaches in a timely fashion, and only a limited number of institutions have the sophisticated equipment and skills required to implement and evaluate such therapies. Therefore, to expeditiously evaluate innovative therapies, a Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC) is required. The University of Washington Pediatric Neuro-Oncology Program brings the requisite personnel, resources and research expertise, discussed in this application, to contribute

Studies

43

substantially to the goals of the PBTCTC. The Pediatric Neuro-Oncology Program was established in 1980 and was thus one of the initial programs recognizing the need for multidisciplinary care of children with brain tumors. The program includes a broad range of clinical and laboratory investigators. The goal of this application is to describe the efforts of this broad multidisciplinary group on issues relevant to improving the outcome of children with brain tumors in concert with PBTCC. In particular, our extensive experience with leadership in national cooperative clinical trials in pediatric brain tumor therapy, together with leading programs in radiation therapy, neuroimaging, neurosurgery, and neuropathology provides the critical mass and expertise required to effectively contribute to clinical evaluation of innovative brain tumor treatments. Our laboratory-based investigations of the molecular aspects of pediatric and adult brain tumors as well as a unique institutional program aimed at developing targeted therapy for malignancies also have the potential to contribute to the development of novel approaches to brain tumor therapy, in concert with the PBTCTC. Specifically we propose to: 1) effectively contribute to the clinical trials program of the PBTCTC; 2) provide laboratory-based analysis of molecular aspects of brain tumors required for the development of novel prognostic and therapeutic approaches; 3) develop novel methods of imaging brain tumors, including methods for rapid assessment of response to therapy; 4) develop novel targeted therapies for brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC BRAIN TUMOR CONSORTIUM--CHOP MEMBERSHIP Principal Investigator & Institution: Phillips, Peter C.; Professor of Neurology, Oncology and Pe; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The overall objective of this proposal is to improve therapeutic outcomes for children with primary brain tumors. This will be accomplished by Phase I and II clinical evaluations of promising new therapeutic drugs, delivery technologies, biological therapies, and radiation treatment strategies conducted by a newly-established Pediatric Brain Tumor Clinical Trials Consortium (PBTC). This consortium will combine the experience and resources of eight outstanding medical institutions in an organizational structure designed to facilitate a rapid and successful study of new therapies for childhood brain tumors. A second objective is to utilize the consortium mechanism to share brain tumor specimens as well as other clinical and laboratory data and to conduct research pertaining to neuroimaging, pharmacology, and the biology of childhood brain tumors. To achieve these objectives, the PBTC must rely on the special strengths and resources of each participating institution. Accordingly, we propose the following Specific Aims to advance PBTC goals: Aim 1. to participate as a Member Institution in PBTC clinical trials, laboratory, and neuroimaging studies; Aim 2. to develop new experimental therapies for CNS tumors in children and propose these strategies for phase I/II clinical trials by the PTBC; Aim 3. to propose and facilitate the development and study of intrathecal therapies for the prophylaxis or treatment of childhood CNS tumors; and Aim 4. to propose and develop neuroimaging studies of regional tumor pharmacokinetics and brain tumor biology for participation by PBTC members. The Children's Hospital of Philadelphia (CHOP) has: (1) an outstanding multi- disciplinary clinical team of internationally-recognized leaders in pediatric neurooncology, radiation oncology, neurosurgery, neuro-radiology, pharmacology, and new drug development; (2) a large number of patients with childhood primary brain tumors available for study; (3) state-of-the-art facilities for diagnostic and research

44

Brain Tumors

neuroimaging (MRI, MRSpectroscopy, PET, SPECT), neurosurgery (computer imageguided surgery), and radiation therapy (stereotaxic radiosurgery, Gamma Knife, brachytherapy); (4) an NIH-funded brain tumor bank which stores brain tumor biopsies from CHOP, NYU, and Beth Israel (NYC) (5) internationally-recognized expertise in neuro-pathology; (6) extensive institutional resources for biostatistics and clinical trial data management and a reputation for excellence in clinical care and research; (7) experience in the organization and coordination of multi-institutional clinical trials; and (8) a large number of high quality, clinically relevant, peer reviewed and NIH funded brain tumor research studies. These programmatic and institutional strengths support the feasibility of our specific aims, are responsive to the criteria for consortium participation specified by the RFA, and substantially enhance the likelihood that the PBTC will achieve its long-term goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC BRAIN TUMOR RESEARCH CENTER Principal Investigator & Institution: Blaney, Susan; Assistant Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The Texas Children s Cancer Center(TCCC) Brain Tumor Program (BTP) is a multidisciplinary, highly integrated program of clinical and laboratory research dedicated to improving survival rates of children with central nervous system(CNS) tumors. The Program is one of the largest of its kind in the United States, each year evaluating more than 50 children. The BTP is composed of clinical and laboratory investigators whose research encompasses the entire spectrum of pediatric neurooncology. They are exceptionally qualified to design, conduct, and monitor clinical trials for children with brain tumors. In national cooperative group clinical research and in numerous studies sponsored by the National Cancer Institute and private industry, the BTP has led new approaches to the treatment of infants with brain tumors, introduced new agents against brain tumors through Phase I and Phase II clinical trials, and pioneered the use of highly conformal radiation therapy (RT) to decrease toxicity to normal structures surrounding brain tumors. The BTP works closely with the Gene Therapy Program, Molecular Neuro-Oncology Program, and Clinical Pharmacology Group, all within TCCC, to translate advances in laboratory and pre-clinical science to treatment of children with brain tumors. Examples of ongoing clinical trials include those seeking to determine the impact of intrathecal chemotherapy and highly conformal radiation therapy on the survival of infants with brain tumors, the activity of various new agents against leptomeningeal disease, the activity of various agents against malignant glioma, the use of bone marrow transplant for recurrent medulloblastoma, and the efficacy of gene therapy for children with refractory brain tumors. The BTP utilizes the most modern diagnostic neuroimaging modalities and innovative technologies such as functional MR, MR spectroscopy, and 18F imaging. Its neurosurgeons utilize state- of-the-art operating microscopes and guidance systems. RT is delivered through the most technically advanced conformal system. The BTP neuropathologists have complete diagnostic capabilities to classify tumors according to WHO criteria. The BTP maintains a storage bank of tumor specimens for institutional and cooperative group correlative studies. The BTP has an innovative molecular neurooncology program that uses high-throughput technologies to study differential gene expression in pediatric brain tumors. BTP investigators are committed to utilizing their resources for the Pediatric Brain Tumor Clinical Trial Consortium (PBTCTC) studies. The TCCC BTP serves a culturally and ethnically diverse population. It receives

Studies

45

considerable research support from Texas Children s Hospital, the largest children s hospital in the United States and from Baylor College of Medicine, one of the top ten medical schools in the country. The unique expertise of the TCCC BTP make it ideally suited to be a Participating Member of the PBTCTC. It offers leadership in the development of new agents, in new uses of sophisticated radiotherapy, and in the application of new approaches to brain tumor therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Breitfeld, Philip P.; Pediatrics; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-JAN-1983; Project End 31-DEC-2002 Summary: The goal of the proposed research is to determine optimum care for children with all types of cancer. The research mechanism involves participation by pediatric investigators in a consortium of medical institutions in North Carolina and West Virginia in collaborative multidisciplinary clinical cancer research protocols generated through the Pediatric Oncology Group. The proposed research grant will allow for the continued participation of Duke University Medical Center, Charlotte Memorial Hospital, East Carolina University School of Medicine and West Virginia University School of Medicine in Pediatric Oncology Group activities. These activities involve studies of the epidemiology and tumor biology of selected neoplasms and the natural history and optimum multimodal therapy of all childhood malignancies. Cooperative studies among physicians from a group of medical centers allow for rapid accrual of a statistically significant number of children with cancer in order to define quickly both those avenues of biologic research which have immediate clinical relevance and those therapeutic approaches which provide prolonged disease-free survival. Through participation in cooperative studies, the entire medical community engaged in the care of children with cancer has a focal point to provide not only improved patient care but also improved multidisciplinary teaching and research. Our objectives for the coming years are: 1) to develop new protocols for the immunologic stratification and chemotherapeutic management of patients with malignant lymphoproliferative and myeloproliferative disorders; 2) to develop protocols for specific brain tumor therapy which take advantage of our expanding knowledge of the biology and pharmacologic sensitivity of human brain tumors in vitro and in vivo; 3) to expand our studies of the pharmacologic agents which influence intermediary metabolism, using our in vitro data as the basis for drug scheduling in clinical trials; 4) to expand our innovative groupwide epidemiology studies to include studies of neuroblastoma and T-cell malignancies which include laboratory investigation (immunologic, biochemical and cytogenetic) where relevant; 5) to expand our multidisciplinary therapeutic research efforts in other pediatric malignancies; and 6) to expand our outreach programs for patient care and education through our regional consortium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Kavan, Petr; Montreal Children's Hospital 2300 Tupper St Montreal, Timing: Fiscal Year 2002; Project Start 01-JAN-1983; Project End 31-DEC-2002 Summary: The Pediatric Oncology Group (POG) is a multi-disciplinary, multiinstitutional research community which collaborates to increase knowledge of and

46

Brain Tumors

improve treatment for cancer and leukemia in children and adolescents. The Montreal Children's Hospital/McGill University (MCH), a founding member, requests funding for itself and its two affiliates, the Children's Hospital of Eastern Ontario (CHEO) and the University of Sherbrooke Medical Center (USMC) to continue to participate fully in administrative and scientific activities of the POG during the next 5 years. We expect to enroll a total of 70 patients a year on therapeutic protocols for childhood leukemias, lymphomas, solid tumors and brain tumors, with continued emphasis on Phase I and II studies of new agents and coordination or co-coordination of a minimum of 13 protocols. We expect to enroll 110 patients per year on non-therapeutic studies of cancer etiology, epidemiology, biology, psychologic impact and late effects of therapy with particular emphasis on the pharmacology and molecular pharmacology of methotrexate in acute lymphoblastic leukemia (ALL). We will comply with all requirements of the POG constitution, with MR regulations governing ethical conduct of clinical research and with OPRR and IRB requirements for informed consent and protection of subjects from research risks. In addition to an anticipated doubling of patient accruals since 5 years ago, our major contributions to POG research will include: confirmation that the extent of accumulation of methotrexate polyglutamates by lymphoblasts in B-progenitor cell ALL correlates with event-free survival (EFS) and characterization of the mechanisms regulating this metabolism (Whitehead); promotion of new agent drug development through New Agents and Pharmacology Committee leadership (Whitehead and Bernstein) and protocol coordination (Bernstein, Baruchel); introduction of stereotactic and fractionated stereotactic radiation therapy in brain tumors (Freeman); coordination of treatment protocols of newly-diagnosed and relapsed B-progenitor cell ALL (Abish, Bernstein); introduction of new agents and combinations in recurrent lymphoid disease as Sub-committee Chair, Lymphoid Relapse (Bernstein); chemotherapy and surgery of brain tumors (Baruchel, Ventureyra); and study of the biology, including p53 gene mutations, and treatment of HIV-related lymphomas (Baruchel, Whitehead). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Castleberry, Robert P.; Professor of Pediatrics; Pediatrics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-MAR-1979; Project End 31-DEC-2002 Summary: The University of Alabama at Birmingham (UAB) is a leading contributor to the ongoing clinical and basic research activities of the Pediatric Oncology Group (POG) which are focused upon improving the care and cure for children with cancer. Current results of these trials are in some cases already published and are available in the Progress Report. The leadership from UAB in POG is evident in several areas: l) through enrollment of substantial numbers of assessable patients on Phase I, II and III therapeutic trials, including multidiscipline (surgery, chemotherapy, and radiotherapy) management studies; through participation in and development of Group-wide biological studies of selected hematopoietic and solid malignancies; through evolving, coordinating and reporting data from POG therapeutic trials; and by providing discipline and disease committee, and administrative leadership within the group. UAB will continue to enroll all eligible patients on active POG therapeutic and biological studies, including phase I investigations, and maintain high evaluability. UAB investigators will continue to coordinate clinical trials for children with neuroblastoma, bone tumors, and juvenile chronic myelogenous leukemia (JCML) and to assess the therapeutic utility of IL6. Further, UAB investigators will be principal to the

Studies

47

development of new studies in neuroblastoma, brain tumors, JCML and acute myelogenous leukemia. UAB will continue to supervise laboratories for POG in the following areas: 1) Banded chromosomal analysis in newly diagnosed patients with lymphoid leukemia; 2) A required reference laboratory for children with JCML (POG #9265) studying the pathogenesis of myeloproliferation; 3) A required serum/plasma repository (POG #9047) with clinical and demographic data referenced on a computer data base; and 4) A non- mandatory reference laboratory to evaluate the biological and clinical significance of rnicrotubular associated protein (MAP) and tubulin isotype expression in neuroblastoma. UAB investigators will continue their scientific and administrative leadership roles on the Neuroblastoma and Other Embryonal Tumors, Myeloid Disease Core, Biologic Response Modifier Core, Executive, Principal Investigator Core, Clinical Research Associate Core, and Diagnostic Imaging Core Committees. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHASE II STUDY OF 44GY FROM 131I-81C6 FOR CNS TUMORS Principal Investigator & Institution: Reardon, David; Surgery; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The outcome for patients with glioblastoma multiforme, the most common primary malignant brain tumor, remains dismal. Median survival with current therapy including surgery, radiotherapy and chemotherapy remains 40-50 weeks from diagnosis while available salvage therapies are ineffective following recurrence. Most cases progress at the primary site indicating that local control is the critical first step to improve outcome. In response to the dire need for effective, innovative therapies for patients with malignant brain tumors, our center has developed radiolabeled monoclonal antibodies (mAB) that specifically target tumor antigens. 81C6, a murine IgG2b mAB reacts with an isoform of the extracellular matrix protein tenascin which is highly upregulated and expressed by malignant glioma. Previously completed phase I and II studies in which a fixed dose of 131I-labeled 81C6 was administered directly into the surgical created resection cavity (SCRC), confirmed that this approach improves survival for patients with malignant glioma with acceptable toxicity. A key observation from dosimetry studies accompanying these trials is the demonstration that outcome correlated most closely with delivered dose to the SCRC perimeter. Specifically, patients who received less than 44 Gy to the SCRC perimeter had minimal toxicity from radionecrosis but had a higher rate of tumor recurrence. Conversely those patients who received more than 44 Gy had a lower rate of tumor recurrence but a higher rate of symptomatic radionecrosis. Our HYPOTHESIS is that our phase II study with 131I -81C6 administered to deliver 44 Gy to the 2 cm SCRC perimeter will improve survival of patients with newly diagnosed malignant glioma while minimizing radiation injury to normal CNS tissue. The SPECIFIC AIMS of this proposal are: Specific Aim 1. To define the efficacy of 131I -labeled anti-tenascin monoclonal antibody 81C6 administered at a dose to deliver 44 Gy to the 2 cm perimeter of resection cavity of patients with newly diagnosed malignant glioma; Specific Aim 2. To further define the toxicity of this approach and Specific Aim 3.To determine the impact of this therapy on quality of life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

48

Brain Tumors

•

Project Title: PHOTODYNAMIC THERAPY--BASIC SCIENCE STUDIES Principal Investigator & Institution: Hetzel, Fredrick W.; Vice President & Dir of Research; Healthone Alliance 899 Logan St, Ste 203 Denver, Co 80203 Timing: Fiscal Year 2001; Project Start 16-MAR-1998; Project End 31-DEC-2002 Summary: This Program Project will continue to investigate Photodynamic Therapy (PDT). The five projects will cover research topics ranging from cellular resistance to PDT to clinical trials for the treatment of brain tumors. The projects are supported by two core activities which are integral to their successful conduct. The synergy of the Program will continue to depend upon the effective interactions between both the scientific projects and the investigators. Project 1 proposes to investigate, in vivo, possible methods to improve the effectiveness of PDT by increasing availability of oxygen in the tumor at the time of treatment. Project 2 proposes clinical trials of PDT for the treatment of malignant brain tumors. Two trials involving Photofrin, one for de novo and one for recurrent lesions, are planned. Project 3 will continue to investigate cellular resistance to PDT. Knowledge regarding the mechanisms by which such resistance develops is critical to the understanding of PDT at the cellular level. Project 4 will continue to investigate PDT dosimetry. The studies proposed in this project will have a direct impact on the clinical application of PDT. Project 5 will continue its in vivo studies examining PDT effects in brain tumor and normal brain. One area of focus will be to investigate alternate methods of drug delivery. Core will provide overall technical support for the program. Calibration of devices and interproject quality assurance will be provided by this core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PLATFORMS FOR IMAGING/TREATMENT OF INTRACRANIAL NEOPLASM Principal Investigator & Institution: Philbert, Martin A.; Associate Professor of Toxicology, Envir; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 05-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): The recent invention in our laboratories of 20-200 nm diameter optical nanosensors presents the opportunity for the development of a new class of drug delivery devices for non-invasive imaging using magnetic imaging resonance, and simultaneous delivery of therapeutic agents to brain tumors. These nano-devices can be passive or active modular entities capable of sensing the physiological environment or reporting the presence of a tumor. This proposal represents the first application of our nano-devices for investigating the delivery of these devices to experimental intracranial tumors. The hypothesis that nano-scale MR image contrast agents can be synthesized, delivered and imaged using MRI in experimental brain tumors will be tested by the following specific aims: Specific Aim 1 (i) Synthesis and in vitro testing of encapsulated gadolinium contrast agent (Magnevist). (ii) Synthesis and in vitro testing of encapsulated MION contrast agent. Specific Aim 2A (i) In vivo evaluation of nanoparticle-encapsulated Magnevist (GdPEBBLEs) following single dose administration to assess dose and time course dependent-changes to intracerebral 9L tumor delivery. (ii) In vivo testing of GdPEBBLES following a multidosage schedule to evaluate maximal brain tumor uptake. Specific Aim 2B As in Specific Aim 2A, in vivo testing of MION PEBBLEs will be accomplished. Preliminary data collected by our group confirms the utility of MION for MRI of brain tumors. We propose incorporation of MION or gadolinium into the core of hydrogel nanoparticles

Studies

49

for enhancement of contrast characteristics and quantification of delivery of DNP's to 9L brain tumors in rats. It is anticipated that the results from the proposed studies will provide the foundation for furthering the development of these novel nano-structurebased strategies for the imaging, characterization and simultaneous destruction of intracranial tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREPHASE I GENE/IMMUNE THERAPY OF MALIGNANT BRAIN TUMOR Principal Investigator & Institution: Fathallah-Shaykh, Hassan M.; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 08-APR-1999; Project End 31-MAR-2002 Summary: (Adapted from applicant's abstract) Malignant brain tumors arise in more than 40,000 people in the United States each year. About half are primary and the remainder are metastatic. Brain metastasis is frequent in patients suffering from many systemic malignancies including lung, breast melanoma, lymphoma, and colon cancers. Brain tumors are the second most common cause of cancer-related death in people up to the age of 35, with a slight peak of incidence in occurrence among children between the ages of 6 and 9. Current standard of care of patients with malignant brain tumor includes surgery, radiation therapy, and possibly chemotherapy. Unfortunately, despite numerous combined modality treatment trials over the part 2 decades, patient survival is still numbered in months. The experiments proposed in this application are designed to study a novel unconventional strategy for the treatment of malignant brain tumors based on gene/immune therapy. The investigators have produced successful vaccination against malignant brain tumors in animals by immunization into the brain with a live growth-competent tumor vaccine. In this animal model, intra-cerebrallyimplanted malignant glial cells, genetically- modified to secrete interferon-gamma, elicit tumor rejection and specific protective systemic anti-tumor immunity. This biologic response is associated with activation of microglia throughout the brain and enhanced infiltration by CD4, CD8, and natural killer cells. The proposed research is intended to: 1) conduct pre- clinical experimentation of gene/immune therapy of established malignant brain tumors in animals by gene transfer of interferon gamma and interleukin 12, and 2) elucidate the basic principles of vaccination in the brain. The concept of anti-tumor immunization by delivering a vaccine directly into the brain, an organ thought to be immunologically-privileged, is novel. Furthermore, this research is important not only because positive results will lead to immediate phase I clinical trials in patients with either primary or metastatic brain tumors, but also because it will shed light on the principle of immunotherapy against central-nervous-system tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: QUANTITATION RESPONSE BY MR

OF

HUMAN

BRAIN

TUMOR

THERAPY

Principal Investigator & Institution: Chenevert, Thomas L.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 05-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Despite advances in surgery, radiation and chemotherapy, the treatment of malignant brain tumors remains one of the most perplexing clinical areas with the fewest advances in treatment in the field of oncology. It is of central importance to determine treatment response or failure, for both patients

50

Brain Tumors

and physicians. Currently, the effectiveness of therapy is monitored by MRI or CT scanning of the tumor, along with neurological assessment of the patient. These indicators are imperfect since changes in tumor volume can take months to appear on conventional imaging, and changes in neurological function are often unrelated to change in tumor growth and volume. Nevertheless, such measures of therapeutic response are currently relied upon to determine when a different treatment option should be pursued. The availability of earlier and more accurate predictive indicators of treatment response would have obvious benefit to individual patients, as well as to advancing the treatment of brain tumors generally by facilitating clinical trials of new agents. This application seeks to advance the use of quantitative MRI for the clinical evaluation of brain tumor patients by adding information related to cellular membrane integrity and vascular volume to the anatomical detail provided by conventional MRI. The proposal is based on promising recent MR data from rodent brain tumor models and preliminary studies of human brain tumors. These have shown that microscopic cellular changes occur in the tissue structure of brain tumors following successful treatment; moreover these occur before changes in tumor volume are manifest. Changes in tumor cellular structure were detected as an increase in the apparent mobility (diffusion) of water within the tumor tissue using a specialized diffusion-sensitive MRI acquisition and processing techniques. The observation of an increase in water diffusion is indicative of therapy-induced tumor necrosis that is manifest as cellular membrane breakdown and cell shrinkage. These events facilitate movement of water within an enlarged extracellular space. It is hypothesized the effectiveness of a treatment can be assessed before there is a reduction in tumor volume, because the rate of cellular breakdown and necrosis is relatively rapid compared with the process of resorption and removal of cellular debris. In addition, specialized MRI techniques allow the mapping tumor blood volume (TBV) and perfusion. We further hypothesize that treatment of brain tumors damages tumor vasculature, thereby decreasing vessel density and total blood volume within tumors responsive to therapy. We propose to initiate a clinical study to further test these hypotheses on brain tumor patients. Clinical and MRI data will be collected on 164 subjects accrued from two institutions, University of Michigan and University of Pittsburgh. Conventional MRI and quantitative images of diffusion, TBV and perfusion will be obtained in these patients prior to and following initiation of treatment with chemotherapy and/or irradiation. Changes in diffusion and blood flow parameters will be quantitated and correlated with later measurement of clinical outcomes via tumor volume change and patient survival in order to determine the predictive value of the quantitative MRI indicators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RADIATION THERAPY ONCOLOGY GROUP Principal Investigator & Institution: Curran, Walter J.; Clinical Director, Kimmel Cancer Center; American College of Radiology 1101 Market St, 14Th Fl Philadelphia, Pa 19107 Timing: Fiscal Year 2001; Project Start 01-FEB-1979; Project End 31-DEC-2001 Summary: The Radiation Therapy Oncology Group (RTOG) is an instrument of cooperative investigations to increase survival, decrease morbidity, preserve function and quality of life, and increase basic understanding of cancer. Its clinical, laboratory, and biostatistical scientists have made progress against major killers of Americans, especially cancer of the esophagus, lung, cervix, prostate, and anal canal. It has demonstrated equivalent outcomes when treatments are comparable for blacks and whites with brain tumors, and carcinomas of the head and neck, lung and esophagus, and similar results for women and men with malignant gliomas, head and neck and

Studies

51

lung cancer. The RTOG plans to continue integration of surgical, radiotherapeutic and chemotherapeutic treatments with emphasis on enhancing local-regional tumor control to improve outcomes. It will continue to investigate 3-dimensional conformal radiation therapy and stereotactic radiosurgery, altered fractionation, and chemical and biologic agents. Phase III trials for brain, head and neck, lung, gastrointestinal and genitourinary tumors are active and new hypotheses will be tested within the RTOG or the integroup mechanism when current studies are completed. A comprehensive quality management program monitors protocol compliance, completeness and accuracy of data, institutional audits and timely reporting of results. The RTOG has an entirely independent data safety and monitoring committee, and its protocols are overseen by an institutional review board with expertise in medical ethics. A Translational Research Program (TRP) chaired by a new Vice-Chair for Basic Science is rapidly advancing correlative studies of clinical, cellular and molecular phenomena; the TRP includes pathologists, tumor biologists and physicians representing all disease sites. A new Vice-Chair for Cancer Control oversees interrelated Community Clinical Oncology Program (CCOP), Special Populations, Epidemiology, Late Effects and Quality of Life investigations. The large databases and long-term observations from RTOG studies serve as unique resources to study major types of cancer. A 19% increase in annual accrual of patients for the last three years compared with the prior four years indicates that the studies of the RTOG investigations will be achieved more rapidly and its results will be available to the practice community and to investigators developing future studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RADIOTHERAPY EFFECTS ON BRAIN FUNCTIONING IN ADULTS Principal Investigator & Institution: Armstrong, Carol L.; Assistant Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-JUL-2004 Summary: The investigators propose a multidisciplinary project to describe the frequency, nature, and longitudinal course of the effects of radiotherapy (RT) on cognition and cerebral white matter in adults with low-grade, supratentorial brain tumors. They have identified a neurobehavioral model of the early-delayed effects of radiotherapy, characterized by decrement and rebound of semantic memory retrieval. They will investigate the validity of these findings in brain tumor groups with and without radiotherapy. They will concurrently validate the model by comparing it with another cognitive memory model, and will identify the onset of other cognitive changes. The investigators plan to investigate dose-dependent effects of radiotherapy by relating neuropsychological measures to reconstructions of dose burden to hypothesized brain regions. They will also relate dose and neuropsychological outcome to serial magnetic resonance imaging (MRI). They will compare magnetization transfer imaging (MTI) with MRI and expect that MTI will show greater sensitivity and specificity to the latedelayed changes, will differentiate axonal degeneration from edema, and will show higher correlations with neuropsychological measures. Over the five years of the project, the investigators will recruit new patients with low-grade gliomas, pituitary and other low-grade tumors because of their long life expectancies. Patients with gliomas who did not receive radiotherapy will be also sought as a control group. They propose to recruit 220 new cases, and will follow 22 cases from their pilot study over the study period. Hypotheses about treatment effects will be tested using subjects as their own controls and treatment group comparisons. They will conduct neuropsychological evaluation (10 domains and mood/fatigue) at baseline (about 6 weeks post surgery and just prior to radiotherapy), 6 weeks post-completion of radiotherapy, trimonthly for one year, and

52

Brain Tumors

then yearly. Cognitive neuropsychological models of memory search and retrieval over time will be investigated to discern the relation of neurocognitive impairment to brain structure. They will correlate cognitive variables with dose and graded MRI scans of all patients. Dose histograms will quantify dose to hypothesized brain structures and radiation portals. They will gather pilot data on the sensitivity of MTI to radiation effects in 37 cases during the early and late delayed periods. Standard brain regions, tumor sites and specific regions will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF ASTROCYTOMA GROWTH Principal Investigator & Institution: Morrison, Richard S.; Professor; Neurological Surgery; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: Loss or mutation of the p53 tumor suppressor gene is thought to be an important event in the malignant transformation of human astrocytes. The loss of wildtype p53 function may render cells more susceptible to genetic instability, predisposing them to neoplastic transformation. However, the specific genetic alterations that occur in astrocytes following the loss of p53 function have not been defined. Using glass- based high-density cDNA arrays we identified a novel gene that was significantly upregulated in malignant mouse astrocytes relative to normal mouse astrocytes. This gene was identified as pescadillo, which was first characterized as a gene that was essential for embryonic development in zebrafish. A yeast homologue of pescadillo has also been identified and its deletion is lethal in yeast. Preliminary data from our laboratory has shown that the pescadillo protein is highly expressed in human brain tumor cells suggesting that it may represent an important molecular change in human glial tumors. Although pescadillo contains several significant structural motifs including the presence of a BRCA1 carboxy terminus domain, its function and its relationship to malignancy remain unknown. The aim of the present proposal is to characterize the biochemical function and the cellular role of pescadillo in normal and malignant astrocytes. We will: 1) Determine if the pescadillo protein is abnormally expressed in human glial tumors; 2) Determine if pescadillo regulates the proliferation and invasiveness of normal and malignant astrocytes; 3) Determine if pescadillo regulates the cellular response of astrocytes to DNA damage and alters their sensitivity to chemotherapeutic agents; and 4) Characterize the biochemical function of pescadillo by analyzing its binding partners using a yeast two hybrid and proteomics screen. Since pescadillo represents a novel gene whose activity is essential for yeast viability and zebrafish development, elucidating its cellular role may provide unique insights into the process of neoplastic transformation and may provide a new target for suppressing the growth of human brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ROLE OF STAT3ALPHA IN MUTANT EGFR SIGNALING IN GLIOMA Principal Investigator & Institution: Schaefer, Timothy S.; Igen, Inc. 16020 Industrial Dr Gaithersburg, Md 20877 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant) Glioblastoma multiforme (GBM) are highly vascularized tumors of the brain. One of the most frequently observed genetic alterations in GBM is the rearrangement of the epidermal growth factor receptor

Studies

53

(EGFR). This mutation EGFRvIII, the result of exons 2-8, results in a receptor that no longer binds ligand and is constitutively activated. The expression of this receptor results in the activation of a number of signaling pathways and confers an increase in the proliferative capacity and tumorigenicity of cells expressing the receptor. Signal transducers and activators of transcription (Stat) proteins are a family of latent transcription factors normally activated by numerous cytokines and growth factors. One member of the family, Stat3, has been implicated in aberrant cell proliferation and constitutively activated Stat3cx has been seen in several types of neoplastic cells and solid tumors. In experiments designed to explore Stat3 signaling in human brain tumors, we have found that Stat3a is constitutively activated in low- and high-grade glioma (compared to normal brain tissue). In other preliminary experiments, we have demonstrated a direct interaction between Stat3a and EGFRvIII in extracts from cells that express both proteins. The expression of EGFRvIII leads to the activation of Stat3a with a concomitant increase in Stat3a-mediated transcription and this activation required serine phosphorylation on serine residue 727 indicating a convergence of more than one signaling event in Stat3a activation by EG FRvIII. In experiments described here, we propose to determine the role of Stat3a in the growth properties imparted by EGFRvIII expression both in vitro and in vivo using EGFRvIII derived mutants that cannot activate Stat3a and by the use of dominant-negative Stat3a molecules to directly block Stat3cx mediated signaling. The in vitro studies will be performed using cultured glioma cells that express EGFRvIII while the In vivo experiments will be performed using a novel intracranial induction system developed in our laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: (SAMMIC)

SMALL

ANIMAL

MULTI-MODALITY

IMAGING

CENTER

Principal Investigator & Institution: Glickson, Jerry D.; Research Professor; Radiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-JUL-2004 Summary: Creation of a Small Animal Imaging Resource Program (SAIRP) at the University of Pennsylvania supporting research by investigators at this institution and also at the Fox Chase Cancer Center and Thomas Jefferson University is proposed. This SAIRP will provide three imaging modalities -- 1) Magnetic Resonance Imaging and Spectroscopy (MRI/S). 2) optical imaging covering the ultraviolet through near infrared (UV-NIR), and positron emission tomography (PET). The MRI/S facilities are now in place; the UV-NIR and PET facilities are now operational on the scale of human patients and will be adapted to studies of small animals (mice and rats) by the end of the first year. The SAIRP will support the research of 13 NIH funded projects dealing with 1) modification of tumor response to radiation and hyperthermia, 2) methods of monitoring tumor hypoxia, 3) gene therapy of brain tumors, 4) immunotherapy of tumors, 5) detection of breast cancer and 6) detection of tumor response to chemotherapy and radiation therapy. Ancillary facilities for redox scanning, NIR time resolved spectroscopoy, electronics, animal management, synthesis of contrast agent and physiological probes, histology, computer resources, biostatistics and MR of perfused cells will be provided. Research and development and D) projects will be directed towards the development of novel NMR capabilities that will enhance the research capabilities of the base projects. These R and D projects are: A. MRI of Small Animal Tumors, including: A1. Small Animal Microimaging. A2. Functional Imaging of Tumors, B. Multinuclear Spectroscopy, including: B1. Chemical Shift Selective MR Imaging of 31P in Animal Tumors, B2. 1H{17O} MRI of Tumors, B3. In Vivo Imaging of

54

Brain Tumors

Intra- and Extracellular Na+ and pH in Tumors, and C. NMR Techniques for Monitoring Gene Therapy of Brain Tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SRC ON PRIMARY AND METASTATIC TUMORS OF THE CNS Principal Investigator & Institution: Bigner, Darell D.; Jones Cancer Research Professor; Pathology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-APR-1984; Project End 31-JAN-2004 Summary: This is the only fully funded Specialized Research Center of the National Institute of Neurological Disease and Stroke on primary and metastatic brain tumors of adults and children. It is presently in its 10th year of funding and this application represents its third submission for competitive review and renewal. As detailed in the body of this application, both primary and metastatic tumors to the CNS remain as significant health problems and are actually increasing in magnitude. Despite intensive research efforts by many investigators there has been little progress made in uncovering etiology, or improving treatment of primary or metastatic brain tumors during the last 30 years. This Specialized Research Center on Primary and Malignant Tumors of the CNS will continue intensification of the brain tumor research efforts of an outstanding group of internationally recognized investigators with a long history of effective collaboration. They will approach primary and metastatic brain tumors in adults and children in areas of etiology, mechanisms of transformation and altered growth control, improved diagnosis, preclinical and clinical therapy. Projects range from basic mechanistic studies on etiology such as tumor suppressor genes in human medulloblastoma, discovery of new drugs and mechanisms of drug resistance, to selection of molecular targets against adult and childhood brain tumors for targeted therapy and growth inhibition. Specific development of targeted therapy with radiolabeled and toxin-conjugated; preclinical and clinical trials of regional or compartmental therapy with radiolabeled MAbs, toxin-conjugated MAbs, and new drugs will ultimately be combined in years 3-5 with Phase 2 and 3 studies of systemic therapy with regional and compartmental therapy to reach tumor cells in the entire neuraxis. We believe that during this five year grant period better control of local and distant recurrence of primary and metastatic brain tumors can be achieved, improvement can be made in therapy of neoplastic meningitis, and quality and quantity of survival of both groups of patients will be improved. Moreover, our basic studies should define new molecular targets for future approach in 5-10 years with additional targeted therapy such as gene therapy replacement of putative suppressor genes and gene therapy of other molecular targets involved in transformation and altered growth control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: STATISTICAL METHODS FOR ANALYSIS OF FAILURE TIME DATA Principal Investigator & Institution: Betensky, Rebecca A.; Associate Professor; Biostatistics; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2003; Project Start 01-JAN-1998; Project End 31-MAR-2006 Summary: (provided by applicant) The goal of this proposal is to develop statistical methods for the analysis of failure time data that involve missing prognostic factors, complicated ascertainment, and/or dependencies. The Specific Aims are motivated by problems arising in natural history clinical studies of brain tumors and laboratory

Studies

55

studies of the molecular biology of brain tumors and by studies of familial aggregation of multiple cancers. Empirical data analysis will play a central role in each of the Specific Aims. Brain tumors typically have histological diagnoses that are only weakly associated with prognosis and genetic features that are only partially known. The impact of the resultant unexplained heterogeneity will be investigated for a general class of failure time models. Adaptive designs to remedy the resultant loss of power will be proposed. The known heterogeneity of brain tumors, and the resultant small numbers of subjects with a given diagnosis, frequently precludes large prospective studies. This leads to the use of natural history studies, and introduces delayed entry (truncation). Tests of independence of truncation and failure for a variety of situations will be derived and evaluated, and methods that appropriately adjust for dependence will be developed. Familial aggregation studies are characterized by dependencies among and within family members and by complex ascertainment schemes. Computationally simple methods will be developed for analysis of scientific quantities of interest, i.e., conditional and partially marginal measures of response and association that retain interpretability with families of varying sizes. Extensions to ordinal and censored data will be derived. Software will be developed, and made freely available, for optimal family study design, allowing for multiple disease outcomes and complex, non-random ascertainment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STJUDE PARTICIPATION IN PEDIATRIC CONSORTIUM

BRAIN TUMOR

Principal Investigator & Institution: Kun, Larry E.; Chairman; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The application indicates the intellectual energy and resources at St. Jude Children's Research Hospital that will be committed to the Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC). The institutional Neurobiology and Brain Tumor Program represents a talented group of experienced clinical and laboratory investigators (including 22 MD's, PhD's, and PharmD's) with particular expertise in pediatric neurooncology, radiation oncology, neurosurgery, molecular pharmacology, pharmacokinetics, neuroimaging, neuropsychology, and biostatistics. The Program accrues an average of 75 newly diagnosed children with brain tumors annually, and is just now positioned to increase accession to phase I and II studies for children with previously treated disease. Amongst the 258 children entered on institutional brain tumor protocols since 1990, significant contributions have been made in medulloblastomas, infant brain tumors, low grade gliomas, and malignant gliomas. During the interval, 154 children have been entered on POG studies, many of which reflect administrative and scientific leadership from St. Jude. Recent protocols highlight collaborations with 2-4 additional institutions to study novel chemotherapeutic and radiotherapeutic interventions, largely derived from laboratory investigation at St. Jude, in medulloblastoma, infant brain tumors, and low grade gliomas/ependymomas. The linear development of protocols (based upon preclinical in vitro and xenograft models, detailed pharmacokinetic studies, and ongoing development of improved means of evaluating tumor response and toxicities) indicates the integration of scientific research and clinical trial design and management that offers considerable expertise as the Program fully commits its resources to the PBTCTC. The development of correlative laboratory studies, including genetic analyses and explorations using the new Patched medulloblastoma model, and translational research evaluating alterations in the Atm

56

Brain Tumors

gene as potential targets to alter radiation sensitivity, offer enormous potential for the identification of novel therapeutic interventions. The institutional contributions to the PBTCTC combine laboratory and clinical science with a sizable patient base that will be dedicated to consortium trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUPPRESSION OF BRAIN TUMOR GROWTH BY INTEGRIN ANTAGONIST Principal Investigator & Institution: Laug, Walter E.; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2003 Summary: Inhibition of angiogenesis has evolved as a promising new tool for the adjuvant treatment of various cancers. Since brain tumors are the most angiogenic neoplasms known, anti-angiogenesis might prove to be especially effective for this deadly disease. A novel antagonist of alphavbeta3 and alphavbeta5 integrins, EMD 121 974, was used in our study. This cyclic RGDfV pentapeptide inhibits neo-vascularization through irreversibly binding to the alphav-integrins of sprouting capillary vessels. Human brain tumors stereotactically xenografted into the forebrain of athymic mice responded with growth arrest and subsequent regression when treated daily with this peptide. In contrast, all animals receiving the cyclic RADfV control peptide died within 6-8 weeks from progressive tumors. We propose to expand on these findings by determining the overall survival, the length and optimal dose of peptide administration for tumor eradication, and to investigate for side effects from this peptide. Tumor growth and neo-vascularization in animals receiving the active or inactive peptide will be monitored with a novel MRI scanning technique, specifically designed for mice, and these data will be compared with histological findings. Since only orthotopically transplanted tumors (brain), but not heterotopically injected brain tumor cells (subcutis) showed growth inhibition, we propose to investigate whether the unique biochemical environment of the brain, or its capillary endothelial cells are responsible for this response. Growth and survival of capillary endothelial cells derived from the brain and subcutis, and cultured on brain specific matrix proteins will be compared in the presence and absence of RGDfV. Furthermore, the possibility of induction of direct brain tumor cell apoptosis by RGDfV will be tested by growing brain tumor cells on various matrix proteins in the presence or absence of the active peptide. In vivo studies to substantiate a direct tumoricidal effect of RGDfV on brain tumors will be with the administration of monoclonal Ab only reacting with human alphav-integrins and the use of tumors not expressing alphav-integrins. These studies will demonstrate whether the growth suppressive effect of RGDfV in brain tumors is solely due its antiangiogenetic action or whether this peptide also has a tumoricidal effect due its prevention of interaction of brain tumor cells with brain specific matrix proteins. Overall, our data may lead to a novel, adjuvant treatment of malignant brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: SYSTEMIC T CELL IMMUNOTHERAPY OF MALIGNANT GLIOMAS Principal Investigator & Institution: Shu, Suyu C.; Director; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-MAY-2003 Summary: Malignant brain tumors such as glioblastoma multiforme and anaplastic astrocytoma usually have a fatal outcome in spite of advances in diagnostic and

Studies

57

treatment procedures. Enthusiasm to utilize immunotherapeutic approached for treatment of brain tumors was dampened by the concept of ~immune privilege~ of the central nervous system (CNS). However, recent data suggest that the CNS may not be an immunologically privileged site, albeit its distinct anatomical and physiological features. The CNS has the capacity to regulate immune responses by allowing a restricted entry of immune cells and providing a microenvironment that is conducive to the activation of effector cells. In animal experiments, tumors established in the brain are reactive to the systemically transferred immun T lymphocytes, resulting in tumor regression in an immunologically specific manner. Principles and methodology defined in animal studies have been extrapolated to develop a novel treatment for humans with high-grade gliomas. Patients will be immunized with irradiated autologous tumor cells along with GM-CSF as an adjuvant to boost the immune response. Draining lymph nodes resected surgically 7 days later will be activated in vitro with a bacterial superantigen, SEA followed by anti-CD3. A large number of such activated cells will be infused intravenously to the patient for adoptive T-cell immunotherapy. In this research-driven clinical trial, immunological and physiological properties of the activated T cells will be analyzed in detail. Toxicity, immunological reactivities and tumor responses of treated patients will be evaluated. It is hoped that this study will provide information for a better understanding of host-tumor interactions and for improving procedures for the generation of potent therapeutically effective T cells. The specific aims in this proposal are: 1) to assess the in vivo immunological reactivity of patients undergoing adoptive immunotherapy; 2) to elucidate mechanisms of antigen presentation and the adjuvant activity of GM-CSF; 3) to seek correlations between in vitro reactivities of lymph node T cells and their antitumor efficacy; and 4) to characterize adhesion/integrin molecules that are important in T cell activation as well as homing to the tumor site. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETING T CELLS AGAINST TUMORS USING BISPECIFIC AGENTS Principal Investigator & Institution: Roy, Edward J.; Biochemistry; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: (Applicant's Abstract) In the past ten years, various strategies that use bispecific antibodies to redirect the activity to T cells against tumor cells have been developed. Despite the advance of several of these agents into clinical trials, there remain significant problems with the bispecific antibody approach. Chief among these problems has been the inability to sustain an active T cell infiltrate at the site of solid tumors. The overall goal of the proposed experiments is to sustain T cell activity at the site of the tumor and redirect the efficient lysis of tumor cells. Bispecific agents that target T cells to the high affinity folate receptor (FR), found on most ovarian carcinomas and some brain tumors, can be produced easily by attaching folate to any anti-T cell antibody of interest. This method will allow evaluation of the tumor-dependent T cell activating potential of various conjugates, including folate conjugates of antibodies to the T cell receptor/CD3 complex, CD28, and LFA-1. Multivalent ligation of these molecules on the surface of T cells stimulates full activation of T cells under normal physiological conditions. In contrast, ligation of the T cell molecule CTLA4 with its ligand B7 leads to T cell inactivation. Inhibition of the CTLA4:B7 interaction can sustain the activity of T cells. Based on these rationales the various folate/anti-T cell antibody conjugates will be tested alone and in combination with monovalent forms (scFv and

58

Brain Tumors

Fab) of an anti-CTLA4 antibody. In Specific Aim 1, in vitro assays will measure T cell proliferation and cytotoxicity after incubation of T cells with folate/anti-TCR conjugates, anti-CTLA4 antibody fragments and FR tumor cells. In Specific Aim 2, mice treated in vivo with various antibody agents will be examined ex vivo for cytotoxicity by splenic T cells or peritoneal exudate cells and by immunohistochemical analysis of T cell infiltrates within tumors. The goal of this aim is to identify agents that optimally maintain activated T cells within the tumor. In Specific Aim 3, antibodies and/or folateconjugates will be tested for their ability to eliminate FR+ tumors in three murine model systems: (a) immunologically defined 2C TCR/RAG mice transplanted with a human FR+ tumor; (b) immunocompetent mice transplanted with a syngeneic FR+ tumor; and (c) immunocompetent transgenic mice that develop endogenous FR+ brain tumors. Endpoints will include survival, tumor progression, and testing for tumor-specific memory by re-transplantation of the appropriate tumor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THERAPEUTICS STUDIES OF PRIMARY CNS MALIGNANCIES Principal Investigator & Institution: Wen, Patrick Y.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 08-APR-1994; Project End 31-DEC-2002 Summary: The overall objective of this UOI application is to provide support for consortia of institutions to perform Phase I and 11 clinical trials of new chemotherapeutic/biologic agents in patients with primary central nervous system (CNS) tumors and to perform ancillary laboratory studies with potential clinical implications. The Harvard/Longwood Brain Tumor Center Trials Group at the DanaFarber Cancer Institute, Brigham and Women's Hospital, The Children's Hospital, and the Beth Israel Hospital has a large and expanding patient population and commitment to clinical and laboratory research of primary brain tumors. As part of the "North American Brain Tumor Consortium" our general goals will be to perform Phase I and II trials of novel cytotoxic and biologic agents, with a special interest in anti-angiogenic agents. Although San Antonio will function as the pharmacologic center for our consortium, our center is in a position to either pilot experimental and/or extensive single institution pharmacologic/pharmacodynamic studies given our large experience in pharmacology-based Phase I trials. Since the specific agents to be studied over the next four years are unknown at this time, we have chosen to develop protocols that build on our previous work in the pre-clinical and clinical development of three agents with anti-angiogenic activity based on our long-standing interest in tumor-associated angiogenesis: a.) Thalidomide, a teratogenic sedative with anti-angiogenic activity, for which we are just completed a promising Phase 11 trial in patients with malignant gliomas: b.) A new human beta interferon with anti-angiogenic activity and significant antiglioma activity demonstrated in our recently completed Phase I trial; and, c.) Angiostatin, a recently discovered endogenous inhibitor of angiogenesis, based on work done principally in our laboratories. The specific aims of this proposal are therefore; I.) To perform a Phase II trial of combination anti-angiogenesis inhibition with thalidornide and beta interferon in patients with recurrent high grade gliomas; and 2.) To perform a Phase I trial of angiostatin, a novel inhibitor of anti-angiogenesis, in patients with recurrent high grade gliomas. Through these examples, we hope to demonstrate our experience in the preclinical development and clinical trial design of novel agents to be evaluated in primary malignant gliomas, and our capability to develop correlative laboratory studies that may ultimately yield useful biologic and clinical endpoints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

59

Project Title: TOPOTECAN BY INTRACEREBRAL CLYSIS FOR BRAIN TUMORS Principal Investigator & Institution: Bruce, Jeffrey N.; Neurological Surgery; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: As with most solid tumors, clinical efficacy with cytotoxic chemotherapy compounds has been discouraging for malignant gliomas, mostly because of systemic drug toxicities and delivery limitations. Because they are locally invasive and rarely metastasize, malignant gliomas have features of a local-regional disease that make them uniquely amenable to new strategies of regional drug delivery. Intracerebral clysis (ICC) is a novel drug delivery strategy that utilizes a microinfusion pump to establish a positive pressure gradient in the brain via an implanted catheter. The pressure gradient produces convective forces that distribute a therapeutic agent throughout the tumor and surrounding interstitial space in the brain. Our preliminary data has shown that glioma cells are sensitive to topoisomerase I inhibitors including topotecan at levels that can be achieved in vivo with ICC. Additionally, topotecan by ICC is expected to have reduced toxicity by virtue of reduced topoisomerase I levels in normal brain compared to gliomas. Although ineffective in clinical trials due to systemic toxicity, topotecan has been safe and effective in our rat glioma model using ICC. The safe use of ICC as a delivery method has already been validated in early human trials. These findings lead us to hypothesize that topotecan delivered by ICC will increase survival in patients with primary malignant brain tumors. Furthermore, non- invasive radiographic methods of monitoring drug distribution and treatment response have been developed which will maximize its clinical application. These data lead to the Specific Aims which are: (1) to evaluate the safety and efficacy of ICC therapy with topotecan in patients with refractory and progressive primary malignant brain tumors; (2) to apply advanced MR imaging as a non-invasive means of optimizing treatment parameters and determining volume of drug distribution with ICC; and (3) determine whether the expression of the topoisomerase target in the tumor influences its response to topotecan by analyzing tumor histopathology, topoisomerase I expression, and in vitro drug sensitivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TRANSDUCTION OF TUMOR SUPPRESSOR PROTEINS INTO GLIOMAS Principal Investigator & Institution: Dowdy, Steven F.; Cellular & Molecular Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 05-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) Brain tumors, gliomas and astrocytomas, are devastating malignancies that account for 2.3 percent of all US cancer deaths and represent the second most common solid tumor of children. Malignant brain tumors respond poorly to current therapies with a mean survival rate of less than one year despite treatment, Due to the invasive nature of gliomas, particularly glioblastoma multiformes (GBM), localized anti-cancer strategies, such as surgical removal, also fail to adequately halt the disease. Gliomas select for genetic inactivation of multiple tumor suppressor genes, including p53 (>60 percent), PTEN (>75 percent), p16/p I4ARF (50 percent), pRB (30 percent), and epigenetic down-regulation of the p27 Cdk inhibitor. A central hypothesis of anti-cancer therapies holds that replacement of tumor suppressor gene functions in malignant cells will result in specific death or apoptosis of the cancer cell while sparing the surrounding normal tissue. Indeed, tumor cells are undergoing continuous DNA damage and therefore, adenovirus expression of wild type p53 in

60

Brain Tumors

gliomas by results in specific apoptosis to the glioma tumor cells. We propose to test this hypothesis by generating transducible tumor suppressor proteins. My laboratory has further developed the methodology of protein transduction. Recombinant, bacterially expressed fusion proteins containing an N' terminal protein transduction domain from HIV TAT rapidly transduce into 100 percent of cells. Using this methodology, we have generated and transduced over 60 TAT-fusion proteins from 15-120 kDa. Recently, we have demonstrated the ability of TAT-B-gal protein to transduce into most, if not all, cells and tissues of mouse models in vivo, including across the blood-brain barrier. Thus, in principle and practice, all mammalian cell types are susceptible to protein transduction. We propose to test the anti-cancer effectiveness and specificity of killing glioma tumors in mouse models by transducible tumor suppressor proteins, namely TAT-ARF and TAT-p53, and by a transducible pro-apoptotic viral protein, TATApoptin. TAT-fusion proteins will be analyzed and optimized in vitro and then tested against xenograft intracranial glioma tumors in nude mice and in de novo derived astrocytomas in B8 transgenic ras about2" mice. In addition, to quantify protein transduction potential in mouse models, we intend to analyze the transduction and refolding rates of TAT-reporter fusion proteins, including TAT-B-gal and TAT-TK. TATTK activity will also be monitored in vivo by microPET imaging using '8Ffluoroganciclovir as a positron emitter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF CHILDHOOD CANCER Principal Investigator & Institution: Brecher, Martin L.; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2001; Project Start 01-JUL-1980; Project End 31-DEC-2002 Summary: Cooperative trials in pediatric cancer patients have played a major role in the remarkable improvement in cure of childhood cancers. Because most childhood cancers are rare, it is only through this mechanism that adequate numbers of patients can be accrued in reasonable lengths of time for randomized controlled studies. The Department of Pediatrics at Roswell Park Cancer Institute (RPCI) has actively participated in cooperative group trials via the Pediatric Oncology Group (POG) to answer treatment questions which would be impossible to answer were we to conduct only single institution studies. Some pediatric solid tumors are so rare that national intergroup studies are required. We also participate in these intergroup studies. RPCI investigators are coordinators for a number of POG protocols including front-line studies for the treatment of advanced Hodgkin's disease, advanced small non- cleaved cell lymphoma, non-rhabdomyosarcoma soft tissue sarcomas, acute lymphoblastic leukemia in relapse, the National Wilms Tumor Study, brain tumors in infants, and the Intergroup Ewing's Sarcoma Study. Roswell Park investigators have also developed POG phase II studies of continuous infusion 5-fluouracil and the combination of cisplatin, ifosfamide and etoposide. Roswell Park investigators chair the Wilms Tumor Committee, the Neuroscience Subcommittee of the Brain Tumor Committee, and cochair the Pathology Discipline Core Committee, as well as being active on a number of other POG Core Committees. They have made major contributions over the last few years in the areas of solid tumor oncology, neuro- oncology and the treatment of lymphoid malignancies. We are strongly committed to the interdisciplinary approach to pediatric cancer and have established collaboration with the necessary clinical specialties including Radiation Medicine, Pediatric Surgery, Pediatric Neurology, Neurosurgery, and Orthopedic Surgery, as well as with researchers in immunology, pharmacology and molecular biology. As more children are cured of their cancers, the

Studies

61

identification and prevention, when feasible, of complications of therapy have become imperative. We have been a major contributor to the identification and understanding of the long-term medical and psychosocial effects of the treatment of leukemia, Hodgkin's disease, and a number of solid tumors, both through the cooperative group mechanism and through institutional studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TUMOR VACCINE BASED IMMUNOTHERAPY OF MALIGNANT GLIOMAS Principal Investigator & Institution: Okada, Hideho; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: The central nervous system (CNS) has long been regarded as an immunologically privileged site. Immunotherapies effective in controlling cancers in other sites have failed to prevent tumor progression in the CNS. Dendritic cells (DCs) are the most efficient antigen-presenting cells (APCs). Following co-culture with tumor antigens, DCS can induce expansion of tumor-specific T-cells. As brain tumors may not be exposed to fully activated APCs in the CNS, exploring DC-based therapies for CNS tumors will provide a valuable opportunity to gain fundamental information about the unique features of the CNS tumor environment that will be of critical significance for developing this innovative therapeutic approach. In this project, we present preliminary data supporting the induction of anti-glioma immunity using DC-based vaccines; and present a plan for the development of effective DC-based therapies for malignant brain tumors. Our Specific Aims include: 1) Optimize the induction of tumor-specific effector cells using DCS in a series of rodent glioma models; 2) Develop strategies that effectively combine DC-based peripheral vaccination and alteration of the tumor microenvironment; 3) Initiate clinical trials to test the feasibility and safety of these approaches. The efficacy of DC-based vaccination appears to be promising, however, still limited for the treatment of established CNS gliomas. To improve the efficacy of DC- based vaccine strategies we will utilize rat glioma cell lines and DCs for preclinical assessment. We will first optimize the loading conditions of DCS with tumor cell antigens by examining different preparations of glioma antigens, and identifying which cytokines or combination of cytokines achieve maximal potentiation of DC activation at the vaccine site. Also, transfection of DCS with a gene vector that expresses the cytokine determined as critical in these analyses will be examined to enhance the anti-tumor response. In addition, we will determine if modification of the target intracranial tumor microenvironment using radiosurgery or cytokine gene delivery can enhance the efficacy of DC- based immunotherapy by up-regulating the trafficking and activity of anti-tumor effector cells. Clinical protocols will be developed on the basis of these preclinical studies. Taken together, the proposed studies may provide a strong basis for the development of DC-based vaccine strategies as independent therapeutic approaches for malignant gliomas; and also demonstrate extensive applications of DC-based vaccines in combination with other biologic therapy appr4oaches (i.e., gene therapy, apoptosis induction, and stereotactic radiosurgery) to enhance the efficacy of each single modality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

62

Brain Tumors

•

Project Title: TWO COMPARTMENT MODELS TO IMPROVE BRAIN TUMOR THERAPY Principal Investigator & Institution: Neuwelt, Edward A.; Professor; Neurology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 15-AUG-1995; Project End 31-MAR-2003 Summary: (Investigator's Abstract): This proposal focuses on the delivery of immunoconjugates to a model of human central nervous system metastatis in the nude rat. we have characterized the LX- 1 small cell lung carcinoma human tumor xenograft model in the nude rat with regard to permeability, growth characteristics, and survival times. We now propose to expand our current intracerebral tumor model using clonal populations of LX- 1 cells that stably express high or low amounts of the Lewis-y antigen for binding of monoclonal antibody (mAb) BR96. We hypothesize that these tumors will have similar growth and permeability characteristics to the parental LX- 1 model, but will have markedly different responses in the imaging and efficacy studies. In addition, these cell lines will provide a unique model to examine issues of tumor heterogeneity in imaging and therapy with immunoconjugates. We propose to examine the potential for specific imaging and diagnosis of intracerebral tumors using paramagnetic iron oxide particles conjugated to mAbs or mAb fragments as a tumorspecific contrast agent for magnetic resonance imaging. Pancarcinoma mAbs BR96 and L6, and the L6-F(ab')/2 and recombinant L6-sFv and BR96-sFv fragments, which may show reduced levels of non-specific binding compared to intact mAb, will be conjugated to the monocrystalline iron oxide nanoparticles (MIONs). We will then determine whether tumor-speclfic imaging can be attained using these agents, when delivery to intracerebral tumor is optimized with osmotic blood-brain barrier disruption (BBBD). The use of these MION antibodies conjugates offer the possibility of noninvasive assessment of tumor type and extent by adding specificity to an already sensitive MR imaging modality. In addition to the imaging studies, we will investigate the potential for therapy of intracerebral tumors using Doxorubicin and Pseudomonas exotoxin conjugated to the BR96 mAb or BR96- sFv fragment, respectively. We have the possibility for chemotherapy specifically targeted to brain tumors. The combination of an effective drug such as doxorubicin with tumor-specific localization and increased tumor delivery using osmotic BBBD is an innovative approach to brain turnor therapy with true practical application in the clinic. Clinical trials, based on previous blood-brain barrier program R01 funding, are resulting in durable tumor responses with no cognitive loss, particularly in CNS lymphoma patients. The proposed studies will further enhance these positive clinical results. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: UB-PROTEOLYSIS OF ALKYLTRANSFERASE IN GLIOMA THERAPY Principal Investigator & Institution: Srivenugopal, Kalkunte S.; Experimental Pediatrics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (Applicant's Abstract) Pediatric and adult brain tumors are among the most therapeutically unresponsive and lethal of human cancers and their incidence continues to rise in the United States. A major reason for this therapeutic failure is the overexpression of O6-alkylguanine-DNA alkyltransferase (AGT), which prevents the formation of G-C cross-links in DNA by the chloroethylnitrosourea (CENU) class of drugs. Currently, a strategy involving the inactivation of AGT by O6-benzylguanine (BG) followed by CENU treatment has shown excellent promise, and clinical trials are

Studies

63

underway for its exploitation. However, an extended suppression of AGT activity is necessary to achieve therapeutic efficacy and a rapid repletion of AGT occurring soon after BG treatment poses a potentially severe limitation to successful chemotherapy. Based on the applicant's recent studies of AGT proteolysis through the ubiquitin (ub)proteasome pathway and preliminary studies showing the inhibition of AGT regeneration by proteasome blockers, the primary goal of this project is to further enhance the BG-based CENU therapy by preventing the repletion of AGT. The applicant's hypothesis is that ubiquitin-mediated break-down of inactive AGT triggers a regeneration of active AGT by enhancing its translation in BG-treated cells. The applicant proposes that the ub-proteasome pathway regulates both the proteolysis and subsequent regeneration of AGT after BG treatment and that specific inhibitors of this pathway will reduce the repletion of AGT to enable increased sensitization of glioma cells to BG-CENU regimen. The specific aims are: 1) to quantitate the expression of ubproteasome components in relation to AGT activity, the levels of AGT proteolysis after BG treatment, and the rate and extent of subsequent AGT regeneration in human glioma cell lines; 2) to examine the ub-requirement for AGT regeneration in a cell line, temperature-sensitive for ub-activation, and study increased translational efficiency of AGT in BG-treated glioma cells; 3) to evaluate ub-components and AGT in primary gliomas and lymphocytes, and to treat glioma cells and glioma xenografts in nude mice with specific inhibitors of the ub-proteasome pathway and examine AGT regeneration and BCNU cytotoxicity following BG treatment. Overall, this project promises to provide novel information on the biochemical modulation of AGT in BG-treated cells and rationalize alternative strategies to improve AGT-targeted chemotherapy of human brain tumors and other tumor types. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ULTRASONIC ENHANCEMENT OF DRUG DELIVERY ACROSS THE BBB Principal Investigator & Institution: Ferrara, Katherine W.; Professor; Biomedical Engineering Div; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2003; Project Start 02-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Many promising studies indicate that ultrasoundenhanced drug delivery vehicles can be used to locally deliver a drug to a region of interest, with ultrasound imaging used to define the region to be treated and to monitor the inflow of the delivery vehicle. We have developed radiation force pulse sequences that first deflect a drug delivery vehicle to a vessel wall and then rupture the vehicle at that site. Drug delivery vehicles can be engineered to be manipulated by this ultrasonic radiation force, through the incorporation of a small volume of gas. We refer to the engineered vehicles as acoustically-active lipospheres (AALs) in that they have properties similar to ultrasound contrast agents, but are also designed to carry a significant drug payload. In addition, the vehicles can be designed such that ultrasound pressure produces fragmentation of a micron-sized sphere into particles on the order of tens to hundreds of nanometers, and these particles may be taken up readily. In the proposed studies, we will specifically explore the development of ultrasound techniques to locally concentrate a chemotherapeutic drug within the brain, crossing the bloodbrain barrier (BBB). This is a unique problem and is critically important as the survival time with primary and metastatic brain tumors is low. Chemotherapy has been unsuccessful in general, and surgical debulking of the tumor and radiotherapy extend the patient survival only by 6-12 months. New research studies have demonstrated that

64

Brain Tumors

BBB permeability can be greatly increased for both hydrophilic and hydrophobic drugs through the application of systemic compounds that include bradykinin analogs and Pglycoprotein (P-gp) modulators. The disadvantage of the global increase in BBB permeability produced by these compounds is that the simultaneous application of chemotherapy at the desired concentrations can result in a severe neurotoxicity. Our new technique may address this problem since the drug will be concentrated on the luminal surface of the endothelial cells in the desired region, and this increased concentration when combined with P-gp modulation should locally increase the drug concentration in the tumor and brain-surrounding tumor region. Thus, ultimately, by combining increased BBB permeability with local delivery of a chemotherapeutic to endothelial cells in a region of interest, we hope to significantly increase the effectiveness of chemotherapy in brain tumors. Our proposal includes the following goals designed to develop and validate ultrasound-enhanced local drug delivery of a hydrophilic drug to the brain. We will develop and evaluate a model for the displacement produced by ultrasonic radiation forces applied to AALs. Next, the transfer of fluorescently-labeled paclitaxel to endothelial cells will be assessed. Finally, we will evaluate the ability of local drug delivery vehicles containing F18-labelled paclitaxel to concentrate the drug within the brain with and without co-administration of a P-glycoprotein blocker. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VARIANTS OF FOCAL BRAIN INJURY Principal Investigator & Institution: Trauner, Doris A.; Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 16-SEP-1985; Project End 31-JUL-2006 Summary: This is a new project that builds on our 15-years of experience studying children with congenital unilateral brain injury. This project will focus on variations in the timing and nature of brain injury, in three experimental groups that have been excluded from our past research on pediatric brain injury: (1) children with late-onset unilateral brain damage, (2) children with early-onset bilateral damage, and (3) children with slow-growing unilateral lesions (tumors). We propose to use both standardized and experimental measures to assess delay, deviance, recovery and developmental trajectories in language, spatial ability, memory, executive function, and attention, as well as temporal processing ability in language, spatial processing ability, memory, executive function, and attention, as well as temporal processing ability in language, spatial processing and spatial attention. Based on pilot findings and on our previous research with early unilateral brain damage we predict that there will be specific differences in profiles of development for the three groups proposed here. Children with later-onset unilateral lesions are expected to exhibit more deficits in all domains than children with congenital lesions. Subjects with bilateral damage are predicted to demonstrate significant dissociations between language and non-verbal cognitive functions. Children with brain tumors are expected to differ from the other groups because of the slowly evolving nature of their lesions, and to demonstrate more sitespecific deficits within the brain. By studying these three groups, and comparing their performance to children with early unilateral brain damage, we can better define the nature and limits of neural specialization of these aspects of language, attention, and non-verbal cognition, and conversely, the nature and limits of neural and behavioral plasticity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

65

Project Title: VIRAL AND MOLECULAR CHEMOTHERAPY OF MALIGNANT CNS TUMORS Principal Investigator & Institution: Buchsbaum, Donald J.; Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-MAY-2007 Summary: This multi-disciplinary group of investigators has several years' experience working together designing and characterizing viral vector approaches to gene therapy of malignant brain tumors. A major focus has been producing and testing both nonreplicative and replicative adenovirus (Ad) and conditionally replicative herpes simplex virus (HSV) vectors that express foreign gene products within infected tumor cells. These studies have been conducted at both the in vitro and in vivo levels to demonstrate proof-of-principle, safety and efficacy in experimental mouse models of intracranial gliomas. We have conducted Phase I and III clinical trials using retrovirus, Ad and HSV administered intratumorally in patients with malignant gliomas. In keeping with the translational theme of this SPORE application, this project seeks to design and deploy effective viral vector therapies of malignant glioma by utilizing rational combinations of foreign gene-viral vectors, oncolytic virus and irradiation., defined by additive, synergistic or antagonistic interactions determined for these various modalities. Aim 1 seeks to optimize the timing and dose of irradiation to achieve greater viral replication and spread and/or enhanced foreign gene expression in glioma cells and in intracranial experimental gliomas. In athymic nude mice. Aim 2 will develop and characterize both replicative HSV and replicative Ad that expression the pro-drug converting enzyme cytosine deaminase and optimize its use in intracranial preclinical models of malignant gliomas in combination with systemic 5-fluorocytosine. Other genetic constructs (uracil phosphoribosyl transferase) and drugs (dihydropyrimidine inhibitors) that facilitate appropriate 5-FU incorporation into host cell DNA synthesis pathways will also be tested to improve the therapeutic effect. Further, the radiation sensitization properties of certain pro-drugs products (5-FU) will be characterized to achieve a greater anti-glioma effect. Aim 3 will combine findings in Aims 1 and 2 to design and test strategies that rationally combine intratumoral viral vector injection, systemic pro-drug administration and low dose external beam irradiation to achieve the most effective and safe antiglioma therapy (ies). Aim 4 will translate our findings in preclinical models for brain tumor therapy into pilot, Phase I and Phase II clinical trials in patients with malignant gliomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: VIRAL MODEL FOR TUMOR PATHOGENESIS IN BRAIN Principal Investigator & Institution: Khalili, Kamel; Professor and Director; Ctr/Neurovirology/Cancer Biol; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2003; Project Start 30-SEP-1996; Project End 31-MAY-2008 Summary: This is a competing renewal program project grant application seeking support for resuming studies on the molecular events leading to the development of brain tumors. In the previous period of funding we utilized human neurotropic virus, JCV, to create experimental animals which developed tumors from external granular layer of the cerebellum modeling human medulloblastoma. In humans, medulloblastoma is the most common malignant brain tumor seen predominantly in children and is considered the prototypical embryonal neuroblastic neoplasm of the central nervous system (CNS). This program project, which is a confederation of three

66

Brain Tumors

inter-related research projects with supporting scientific and administrative cores, each representing the natural evolution of the previously funded program, plans to launch a multidisciplinary approach utilizing experimental animals to decipher molecular events involved in the genesis of medulloblastoma. In Project #1, experiments are designed to investigate the regulation of gene expression involved in control of cell proliferation by the tumor suppressor protein, p53 and [g-catenin, a key component of the Wnt pathway which is involved in the oncogenesis and neurogenesis. By studying pl30/pRb2 pathway in Project #2, we will evaluate the the mechanism of regulation of this potent tumor suppressor and its well celebrated partner, p27 Kipl in medulloblastoma, determine the functional interaction of p130/pRb2 with JCV T-antigen, both in vitro and in pRb-knockout experimental animals. Finally, in Project #3, we will investigate the role of IGF-1 signal transduction pathway as our recent studies have provided compelling evidence for the involvement of major components of the IGF-1 receptor, IRS-1, which is induced by IGF-1 and triggers a cascade of cytoplasmid events involving AKT/PKB and MAP kinases in the development of medulloblastoma. These projects will be supported by the Experimental Animal Core (Core A) and the Neuropathology and Tissue Culture Core (Core B). The participants of this program project, who have worked synergistically to study CNS neoplasia, will convert the information from these molecular studies to translational research in devising therapeutic strategies toward brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “brain tumors” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for brain tumors in the PubMed Central database: •

Borocaptate Sodium: A Potential Boron Delivery Compound for Boron Neutron Capture Therapy Evaluated in Dogs with Spontaneous Intracranial Tumors. by Kraft SL, Gavin PR, DeHaan CE, Leathers CW, Bauer WF, Miller DL, Dorn RV III.; 1992 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50680

•

Can neural stem cells be used to track down and destroy migratory brain tumor cells while also providing a means of repairing tumor-associated damage? by Noble M.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34055

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

Studies

67

•

Comparison of Genetically Engineered Herpes Simplex Viruses for the Treatment of Brain Tumors in a Scid Mouse Model of Human Malignant Glioma. by Chambers R, Gillespie GY, Soroceanu L, Andreansky S, Chatterjee S, Chou J, Roizman B, Whitley RJ.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42529

•

Complement Depletion Facilitates the Infection of Multiple Brain Tumors by an Intravascular, Replication-Conditional Herpes Simplex Virus Mutant. by Ikeda K, Wakimoto H, Ichikawa T, Jhung S, Hochberg FH, Louis DN, Chiocca EA.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111999

•

Development of Anti-Tumor Immunity Following Thymidine Kinase-Mediated Killing of Experimental Brain Tumors. by Barba D, Hardin J, Sadelain M, Gage FH.; 1994 May 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43782

•

Differential Expression of Arachidonate 5-Lipoxygenase Transcripts in Human Brain Tumors: Evidence for the Expression of a Multitranscript Family. by Boado RJ, Pardridge WM, Vinters HV, Black KL.; 1992 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50061

•

Efficient and Selective Gene Transfer into Primary Human Brain Tumors by Using Single-Chain Antibody-Targeted Adenoviral Vectors with Native Tropism Abolished. by van Beusechem VW, Grill J, Mastenbroek DC, Wickham TJ, Roelvink PW, Haisma HJ, Lamfers ML, Dirven CM, Pinedo HM, Gerritsen WR.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135966

•

Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors. by Parker JN, Gillespie GY, Love CE, Randall S, Whitley RJ, Markert JM.; 2000 Feb 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15779

•

Expression of oligodendrocyte progenitor cell antigens by gliomas: Implications for the histogenesis of brain tumors. by Shoshan Y, Nishiyama A, Chang A, Mork S, Barnett GH, Cowell JK, Trapp BD, Staugaitis SM.; 1999 Aug 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17893

•

Free Magnesium Levels in Normal Human Brain and Brain Tumors: 31P ChemicalShift Imaging Measurements at 1.5 T. by Taylor JS, Vigneron DB, Murphy-Boesch J, Nelson SJ, Kessler HB, Coia L, Curran W, Brown TR.; 1991 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52178

•

Gene Therapy for Brain Tumors: Regression of Experimental Gliomas by Adenovirus-Mediated Gene Transfer in vivo. by Chen S, Shine HD, Goodman JC, Grossman RG, Woo SL.; 1994 Apr 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43513

68

Brain Tumors

•

Lack of the DNA Repair Protein O6-Methylguanine-DNA Methyltransferase in Histologically Normal Brain Adjacent to Primary Human Brain Tumors. by Silber JR, Blank A, Bobola MS, Mueller BA, Kolstoe DD, Ojemann GA, Berger MS.; 1996 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38913

•

Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors. by Lu QR, Park JK, Noll E, Chan JA, Alberta J, Yuk D, Alzamora MG, Louis DN, Stiles CD, Rowitch DH, Black PM.; 2001 Sep 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58563

•

The Application of Genetically Engineered Herpes Simplex Viruses to the Treatment of Experimental Brain Tumors. by Andreansky SS, He B, Gillespie GY, Soroceanu L, Markert J, Chou J, Roizman B, Whitley RJ.; 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38054

•

Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors. by Sampson JH, Crotty LE, Lee S, Archer GE, Ashley DM, Wikstrand CJ, Hale LP, Small C, Dranoff G, Friedman AH, Friedman HS, Bigner DD.; 2000 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16575

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with brain tumors, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “brain tumors” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for brain tumors (hyperlinks lead to article summaries): •

6

A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors. Author(s): Torres IJ, Mundt AJ, Sweeney PJ, Llanes-Macy S, Dunaway L, Castillo M, Macdonald RL. Source: Neurology. 2003 April 8; 60(7): 1113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682316&dopt=Abstract

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

Studies

69

•

A mathematical model for self-limiting brain tumors. Author(s): Newman WI, Lazareff JA. Source: Journal of Theoretical Biology. 2003 June 7; 222(3): 361-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732482&dopt=Abstract

•

A multispectral fluorescence imaging system: design and initial clinical tests in intraoperative Photofrin-photodynamic therapy of brain tumors. Author(s): Yang VX, Muller PJ, Herman P, Wilson BC. Source: Lasers in Surgery and Medicine. 2003; 32(3): 224-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605430&dopt=Abstract

•

A new approach for analyzing proton magnetic resonance spectroscopic images of brain tumors: nosologic images. Author(s): De Edelenyi FS, Rubin C, Esteve F, Grand S, Decorps M, Lefournier V, Le Bas JF, Remy C. Source: Nature Medicine. 2000 November; 6(11): 1287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11062544&dopt=Abstract

•

A novel germline in frame deletion (4128del3) of the BRCA2 gene detected in a breast/ovarian cancer family with fallopian tube and brain tumors identified in the north of France. Author(s): Demange L, Noguchi T, Sauvan R, Moyal-Amsellem N, Birnbaum D, Eisinger F, Sobol H. Source: Human Mutation. 2001 February; 17(2): 155. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180606&dopt=Abstract

•

Accelerator-based epithermal neutron sources for boron neutron capture therapy of brain tumors. Author(s): Blue TE, Yanch JC. Source: Journal of Neuro-Oncology. 2003 March-April; 62(1-2): 19-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749700&dopt=Abstract

•

Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors. Author(s): Iida T, Furuta A, Kawashima M, Nishida J, Nakabeppu Y, Iwaki T. Source: Neuro-Oncology. 2001 April; 3(2): 73-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296483&dopt=Abstract

•

Acetylcholinesterase and butyrylcholinesterase histochemical activities and tumor cell growth in several brain tumors. Author(s): Barbosa M, Rios O, Velasquez M, Villalobos J, Ehrmanns J. Source: Surgical Neurology. 2001 February; 55(2): 106-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301094&dopt=Abstract

70

Brain Tumors

•

Acute focal demyelinating disease simulating brain tumors: histopathologic guidelines for an accurate diagnosis. Author(s): Sugita Y, Terasaki M, Shigemori M, Sakata K, Morimatsu M. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2001 March; 21(1): 25-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304039&dopt=Abstract

•

Advances in molecular therapies in patients with brain tumors. Author(s): Tremont-Lukats IW, Gilbert MR. Source: Cancer Control : Journal of the Moffitt Cancer Center. 2003 March-April; 10(2): 125-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712007&dopt=Abstract

•

Analysis of 76Br-BrdU in DNA of brain tumors after a PET study does not support its use as a proliferation marker. Author(s): Gudjonssona O, Bergstrom M, Kristjansson S, Wu F, Nyberg G, Fasth KJ, Langstrom B. Source: Nuclear Medicine and Biology. 2001 January; 28(1): 59-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182565&dopt=Abstract

•

Analysis of DNA-ploidy using laser scanning cytometer in brain tumors and its clinical application. Author(s): Tsukazaki Y, Numa Y, Zhao S, Kawamoto K. Source: Hum Cell. 2000 December; 13(4): 221-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11329938&dopt=Abstract

•

Angiogenesis in malignant primary and metastatic brain tumors. Author(s): Reijneveld JC, Voest EE, Taphoorn MJ. Source: Journal of Neurology. 2000 August; 247(8): 597-608. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11041327&dopt=Abstract

•

Antiangiogenesis -- therapeutic strategies and clinical implications for brain tumors. Author(s): Puduvalli VK, Sawaya R. Source: Journal of Neuro-Oncology. 2000 October-November; 50(1-2): 189-200. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245279&dopt=Abstract

•

Anti-angiogenic agents for the treatment of brain tumors. Author(s): Fisher MJ, Adamson PC. Source: Neuroimaging Clin N Am. 2002 November; 12(4): 477-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687907&dopt=Abstract

Studies

71

•

Anti-angiogenic treatment strategies for malignant brain tumors. Author(s): Kirsch M, Schackert G, Black PM. Source: Journal of Neuro-Oncology. 2000 October-November; 50(1-2): 149-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245274&dopt=Abstract

•

Anticancer drug resistance in primary human brain tumors. Author(s): Bredel M. Source: Brain Research. Brain Research Reviews. 2001 April; 35(2): 161-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336781&dopt=Abstract

•

Application of advances in molecular biology to the treatment of brain tumors. Author(s): Takeshima H, Sawamura Y, Gilbert MR, Van Meir EG. Source: Current Oncology Reports. 2000 September; 2(5): 425-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122874&dopt=Abstract

•

Automated segmentation of MR images of brain tumors. Author(s): Kaus MR, Warfield SK, Nabavi A, Black PM, Jolesz FA, Kikinis R. Source: Radiology. 2001 February; 218(2): 586-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161183&dopt=Abstract

•

Automatic segmentation of non-enhancing brain tumors in magnetic resonance images. Author(s): Fletcher-Heath LM, Hall LO, Goldgof DB, Murtagh FR. Source: Artificial Intelligence in Medicine. 2001 January-March; 21(1-3): 43-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11154873&dopt=Abstract

•

Biochemical characterization of pediatric brain tumors by using in vivo and ex vivo magnetic resonance spectroscopy. Author(s): Tzika AA, Cheng LL, Goumnerova L, Madsen JR, Zurakowski D, Astrakas LG, Zarifi MK, Scott RM, Anthony DC, Gonzalez RG, Black PM. Source: Journal of Neurosurgery. 2002 June; 96(6): 1023-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066902&dopt=Abstract

•

Boron neutron capture therapy of brain tumors: clinical trials at the finnish facility using boronophenylalanine. Author(s): Joensuu H, Kankaanranta L, Seppala T, Auterinen I, Kallio M, Kulvik M, Laakso J, Vahatalo J, Kortesniemi M, Kotiluoto P, Seren T, Karila J, Brander A, Jarviluoma E, Ryynanen P, Paetau A, Ruokonen I, Minn H, Tenhunen M, Jaaskelainen J, Farkkila M, Savolainen S. Source: Journal of Neuro-Oncology. 2003 March-April; 62(1-2): 123-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749708&dopt=Abstract

72

Brain Tumors

•

Boron neutron capture therapy of brain tumors: investigation of urinary metabolites and oxidation products of sodium borocaptate by electrospray ionization mass spectrometry. Author(s): Gibson CR, Staubus AE, Barth RF, Yang W, Kleinholz NM, Jones RB, GreenChurch K, Tjarks W, Soloway AH. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 December; 29(12): 1588-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717178&dopt=Abstract

•

Botulinum toxin for sixth nerve palsies in children with brain tumors. Author(s): Kerr NC, Hoehn MB. Source: J Aapos. 2001 February; 5(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182668&dopt=Abstract

•

Brain tumors and polyomaviruses. Author(s): Croul S, Otte J, Khalili K. Source: Journal of Neurovirology. 2003 April; 9(2): 173-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707848&dopt=Abstract

•

Brain tumors and salivary gland cancers among cellular telephone users. Author(s): Auvinen A, Hietanen M, Luukkonen R, Koskela RS. Source: Epidemiology (Cambridge, Mass.). 2002 May; 13(3): 356-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964939&dopt=Abstract

•

Brain tumors in children under 1 year of age: emphasis on the relationship of prognostic factors. Author(s): Duffner P. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2003 June; 19(5-6): 315. Epub 2003 May 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732941&dopt=Abstract

•

Brain tumors in children under 1 year of age: emphasis on the relationship of prognostic factors. Author(s): Rivera-Luna R, Medina-Sanson A, Leal-Leal C, Pantoja-Guillen F, ZapataTarres M, Cardenas-Cardos R, Barrera-Gomez R, Rueda-Franco F. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2003 June; 19(5-6): 311-4. Epub 2003 May 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732940&dopt=Abstract

Studies

73

•

Brain tumors in children with neurofibromatosis: additional neuropsychological morbidity? Author(s): De Winter AE, Moore BD 3rd, Slopis JM, Ater JL, Copeland DR. Source: Neuro-Oncology. 1999 October; 1(4): 275-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550319&dopt=Abstract

•

Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). Author(s): Heimberger AB, Learn CA, Archer GE, McLendon RE, Chewning TA, Tuck FL, Pracyk JB, Friedman AH, Friedman HS, Bigner DD, Sampson JH. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 November; 8(11): 3496-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429640&dopt=Abstract

•

Brain tumors in the older person. Author(s): Flowers A. Source: Cancer Control : Journal of the Moffitt Cancer Center. 2000 NovemberDecember; 7(6): 523-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11088061&dopt=Abstract

•

Brain tumors might not be able to escape gastrin. Author(s): Gierdalski M. Source: Trends in Pharmacological Sciences. 2002 October; 23(10): 452. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368063&dopt=Abstract

•

Brain tumors. Author(s): Hill CI, Nixon CS, Ruehmeier JL, Wolf LM. Source: Physical Therapy. 2002 May; 82(5): 496-502. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991802&dopt=Abstract

•

Brain tumors. Author(s): Peterson K. Source: Neurologic Clinics. 2001 November; 19(4): 887-902. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854105&dopt=Abstract

•

Brain tumors. Author(s): Alderson LM. Source: Medicine and Health, Rhode Island. 2002 January; 85(1): 23-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824151&dopt=Abstract

74

Brain Tumors

•

Brain tumors. Author(s): Ashby LS, Shapiro WR. Source: Cancer Chemother Biol Response Modif. 2001; 19: 653-90. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11686038&dopt=Abstract

•

Brain tumors. Author(s): Sullivan PR. Source: The New England Journal of Medicine. 2001 May 10; 344(19): 1478; Author Reply 1479. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357844&dopt=Abstract

•

Brain tumors. Author(s): Lubin E. Source: The New England Journal of Medicine. 2001 May 10; 344(19): 1478; Author Reply 1479. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357843&dopt=Abstract

•

Brain tumors. Author(s): DeAngelis LM. Source: The New England Journal of Medicine. 2001 January 11; 344(2): 114-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150363&dopt=Abstract

•

Brain tumors. Author(s): Ashby LS, Shapiro WR. Source: Cancer Chemother Biol Response Modif. 2002; 20: 575-604. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703225&dopt=Abstract

•

Case-control study on radiology work, medical x-ray investigations, and use of cellular telephones as risk factors for brain tumors. Author(s): Hardell L, Nasman A, Pahlson A, Hallquist A. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2000 May 4; 2(2): E2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11104448&dopt=Abstract

•

Cellular telephones and brain tumors. Author(s): Trichopoulos D, Adami HO. Source: The New England Journal of Medicine. 2001 January 11; 344(2): 133-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150365&dopt=Abstract

Studies

75

•

Cellular telephones and brain tumors. Author(s): Kane RC. Source: The New England Journal of Medicine. 2001 April 26; 344(17): 1332. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336025&dopt=Abstract

•

Cellular telephones and brain tumors. Author(s): Erman M, Celik I, Kars A. Source: The New England Journal of Medicine. 2001 April 26; 344(17): 1331; Author Reply 1332. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336024&dopt=Abstract

•

Cellular telephones and brain tumors. Author(s): Kundi M. Source: The New England Journal of Medicine. 2001 April 26; 344(17): 1331-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336023&dopt=Abstract

•

Cellular-telephone use and brain tumors. Author(s): Inskip PD, Tarone RE, Hatch EE, Wilcosky TC, Shapiro WR, Selker RG, Fine HA, Black PM, Loeffler JS, Linet MS. Source: The New England Journal of Medicine. 2001 January 11; 344(2): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150357&dopt=Abstract

•

Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy. Author(s): Andersen PB, Krabbe K, Leffers AM, Schmiegelow M, Holm S, Laursen H, Muller JR, Paulson OB. Source: Journal of Neuro-Oncology. 2003 May; 62(3): 305-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777083&dopt=Abstract

•

Chemotherapy for malignant brain tumors of astrocytic and oligodendroglial lineage. Author(s): Hofer S, Herrmann R. Source: Journal of Cancer Research and Clinical Oncology. 2001 February; 127(2): 91-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216919&dopt=Abstract

•

Chemotherapy of brain tumors. Author(s): Galanis E, Buckner JC. Source: Current Opinion in Neurology. 2000 December; 13(6): 619-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11148660&dopt=Abstract

76

Brain Tumors

•

Childhood brain tumors and depressive disorders. Author(s): Connemann BJ, Kassubek J. Source: The New England Journal of Medicine. 2003 November 6; 349(19): 1868-9; Author Reply 1868-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602887&dopt=Abstract

•

Childhood brain tumors: children's and siblings' concerns regarding the diagnosis and phase of illness. Author(s): Freeman K, O'Dell C, Meola C. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 2003 May-June; 20(3): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776261&dopt=Abstract

•

Cloning, expression and chromosomal location of NKX6B TO 10Q26, a region frequently deleted in brain tumors. Author(s): Lee SH, Davison JA, Vidal SM, Belouchi A. Source: Mammalian Genome : Official Journal of the International Mammalian Genome Society. 2001 February; 12(2): 157-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11210186&dopt=Abstract

•

Common challenges and problems in clinical trials of boron neutron capture therapy of brain tumors. Author(s): Gupta N, Gahbauer RA, Blue TE, Albertson B. Source: Journal of Neuro-Oncology. 2003 March-April; 62(1-2): 197-210. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749714&dopt=Abstract

•

Comparative immunohistochemical study of insulin-like growth factor II and insulin-like growth factor receptor type 1 in pediatric brain tumors. Author(s): Ogino S, Kubo S, Abdul-Karim FW, Cohen ML. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2001 January-February; 4(1): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11200487&dopt=Abstract

•

Comparison of two immobilization techniques using portal film and digitally reconstructed radiographs for pediatric patients with brain tumors. Author(s): Zhu Y, Stovall J Jr, Butler L, Ji Q, Gaber MW, Samant S, Sontag MR, de Armendi AJ, Merchant TE. Source: International Journal of Radiation Oncology, Biology, Physics. 2000 November 1; 48(4): 1233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072183&dopt=Abstract

Studies

77

•

Consistent and selective expression of the discoidin domain receptor-1 tyrosine kinase in human brain tumors. Author(s): Weiner HL, Huang H, Zagzag D, Boyce H, Lichtenbaum R, Ziff EB. Source: Neurosurgery. 2000 December; 47(6): 1400-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126911&dopt=Abstract

•

Correlation of emmprin expression in vascular endothelial cells with blood-brainbarrier function: a study using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors. Author(s): Sameshima T, Nabeshima K, Toole BP, Inoue T, Yokogami K, Nakano S, Ohi T, Wakisaka S. Source: Virchows Archiv : an International Journal of Pathology. 2003 June; 442(6): 57784. Epub 2003 April 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719975&dopt=Abstract

•

Correlation of microvascular permeability derived from dynamic contrast-enhanced MR imaging with histologic grade and tumor labeling index: a study in human brain tumors. Author(s): Roberts HC, Roberts TP, Bollen AW, Ley S, Brasch RC, Dillon WP. Source: Academic Radiology. 2001 May; 8(5): 384-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11345268&dopt=Abstract

•

CRP-ductin, the mouse homologue of gp-340/deleted in malignant brain tumors 1 (DMBT1), binds gram-positive and gram-negative bacteria and interacts with lung surfactant protein D. Author(s): Madsen J, Tornoe I, Nielsen O, Lausen M, Krebs I, Mollenhauer J, Kollender G, Poustka A, Skjodt K, Holmskov U. Source: European Journal of Immunology. 2003 August; 33(8): 2327-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884308&dopt=Abstract

•

Cytotoxins directed at interleukin-4 receptors as therapy for human brain tumors. Author(s): Puri RK. Source: Methods in Molecular Biology (Clifton, N.J.). 2001; 166: 155-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217365&dopt=Abstract

•

Darts in the dark cure animal, but not human, brain tumors. Author(s): Fathallah-Shaykh HM. Source: Archives of Neurology. 2002 May; 59(5): 721-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020251&dopt=Abstract

78

Brain Tumors

•

Delayed sodium thiosulfate as an otoprotectant against carboplatin-induced hearing loss in patients with malignant brain tumors. Author(s): Doolittle ND, Muldoon LL, Brummett RE, Tyson RM, Lacy C, Bubalo JS, Kraemer DF, Heinrich MC, Henry JA, Neuwelt EA. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 March; 7(3): 493-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297239&dopt=Abstract

•

Deleted in Malignant Brain Tumors 1 is a versatile mucin-like molecule likely to play a differential role in digestive tract cancer. Author(s): Mollenhauer J, Herbertz S, Helmke B, Kollender G, Krebs I, Madsen J, Holmskov U, Sorger K, Schmitt L, Wiemann S, Otto HF, Grone HJ, Poustka A. Source: Cancer Research. 2001 December 15; 61(24): 8880-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751412&dopt=Abstract

•

Dendritic cell therapy of primary brain tumors. Author(s): Soling A, Rainov NG. Source: Molecular Medicine (Cambridge, Mass.). 2001 October; 7(10): 659-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713365&dopt=Abstract

•

Descriptive analysis and quantification of angiogenesis in human brain tumors. Author(s): Folkerth RD. Source: Journal of Neuro-Oncology. 2000 October-November; 50(1-2): 165-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245275&dopt=Abstract

•

Detection of tumor necrosis factor-alpha protein and messenger RNA in human glial brain tumors: comparison of immunohistochemistry with in situ hybridization using molecular probes. Author(s): Roessler K, Suchanek G, Breitschopf H, Kitz K, Matula C, Lassmann H, Koos WT. Source: Journal of Neurosurgery. 1995 August; 83(2): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7616275&dopt=Abstract

•

Determination of histopathological tumor grade in neuroepithelial brain tumors by using spectral pattern analysis of in vivo spectroscopic data. Author(s): Herminghaus S, Dierks T, Pilatus U, Moller-Hartmann W, Wittsack J, Marquardt G, Labisch C, Lanfermann H, Schlote W, Zanella FE. Source: Journal of Neurosurgery. 2003 January; 98(1): 74-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546355&dopt=Abstract

Studies

79

•

Dexamethasone treatment in patients with brain metastases and primary brain tumors: do the benefits outweigh the side-effects? Author(s): Hempen C, Weiss E, Hess CF. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2002 May; 10(4): 322-8. Epub 2002 February 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029432&dopt=Abstract

•

Differential display of messenger ribonucleic acid: a useful technique for analyzing differential gene expression in human brain tumors. Author(s): Uchiyama CM, Zhu J, Carroll RS, Leon SP, Black PM. Source: Neurosurgery. 1995 September; 37(3): 464-9; Discussion 469-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7501111&dopt=Abstract

•

Differential expression of Wnt genes, beta-catenin and E-cadherin in human brain tumors. Author(s): Howng SL, Wu CH, Cheng TS, Sy WD, Lin PC, Wang C, Hong YR. Source: Cancer Letters. 2002 September 8; 183(1): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049819&dopt=Abstract

•

Differential gene expression profiling in human brain tumors. Author(s): Markert JM, Fuller CM, Gillespie GY, Bubien JK, McLean LA, Hong RL, Lee K, Gullans SR, Mapstone TB, Benos DJ. Source: Physiological Genomics. 2001 February 7; 5(1): 21-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161003&dopt=Abstract

•

Diffusion imaging in brain tumors. Author(s): Holodny AI, Ollenschlager M. Source: Neuroimaging Clin N Am. 2002 February; 12(1): 107-24, X. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11998248&dopt=Abstract

•

Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. Author(s): Chenevert TL, Stegman LD, Taylor JM, Robertson PL, Greenberg HS, Rehemtulla A, Ross BD. Source: Journal of the National Cancer Institute. 2000 December 20; 92(24): 2029-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121466&dopt=Abstract

•

Diffusion-weighted MRI features of brain abscess and cystic or necrotic brain tumors: comparison with conventional MRI. Author(s): Chang SC, Lai PH, Chen WL, Weng HH, Ho JT, Wang JS, Chang CY, Pan HB, Yang CF. Source: Clinical Imaging. 2002 July-August; 26(4): 227-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140151&dopt=Abstract

80

Brain Tumors

•

Distinct expression patterns and levels of enzymatic activity of matrix metalloproteinases and their inhibitors in primary brain tumors. Author(s): Pagenstecher A, Wussler EM, Opdenakker G, Volk B, Campbell IL. Source: Journal of Neuropathology and Experimental Neurology. 2001 June; 60(6): 598612. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398836&dopt=Abstract

•

DNA repair gene O6-methylguanine-DNA methyltransferase: promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors. Author(s): Yin D, Xie D, Hofmann WK, Zhang W, Asotra K, Wong R, Black KL, Koeffler HP. Source: Molecular Carcinogenesis. 2003 January; 36(1): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503076&dopt=Abstract

•

Do electromagnetic fields cause brain tumors and other cancers? Author(s): Deutsch S. Source: Seminars in Neurology. 1995 September; 15(3): 304-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8570933&dopt=Abstract

•

Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors. Author(s): Shostak KO, Dmitrenko VV, Garifulin OM, Rozumenko VD, Khomenko OV, Zozulya YA, Zehetner G, Kavsan VM. Source: Journal of Surgical Oncology. 2003 January; 82(1): 57-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501169&dopt=Abstract

•

Dynamic contrast-enhanced computed tomography (CT) for quantitative estimation of microvascular permeability in human brain tumors. Author(s): Roberts HC, Roberts TP, Lee TY, Dillon WP. Source: Academic Radiology. 2002 August; 9 Suppl 2: S364-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188277&dopt=Abstract

•

Dynamic, contrast-enhanced CT of human brain tumors: quantitative assessment of blood volume, blood flow, and microvascular permeability: report of two cases. Author(s): Roberts HC, Roberts TP, Lee TY, Dillon WP. Source: Ajnr. American Journal of Neuroradiology. 2002 May; 23(5): 828-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006286&dopt=Abstract

•

Effect of expression of P-glycoprotein on technetium-99m methoxyisobutylisonitrile single photon emission computed tomography of brain tumors. Author(s): Shibata Y, Matsumura A, Nose T. Source: Neurol Med Chir (Tokyo). 2002 August; 42(8): 325-30; Discussion 330-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206484&dopt=Abstract

Studies

81

•

Efficient and selective gene transfer into primary human brain tumors by using single-chain antibody-targeted adenoviral vectors with native tropism abolished. Author(s): van Beusechem VW, Grill J, Mastenbroek DC, Wickham TJ, Roelvink PW, Haisma HJ, Lamfers ML, Dirven CM, Pinedo HM, Gerritsen WR. Source: Journal of Virology. 2002 March; 76(6): 2753-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861842&dopt=Abstract

•

Elevated JNK activation contributes to the pathogenesis of human brain tumors. Author(s): Antonyak MA, Kenyon LC, Godwin AK, James DC, Emlet DR, Okamoto I, Tnani M, Holgado-Madruga M, Moscatello DK, Wong AJ. Source: Oncogene. 2002 August 1; 21(33): 5038-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140754&dopt=Abstract

•

Elevated residential exposure to power frequency magnetic field associated with greater average age at diagnosis for patients with brain tumors. Author(s): Li CY, Lin RS, Sung FC. Source: Bioelectromagnetics. 2003 April; 24(3): 218-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669307&dopt=Abstract

•

Encephalomyelitis, brain tumors, neuromuscular diseases and miscellaneous disorders. Author(s): Nakazato Y, Nagashima K. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2000 September; 20 Suppl: S8-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11037180&dopt=Abstract

•

Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Author(s): Gurney JG, Kadan-Lottick NS, Packer RJ, Neglia JP, Sklar CA, Punyko JA, Stovall M, Yasui Y, Nicholson HS, Wolden S, McNeil DE, Mertens AC, Robison LL; Childhood Cancer Survivor Study. Source: Cancer. 2003 February 1; 97(3): 663-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548609&dopt=Abstract

•

Endocrine complications of pediatric brain tumors: case series and literature review. Author(s): Muirhead SE, Hsu E, Grimard L, Keene D. Source: Pediatric Neurology. 2002 September; 27(3): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393125&dopt=Abstract

•

Epidemiology of brain tumors. Author(s): Davis FG, McCarthy BJ. Source: Current Opinion in Neurology. 2000 December; 13(6): 635-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11148662&dopt=Abstract

82

Brain Tumors

•

Epidemiology of primary brain tumors: current concepts and review of the literature. Author(s): Wrensch M, Minn Y, Chew T, Bondy M, Berger MS. Source: Neuro-Oncology. 2002 October; 4(4): 278-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356358&dopt=Abstract

•

Epigenetics in high-grade astrocytomas: opportunities for prevention and detection of brain tumors. Author(s): Debinski W, Gibo D, Mintz A. Source: Annals of the New York Academy of Sciences. 2003 March; 983: 232-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724228&dopt=Abstract

•

Evaluation of a social-skills training group intervention with children treated for brain tumors: a pilot study. Author(s): Barakat LP, Hetzke JD, Foley B, Carey ME, Gyato K, Phillips PC. Source: Journal of Pediatric Psychology. 2003 July-August; 28(5): 299-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808006&dopt=Abstract

•

Expression microarray analysis of brain tumors: what have we learned so far. Author(s): Hunter SB, Moreno CS. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2002 August 1; 7: C74-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133823&dopt=Abstract

•

Expression of antioxidant enzymes in astrocytic brain tumors. Author(s): Haapasalo H, Kylaniemi M, Paunul N, Kinnula VL, Soini Y. Source: Brain Pathology (Zurich, Switzerland). 2003 April; 13(2): 155-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744469&dopt=Abstract

•

Expression of cancer testis genes in human brain tumors. Author(s): Sahin U, Koslowski M, Tureci O, Eberle T, Zwick C, Romeike B, Moringlane JR, Schwechheimer K, Feiden W, Pfreundschuh M. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 October; 6(10): 3916-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051238&dopt=Abstract

•

Expression of multidrug-resistance P-glycoprotein (MDR1) in human brain tumors. Author(s): Demeule M, Shedid D, Beaulieu E, Del Maestro RF, Moghrabi A, Ghosn PB, Moumdjian R, Berthelet F, Beliveau R. Source: International Journal of Cancer. Journal International Du Cancer. 2001 July 1; 93(1): 62-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391622&dopt=Abstract

Studies

83

•

Expression of Nedd5, a mammalian septin, in human brain tumors. Author(s): Sakai K, Kurimoto M, Tsugu A, Hubbard SL, Trimble WS, Rutka JT. Source: Journal of Neuro-Oncology. 2002 May; 57(3): 169-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125979&dopt=Abstract

•

Expression of proline-directed protein kinase, (p34cdc2/p58cyclin A), a novel cell proliferation marker in childhood brain tumors. Author(s): Bodey B, Siegel SE, Kaiser HE. Source: In Vivo. 2002 November-December; 16(6): 589-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494905&dopt=Abstract

•

Expression of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 in human brain tumors and their involvement in glial proliferation in vitro. Author(s): Barbero S, Bajetto A, Bonavia R, Porcile C, Piccioli P, Pirani P, Ravetti JL, Zona G, Spaziante R, Florio T, Schettini G. Source: Annals of the New York Academy of Sciences. 2002 November; 973: 60-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485835&dopt=Abstract

•

Expression of type II iodothyronine deiodinase in brain tumors. Author(s): Murakami M, Araki O, Morimura T, Hosoi Y, Mizuma H, Yamada M, Kurihara H, Ishiuchi S, Tamura M, Sasaki T, Mori M. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 November; 85(11): 4403-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095486&dopt=Abstract

•

Extreme drug resistance in primary brain tumors: in vitro analysis of 64 resection specimens. Author(s): Haroun RI, Clatterbuck RE, Gibbons MC, Burger PC, Parker R, Fruehauf JP, Brem H. Source: Journal of Neuro-Oncology. 2002 June; 58(2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164682&dopt=Abstract

•

False positive images in the follow-up of patients with brain tumors. Author(s): Moghrabi A, Tien R, Fuchs H, Longee D, McLendon R, Friedman HS. Source: Medical and Pediatric Oncology. 1997 February; 28(2): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8986148&dopt=Abstract

•

Familial posterior fossa brain tumors of infancy secondary to germline mutation of the hSNF5 gene. Author(s): Taylor MD, Gokgoz N, Andrulis IL, Mainprize TG, Drake JM, Rutka JT. Source: American Journal of Human Genetics. 2000 April; 66(4): 1403-6. Epub 2000 March 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10739763&dopt=Abstract

84

Brain Tumors

•

Farm and animal exposures and pediatric brain tumors: results from the United States West Coast Childhood Brain Tumor Study. Author(s): Holly EA, Bracci PM, Mueller BA, Preston-Martin S. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1998 September; 7(9): 797-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9752988&dopt=Abstract

•

Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors. Author(s): Gratas C, Tohma Y, Van Meir EG, Klein M, Tenan M, Ishii N, Tachibana O, Kleihues P, Ohgaki H. Source: Brain Pathology (Zurich, Switzerland). 1997 July; 7(3): 863-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9217971&dopt=Abstract

•

Fast fluid-attenuated inversion-recovery (FLAIR) MRI in the assessment of intraaxial brain tumors. Author(s): Essig M, Hawighorst H, Schoenberg SO, Engenhart-Cabillic R, Fuss M, Debus J, Zuna I, Knopp MV, van Kaick G. Source: Journal of Magnetic Resonance Imaging : Jmri. 1998 July-August; 8(4): 789-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9702879&dopt=Abstract

•

F-Dopa as an amino acid tracer to detect brain tumors. Author(s): Heiss WD, Wienhard K, Wagner R, Lanfermann H, Thiel A, Herholz K, Pietrzyk U. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1996 July; 37(7): 1180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965194&dopt=Abstract

•

Feasibility of long-term intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain tumors. Author(s): Slavc I, Schuller E, Falger J, Gunes M, Pillwein K, Czech T, Dietrich W, Rossler K, Dieckmann K, Prayer D, Hainfellner J. Source: Journal of Neuro-Oncology. 2003 September; 64(3): 239-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14558599&dopt=Abstract

•

Fetal dose estimates for radiotherapy of brain tumors during pregnancy. Author(s): Sneed PK, Albright NW, Wara WM, Prados MD, Wilson CB. Source: International Journal of Radiation Oncology, Biology, Physics. 1995 June 15; 32(3): 823-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7790270&dopt=Abstract

Studies

85

•

First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx). Author(s): Rose JH, Norman A, Ingram M, Aoki C, Solberg T, Mesa A. Source: International Journal of Radiation Oncology, Biology, Physics. 1999 December 1; 45(5): 1127-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10613304&dopt=Abstract

•

Fluorine-18-FDG PET and iodine-123-IMT SPECT in the evaluation of brain tumors. Author(s): Weber W, Bartenstein P, Gross MW, Kinzel D, Daschner H, Feldmann HJ, Reidel G, Ziegler SI, Lumenta C, Molls M, Schwaiger M. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1997 May; 38(5): 802-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9170450&dopt=Abstract

•

Foot drop following brain tumors: case reports. Author(s): Baysefer A, Erdogan E, Sali A, Sirin S, Seber N. Source: Minimally Invasive Neurosurgery : Min. 1998 June; 41(2): 97-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9651919&dopt=Abstract

•

Fractionated stereotactic radiotherapy for pediatric brain tumors: the Chicago children's experience. Author(s): Kalapurakal JA, Kepka A, Bista T, Goldman S, Tomita T, Marymont MH. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2000 May; 16(5): 296-302; Discussion 303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10883373&dopt=Abstract

•

Frequent and frequently overlooked: treatment-induced endocrine dysfunction in adult long-term survivors of primary brain tumors. Author(s): Arlt W, Hove U, Muller B, Reincke M, Berweiler U, Schwab F, Allolio B. Source: Neurology. 1997 August; 49(2): 498-506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9270585&dopt=Abstract

•

Functional activity within brain tumors: a magnetic source imaging study. Author(s): Schiffbauer H, Ferrari P, Rowley HA, Berger MS, Roberts TP. Source: Neurosurgery. 2001 December; 49(6): 1313-20; Discussion 1320-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846930&dopt=Abstract

•

Functional brain mapping using positron emission tomography scanning in preoperative neurosurgical planning for pediatric brain tumors. Author(s): Kaplan AM, Bandy DJ, Manwaring KH, Chen K, Lawson MA, Moss SD, Duncan JD, Wodrich DL, Schnur JA, Reiman EM. Source: Journal of Neurosurgery. 1999 November; 91(5): 797-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10541237&dopt=Abstract

86

Brain Tumors

•

Functional characterization of brain tumors: an overview of the potential clinical value. Author(s): Brunetti A, Alfano B, Soricelli A, Tedeschi E, Mainolfi C, Covelli EM, Aloj L, Panico MR, Bazzicalupo L, Salvatore M. Source: Nuclear Medicine and Biology. 1996 August; 23(6): 699-715. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8940713&dopt=Abstract

•

Functional MRI: primary motor cortex localization in patients with brain tumors. Author(s): Righini A, de Divitiis O, Prinster A, Spagnoli D, Appollonio I, Bello L, Scifo P, Tomei G, Villani R, Fazio F, Leonardi M. Source: Journal of Computer Assisted Tomography. 1996 September-October; 20(5): 7028. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8797897&dopt=Abstract

•

Functional outcome of inpatient rehabilitation in persons with brain tumors. Author(s): O'Dell MW, Barr K, Spanier D, Warnick RE. Source: Archives of Physical Medicine and Rehabilitation. 1998 December; 79(12): 15304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9862294&dopt=Abstract

•

Functional outcomes and quality of life in patients with brain tumors: a preliminary report. Author(s): Huang ME, Wartella JE, Kreutzer JS. Source: Archives of Physical Medicine and Rehabilitation. 2001 November; 82(11): 15406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689973&dopt=Abstract

•

Functional outcomes of persons with brain tumors after inpatient rehabilitation. Author(s): Marciniak CM, Sliwa JA, Heinemann AW, Semik PE. Source: Archives of Physical Medicine and Rehabilitation. 2001 April; 82(4): 457-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295004&dopt=Abstract

•

Gains and losses of DNA sequences in childhood brain tumors analyzed by comparative genomic hybridization. Author(s): Shlomit R, Ayala AG, Michal D, Ninett A, Frida S, Boleslaw G, Gad B, Gideon R, Shlomi C. Source: Cancer Genetics and Cytogenetics. 2000 August; 121(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958944&dopt=Abstract

Studies

87

•

Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a comparison between small cell and non-small cell carcinoma. Author(s): Serizawa T, Ono J, Iichi T, Matsuda S, Sato M, Odaki M, Hirai S, Osato K, Saeki N, Yamaura A. Source: Journal of Neurosurgery. 2002 December; 97(5 Suppl): 484-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507082&dopt=Abstract

•

Gamma knife radiosurgery for metastatic brain tumors. Author(s): Park YG, Choi JY, Chang JW, Chung SS. Source: Stereotactic and Functional Neurosurgery. 2001; 76(3-4): 201-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378097&dopt=Abstract

•

Gamma knife radiosurgery for simultaneous multiple metastatic brain tumors. Author(s): Suzuki S, Omagari J, Nishio S, Nishiye E, Fukui M. Source: Journal of Neurosurgery. 2000 December; 93 Suppl 3: 30-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11143258&dopt=Abstract

•

Gamma knife treatment for multiple metastatic brain tumors compared with wholebrain radiation therapy. Author(s): Serizawa T, Iuchi T, Ono J, Saeki N, Osato K, Odaki M, Ushikubo O, Hirai S, Sato M, Matsuda S. Source: Journal of Neurosurgery. 2000 December; 93 Suppl 3: 32-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11143259&dopt=Abstract

•

Ganglioside composition and its relation to clinical data in brain tumors. Author(s): Shinoura N, Dohi T, Kondo T, Yoshioka M, Takakura K, Oshima M. Source: Neurosurgery. 1992 September; 31(3): 541-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1407435&dopt=Abstract

•

Gene aberrations in childhood brain tumors. Author(s): Kucerova H, Stejskalova E, Vicha A, Tichy M, Chanova M, Sumerauer D, Koutecky J, Eckschlager T. Source: Folia Biol (Krakow). 2000; 46(5): 187-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11271663&dopt=Abstract

•

Gene aberrations in childhood brain tumors. Author(s): Kucerova H, Stejskalova E, Vicha A, Tichy M, Chanova M, Sumerauer D, Koutechky J, Eckschlager T. Source: Folia Biol (Praha). 2000; 46(5): 187-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055797&dopt=Abstract

88

Brain Tumors

•

Gene therapy for brain tumors. Author(s): Bansal K, Engelhard HH. Source: Current Oncology Reports. 2000 September; 2(5): 463-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122879&dopt=Abstract

•

Gene therapy for brain tumors: the fundamentals. Author(s): Engelhard HH. Source: Surgical Neurology. 2000 July; 54(1): 3-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11024501&dopt=Abstract

•

Gene therapy of experimental brain tumors using neural progenitor cells. Author(s): Benedetti S, Pirola B, Pollo B, Magrassi L, Bruzzone MG, Rigamonti D, Galli R, Selleri S, Di Meco F, De Fraja C, Vescovi A, Cattaneo E, Finocchiaro G. Source: Nature Medicine. 2000 April; 6(4): 447-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10742153&dopt=Abstract

•

Genetic alterations of human brain tumors as molecular prognostic factors. Author(s): Shiraishi T, Tabuchi K. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2003 March; 23(1): 95-108. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722932&dopt=Abstract

•

Genetic polymorphisms in GSTM1, -P1, -T1, and CYP2E1 and the risk of adult brain tumors. Author(s): De Roos AJ, Rothman N, Inskip PD, Linet MS, Shapiro WR, Selker RG, Fine HA, Black PM, Pittman GS, Bell DA. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 January; 12(1): 14-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540498&dopt=Abstract

•

Genetically engineered herpes simplex viral vectors in the treatment of brain tumors: a review. Author(s): Aghi M, Chiocca EA. Source: Cancer Investigation. 2003 April; 21(2): 278-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743992&dopt=Abstract

•

Genetics of brain tumors. Author(s): Weiss WA. Source: Current Opinion in Pediatrics. 2000 December; 12(6): 543-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11106272&dopt=Abstract

Studies

89

•

Genomic organization, chromosomal localization and regulation of expression of the neuronal nuclear matrix protein NRP/B in human brain tumors. Author(s): Kim TA, Ota S, Jiang S, Pasztor LM, White RA, Avraham S. Source: Gene. 2000 September 5; 255(1): 105-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10974570&dopt=Abstract

•

Gonadal status in male survivors following childhood brain tumors. Author(s): Schmiegelow M, Lassen S, Poulsen HS, Schmiegelow K, Hertz H, Andersson AM, Skakkebaek NE, Muller J. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 June; 86(6): 2446-52. Erratum In: J Clin Endocrinol Metab 2001 August; 86(8): 3967. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11397837&dopt=Abstract

•

Growth hormone response to a growth hormone-releasing hormone stimulation test in a population-based study following cranial irradiation of childhood brain tumors. Author(s): Schmiegelow M, Lassen S, Poulsen HS, Feldt-Rasmussen U, Schmiegelow K, Hertz H, Muller J. Source: Hormone Research. 2000; 54(2): 53-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251367&dopt=Abstract

•

Growth hormone treatment of children with brain tumors and risk of tumor recurrence. Author(s): Swerdlow AJ, Reddingius RE, Higgins CD, Spoudeas HA, Phipps K, Qiao Z, Ryder WD, Brada M, Hayward RD, Brook CG, Hindmarsh PC, Shalet SM. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 December; 85(12): 4444-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11134091&dopt=Abstract

•

Growth patterns of microscopic brain tumors. Author(s): Sander LM, Deisboeck TS. Source: Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. 2002 November; 66(5 Pt 1): 051901. Epub 2002 November 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513517&dopt=Abstract

•

Health status in 52 long-term survivors of pediatric brain tumors. Author(s): Foreman NK, Faestel PM, Pearson J, Disabato J, Poole M, Wilkening G, Arenson EB, Greffe B, Thorne R. Source: Journal of Neuro-Oncology. 1999 January; 41(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10222422&dopt=Abstract

90

Brain Tumors

•

Hemorrhage within brain tumors in association with long air travel. Author(s): Goldberg CR, Hirschfeld A. Source: Acta Neurochirurgica. 2002 March; 144(3): 289-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956943&dopt=Abstract

•

High dose chemotherapy with autologous stem cell rescue in adults with malignant primary brain tumors. Author(s): Abrey LE, Rosenblum MK, Papadopoulos E, Childs BH, Finlay JL. Source: Journal of Neuro-Oncology. 1999 September; 44(2): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10619498&dopt=Abstract

•

High microvessel density in primitive neuroectodermal brain tumors of childhood. Author(s): Grotzer MA, Wiewrodt R, Janss AJ, Zhao H, Cnaan A, Sutton LN, Rorke LB, Phillips PC. Source: Neuropediatrics. 2001 April; 32(2): 75-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11414647&dopt=Abstract

•

High-dose chemotherapy with autologous stem cell rescue for brain tumors. Author(s): Dunkel IJ, Finlay JL. Source: Critical Reviews in Oncology/Hematology. 2002 February; 41(2): 197-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856595&dopt=Abstract

•

High-dose chemotherapy with autologous stem cell rescue for malignant brain tumors. Author(s): Dunkel IJ. Source: Cancer Investigation. 2000; 18(5): 492-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10834034&dopt=Abstract

•

High-dose tamoxifen in treatment of brain tumors: interaction with antiepileptic drugs. Author(s): Rabinowicz AL, Hinton DR, Dyck P, Couldwell WT. Source: Epilepsia. 1995 May; 36(5): 513-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7614929&dopt=Abstract

•

High-performance liquid chromatographic analysis of physiological amino acids in human brain tumors by pre-column derivatization with phenylisothiocyanate. Author(s): Battaglia A, Bertoluzza A, Calbucci F, Eusebi V, Giorgianni P, Ricci R, Tosi R, Tugnoli V. Source: J Chromatogr B Biomed Sci Appl. 1999 June 25; 730(1): 81-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437675&dopt=Abstract

Studies

91

•

High-resolution three-dimensional contrast-enhanced blood oxygenation leveldependent magnetic resonance venography of brain tumors at 3 Tesla: first clinical experience and comparison with 1.5 Tesla. Author(s): Barth M, Nobauer-Huhmann IM, Reichenbach JR, Mlynarik V, Schoggl A, Matula C, Trattnig S. Source: Investigative Radiology. 2003 July; 38(7): 409-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821854&dopt=Abstract

•

History of allergies and autoimmune diseases and risk of brain tumors in adults. Author(s): Brenner AV, Linet MS, Fine HA, Shapiro WR, Selker RG, Black PM, Inskip PD. Source: International Journal of Cancer. Journal International Du Cancer. 2002 May 10; 99(2): 252-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979441&dopt=Abstract

•

HIT '91 (prospective, co-operative study for the treatment of malignant brain tumors in childhood): accuracy and acute toxicity of the irradiation of the craniospinal axis. Results of the quality assurance program. Author(s): Kortmann RD, Timmermann B, Kuhl J, Willich N, Flentje M, Meisner C, Bamberg M. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 1999 April; 175(4): 162-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10230458&dopt=Abstract

•

Homozygous deletions of the MTS1 gene are rare in non-astrocytic brain tumors. Author(s): Walker DG, Duan W, Kaye AH, Lavin MF. Source: Biochemical and Biophysical Research Communications. 1995 June 15; 211(2): 404-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7794250&dopt=Abstract

•

How to manage metastatic brain tumors. Author(s): Shibui S. Source: Japanese Journal of Clinical Oncology. 1999 May; 29(5): 243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10379334&dopt=Abstract

•

HSV-1-based vectors for gene therapy of neurological diseases and brain tumors: part I. HSV-1 structure, replication and pathogenesis. Author(s): Jacobs A, Breakefield XO, Fraefel C. Source: Neoplasia (New York, N.Y.). 1999 November; 1(5): 387-401. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10933054&dopt=Abstract

92

Brain Tumors

•

HSV-1-based vectors for gene therapy of neurological diseases and brain tumors: part II. Vector systems and applications. Author(s): Jacobs A, Breakefield XO, Fraefel C. Source: Neoplasia (New York, N.Y.). 1999 November; 1(5): 402-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10933055&dopt=Abstract

•

Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors. Author(s): Velasco G, Cal S, Merlos-Suarez A, Ferrando AA, Alvarez S, Nakano A, Arribas J, Lopez-Otin C. Source: Cancer Research. 2000 February 15; 60(4): 877-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10706098&dopt=Abstract

•

Human neurotropic JC virus and its association with brain tumors. Author(s): Khalili K. Source: Disease Markers. 2001; 17(3): 143-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790878&dopt=Abstract

•

HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3' untranslated regions of cytokine and angiogenic factor mRNAs. Author(s): Nabors LB, Gillespie GY, Harkins L, King PH. Source: Cancer Research. 2001 March 1; 61(5): 2154-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280780&dopt=Abstract

•

Hyperacute changes in glucose metabolism of brain tumors after stereotactic radiosurgery: a PET study. Author(s): Maruyama I, Sadato N, Waki A, Tsuchida T, Yoshida M, Fujibayashi Y, Ishii Y, Kubota T, Yonekura Y. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1999 July; 40(7): 1085-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10405124&dopt=Abstract

•

Hypoxia imaging in brain tumors. Author(s): Yetkin FZ, Mendelsohn D. Source: Neuroimaging Clin N Am. 2002 November; 12(4): 537-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687910&dopt=Abstract

Studies

93

•

Identification of MG-160, a FGF binding medial Golgi sialoglycoprotein, in brain tumors: an index of malignancy in astrocytomas. Author(s): Yamaguchi F, Morrison RS, Gonatas NK, Takahashi H, Sugisaki Y, Teramoto A. Source: International Journal of Oncology. 2003 May; 22(5): 1045-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684670&dopt=Abstract

•

Identification of the corticospinal tracts achieved using blood-oxygen-leveldependent and diffusion functional MR imaging in patients with brain tumors. Author(s): Holodny AI, Ollenschleger MD, Liu WC, Schulder M, Kalnin AJ. Source: Ajnr. American Journal of Neuroradiology. 2001 January; 22(1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158892&dopt=Abstract

•

Identification of tumor-related proteins by proteomic analysis of cerebrospinal fluid from patients with primary brain tumors. Author(s): Zheng PP, Luider TM, Pieters R, Avezaat CJ, van den Bent MJ, Sillevis Smitt PA, Kros JM. Source: Journal of Neuropathology and Experimental Neurology. 2003 August; 62(8): 855-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14503641&dopt=Abstract

•

II. Perinatal brain tumors: a review of 250 cases. Author(s): Isaacs H Jr. Source: Pediatric Neurology. 2002 November; 27(5): 333-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504200&dopt=Abstract

•

Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in human brain tumors: relationships of iNOS to superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (MIB-1) and p53 protein. Author(s): Kato S, Esumi H, Hirano A, Kato M, Asayama K, Ohama E. Source: Acta Neuropathologica. 2003 April; 105(4): 333-40. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624786&dopt=Abstract

•

Immunotherapy and biological modifiers for the treatment of malignant brain tumors. Author(s): Marras C, Mendola C, Legnani FG, DiMeco F. Source: Current Opinion in Oncology. 2003 May; 15(3): 204-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778012&dopt=Abstract

•

Immunotoxin treatment of brain tumors. Author(s): Hall WA. Source: Methods in Molecular Biology (Clifton, N.J.). 2001; 166: 139-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217364&dopt=Abstract

94

Brain Tumors

•

Importance of hypoxia in the biology and treatment of brain tumors. Author(s): Knisely JP, Rockwell S. Source: Neuroimaging Clin N Am. 2002 November; 12(4): 525-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687909&dopt=Abstract

•

Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement. Author(s): Gleeson HK, Stoeter R, Ogilvy-Stuart AL, Gattamaneni HR, Brennan BM, Shalet SM. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3682-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915655&dopt=Abstract

•

In response - case control study on radiology work, medical X-ray investigations and use of cellular phones as risk factors for brain tumors. Author(s): Friedell PE. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2000 December 1; 2(6): E1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11335851&dopt=Abstract

•

In vivo proton magnetic resonance spectroscopy of brain tumors. Author(s): Fountas KN, Kapsalaki EZ, Gotsis SD, Kapsalakis JZ, Smisson HF 3rd, Johnston KW, Robinson JS Jr, Papadakis N. Source: Stereotactic and Functional Neurosurgery. 2000; 74(2): 83-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251398&dopt=Abstract

•

In vivo temperature measurements in brain tumors using proton MR spectroscopy. Author(s): Jayasundar R, Singh VP. Source: Neurology India. 2002 December; 50(4): 436-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577091&dopt=Abstract

•

Incidence of neurologic deficits and rehabilitation of patients with brain tumors. Author(s): Mukand JA, Blackinton DD, Crincoli MG, Lee JJ, Santos BB. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2001 May; 80(5): 346-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11327556&dopt=Abstract

•

Increased locoregional blood flow in brain tumors after cervical spinal cord stimulation. Author(s): Clavo B, Robaina F, Catala L, Valcarcel B, Morera J, Carames MA, Ruiz-Egea E, Panero F, Lloret M, Hernandez MA. Source: Journal of Neurosurgery. 2003 June; 98(6): 1263-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816274&dopt=Abstract

Studies

95

•

Innovations in design and delivery of chemotherapy for brain tumors. Author(s): Gururangan S, Friedman HS. Source: Neuroimaging Clin N Am. 2002 November; 12(4): 583-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687913&dopt=Abstract

•

Integration of the metabolic data of positron emission tomography in the dosimetry planning of radiosurgery with the gamma knife: early experience with brain tumors. Technical note. Author(s): Levivier M, Wikier D, Goldman S, David P, Metens T, Massager N, Gerosa M, Devriendt D, Desmedt F, Simon S, Van Houtte P, Brotchi J. Source: Journal of Neurosurgery. 2000 December; 93 Suppl 3: 233-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11143256&dopt=Abstract

•

Intra-arterial carboplatin and intravenous etoposide for the treatment of metastatic brain tumors. Author(s): Newton HB, Slivka MA, Volpi C, Bourekas EC, Christoforidis GA, Baujan MA, Slone W, Chakeres DW. Source: Journal of Neuro-Oncology. 2003 January; 61(1): 35-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587794&dopt=Abstract

•

Intraarterial chemotherapy for brain tumors by using a spatial dose fractionation algorithm and pulsatile delivery. Author(s): Gobin YP, Cloughesy TF, Chow KL, Duckwiler GR, Sayre JW, Milanese K, Vinuela F. Source: Radiology. 2001 March; 218(3): 724-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11230646&dopt=Abstract

•

Intraoperative magnetic resonance imaging and magnetic resonance imaging-guided therapy for brain tumors. Author(s): Jolesz FA, Talos IF, Schwartz RB, Mamata H, Kacher DF, Hynynen K, McDannold N, Saivironporn P, Zao L. Source: Neuroimaging Clin N Am. 2002 November; 12(4): 665-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687918&dopt=Abstract

•

Intraoperative MR imaging: making an impact on outcomes for patients with brain tumors. Author(s): Berger MS. Source: Ajnr. American Journal of Neuroradiology. 2001 January; 22(1): 2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158878&dopt=Abstract

96

Brain Tumors

•

Kinetic characterization of hexokinase isoenzymes from glioma cells: implications for FDG imaging of human brain tumors. Author(s): Muzi M, Freeman SD, Burrows RC, Wiseman RW, Link JM, Krohn KA, Graham MM, Spence AM. Source: Nuclear Medicine and Biology. 2001 February; 28(2): 107-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295420&dopt=Abstract

•

Kinetics of 111In-labeled bleomycin in patients with brain tumors: compartmental vs. non-compartmental models. Author(s): Ryynanen PM, Savolainen SE, Aronen HJ, Korppi-Tommola ET, Huhmar HM, Kallio ME, Hiltunen JV. Source: Ann Nucl Med. 1998 December; 12(6): 313-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972368&dopt=Abstract

•

Latency between symptom onset and diagnosis of pediatric brain tumors: an Eastern Canadian geographic study. Author(s): Mehta V, Chapman A, McNeely PD, Walling S, Howes WJ. Source: Neurosurgery. 2002 August; 51(2): 365-72; Discussion 372-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182774&dopt=Abstract

•

Laterality of brain tumors. Author(s): Inskip PD, Tarone RE, Hatch EE, Wilcosky TC, Selker RG, Fine HA, Black PM, Loeffler JS, Shapiro WR, Linet MS. Source: Neuroepidemiology. 2003 March-April; 22(2): 130-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629279&dopt=Abstract

•

Letter to the editor regarding our previous publication: “Secondary narcolepsy in children with brain tumors,” SLEEP 2002; 25:435-439. Author(s): Marcus CL, Mignot E. Source: Sleep. 2003 March 15; 26(2): 228. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683485&dopt=Abstract

•

Leukemia, brain tumors, and exposure to extremely low frequency electromagnetic fields in Swiss railway employees. Author(s): Minder CE, Pfluger DH. Source: American Journal of Epidemiology. 2001 May 1; 153(9): 825-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11323311&dopt=Abstract

•

Levels of cadmium, lead, and mercury in human brain tumors. Author(s): Al-Saleh I, Shinwari N. Source: Biological Trace Element Research. 2001 March; 79(3): 197-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11354345&dopt=Abstract

Studies

97

•

Local delivery of mitoxantrone for the treatment of malignant brain tumors in rats. Author(s): Broggi G, Ferroli P, Franzini A, Silvani A, Salmaggi A, Eoli M, Boiardi A. Source: Journal of Neurosurgery. 2003 April; 98(4): 935-6; Author Reply 936. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691429&dopt=Abstract

•

Local delivery of mitoxantrone for the treatment of malignant brain tumors in rats. Author(s): DiMeco F, Li KW, Tyler BM, Wolf AS, Brem H, Olivi A. Source: Journal of Neurosurgery. 2002 November; 97(5): 1173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450040&dopt=Abstract

•

Local treatment of brain tumors with targeted chimera cytotoxic proteins. Author(s): Debinski W. Source: Cancer Investigation. 2002; 20(5-6): 801-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197239&dopt=Abstract

•

Localization of fast MEG waves in patients with brain tumors and epilepsy. Author(s): de Jongh A, de Munck JC, Baayen JC, Puligheddu M, Jonkman EJ, Stam CJ. Source: Brain Topography. 2003 Spring; 15(3): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705813&dopt=Abstract

•

Long-term neurological outcome of childhood brain tumors treated by surgery only. Author(s): Sonderkaer S, Schmiegelow M, Carstensen H, Nielsen LB, Muller J, Schmiegelow K. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 April 1; 21(7): 1347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663725&dopt=Abstract

•

Long-term sequelae in children treated for brain tumors: impairments, disability, and handicap. Author(s): Macedoni-Luksic M, Jereb B, Todorovski L. Source: Pediatric Hematology and Oncology. 2003 March; 20(2): 89-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554520&dopt=Abstract

•

Magnetic resonance imaging of patched heterozygous and xenografted mouse brain tumors. Author(s): Nelson AL, Algon SA, Munasinghe J, Graves O, Goumnerova L, Burstein D, Pomeroy SL, Kim JY. Source: Journal of Neuro-Oncology. 2003 May; 62(3): 259-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777077&dopt=Abstract

98

Brain Tumors

•

Measurement of the extracellular space in brain tumors using 76Br-bromide and PET. Author(s): Bruehlmeier M, Roelcke U, Blauenstein P, Missimer J, Schubiger PA, Locher JT, Pellikka R, Ametamey SM. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 August; 44(8): 1210-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902409&dopt=Abstract

•

Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Author(s): Howe FA, Barton SJ, Cudlip SA, Stubbs M, Saunders DE, Murphy M, Wilkins P, Opstad KS, Doyle VL, McLean MA, Bell BA, Griffiths JR. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2003 February; 49(2): 223-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541241&dopt=Abstract

•

Metastatic brain tumors: diagnosis, treatment, and nursing interventions. Author(s): Armstrong TS, Gilbert MR. Source: Clinical Journal of Oncology Nursing. 2000 September-October; 4(5): 217-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11111453&dopt=Abstract

•

Methylation, expression, and mutation analysis of the cell cycle control genes in human brain tumors. Author(s): Yin D, Xie D, Hofmann WK, Miller CW, Black KL, Koeffler HP. Source: Oncogene. 2002 November 28; 21(54): 8372-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447702&dopt=Abstract

•

Microglia in brain tumors. Author(s): Graeber MB, Scheithauer BW, Kreutzberg GW. Source: Glia. 2002 November; 40(2): 252-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379912&dopt=Abstract

•

Microsatellite instability in primary brain tumors. Author(s): Alvino E, Fernandez E, Pallini R. Source: Neurological Research. 2000 September; 22(6): 571-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11045018&dopt=Abstract

•

MR imaging of brain tumors: toward physiologic imaging. Author(s): Roberts HC, Dillon WP. Source: Ajnr. American Journal of Neuroradiology. 2000 October; 21(9): 1570-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11039332&dopt=Abstract

Studies

99

•

Multimodality image fusion in dose escalation studies of brain tumors. Author(s): Rajasekar D, Datta NR, Gupta RK, Pradhan PK, Ayyagari S. Source: Journal of Applied Clinical Medical Physics [electronic Resource] / American College of Medical Physics. 2003 Winter; 4(1): 8-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540814&dopt=Abstract

•

Multiparametric MR assessment of pediatric brain tumors. Author(s): Tzika AA, Astrakas LG, Zarifi MK, Petridou N, Young-Poussaint T, Goumnerova L, Zurakowski D, Anthony DC, Black PM. Source: Neuroradiology. 2003 January; 45(1): 1-10. Epub 2002 November 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525947&dopt=Abstract

•

Neurogenic stunned myocardium in a patient with metastatic brain tumors. Author(s): Chuang CP, Chao CL. Source: International Journal of Cardiology. 2000 November-December; 76(2-3): 251-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229412&dopt=Abstract

•

Neuroimaging and cartography: mapping brain tumors. Author(s): Castillo M. Source: Ajnr. American Journal of Neuroradiology. 2001 April; 22(4): 597-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11290462&dopt=Abstract

•

Neuroimaging in pediatric brain tumors: Gd-DTPA-enhanced, hemodynamic, and diffusion MR imaging compared with MR spectroscopic imaging. Author(s): Tzika AA, Zarifi MK, Goumnerova L, Astrakas LG, Zurakowski D, YoungPoussaint T, Anthony DC, Scott RM, Black PM. Source: Ajnr. American Journal of Neuroradiology. 2002 February; 23(2): 322-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847064&dopt=Abstract

•

Neurosurgical advances in the treatment of brain tumors. Author(s): Olson JJ. Source: Current Oncology Reports. 2000 September; 2(5): 434-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122875&dopt=Abstract

•

Neurotrophin receptor TrkC predicts good clinical outcome in medulloblastoma and other primitive neuroectodermal brain tumors. Author(s): Grotzer MA, Janss AJ, Phillips PC, Trojanowski JQ. Source: Klinische Padiatrie. 2000 July-August; 212(4): 196-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994550&dopt=Abstract

100 Brain Tumors

•

New techniques in MR imaging of brain tumors. Author(s): Pomper MG, Port JD. Source: Magn Reson Imaging Clin N Am. 2000 November; 8(4): 691-713. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11175983&dopt=Abstract

•

Nonmalignant pediatric brain tumors. Author(s): Rashidi M, DaSilva VR, Minagar A, Rutka JT. Source: Curr Neurol Neurosci Rep. 2003 May; 3(3): 200-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691624&dopt=Abstract

•

Nosocomial fungemia due to amphotericin B-resistant Candida spp. in three pediatric patients after previous neurosurgery for brain tumors. Author(s): Kovacicova G, Hanzen J, Pisarcikova M, Sejnova D, Horn J, Babela R, Svetlansky I, Lovaszova M, Gogova M, Krcmery V. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2001 March; 7(1): 45-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406756&dopt=Abstract

•

Novel approaches to imaging brain tumors. Author(s): Matthews PM, Wylezinska M, Cadoux-Hudson T. Source: Hematology/Oncology Clinics of North America. 2001 August; 15(4): 609-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11676276&dopt=Abstract

•

Novel chemotherapeutic approaches to brain tumors. Author(s): Dropcho EJ. Source: Hematology/Oncology Clinics of North America. 2001 December; 15(6): 102752. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770297&dopt=Abstract

•

O6-methylguanine-DNA methyltransferase activity in breast and brain tumors. Author(s): Preuss I, Eberhagen I, Haas S, Eibl RH, Kaufmann M, von Minckwitz G, Kaina B. Source: International Journal of Cancer. Journal International Du Cancer. 1995 May 4; 61(3): 321-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7729942&dopt=Abstract

•

O6-Methylguanine-DNA methyltransferase in pediatric primary brain tumors: relation to patient and tumor characteristics. Author(s): Bobola MS, Berger MS, Ellenbogen RG, Roberts TS, Geyer JR, Silber JR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 March; 7(3): 613-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297257&dopt=Abstract

Studies

101

•

Obstetric emergencies precipitated by malignant brain tumors. Author(s): Tewari KS, Cappuccini F, Asrat T, Flamm BL, Carpenter SE, Disaia PJ, Quilligan EJ. Source: American Journal of Obstetrics and Gynecology. 2000 May; 182(5): 1215-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10819861&dopt=Abstract

•

Olfactory event-related potentials in patients with brain tumors. Author(s): Daniels C, Gottwald B, Pause BM, Sojka B, Mehdorn HM, Ferstl R. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2001 August; 112(8): 1523-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11459693&dopt=Abstract

•

Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors. Author(s): Lu QR, Park JK, Noll E, Chan JA, Alberta J, Yuk D, Alzamora MG, Louis DN, Stiles CD, Rowitch DH, Black PM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 September 11; 98(19): 10851-6. Epub 2001 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11526205&dopt=Abstract

•

One-dimensional phosphorus-31 chemical shift imaging of human brain tumors. Author(s): Rutter A, Hugenholtz H, Saunders JK, Smith IC. Source: Investigative Radiology. 1995 June; 30(6): 359-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7490188&dopt=Abstract

•

Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of lowgrade from high-grade brain tumors with PET. Author(s): Delbeke D, Meyerowitz C, Lapidus RL, Maciunas RJ, Jennings MT, Moots PL, Kessler RM. Source: Radiology. 1995 April; 195(1): 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7892494&dopt=Abstract

•

Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors. Author(s): Krishnamurthy S, Powers SK, Witmer P, Brown T. Source: Lasers in Surgery and Medicine. 2000; 27(3): 224-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11013384&dopt=Abstract

102 Brain Tumors

•

Oral methotrexate for recurrent brain tumors in children: a Pediatric Oncology Group study. Author(s): Mulne AF, Ducore JM, Elterman RD, Friedman HS, Krischer JP, Kun LE, Shuster JJ, Kadota RP. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2000 January-February; 22(1): 41-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695820&dopt=Abstract

•

Original memoirs: the control of bleeding in operations for brain tumors: with the description of silver “clips” for the occlusion of vessels inaccessible to the ligature. 1911. Author(s): Cushing H. Source: Yale J Biol Med. 2001 November-December; 74(6): 399-412. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922187&dopt=Abstract

•

Parental cigarette smoking, hard liquor consumption and the risk of childhood brain tumors--a case-control study in northeast China. Author(s): Hu J, Mao Y, Ugnat AM. Source: Acta Oncologica (Stockholm, Sweden). 2000; 39(8): 979-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207006&dopt=Abstract

•

Pediatric brain tumors: a contemporary prospectus. Author(s): Mainprize TG, Taylor MD, Rutka JT. Source: Clin Neurosurg. 2000; 47: 259-302. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197707&dopt=Abstract

•

Pediatric brain tumors: introduction. Author(s): Armstrong DD, Giangaspero F. Source: Brain Pathology (Zurich, Switzerland). 2003 July; 13(3): 373-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946026&dopt=Abstract

•

Permanent low-activity (125)I seed placement for the treatment of pediatric brain tumors: preliminary experience. Author(s): Rostomily RC, Halligan J, Geyer R, Stelzer K, Lindsley K, Berger MS. Source: Pediatric Neurosurgery. 2001 April; 34(4): 198-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359113&dopt=Abstract

•

Phase II trial of cystemustine, a new nitrosourea, as treatment of high-grade brain tumors in adults. Author(s): Roche H, Cure H, Adenis A, Fargeot P, Terret C, Lentz MA, Madelmont JC, Fumoleau P, Hanausk A, Chollet P. Source: Journal of Neuro-Oncology. 2000 September; 49(2): 141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11206009&dopt=Abstract

Studies

103

•

Pneumocystis carinii pneumonia in HIV negative patients with primary brain tumors. Author(s): Mahindra AK, Grossman SA. Source: Journal of Neuro-Oncology. 2003 July; 63(3): 263-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892232&dopt=Abstract

•

Population pharmacokinetics of low-dose paclitaxel in patients with brain tumors. Author(s): Hempel G, Rube C, Mosler C, Wienstroer M, Wagner-Bohn A, Schuck A, Willich N, Boos J. Source: Anti-Cancer Drugs. 2003 July; 14(6): 417-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853882&dopt=Abstract

•

Potential of gene therapy for brain tumors. Author(s): Lam PY, Breakefield XO. Source: Human Molecular Genetics. 2001 April; 10(7): 777-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257112&dopt=Abstract

•

Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha(v) integrin antagonist. Author(s): MacDonald TJ, Taga T, Shimada H, Tabrizi P, Zlokovic BV, Cheresh DA, Laug WE. Source: Neurosurgery. 2001 January; 48(1): 151-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152340&dopt=Abstract

•

Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens. Author(s): Dowling C, Bollen AW, Noworolski SM, McDermott MW, Barbaro NM, Day MR, Henry RG, Chang SM, Dillon WP, Nelson SJ, Vigneron DB. Source: Ajnr. American Journal of Neuroradiology. 2001 April; 22(4): 604-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11290466&dopt=Abstract

•

Quality assurance procedures in radiotherapy of brain tumors. Author(s): De Santis M, Mantello G, Salvi G, Basilico L. Source: Rays. 1996 October-December; 21(4): 590-9. English, Italian. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9122444&dopt=Abstract

•

Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging. Author(s): Warmuth C, Gunther M, Zimmer C. Source: Radiology. 2003 August; 228(2): 523-32. Epub 2003 June 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819338&dopt=Abstract

104 Brain Tumors

•

Quantification of endothelial permeability, leakage space, and blood volume in brain tumors using combined T1 and T2* contrast-enhanced dynamic MR imaging. Author(s): Zhu XP, Li KL, Kamaly-Asl ID, Checkley DR, Tessier JJ, Waterton JC, Jackson A. Source: Journal of Magnetic Resonance Imaging : Jmri. 2000 June; 11(6): 575-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10862055&dopt=Abstract

•

Quantification of O6-methylguanine-DNA methyltransferase mRNA in human brain tumors. Author(s): Mineura K, Watanabe K, Yanagisawa T, Kowada M. Source: Biochimica Et Biophysica Acta. 1996 February 9; 1289(1): 105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8605218&dopt=Abstract

•

Quantifying efficacy of chemotherapy of brain tumors with homogeneous and heterogeneous drug delivery. Author(s): Swanson KR, Alvord EC Jr, Murray JD. Source: Acta Biotheoretica. 2002; 50(4): 223-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675529&dopt=Abstract

•

Quantitative estimation of microvascular permeability in human brain tumors: correlation of dynamic Gd-DTPA-enhanced MR imaging with histopathologic grading. Author(s): Roberts HC, Roberts TP, Ley S, Dillon WP, Brasch RC. Source: Academic Radiology. 2002 May; 9 Suppl 1: S151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019855&dopt=Abstract

•

Quantitative imaging of iodine-131 distributions in brain tumors with pinhole SPECT: a phantom study. Author(s): Smith MF, Gilland DR, Coleman RE, Jaszczak RJ. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1998 May; 39(5): 856-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9591589&dopt=Abstract

•

Quantitative measurement of microvascular permeability in human brain tumors achieved using dynamic contrast-enhanced MR imaging: correlation with histologic grade. Author(s): Roberts HC, Roberts TP, Brasch RC, Dillon WP. Source: Ajnr. American Journal of Neuroradiology. 2000 May; 21(5): 891-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10815665&dopt=Abstract

Studies

105

•

Quantitative metabolite patterns of human brain tumors: detection by 1H NMR spectroscopy in vivo and in vitro. Author(s): Usenius JP, Kauppinen RA, Vainio PA, Hernesniemi JA, Vapalahti MP, Paljarvi LA, Soimakallio S. Source: Journal of Computer Assisted Tomography. 1994 September-October; 18(5): 70513. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8089316&dopt=Abstract

•

Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2 in human brain tumors. Author(s): Arbit E, Cheung NK, Yeh SD, Daghighian F, Zhang JJ, Cordon-Cardo C, Pentlow K, Canete A, Finn R, Larson SM. Source: European Journal of Nuclear Medicine. 1995 May; 22(5): 419-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7641750&dopt=Abstract

•

Radiation therapy in the management of childhood brain tumors. Author(s): Habrand JL, De Crevoisier R. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2001 February; 17(3): 121-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305764&dopt=Abstract

•

Radiofrequency exposure and the risk for brain tumors. Author(s): Hardell L, Mild KH, Hallquist A. Source: Epidemiology (Cambridge, Mass.). 2001 January; 12(1): 135-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11138811&dopt=Abstract

•

Radiotherapy for brain tumors. Author(s): Mehta MP, Tome WA, Olivera GH. Source: Current Oncology Reports. 2000 September; 2(5): 438-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122876&dopt=Abstract

•

Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumorreactive cytotoxic T lymphocytes from patients with brain tumors. Author(s): Nonaka Y, Tsuda N, Shichijo S, Ito M, Maeda Y, Harada M, Kamura T, Shigemori M, Itoh K. Source: Tissue Antigens. 2002 October; 60(4): 319-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472661&dopt=Abstract

•

Recombinant retrovirus vectors for treatment of malignant brain tumors. Author(s): Rainov NG, Kramm CM. Source: Int Rev Neurobiol. 2003; 55: 185-203. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968537&dopt=Abstract

106 Brain Tumors

•

Redifferentiation therapy in brain tumors: long-lasting complete regression of glioblastomas and an anaplastic astrocytoma under long term 1-alphahydroxycholecalciferol. Author(s): Trouillas P, Honnorat J, Bret P, Jouvet A, Gerard JP. Source: Journal of Neuro-Oncology. 2001 January; 51(1): 57-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349882&dopt=Abstract

•

Repositioning accuracy with the Laitinen frame for fractionated stereotactic radiation therapy in adult and pediatric brain tumors: preliminary report. Author(s): Kalapurakal JA, Ilahi Z, Kepka AG, Bista T, Goldman S, Tomita T, Marymont MH. Source: Radiology. 2001 January; 218(1): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152795&dopt=Abstract

•

Results of interstitial brachytherapy for malignant brain tumors. Author(s): Mayr MT, Crocker IR, Butker EK, Williams H, Cotsonis GA, Olson JJ. Source: International Journal of Oncology. 2002 October; 21(4): 817-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239621&dopt=Abstract

•

Risk estimation of radiation-induced thyroid cancer from treatment of brain tumors in adults and children. Author(s): Mazonakis M, Damilakis J, Varveris H, Fasoulaki M, Gourtsoyiannis N. Source: International Journal of Oncology. 2003 January; 22(1): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469208&dopt=Abstract

•

Risk factors for the development of obesity in children surviving brain tumors. Author(s): Lustig RH, Post SR, Srivannaboon K, Rose SR, Danish RK, Burghen GA, Xiong X, Wu S, Merchant TE. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 February; 88(2): 611-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574189&dopt=Abstract

•

Secondary narcolepsy in children with brain tumors. Author(s): Marcus CL, Trescher WH, Halbower AC, Lutz J. Source: Sleep. 2002 June 15; 25(4): 435-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071545&dopt=Abstract

•

Seizure disorders in patients with brain tumors. Author(s): Liigant A, Haldre S, Oun A, Linnamagi U, Saar A, Asser T, Kaasik AE. Source: European Neurology. 2001; 45(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150841&dopt=Abstract

Studies

107

•

Serum antibodies to JC virus, BK virus, simian virus 40, and the risk of incident adult astrocytic brain tumors. Author(s): Rollison DE, Helzlsouer KJ, Alberg AJ, Hoffman S, Hou J, Daniel R, Shah KV, Major EO. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 May; 12(5): 460-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750243&dopt=Abstract

•

Serum concentrations of soluble interleukin-2 receptor in patients with malignant brain tumors. Author(s): Yoshida S, Morii K. Source: Journal of Surgical Oncology. 2000 October; 75(2): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064393&dopt=Abstract

•

Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. Author(s): Offit K, Levran O, Mullaney B, Mah K, Nafa K, Batish SD, Diotti R, Schneider H, Deffenbaugh A, Scholl T, Proud VK, Robson M, Norton L, Ellis N, Hanenberg H, Auerbach AD. Source: Journal of the National Cancer Institute. 2003 October 15; 95(20): 1548-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14559878&dopt=Abstract

•

Simian virus 40 large tumor antigen forms specific complexes with p53 and pRb in human brain tumors. Author(s): Zhen H, Zhang X, Zhang Z, Fei Z, He X, Liang J, Huang W, Liu X, Zhang P. Source: Chinese Medical Journal. 2001 April; 114(4): 382-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11780459&dopt=Abstract

•

Simian virus 40 regulatory region structural diversity and the association of viral archetypal regulatory regions with human brain tumors. Author(s): Lednicky JA, Butel JS. Source: Seminars in Cancer Biology. 2001 February; 11(1): 39-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243898&dopt=Abstract

•

Studying the heterogeneity of brain tumors using medium throughput LOH analysis. Author(s): Bogler O, Finniss S, Kittiniyom K, Rempel S, Rosenblum M, Mikkelsen T, Newsham I. Source: Cytometry : the Journal of the Society for Analytical Cytology. 2002 January 1; 47(1): 52-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11774351&dopt=Abstract

108 Brain Tumors

•

Survivors of childhood brain tumors: behavioral, emotional, and social adjustment. Author(s): Fuemmeler BF, Elkin TD, Mullins LL. Source: Clinical Psychology Review. 2002 May; 22(4): 547-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094511&dopt=Abstract

•

SV40 and human brain tumors. Author(s): Carbone M, Bocchetta M, Cristaudo A, Emri S, Gazdar A, Jasani B, Lednicky J, Miele L, Mutti L, Pass HI, Ramael M, Rizzo P, Testa JR, Weggen S, Yeung A. Source: International Journal of Cancer. Journal International Du Cancer. 2003 August 10; 106(1): 140-2; Author Reply 143-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794770&dopt=Abstract

•

The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors. Author(s): Yoshida S, Fukino K, Harada H, Nagai H, Imoto I, Inazawa J, Takahashi H, Teramoto A, Emi M. Source: Journal of Human Genetics. 2001; 46(4): 182-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322657&dopt=Abstract

•

The developmental biology of brain tumors. Author(s): Wechsler-Reya R, Scott MP. Source: Annual Review of Neuroscience. 2001; 24: 385-428. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11283316&dopt=Abstract

•

The effects of hydrogen peroxide on brain and brain tumors. Author(s): Mesiwala AH, Farrell L, Santiago P, Ghatan S, Silbergeld DL. Source: Surgical Neurology. 2003 May; 59(5): 398-407; Discussion 407. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765817&dopt=Abstract

•

The effects of isoflurane and desflurane on intracranial pressure, cerebral perfusion pressure, and cerebral arteriovenous oxygen content difference in normocapnic patients with supratentorial brain tumors. Author(s): Fraga M, Rama-Maceiras P, Rodino S, Aymerich H, Pose P, Belda J. Source: Anesthesiology. 2003 May; 98(5): 1085-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717129&dopt=Abstract

•

The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors. Author(s): Friedman HS, Keir ST, Houghton PJ. Source: Cancer. 2003 May 1; 97(9 Suppl): 2359-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712457&dopt=Abstract

Studies

109

•

The human leukemic T-cell line, TALL-104, is cytotoxic to human malignant brain tumors and traffics through brain tissue: implications for local adoptive immunotherapy. Author(s): Kruse CA, Visonneau S, Kleinschmidt-DeMasters BK, Gup CJ, Gomez GG, Paul DB, Santoli D. Source: Cancer Research. 2000 October 15; 60(20): 5731-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11059767&dopt=Abstract

•

The role of gamma knife radiosurgery in the treatment of primary and metastatic brain tumors. Author(s): Gerosa M, Nicolato A, Foroni R. Source: Current Opinion in Oncology. 2003 May; 15(3): 188-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778010&dopt=Abstract

•

Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors. Author(s): Vigneron D, Bollen A, McDermott M, Wald L, Day M, Moyher-Noworolski S, Henry R, Chang S, Berger M, Dillon W, Nelson S. Source: Magnetic Resonance Imaging. 2001 January; 19(1): 89-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295350&dopt=Abstract

•

Tissue sodium concentration in human brain tumors as measured with 23Na MR imaging. Author(s): Ouwerkerk R, Bleich KB, Gillen JS, Pomper MG, Bottomley PA. Source: Radiology. 2003 May; 227(2): 529-37. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663825&dopt=Abstract

•

TMEFF1 and brain tumors. Author(s): Gery S, Yin D, Xie D, Black KL, Koeffler HP. Source: Oncogene. 2003 May 8; 22(18): 2723-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743596&dopt=Abstract

•

Ultrasonic surgical system (SONOPET) for microsurgical removal of brain tumors. Author(s): Inoue T, Ikezaki K, Sato Y. Source: Neurological Research. 2000 July; 22(5): 490-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10935222&dopt=Abstract

•

Ultrastructural analysis of brain tumors using collagen gel culture. Author(s): Yamada A, Tsuchida T, Kato T, Kawamoto K. Source: Brain Tumor Pathol. 2002; 19(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455883&dopt=Abstract

110 Brain Tumors

•

Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors. Author(s): Sampson JH, Crotty LE, Lee S, Archer GE, Ashley DM, Wikstrand CJ, Hale LP, Small C, Dranoff G, Friedman AH, Friedman HS, Bigner DD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 June 20; 97(13): 7503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852962&dopt=Abstract

•

Understanding regulation of cell growth in childhood brain tumors. Author(s): Khakoo Y, Rosenfeld MR. Source: Current Opinion in Pediatrics. 1998 December; 10(6): 551-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9848011&dopt=Abstract

•

Unexpected death in persons with symptomatic epilepsy due to glial brain tumors: a report of two cases and review of the literature. Author(s): Buttner A, Gall C, Mall G, Weis S. Source: Forensic Science International. 1999 March 15; 100(1-2): 127-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10356781&dopt=Abstract

•

Use of half-dose gadolinium-enhanced MRI and magnetization transfer saturation in brain tumors. Author(s): Haba D, Pasco Papon A, Tanguy JY, Burtin P, Aube C, Caron-Poitreau C. Source: European Radiology. 2001; 11(1): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194902&dopt=Abstract

•

Use of chlorotoxin for targeting of primary brain tumors. Author(s): Soroceanu L, Gillespie Y, Khazaeli MB, Sontheimer H. Source: Cancer Research. 1998 November 1; 58(21): 4871-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9809993&dopt=Abstract

•

Use of diffusion-weighted magnetic resonance imaging in differentiating purulent brain processes from cystic brain tumors. Author(s): Guzman R, Barth A, Lovblad KO, El-Koussy M, Weis J, Schroth G, Seiler RW. Source: Journal of Neurosurgery. 2002 November; 97(5): 1101-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450032&dopt=Abstract

•

Usefulness of whole-body (18)F-FDG PET in patients with suspected metastatic brain tumors. Author(s): Jeong HJ, Chung JK, Kim YK, Kim CY, Kim DG, Jeong JM, Lee DS, Jung HW, Lee MC. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2002 November; 43(11): 1432-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411544&dopt=Abstract

Studies

111

•

Using mice to decipher the molecular genetics of brain tumors. Author(s): Hesselager G, Holland EC. Source: Neurosurgery. 2003 September; 53(3): 685-94; Discussion 695. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943584&dopt=Abstract

•

Variations in the levels of the JAK/STAT and ShcA proteins in human brain tumors. Author(s): Cattaneo E, Magrassi L, De-Fraja C, Conti L, Di Gennaro I, Butti G, Govoni S. Source: Anticancer Res. 1998 July-August; 18(4A): 2381-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9703883&dopt=Abstract

•

Various findings in surgically treated epilepsy patients with dysembryoplastic neuroepithelial tumors in comparison with those of patients with other low-grade brain tumors and other neuronal migration disorders. Author(s): Degen R, Ebner A, Lahl R, Leonhardt S, Pannek HW, Tuxhorn I. Source: Epilepsia. 2002 November; 43(11): 1379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423388&dopt=Abstract

•

Vascular endothelial growth factor expression, vascular volume, and, capillary permeability in human brain tumors. Author(s): Machein MR, Kullmer J, Fiebich BL, Plate KH, Warnke PC. Source: Neurosurgery. 1999 April; 44(4): 732-40; Discussion 740-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10201297&dopt=Abstract

•

Vector delivery methods and targeting strategies for gene therapy of brain tumors. Author(s): Rainov NG, Kramm CM. Source: Current Gene Therapy. 2001 November; 1(4): 367-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109063&dopt=Abstract

•

VEGF in brain tumors. Author(s): Machein MR, Plate KH. Source: Journal of Neuro-Oncology. 2000 October-November; 50(1-2): 109-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245271&dopt=Abstract

•

Viruses and oncogenes in brain tumors. Author(s): Archer GE, Sampson JH, Bigner DD. Source: Journal of Neurovirology. 1997 May; 3 Suppl 1: S76-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9179801&dopt=Abstract

•

Viruses in the treatment of brain tumors. Author(s): Fecci PE, Gromeier M, Sampson JH. Source: Neuroimaging Clin N Am. 2002 November; 12(4): 553-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687911&dopt=Abstract

112 Brain Tumors

•

Vitamins during pregnancy linked to lower risk of childhood brain tumors. Author(s): McNeil C. Source: Journal of the National Cancer Institute. 1997 October 15; 89(20): 1481-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9337342&dopt=Abstract

•

Volume MRI and MRSI techniques for the quantitation of treatment response in brain tumors: presentation of a detailed case study. Author(s): Nelson SJ, Huhn S, Vigneron DB, Day MR, Wald LL, Prados M, Chang S, Gutin PH, Sneed PK, Verhey L, Hawkins RA, Dillon WP. Source: Journal of Magnetic Resonance Imaging : Jmri. 1997 November-December; 7(6): 1146-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9400861&dopt=Abstract

•

Volumetric measurement of brain tumors from MR imaging. Author(s): Shi WM, Wildrick DM, Sawaya R. Source: Journal of Neuro-Oncology. 1998 March; 37(1): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9525843&dopt=Abstract

•

Water and sodium disorders in children undergoing surgical treatment of brain tumors. Author(s): Hiranrat P, Katavetin P, Supornsilchai V, Wacharasindhu S, Srivuthana S. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S152-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929983&dopt=Abstract

•

Weekly, outpatient paclitaxel and concurrent cranial irradiation in adults with brain tumors: preliminary results and promising directions. Author(s): Glantz MJ, Choy H, Kearns CM, Akerley W, Egorin MJ. Source: Seminars in Oncology. 1995 October; 22(5 Suppl 12): 26-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7481858&dopt=Abstract

•

What causes childhood brain tumors? Limited knowledge, many clues. Author(s): Bunin G. Source: Pediatric Neurosurgery. 2000 June; 32(6): 321-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971194&dopt=Abstract

•

What infants can teach us about brain tumors. Author(s): Allen JC. Source: The New England Journal of Medicine. 1993 June 17; 328(24): 1780-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8497288&dopt=Abstract

Studies

113

•

What is the etiology of human brain tumors? Author(s): Hardell L, Holmberg B, Malker H, Paulsson LE. Source: Cancer. 1996 March 1; 77(5): 1006-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8608467&dopt=Abstract

•

What is the etiology of human brain tumors? A report on the first Lebow conference. Author(s): Brem S, Rozental JM, Moskal JR. Source: Cancer. 1995 August 15; 76(4): 709-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8625170&dopt=Abstract

•

White matter disease in children treated for malignant brain tumors. Author(s): Dietrich U, Wanke I, Mueller T, Wieland R, Moellers M, Forsting M, Stolke D. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2001 December; 17(12): 731-8. Epub 2001 November 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862439&dopt=Abstract

115

CHAPTER 2. NUTRITION AND BRAIN TUMORS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and brain tumors.

Finding Nutrition Studies on Brain Tumors The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “brain tumors” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

116 Brain Tumors

The following information is typical of that found when using the “Full IBIDS Database” to search for “brain tumors” (or a synonym): •

A new gadolinium-based contrast agent for magnetic resonance imaging of brain tumors: kinetic study on a C6 rat glioma model. Author(s): Unite mixte INSERM/Universite Joseph Fourier, RMN Bioclinique U 438, LRC-CEA, Hopital Albert Michallon, Grenoble, France. Source: Fonchy, E Lahrech, H Francois Joubert, A Dupeyre, R Benderbous, S Corot, C Farion, R Rubin, C Decorps, M Remy, C J-Magn-Reson-Imaging. 2001 August; 14(2): 97105 1053-1807

•

A phase I study of cranial radiation therapy with concomitant continuous infusion paclitaxel in children with brain tumors. Author(s): Department of Radiation Oncology, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA. Source: Liu, L Vapiwala, N Munoz, L K Winick, N J Weitman, S Strauss, L C Frankel, L S Rosenthal, D I Med-Pediatr-Oncol. 2001 October; 37(4): 390-2 0098-1532

•

A phase II trial of oral melphalan in recurrent primary brain tumors. Author(s): Department of Neurological Surgery, University of California School of Medicine, San Francisco. Source: Chamberlain, M C Prados, M D Silver, P Levin, V A Am-J-Clin-Oncol. 1988 February; 11(1): 52-4 0277-3732

•

A role for preirradiation PCV chemotherapy for oligodendroglial brain tumors. Author(s): Department of Neurology, Medical School, University of Tubingen, Germany. Source: Streffer, J Schabet, M Bamberg, M Grote, E H Meyermann, R Voigt, K Dichgans, J Weller, M J-Neurol. 2000 April; 247(4): 297-302 0340-5354

•

Bispecific antibodies as targeting agents for boron neutron capture therapy of brain tumors. Author(s): Department of Pathology, Ohio State University, Columbus 43210, USA. Source: Liu, L Barth, R F Adams, D M Soloway, A H Reisfeld, R A J-Hematother. 1995 October; 4(5): 477-83 1061-6128

•

Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors. Author(s): Klinik fur Padiatrische Hamatologie und Onkologie, Universitat Dusseldorf. Source: Janssen, G Bode, U Breu, H Dohrn, B Engelbrecht, V Gobel, U Klin-Padiatr. 2000 Jul-August; 212(4): 189-95 0300-8630

•

Brachytherapy of brain tumors. Author(s): Department of Radiation Oncology, University of California, San Francisco. Source: Sneed, P K Gutin, P H Prados, M D Phillips, T L Weaver, K A Wara, W M Larson, D A Stereotact-Funct-Neurosurg. 1992; 59(1-4): 157-65 1011-6125

•

Carboplatin pharmacokinetics in young children with brain tumors. Author(s): Pharmaceutical Sciences Department, St Jude Children's Research Hospital, Memphis, TN 38105, USA. Source: Tonda, M E Heideman, R L Petros, W P Friedman, H S Murry, D J Rodman, J H Cancer-Chemother-Pharmacol. 1996; 38(5): 395-400 0344-5704

Nutrition

117

•

Characteristics of growth hormone therapy for pediatric patients with brain tumors in the National Cooperative Growth Study (NCGS) and from a survey of pediatric endocrinologists. Author(s): Emory University and Children's Healthcare of Atlanta, GA 30033, USA. [email protected] Source: Meacham, L R Sullivan, K J-Pediatr-Endocrinol-Metab. 2002 May; 15 Suppl 2: 689-96

•

Comparison of the accumulation kinetics of L-(methyl-11C)-methionine and D(methyl-11C)-methionine in brain tumors studied with positron emission tomography. Author(s): Department of Neuroradiology, Karolinska Sjukhuset, Stockholm, Sweden. Source: Bergstrom, M Lundqvist, H Ericson, K Lilja, A Johnstrom, P Langstrom, B von Holst, H Eriksson, L Blomqvist, G Acta-Radiol. 1987 May-June; 28(3): 225-9 0284-1851

•

Differential expression of versican isoforms in brain tumors. Author(s): Institute of Neuropathology, University Hospital, Zurich, Switzerland. Source: Paulus, W Baur, I Dours Zimmermann, M T Zimmermann, D R J-NeuropatholExp-Neurol. 1996 May; 55(5): 528-33 0022-3069

•

Distribution of [32P]-chromic phosphate colloid in cystic brain tumors. Author(s): University of Michigan Hospital, Ann Arbor. Source: Fig, L M Shapiro, B Taren, J Stereotact-Funct-Neurosurg. 1992; 59(1-4): 166-8 1011-6125

•

Dose administration of gadolinium-DTPA in MR imaging of intracranial tumors. Author(s): Department of Radiology, Schering AG, Berlin, West Germany. Source: Niendorf, H P Laniado, M Semmler, W Schorner, W Felix, R AJNR-Am-JNeuroradiol. 1987 Sep-October; 8(5): 803-15 0195-6108

•

Effects of type beta transforming growth factor in combination with retinoic acid or tumor necrosis factor on proliferation of a human glioblastoma cell line and clonogenic cells from freshly resected human brain tumors. Author(s): Institute of Cancer Research, University of Trondheim, Norway. Source: Helseth, E Unsgaard, G Dalen, A Vik, R Cancer-Immunol-Immunother. 1988; 26(3): 273-9 0340-7004

•

Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors. Author(s): Division of Pediatric Oncology, Johns Hopkins Oncology Center, Baltimore, MD 21205. Source: Strauss, L C Killmond, T M Carson, B S Maria, B L Wharam, M D Leventhal, B G Med-Pediatr-Oncol. 1991; 19(1): 16-21 0098-1532

•

Eight drugs in one day chemotherapy for brain tumors: experience in 107 children and rationale for preradiation chemotherapy. Source: Pendergrass, T W Milstein, J M Geyer, J R Mulne, A F Kosnik, E J Morris, J D Heideman, R L Ruymann, F B Stuntz, J T Bleyer, W A J-Clin-Oncol. 1987 August; 5(8): 1221-31 0732-183X

•

Enhanced detection of brain tumors by [18F]fluorodeoxyglucose PET with glucose loading. Author(s): Department of Nuclear Medicine, Faculty of Medicine, Kyoto University, Japan.

118 Brain Tumors

Source: Ishizu, K Sadato, N Yonekura, Y Nishizawa, S Magata, Y Tamaki, N Tsuchida, T Okazawa, H Tanaka, F Miyatake, S et al. J-Comput-Assist-Tomogr. 1994 Jan-February; 18(1): 12-5 0363-8715 •

Epidemiology of brain tumors. Author(s): Division of Epidemiology and Biostatistics, Chicago, Illinois, USA. [email protected] Source: Davis, F G McCarthy, B J Curr-Opin-Neurol. 2000 December; 13(6): 635-40 13507540

•

Epidemiology of primary brain tumors: current concepts and review of the literature. Author(s): Department of Epidemiology and Biostatistics University of California at San Francisco, San Francisco, CA 94143, USA. Source: Wrensch, M Minn, Y Chew, T Bondy, M Berger, M S Neuro-oncol. 2002 October; 4(4): 278-99 1522-8517

•

Epidermal growth factor radiopharmaceuticals: 111In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors. Author(s): Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095-1682, USA. Source: Kurihara, A Deguchi, Y Pardridge, W M Bioconjug-Chem. 1999 May-June; 10(3): 502-11 1043-1802

•

Expression of bisecting GlcNAc in pediatric brain tumors and its association with tumor cell response to vinblastine. Author(s): Cancer Biology and Chemotherapy Program, Children's Memorial Hospital, Chicago, Illinois 60614, USA. Source: Rebbaa, A Chou, P M Vucic, I Mirkin, B L Tomita, T Bremer, E G Clin-CancerRes. 1999 November; 5(11): 3661-8 1078-0432

•

Expression pattern of chemoresistance-related genes in human malignant brain tumors: a working knowledge for proper selection of anticancer drugs. Author(s): Department of Neurosurgery, National Cancer Center Hospital, Tokyo, Japan. Source: Nagane, M Asai, A Shibui, S Oyama, H Nomura, K Kuchino, Y Jpn-J-Clin-Oncol. 1999 November; 29(11): 527-34 0368-2811

•

Foreign body reaction to hemostatic materials mimicking recurrent brain tumor. Report of three cases. Author(s): Department of Neurosurgery, Beth Israel Medical Center, New York, New York 10128, USA. [email protected] Source: Kothbauer, K F Jallo, G I Siffert, J Jimenez, E Allen, J C Epstein, F J J-Neurosurg. 2001 September; 95(3): 503-6 0022-3085

•

Gadolinium neutron capture therapy for brain tumors: a computer study. Author(s): Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston 77030. Source: Masiakowski, J T Horton, J L Peters, L J Med-Phys. 1992 Sep-October; 19(5): 1277-84 0094-2405

•

Immunohistochemical study on the distribution of alpha and beta subunits of S-100 protein in brain tumors. Author(s): Second Department of Pathology, Okayama University Medical School, Japan.

Nutrition

119

Source: Hayashi, K Hoshida, Y Horie, Y Takahashi, K Taguchi, K Sonobe, H Ohtsuki, Y Akagi, T Acta-Neuropathol-(Berl). 1991; 81(6): 657-63 0001-6322 •

Improved delineation of human brain tumors on MR images using a long-circulating, superparamagnetic iron oxide agent. Author(s): Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston 02114, USA. Source: Enochs, W S Harsh, G Hochberg, F Weissleder, R J-Magn-Reson-Imaging. 1999 February; 9(2): 228-32 1053-1807

•

Improved targeting of brain tumors using dexrazoxane rescue of topoisomerase II combined with supralethal doses of etoposide and teniposide. Author(s): Laboratory of Experimental Medical Oncology, Finsen Center, Copenhagen, Denmark. Source: Holm, B Sehested, M Jensen, P B Clin-Cancer-Res. 1998 June; 4(6): 1367-73 10780432

•

In vitro chemosensitivity of brain tumors to cisplatin and its analogues, iproplatin and carboplatin. Author(s): Laboratoire d'Investigation Clinique H. J. Tagnon, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium. Source: Dodion, P Sanders, C Georges, P Kenis, Y Cancer-Chemother-Pharmacol. 1988; 22(1): 80-2 0344-5704

•

Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors. Author(s): Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Source: Mason, W P Grovas, A Halpern, S Dunkel, I J Garvin, J Heller, G Rosenblum, M Gardner, S Lyden, D Sands, S Puccetti, D Lindsley, K Merchant, T E O'Malley, B Bayer, L Petriccione, M M Allen, J Finlay, J L J-Clin-Oncol. 1998 January; 16(1): 210-21 0732-183X

•

Intracranial tumors and West syndrome. Author(s): Department of Neurology, Pediatric Hospital, Buenos Aires, Argentina. Source: Ruggieri, V Caraballo, R Fejerman, N Pediatr-Neurol. 1989 Sep-October; 5(5): 327-9 0887-8994

•

Maternal diet during pregnancy and risk of brain tumors in children. Author(s): Division of Oncology, Children's Hospital of Philadelphia, PA 19104-4399, USA. Source: Bunin, G R Int-J-Cancer-Suppl. 1998; 1123-5 0898-6924

•

Methionine transport in brain tumors. Author(s): Department of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland. Source: O'Tuama, L A J-Neuropsychiatry-Clin-Neurosci. 1989 Winter; 1(1): S37-44 08950172

•

Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors. Author(s): Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [email protected] Source: Guruangan, S Dunkel, I J Goldman, S Garvin, J H Rosenblum, M Boyett, J M Gardner, S Merchant, T E Gollamudi, S Finlay, J L J-Clin-Oncol. 1998 July; 16(7): 2486-93 0732-183X

120 Brain Tumors

•

No responses to oral etoposide in 15 patients with recurrent brain tumors. Author(s): Children's Hospital at Strong and The University of Rochester Cancer Center, NY 14642, USA. [email protected] Source: Korones, D N Fisher, P G Cohen, K J Dubowy, R L Med-Pediatr-Oncol. 2000 July; 35(1): 80-2 0098-1532

•

Nucleolar organizer regions in various human brain tumors. Author(s): Department of Neurosurgery, Saga Medical School, Japan. Source: Shiraishi, T Tabuchi, K Mineta, T Momozaki, N Takagi, M J-Neurosurg. 1991 June; 74(6): 979-84 0022-3085

•

Olfactory event-related potentials in patients with brain tumors. Author(s): Department of Neurosurgery, University of Kiel, Kiel, Germany. [email protected] Source: Daniels, C Gottwald, B Pause, B M Sojka, B Mehdorn, H M Ferstl, R ClinNeurophysiol. 2001 August; 112(8): 1523-30 1388-2457

•

Penetration of etoposide into human malignant brain tumors after intravenous and oral administration. Author(s): Department of Neurosurgery, Hiroshima University School of Medicine, Japan. Source: Kiya, K Uozumi, T Ogasawara, H Sugiyama, K Hotta, T Mikami, T Kurisu, K Cancer-Chemother-Pharmacol. 1992; 29(5): 339-42 0344-5704

•

Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience. Author(s): The Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA. Source: Turner, Christopher D Gururangan, Sridharan Eastwood, James Bottom, Krystal Watral, Melody Beason, Rodney McLendon, Roger E Friedman, Allan H Tourt Uhlig, Sandra Miller, Langdon L Friedman, Henry S Neuro-oncol. 2002 April; 4(2): 102-8 15228517

•

Potential risk factors for brain tumors in children. An analysis of 200 cases. Author(s): Division of Neurosurgery, Tor Vergata, 2nd State University of Rome, Italy. Source: Giuffre, R Liccardo, G Pastore, F S Spallone, A Vagnozzi, R Childs-Nerv-Syst. 1990 January; 6(1): 8-12 0256-7040

•

Prenatal vitamin supplementation and pediatric brain tumors: huge international variation in use and possible reduction in risk. Author(s): Department of Preventive Medicine, University of Southern California, USC/Norris Cancer Center, Los Angeles 90033-0800, USA. Source: Preston Martin, S Pogoda, J M Mueller, B A Lubin, F Modan, B Holly, E A Filippini, G Cordier, S Peris Bonet, R Choi, W Little, J Arslan, A Childs-Nerv-Syst. 1998 October; 14(10): 551-7 0256-7040

•

Preradiation high-dose intravenous methotrexate with leucovorin rescue for untreated primary childhood brain tumors. Author(s): Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY. Source: Allen, J C Walker, R Rosen, G J-Clin-Oncol. 1988 April; 6(4): 649-53 0732-183X

•

Procarbazine, CCNU, vincristine combination in the treatment of brain tumors. Author(s): Hacettepe University Institute of Oncology, Ankara, Turkey. Source: Gullu, I H Celik, I Tekuzman, G Altunbas, M Guler, N Barista, I Alkis, N Yalcin, S Kars, A Baltali, E Kansu, E Firat, D Tumori. 1996 May-June; 82(3): 228-31 0300-8916

Nutrition

121

•

Prostaglandins in human brain tumors. Author(s): Department of Surgery, Universita di Pavia, Italy. Source: Paoletti, P Chiabrando, C Gaetani, P Castelli, M G Butti, G Martelli, L Rolli, M JNeurosurg-Sci. 1989 Jan-Mar; 33(1): 65-9 0390-5616

•

Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. Author(s): Department of Radiooncology, and Institute of Medical Information Processing, University of Tubingen, Tubingen, Germany. [email protected] Source: Timmermann, Beate Kortmann, Rolf Dieter Kuhl, Joachim Meisner, Christoph Dieckmann, Karin Pietsch, Torsten Bamberg, Michael J-Clin-Oncol. 2002 February 1; 20(3): 842-9 0732-183X

•

Salvage chemotherapy with paclitaxel for recurrent primary brain tumors. Author(s): Department of Neurosciences, University of California, San Diego, La Jolla 92093-0812, USA. Source: Chamberlain, M C Kormanik, P J-Clin-Oncol. 1995 August; 13(8): 2066-71 0732183X

•

Somatostatin receptor scintigraphy in brain tumors and pituitary tumors: first experiences. Author(s): Department of Nuclear Medicine, University of Cologne, Germany. Source: Scheidhauer, K Hildebrandt, G Luyken, C Schomacker, K Klug, N Schicha, H Horm-Metab-Res-Suppl. 1993; 2759-62 0170-5903

•

The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in experimental brain tumors. Author(s): Brain Research Institute, University of California Medical Center, Los Angeles. Source: Baba, T Chio, C C Black, K L J-Neurosurg. 1992 September; 77(3): 403-6 00223085

•

The expression of Gal beta 1,4GlcNAc alpha 2,6 sialyltransferase and alpha 2,6-linked sialoglycoconjugates in human brain tumors. Author(s): Chicago Institute for Neurosurgery and Neuroresearch, IL 60614, USA. Source: Kaneko, Y Yamamoto, H Kersey, D S Colley, K J Leestma, J E Moskal, J R ActaNeuropathol-(Berl). 1996; 91(3): 284-92 0001-6322

•

The potential for complete and durable response in nonglial primary brain tumors in children and young adults with enhanced chemotherapy delivery. Author(s): Department of Neurology, Oregon Health Sciences University, Portland 97201-3098, USA. Source: Dahlborg, S A Petrillo, A Crossen, J R Roman Goldstein, S Doolittle, N D Fuller, K H Neuwelt, E A Cancer-J-Sci-Am. 1998 Mar-April; 4(2): 110-24 1081-4442

•

The role of paclitaxel in the treatment of primary and metastatic brain tumors. Author(s): Department of Medicine, University of Massachusetts School of Public Health, Amherst, MA 01003-0430, USA. Source: Glantz, M J Chamberlain, M C Chang, S M Prados, M D Cole, B F Semin-RadiatOncol. 1999 April; 9(2 Suppl 1): 27-33 1053-4296

122 Brain Tumors

•

Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults. Author(s): Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Source: Kushner, B H Cheung, N K Kramer, K Dunkel, I J Calleja, E Boulad, F BoneMarrow-Transplant. 2001 September; 28(6): 551-6 0268-3369

•

Treatment of malignant scala posterior brain tumors in children: the chemotherapy of relapsed medulloblastoma with a dibromdulcitol containing drug regime and pharmacokinetic studies of dibromdulcitol in children. Author(s): Department of Paediatrics No. II, Semmelweis University Medical School, Budapest, Hungary. Source: Schuler, D Somlo, P Kooos, R Kalmanchey, R Paraicz, E Med-Pediatr-Oncol. 1992; 20(4): 312-4 0098-1532

•

Two-phase [11C]L-methionine PET in childhood brain tumors. Author(s): Department of Radiology, Johns Hopkins Hospital, Baltimore, Maryland. Source: O'Tuama, L A Phillips, P C Strauss, L C Carson, B C Uno, Y Smith, Q R Dannals, R F Wilson, A A Ravert, H T Loats, S et al. Pediatr-Neurol. 1990 May-June; 6(3): 163-70 0887-8994

•

Vitamin D receptor expression in human brain tumors. Author(s): Dipartimento di Chirurgia-Neurochirurgia, Universita di Pavia, Italy. Source: Magrassi, L Bono, F Milanesi, G Butti, G J-Neurosurg-Sci. 1992 Jan-March; 36(1): 27-30 0390-5616

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

•

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

Nutrition

•

123

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

•

Open Directory Project: http://dmoz.org/Health/Nutrition/

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

•

WebMDHealth: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

125

CHAPTER TUMORS

3.

ALTERNATIVE

MEDICINE

AND

BRAIN

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to brain tumors. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to brain tumors and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “brain tumors” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to brain tumors: •

3. Utility of PET and 11C-Methionine in the Paediatric Brain Tumors. Author(s): Sorensen J, Savitcheva I I, Engler H, Langstrom B. Source: Clinical Positron Imaging : Official Journal of the Institute for Clinical P.E.T. 2000 July; 3(4): 157. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150760&dopt=Abstract

•

A phase I study of cranial radiation therapy with concomitant continuous infusion paclitaxel in children with brain tumors. Author(s): Liu L, Vapiwala N, Munoz LK, Winick NJ, Weitman S, Strauss LC, Frankel LS, Rosenthal DI. Source: Medical and Pediatric Oncology. 2001 October; 37(4): 390-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568904&dopt=Abstract

126 Brain Tumors

•

A role for preirradiation PCV chemotherapy for oligodendroglial brain tumors. Author(s): Streffer J, Schabet M, Bamberg M, Grote EH, Meyermann R, Voigt K, Dichgans J, Weller M. Source: Journal of Neurology. 2000 April; 247(4): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10836623&dopt=Abstract

•

Acute effects of stereotactic radiosurgery on the kinetics of glucose metabolism in metastatic brain tumors: FDG PET study. Author(s): Yamamoto T, Nishizawa S, Maruyama I, Yoshida M, Tsuchida T, Waki A, Fujibayashi Y, Kubota T, Yonekura Y, Itoh H. Source: Ann Nucl Med. 2001 April; 15(2): 103-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448067&dopt=Abstract

•

Antiangiogenesis -- therapeutic strategies and clinical implications for brain tumors. Author(s): Puduvalli VK, Sawaya R. Source: Journal of Neuro-Oncology. 2000 October-November; 50(1-2): 189-200. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245279&dopt=Abstract

•

Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors. Author(s): Janssen G, Bode U, Breu H, Dohrn B, Engelbrecht V, Gobel U. Source: Klinische Padiatrie. 2000 July-August; 212(4): 189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994549&dopt=Abstract

•

Brain tumors. Author(s): Hill CI, Nixon CS, Ruehmeier JL, Wolf LM. Source: Physical Therapy. 2002 May; 82(5): 496-502. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991802&dopt=Abstract

•

Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy. Author(s): Andersen PB, Krabbe K, Leffers AM, Schmiegelow M, Holm S, Laursen H, Muller JR, Paulson OB. Source: Journal of Neuro-Oncology. 2003 May; 62(3): 305-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777083&dopt=Abstract

•

Clinical immunotherapy for brain tumors. Author(s): Fecci PE, Sampson JH. Source: Neuroimaging Clin N Am. 2002 November; 12(4): 641-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687917&dopt=Abstract

•

Clinical value of iodine-123-alpha-methyl-L-tyrosine single-photon emission tomography in the differential diagnosis of recurrent brain tumor in patients

Alternative Medicine 127

pretreated for glioma at follow-up. Author(s): Samnick S, Bader JB, Hellwig D, Moringlane JR, Alexander C, Romeike BF, Feiden W, Kirsch CM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 January 15; 20(2): 396-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786566&dopt=Abstract •

Contribution of the combination of (201)Tl SPECT and (99m)T(c)O(4)(-) SPECT to the differential diagnosis of brain tumors and tumor-like lesions. A preliminary report. Author(s): Terada H, Kamata N. Source: Journal of Neuroradiology. Journal De Neuroradiologie. 2003 March; 30(2): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717294&dopt=Abstract

•

Dendritic cell therapy of primary brain tumors. Author(s): Soling A, Rainov NG. Source: Molecular Medicine (Cambridge, Mass.). 2001 October; 7(10): 659-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713365&dopt=Abstract

•

Evaluation of a social-skills training group intervention with children treated for brain tumors: a pilot study. Author(s): Barakat LP, Hetzke JD, Foley B, Carey ME, Gyato K, Phillips PC. Source: Journal of Pediatric Psychology. 2003 July-August; 28(5): 299-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808006&dopt=Abstract

•

Evaluation of radiofrequency ablation as an alternative for the treatment of brain tumor in rabbits. Author(s): Mia Y, Ni Y, Yu J, Zhang H, Marchal G. Source: Journal of Neuro-Oncology. 2002 January; 56(2): 119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995812&dopt=Abstract

•

Ex vivo pediatric brain tumors express Fas (CD95) and FasL (CD95L) and are resistant to apoptosis induction. Author(s): Riffkin CD, Gray AZ, Hawkins CJ, Chow CW, Ashley DM. Source: Neuro-Oncology. 2001 October; 3(4): 229-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11584892&dopt=Abstract

•

Expression of p33ING1 mRNA and chemosensitivity in brain tumor cells. Author(s): Tallen G, Riabowol K, Wolff JE. Source: Anticancer Res. 2003 March-April; 23(2B): 1631-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820433&dopt=Abstract

•

Feasibility of long-term intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain

128 Brain Tumors

tumors. Author(s): Slavc I, Schuller E, Falger J, Gunes M, Pillwein K, Czech T, Dietrich W, Rossler K, Dieckmann K, Prayer D, Hainfellner J. Source: Journal of Neuro-Oncology. 2003 September; 64(3): 239-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14558599&dopt=Abstract •

Gamma probe-assisted brain tumor microsurgical resection: a new technique. Author(s): Vilela Filho O, Carneiro Filho O. Source: Arquivos De Neuro-Psiquiatria. 2002 December; 60(4): 1042-7. Epub 2003 January 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563405&dopt=Abstract

•

Imaging changes after stereotactic radiosurgery of primary and secondary malignant brain tumors. Author(s): Ross DA, Sandler HM, Balter JM, Hayman JA, Archer PG, Auer DL. Source: Journal of Neuro-Oncology. 2002 January; 56(2): 175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995819&dopt=Abstract

•

Increased locoregional blood flow in brain tumors after cervical spinal cord stimulation. Author(s): Clavo B, Robaina F, Catala L, Valcarcel B, Morera J, Carames MA, Ruiz-Egea E, Panero F, Lloret M, Hernandez MA. Source: Journal of Neurosurgery. 2003 June; 98(6): 1263-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816274&dopt=Abstract

•

Influence of anticonvulsants on the metabolism and elimination of irinotecan. A North American Brain Tumor Consortium preliminary report. Author(s): Kuhn JG. Source: Oncology (Huntingt). 2002 August; 16(8 Suppl 7): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199631&dopt=Abstract

•

Integration of the metabolic data of positron emission tomography in the dosimetry planning of radiosurgery with the gamma knife: early experience with brain tumors. Technical note. Author(s): Levivier M, Wikier D, Goldman S, David P, Metens T, Massager N, Gerosa M, Devriendt D, Desmedt F, Simon S, Van Houtte P, Brotchi J. Source: Journal of Neurosurgery. 2000 December; 93 Suppl 3: 233-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11143256&dopt=Abstract

•

Intra-arterial carboplatin and intravenous etoposide for the treatment of metastatic brain tumors. Author(s): Newton HB, Slivka MA, Volpi C, Bourekas EC, Christoforidis GA, Baujan MA, Slone W, Chakeres DW.

Alternative Medicine 129

Source: Journal of Neuro-Oncology. 2003 January; 61(1): 35-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587794&dopt=Abstract •

Intractable epilepsy associated with brain tumors in children: surgical modality and outcome. Author(s): Kim SK, Wang KC, Hwang YS, Kim KJ, Cho BK. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2001 August; 17(8): 445-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508532&dopt=Abstract

•

Kinetic analysis of 2-[11C]thymidine PET imaging studies of malignant brain tumors: compartmental model investigation and mathematical analysis. Author(s): Wells JM, Mankoff DA, Muzi M, O'Sullivan F, Eary JF, Spence AM, Krohn KA. Source: Molecular Imaging : Official Journal of the Society for Molecular Imaging. 2002 July; 1(3): 151-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920853&dopt=Abstract

•

Kinetic analysis of 2-[11C]thymidine PET imaging studies of malignant brain tumors: preliminary patient results. Author(s): Wells JM, Mankoff DA, Eary JF, Spence AM, Muzi M, O'Sullivan F, Vernon CB, Link JM, Krohn KA. Source: Molecular Imaging : Official Journal of the Society for Molecular Imaging. 2002 July; 1(3): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920852&dopt=Abstract

•

Long-term sequelae in children treated for brain tumors: impairments, disability, and handicap. Author(s): Macedoni-Luksic M, Jereb B, Todorovski L. Source: Pediatric Hematology and Oncology. 2003 March; 20(2): 89-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554520&dopt=Abstract

•

Methionine positron emission tomography of recurrent metastatic brain tumor and radiation necrosis after stereotactic radiosurgery: is a differential diagnosis possible? Author(s): Tsuyuguchi N, Sunada I, Iwai Y, Yamanaka K, Tanaka K, Takami T, Otsuka Y, Sakamoto S, Ohata K, Goto T, Hara M. Source: Journal of Neurosurgery. 2003 May; 98(5): 1056-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744366&dopt=Abstract

•

Molecular imaging of regional brain tumor biology. Author(s): Spence AM, Muzi M, Krohn KA.

130 Brain Tumors

Source: J Cell Biochem Suppl. 2002; 39: 25-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552599&dopt=Abstract •

Multimodality image fusion in dose escalation studies of brain tumors. Author(s): Rajasekar D, Datta NR, Gupta RK, Pradhan PK, Ayyagari S. Source: Journal of Applied Clinical Medical Physics [electronic Resource] / American College of Medical Physics. 2003 Winter; 4(1): 8-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540814&dopt=Abstract

•

New techniques in MR imaging of brain tumors. Author(s): Pomper MG, Port JD. Source: Magn Reson Imaging Clin N Am. 2000 November; 8(4): 691-713. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11175983&dopt=Abstract

•

New trends in the radiotherapy of brain neoplasms. Author(s): De Santis M, Salvi G, Niespolo RM. Source: Rays. 2000 July-September; 25(3): 379-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11367906&dopt=Abstract

•

No responses to oral etoposide in 15 patients with recurrent brain tumors. Author(s): Korones DN, Fisher PG, Cohen KJ, Dubowy RL. Source: Medical and Pediatric Oncology. 2000 July; 35(1): 80-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10881014&dopt=Abstract

•

Novel approaches to imaging brain tumors. Author(s): Matthews PM, Wylezinska M, Cadoux-Hudson T. Source: Hematology/Oncology Clinics of North America. 2001 August; 15(4): 609-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11676276&dopt=Abstract

•

Paclitaxel for the treatment of progressive or recurrent childhood brain tumors: a pediatric oncology phase II study. Author(s): Hurwitz CA, Strauss LC, Kepner J, Kretschmar C, Harris MB, Friedman H, Kun L, Kadota R. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2001 June-July; 23(5): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11464982&dopt=Abstract

•

Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience. Author(s): Turner CD, Gururangan S, Eastwood J, Bottom K, Watral M, Beason R, McLendon RE, Friedman AH, Tourt-Uhlig S, Miller LL, Friedman HS.

Alternative Medicine 131

Source: Neuro-Oncology. 2002 April; 4(2): 102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916501&dopt=Abstract •

Population pharmacokinetics of low-dose paclitaxel in patients with brain tumors. Author(s): Hempel G, Rube C, Mosler C, Wienstroer M, Wagner-Bohn A, Schuck A, Willich N, Boos J. Source: Anti-Cancer Drugs. 2003 July; 14(6): 417-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853882&dopt=Abstract

•

Positron emission tomography imaging of brain tumors. Author(s): Wong TZ, van der Westhuizen GJ, Coleman RE. Source: Neuroimaging Clin N Am. 2002 November; 12(4): 615-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687915&dopt=Abstract

•

Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. Author(s): Timmermann B, Kortmann RD, Kuhl J, Meisner C, Dieckmann K, Pietsch T, Bamberg M. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 February 1; 20(3): 842-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821469&dopt=Abstract

•

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. Author(s): van den Bent MJ, Chinot O, Boogerd W, Bravo Marques J, Taphoorn MJ, Kros JM, van der Rijt CC, Vecht CJ, De Beule N, Baron B. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 April; 14(4): 599-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649108&dopt=Abstract

•

Single photon emission computed tomography of an acute focal demyelinating disease mimicking a brain tumor. Author(s): Yoritaka A, Arai N, Ohta K, Okamoto K, Kishida S. Source: European Neurology. 2002; 48(4): 222-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422072&dopt=Abstract

•

Targeted therapy of brain tumors utilizing neural stem and progenitor cells. Author(s): Burns MJ, Weiss W.

132 Brain Tumors

Source: Frontiers in Bioscience : a Journal and Virtual Library. 2003 January 1; 8: E22834. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456351&dopt=Abstract •

The Brain Tumor Foundation of Canada: the role of facilitators for its support groups. Author(s): Ellis KM. Source: Axone. 2000 December; 22(2): 10-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901485&dopt=Abstract

•

The effect of P-glycoprotein on paclitaxel brain and brain tumor distribution in mice. Author(s): Gallo JM, Li S, Guo P, Reed K, Ma J. Source: Cancer Research. 2003 August 15; 63(16): 5114-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941842&dopt=Abstract

•

The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors. Author(s): Friedman HS, Keir ST, Houghton PJ. Source: Cancer. 2003 May 1; 97(9 Suppl): 2359-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712457&dopt=Abstract

•

Treatment of malignant brain tumors. Author(s): Takakura K, Kubo O. Source: Gan to Kagaku Ryoho. 2000 May; 27 Suppl 2: 449-53. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895194&dopt=Abstract

•

Usefulness of semiquantitative FDG-PET in the prediction of brain tumor treatment response to gamma knife radiosurgery. Author(s): Lee JK, Liu RS, Shiang HR, Pan DH. Source: Journal of Computer Assisted Tomography. 2003 July-August; 27(4): 525-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886136&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

•

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

•

Chinese Medicine: http://www.newcenturynutrition.com/

•

drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

•

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

Alternative Medicine 133

•

Google: http://directory.google.com/Top/Health/Alternative/

•

Healthnotes: http://www.healthnotes.com/

•

MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

•

Open Directory Project: http://dmoz.org/Health/Alternative/

•

HealthGate: http://www.tnp.com/

•

WebMDHealth: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

•

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to brain tumors; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Birth Defects Prevention Source: Healthnotes, Inc.; www.healthnotes.com Brain Cancer Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Dementia Source: Integrative Medicine Communications; www.drkoop.com Edema Source: Integrative Medicine Communications; www.drkoop.com Senile Dementia Source: Integrative Medicine Communications; www.drkoop.com Water Retention Source: Integrative Medicine Communications; www.drkoop.com

•

Alternative Therapy Chelation Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,679,00.html

134 Brain Tumors

•

Herbs and Supplements Echinacea Alternative names: Echinacea angustifolia, Echinacea pallida, Echinacea purpurea, Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Echinacea Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Echinacea Pallida Source: Integrative Medicine Communications; www.drkoop.com Echinacea Purpurea Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Prima Communications, Inc.www.personalhealthzone.com Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

135

CHAPTER 4. DISSERTATIONS ON BRAIN TUMORS Overview In this chapter, we will give you a bibliography on recent dissertations relating to brain tumors. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “brain tumors” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on brain tumors, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Brain Tumors ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to brain tumors. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Computational Studies of Brain Tumor Growth and Other Biological Processes by Kansal, Anuraag R.; Phd from Princeton University, 2002, 216 pages http://wwwlib.umi.com/dissertations/fullcit/3048731

•

Epidemiology of Brain Tumors and Methodology Research by Choi, Bernard C. K; Phd from University of Toronto (canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK62210

•

Immunochemical Studies of Experimental Brain Tumors by Lo, James Shui-ip; Phd from University of Toronto (canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK35255

•

Magnetic Resonance-based Markers of Treatment Response and Transgene Expression for Use in Brain Tumor Gene Therapy by Stegman, Lauren Daniel; Phd from University of Michigan, 2002, 200 pages http://wwwlib.umi.com/dissertations/fullcit/3042174

136 Brain Tumors

•

Molecular Genetic Investigations of Brain Tumors with Neuronal Differentiation by Yin, Xiao-lu; Phd from Chinese University of Hong Kong (people's Republic of China), 2002, 160 pages http://wwwlib.umi.com/dissertations/fullcit/3052115

•

The Association between the Polyomaviruses, Jc Virus, Bk Virus, and Simian Virus 40, and Human Brain Tumors by Rollison, Dana Elise Maher; Phd from The Johns Hopkins University, 2003, 212 pages http://wwwlib.umi.com/dissertations/fullcit/3080754

•

The Continuous Distribution of Restricted Water Diffusion Rates in Brain Tumors by Bennett, Kevin Michael; Phd from The Medical College of Wisconsin, 2003, 143 pages http://wwwlib.umi.com/dissertations/fullcit/3090050

•

The Educational Quality of Life of Students Treated for Brain Tumors by Witkowski, Casimir B., Edd from Temple University, 1990, 176 pages http://wwwlib.umi.com/dissertations/fullcit/9107941

•

The Effectiveness of the Child Behavior Checklist in Detecting Attention Deficits among the Pediatric Brain Tumor Population by Lai, Judy Y.; Phd from Alliant International University, Los Angeles, 2003, 113 pages http://wwwlib.umi.com/dissertations/fullcit/3058299

•

The Effects of Acquired Memory Disorders on Academic Achievement (brain Tumors) by Moon, Frances Richards, Phd from Georgia State University, 1995, 59 pages http://wwwlib.umi.com/dissertations/fullcit/9524238

•

The Effects of Pediatric Brain Tumors on Family Functioning by Burgin, James Kelly, Phd from Georgia State University, 1990, 129 pages http://wwwlib.umi.com/dissertations/fullcit/9107497

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

137

CHAPTER 5. CLINICAL TRIALS AND BRAIN TUMORS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning brain tumors.

Recent Trials on Brain Tumors The following is a list of recent trials dedicated to brain tumors.8 Further information on a trial is available at the Web site indicated. •

A Pilot Study of 1H-Nuclear Magnetic Resonance Spectroscopic Imaging in Pediatric Patients with Primary and Metastatic Brain Tumors Condition(s): Brain Neoplasm; Neoplasm Metastasis Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Brain tumors represent the most common solid tumor of childhood. Treatment generally entails surgery and radiation, but local recurrence is frequent. Chemotherapy is often used in an adjuvant setting, to delay radiation therapy or for resistant disease. Children with brain tumors are generally followed by imaging studies, such as CT or MRI. Difficulty arises in trying to distinguish tumor regrowth from treatment related edema, necrosis or radiation injury. Proton Nuclear Magnetic Resonance Spectroscopic (NMRS) Imaging is a non-invasive method of detecting and measuring cellular metabolites in vivo. NMRS imaging complements routine MRI by giving chemical information in conjunction with spatial information obtained by MRI. This study will be conducted to determine NMRS imaging patterns before, during and after chemotherapy in pediatric patients with primary or metastatic brain tumors in an attempt to identify and characterize specific patterns of metabolites related to tumor regrowth, tumor response to therapy, edema or necrosis. Phase(s): Phase I Study Type: Interventional

8

These are listed at www.ClinicalTrials.gov.

138 Brain Tumors

Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001574 •

Antineoplaston Therapy in Treating Children With Brain Tumors Condition(s): childhood brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally-occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating children with brain tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003458

•

Antineoplaston Therapy in Treating Children With Primary Malignant Brain Tumors Condition(s): childhood brain tumor; childhood meningioma Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating children who have primary malignant brain tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003476

•

Antineoplaston Therapy in Treating Patients With Brain Tumors Condition(s): ACTH-producing pituitary tumor; TSH producing pituitary tumor; adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally-occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with brain tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003457

Clinical Trials 139

•

Antineoplaston Therapy in Treating Patients With Primary Malignant Brain Tumors Condition(s): adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with primary malignant brain tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003475

•

Biological Therapy Following Surgery and Radiation Therapy in Treating Patients With Primary or Recurrent Astrocytoma or Oligodendroglioma Condition(s): adult brain tumor; adult infiltrating astrocytoma; adult noninfiltrating astrocytoma; Adult Oligodendroglioma Study Status: This study is currently recruiting patients. Sponsor(s): Barbara Ann Karmanos Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining different types of biological therapies may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of biological therapy following surgery and radiation therapy in treating patients who have primary or recurrent astrocytoma or oligodendroglioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004024

•

Brain Neoplasms, Leukemia and Petrochemical Exposures Condition(s): Leukemia; Brain Neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS); Harvard School of Public Health; Kaohsiung Medical University Purpose - Excerpt: The aim of this study is to examine the association of exposure to air contaminants (PAH & VOC) emitted from the petrochemical industries, specific genetic polymorphisms (P4501A1 (MspI & exon 7) and GSTM1 & T1) of study subjects and their parents, and the risks of brain tumors and leukemia among children and youths in metropolitan Kaohsiung, southern Taiwan. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042445

140 Brain Tumors

•

CCI-779 in Treating Patients With Malignant Glioma Condition(s): recurrent adult brain tumor; adult glioblastoma multiforme; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; Mixed Gliomas Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of CCI-779 in treating patients who have malignant glioma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022724

•

Chemotherapy and Radiation Therapy in Treating Infants With Brain Tumors Condition(s): childhood brain tumor; Neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy and radiation therapy in treating infants who have tumors of the brain. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005063

•

Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Central Nervous System Cancer Condition(s): adult brain tumor; paranasal sinus and nasal cavity cancer; primary central nervous system lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy combined with peripheral stem cell transplantation in treating patients who have central nervous system cancer. Phase(s): Phase II Study Type: Interventional

Clinical Trials 141

Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007982 •

Cilengitide in Treating Children With Refractory Primary Brain Tumors Condition(s): childhood brain tumor; childhood meningioma; childhood spinal cord tumors Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Cilengitide may slow the growth of brain cancer cells by stopping blood flow to the tumor. PURPOSE: Phase I trial to study the effectiveness of cilengitide in treating children who have recurrent, progressive, or refractory primary CNS tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063973

•

Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Brain Cancer Condition(s): adult brain tumor; childhood central nervous system germ cell tumor; childhood ependymoma; Childhood Medulloblastoma; childhood supratentorial primitive neuroectodermal tumors Study Status: This study is currently recruiting patients. Sponsor(s): Kaplan Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining temozolomide, thiotepa, and carboplatin followed by peripheral stem cell transplantation or bone marrow transplantation in treating patients who have brain cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025558

•

Comparison of PET and Proton MRS Imaging to Evaluate Pediatric Brain Tumor Activity Condition(s): Brain Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study in children and young adults will compare two types of imaging, positron emission tomography ([18F]-DG PET) and proton magnetic resonance

142 Brain Tumors

spectroscopy (1H-MRSI), to determine activity of a brain tumor or abnormal tissue in the brain following treatment for a brain tumor. Children with brain tumors are generally followed with magnetic resonance imaging (MRI) scans to evaluate response to treatment. However, because MRI only provides information on the structure of the brain, it may difficult to tell if an abnormal finding is due to tumor, swelling, scar tissue, or dead tissue. 1H-MRSI and [18F]-DG PET, on the other hand, provide information on the metabolic activity of brain lesions. These two methods will be compared and evaluated for their ability to provide important additional information on childhood brain tumors. Patients between 4 and 21 years of age with a brain tumor or brain tissue abnormality following treatment for a brain tumor may be eligible for this study. Candidates will be screened with a medical history and physical examination, pregnancy test in women who are able to become pregnant, and a blood test for glucose. Participants will undergo the following procedures: 1H-MRSI - This test is similar to MRI and is done in the same scanning machine. In MRI, scans of the brain are obtained by applying a strong magnetic field and then collecting the signals released from water after the magnetic field is changed. Pictures of the brain are then obtained by computer analysis of these signals. In 1H-MRSI, the computer blocks the signal from water to get information on brain chemicals that can indicate whether an abnormality is tumor or dead tissue. Both MRI and MRI and 1H-MRSI are done in this study. For these tests, the child lies on a stretcher that moves into the scanner - a narrow metal cylinder with a strong magnetic field. The child's head is placed in a headrest to prevent movement during the scan. He or she will hear loud thumping noises caused by the electrical switching of the magnetic field. A contrast agent is given through an intravenous (IV) catheter (plastic tube placed in an arm vein) or through a central line if one is in place. The contrast material brightens the images to provide a clearer picture of abnormalities. Children who have difficulty holding still or being in a scanning machine are given medications by an anesthesiologist to make them sleep through the procedure. Children who are awake during the procedure can communicate with the MRI technician at all times and ask to be removed from the scanner at any time. The MRI and 1H-MRSI take 1-1/2 to 2 hours to complete. [18F]-DG PET - For this test, [18F]-DG (a radioactive form of glucose) is injected into the patient's arm vein through a catheter, followed by the PET scan, similar to a very open MRI scan without the noise. The PET scan tells how active the patient's tumor is by tracking the radioactive glucose. All cells use glucose, but cells with increased metabolism, such as cancer cells, use more glucose than normal cells. After the glucose injection, the patient lies quietly in a darkened room for 30 minutes, after which he or she is asked to urinate to help reduce the dose of radiation to the bladder. Then, the scan begins. When the scan is finished (after about 1 hour), the child is asked to urinate again and then every 3 to 4 hours for the rest of the day. Patients remain in the study for 2 years unless they withdraw, become pregnant, or require sedation but can no longer use an anesthetic. MRI and 1H-MRSI scans may be repeated every few months during the study period, if necessary. Only one PET scan is done each year. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067821

Clinical Trials 143

•

Cyproheptadine and Megestrol in Preventing Weight Loss in Children With Cachexia Caused By Cancer or Cancer Treatment Condition(s): Cachexia; childhood Hodgkin's lymphoma; childhood brain tumor; childhood non-Hodgkin's lymphoma; childhood solid tumor; hematopoietic and lymphoid cancer Study Status: This study is currently recruiting patients. Sponsor(s): H. Lee Moffitt Cancer Center and Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Cyproheptadine and megestrol may improve appetite and help prevent weight loss in children with cancer. PURPOSE: Clinical trial to study the effectiveness of cyproheptadine and megestrol in improving appetite and preventing weight loss in children who have cachexia caused by cancer or cancer treatment. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066248

•

Erlotinib in Treating Patients With Recurrent Malignant Glioma Condition(s): adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult glioblastoma multiforme; adult malignant meningioma; Mixed Gliomas; recurrent adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase I/II trial to study the effectiveness of erlotinib in treating patients who have recurrent or progressive malignant glioma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045110

•

Gefitinib in Treating Patients With Recurrent or Progressive CNS Tumors Condition(s): adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of CNS tumors. PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have recurrent or progressive CNS tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

144 Brain Tumors

Web Site: http://clinicaltrials.gov/ct/show/NCT00025675 •

Gefitinib Plus Temozolomide in Treating Patients With Malignant Primary Glioma Condition(s): recurrent adult brain tumor; adult glioblastoma multiforme; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; Mixed Gliomas Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Biological therapies such as gefitinib may interfere with the growth of cancer cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining gefitinib with temozolomide in treating patients who have malignant primary glioma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027625

•

Gene Testing to Help in the Diagnosis and Treatment of Childhood Brain Tumors Condition(s): untreated childhood supratentorial primitive neuroectodermal tumors; untreated childhood medulloblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Analyzing the number and structure of genes found in a child's cancer cells may help doctors improve methods of diagnosing and treating children with brain tumors. PURPOSE: Clinical trial to study the number and structure of genes in cancer cells of children who have brain tumors. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003096

•

Gene Therapy Plus Chemotherapy in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma Condition(s): adult brain tumor; adult non-Hodgkin's lymphoma; adult solid tumor Study Status: This study is currently recruiting patients. Sponsor(s): Ireland Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Gene therapy may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of combining gene therapy with chemotherapy in treating patients who have advanced solid tumors or non-Hodgkin's lymphoma. Phase(s): Phase I

Clinical Trials 145

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003567 •

Genetic Analysis of Brain Tumors Condition(s): Glioma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will analyze tissue and blood samples from patients with gliomas (a type of brain tumor) to develop a new classification system for these tumors. Tumor classification can help guide treatment, in part by predicting how aggressive a tumor may be. Gliomas are currently classified according to their grade (how quickly they may grow) and the type of cells they are composed of. This system, however, is not always accurate, and sometimes two tumors that appear to be identical under the microscope will have very different growth patterns and responses to treatment. The new classification system is based on tumor genes and proteins, and may be used in the future to better predict a given tumor's behavior and response to therapy. Patients with evidence of a primary brain tumor and patients with a known glioma who will be undergoing surgery to remove the tumor may participate in this study. A sample of tumor tissue removed in the course of a participant's normal clinical care will be used in this study for laboratory analysis of genes and chromosome abnormalities. A small blood sample will also be collected for genetic analysis. In addition, clinical information on patients' condition and response to treatment will be collected every 6 months over several years. This information will include findings from physical and neurologic examinations, radiographic findings, and response to therapy, including surgery, radiation and chemotherapy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031538

•

Genetic Study of Brain Tumors in Young Children Condition(s): childhood choroid plexus tumor; untreated childhood supratentorial primitive neuroectodermal tumors; untreated childhood medulloblastoma; childhood rhabdoid tumor of the central nervous system Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer. PURPOSE: Genetic study to understand how genes may be involved in the development of brain tumors in young children. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010101

146 Brain Tumors

•

Imatinib Mesylate in Treating Patients With Gliomas Condition(s): adult brain tumor; adult infiltrating astrocytoma; adult noninfiltrating astrocytoma; Adult Oligodendroglioma; Mixed Gliomas Study Status: This study is currently recruiting patients. Sponsor(s): EORTC New Drug Development Group; EORTC Brain Tumor Cooperative Group Purpose - Excerpt: RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and slow the growth of the tumor. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have gliomas. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039364

•

Imatinib Mesylate in Treating Patients With Recurrent Brain Tumor Condition(s): adult anaplastic oligodendroglioma; adult oligodendroglioma; recurrent adult brain tumor; Mixed Gliomas

well-differentiated

Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent brain tumor that has not responded to previous surgery and radiation therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049127 •

Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma Condition(s): adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and may be an effective treatment for recurrent glioma and meningioma. PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate in treating patients who have progressive, recurrent, or unresectable malignant glioma or meningioma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010049

Clinical Trials 147

•

Imatinib Mesylate in Treating Patients With Recurrent Meningioma Condition(s): adult anaplastic astrocytoma; adult brain malignant hemangiopericytoma; adult meningioma; adult papillary meningioma; recurrent adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent meningioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045734

•

Light Scattering Spectroscopy to Determine Brain Tumors Condition(s): Epilepsy, Temporal Lobe; Temporal Lobe Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will use light scattering spectroscopy (LSS) to analyze brain tissue removed from patients during brain surgery to determine if this new technology can be used to differentiate between normal and cancerous cells. LSS focuses light on cells or tissues, and the way that light is reflected back from the tissues provides information about the size of cells and the density of the cell nuclei (the part of the cell that contains the genes). Patients between 18 and 75 years of age with a known or suspected brain tumor and patients with temporal lobe epilepsy that does not respond to medication may be eligible for this study. (Examination of tissue from patients with epilepsy will allow comparison of tumor and non-tumor brain cells.) All patients must require surgery to treat their condition. Participants will be admitted to the Clinical Center for 3 to 10 days for physical and neurological examinations, blood and urine tests, and other tests needed to prepare for surgery. They will then undergo surgery. A small amount of tissue removed during surgery for pathological review will be collected for use in this study. Half of the tissue will be examined using LSS to help determine the size of the cell and its nucleus. Studies will be done to measure how many of the cells are actively dividing and which proteins are expressed more often in tumor cells compared with normal cells. This information may shed light on how tumor cells are different from normal cells. Participants may be contacted for up to 3 years to follow their health status. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067418

•

Methylphenidate to Improve Quality of Life in Patients Undergoing Radiation Therapy for Brain Tumors Condition(s): adult brain tumor; brain metastases; cognitive and functional effects; Depression; Fatigue; Quality of Life

148 Brain Tumors

Study Status: This study is currently recruiting patients. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Methylphenidate may decrease side effects of radiation therapy. It is not yet known if methylphenidate is effective in improving quality of life in patients with primary or metastatic brain tumors. PURPOSE: Randomized phase III trial to determine the effectiveness of methylphenidate in improving quality of life in patients who have brain tumors and are undergoing radiation therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031798 •

Modafinil in Treating Fatigue and Behavioral Change in Patients With Primary Brain Cancer Condition(s): adult brain tumor; Fatigue; cognitive/functional effects Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Modafinil may be effective in relieving fatigue and improving behavioral changes such as memory loss in patients who have undergone treatment for primary brain cancer. The effectiveness of modafinil in relieving fatigue and improving behavioral change is not yet known. PURPOSE: Randomized clinical trial to determine the effectiveness of modafinil in treating fatigue and behavioral changes in patients who have undergone treatment for primary brain cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052286

•

OSI-774 to Treat Patients with Recurrent Malignant Glioma (Brain Tumor) and Patients with Glioma After Radiation Therapy Condition(s): Glioma; Meningioma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will determine 1) a safe dose of the experimental drug OSI-774 in patients with malignant glioma (a type of cancerous brain tumor), and 2) the drug's effectiveness in treating this disease. Genetic changes in glioma cells may lead to an excess of certain growth factors and the receptors (proteins on cell surfaces) that they bind to, resulting in uncontrolled tumor growth. A growth factor called EGF is seen in high concentrations in malignant gliomas and may be an important contributor to the growth of these tumors. OSI-774 blocks the EGF receptor and may prevent it from causing tumor growth. Patients 18 years of age and older with a primary glioma that is growing and does not respond to standard treatment, such as surgery, chemotherapy or radiation therapy, may be eligible for this study. Candidates will be screened with physical and neurologic examinations, blood and urine tests, an electrocardiogram

Clinical Trials 149

(ECG), and magnetic resonance imaging (MRI) or computed tomograpy (CT) of the head. There are two phases to this study. Participants will be assigned to phase I or phase II depending on whether they are taking certain anti-seizure medicines. Some seizure medicines can affect the metabolism and blood levels of OSI-774. Phase I will examine the safety of OSI-774 in patients who are taking such medications. Phase II will examine the effectiveness of OSI-774 in controlling tumor growth in 1) patients who are not taking such seizure medications, and 2) patients who are taking such medications, after the safe dose of OSI-774 has been determined in phase I. All patients will take OSI774 tablets daily for up to a year, or possibly longer, as long as they do not develop unacceptable drug side effects and their tumor either remains stable or shrinks. They will have routine blood tests every 1 to 2 weeks and a physical examination and MRI or CT scans every 8 weeks. Additional blood tests will be done to measure blood levels of OSI-774, blood levels of a protein that may alter OSI-774 levels, and whether EGF receptor can be detected in the blood. Patients may also be asked to undergo a scan called dynamic MR with spectroscopy- a test that is identical in experience to standard MRI-or positron emission tomography (PET), which is similar to CT and MRI. These scans, although not required for this study, may be helpful in determining the effect of OSI-774 on the glioma. Patients in phase II who were scheduled for surgery before entering the study will have the option of participating in an additional study. They will receive OSI-774 for 7 days before surgery, but not on the day of surgery. During surgery, a piece of tumor tissue will be analyzed for the effects of OSI-774 on certain pathways of cell growth. With the patient's permission, some of the tissue from this surgery, and from any previous brain surgeries, will be sent to the company providing OSI-774 for further investigation. After patients have recovered from surgery, they will continue OSI-774 treatment as described above. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055276 •

P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors Condition(s): Brain Tumor; Ewing's Sarcoma; Neuroblastoma; Rhabdomyosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the safety and side effects of tariquidar in children and adolescents with cancer and test whether it can improve current anticancer drug treatments. Tumor resistance to chemotherapy is a major problem in cancer treatment. Studies have found that a protein (P-glycoprotein) on some cancer cells pumps anticancer drugs out of the cells, reducing treatment effectiveness. In laboratory tests, an experimental drug called tariquidar has blocked pumping by this protein. It is being used in this study to try to increase amounts of the anticancer drugs vinorelbine (Navelbinea), doxorubicin (Adriamycin) or docetaxel (Taxotere) in cancer cells. Patients between 2 and 18 years of age with solid tumors-including rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, liver tumors, germ cell tumors, and primary brain tumors-who have relapsed or who do not respond to frontline therapy and have no other treatment options may be eligible for this study. Candidates will be screened with

150 Brain Tumors

a medical history, physical and neurological examinations, blood and urine tests, electrocardiogram, MUGA (nuclear medicine scan of the heart) and radiologic studies to evaluate the extent of disease. Participants will receive tariquidar plus either doxorubicin, vinorelbine or docetaxel, depending on the type of cancer, previous treatments, and side effects of prior treatment. Patients taking doxorubicin will also receive GCSF, a drug that helps boost the immune system, and dexrazoxane, a medicine to lessen the harmful effects of doxorubicin on the heart. Patients taking docetaxel will also receive GCSF, plus medicines to prevent an allergic reaction to the docetaxel. Treatment will be given in 21-day cycles for no more than eight cycles. The first treatment cycle for each regimen begins with a baseline Sestamibi scan-an imaging procedure that uses the radioactive drug Tc-99m Sestamibi. This drug accumulates in tumor cells and is eliminated from them in much the same way that some cancer drugs are eliminated from cells. The drug is injected into a vein and a series of pictures taken with a camera that detects radioactivity shows where the radioactive Sestamibi distributes in the body, including in the cancer, liver and heart. This procedure can monitor for effects of tariquidar on resistance to therapy. The day after the Sestamibi scan, tariquidar is given intravenously (through a vein), followed by another Sestamibi scan. On the third day, tariquidar is given, followed by the treatment drug (doxorubicin, vinorelbine or docetaxel). Patients taking vinorelbine will repeat the tariquidar and vinorelbine doses 1 week after the first. Sestamibi scans are done during the first treatment cycle only for each drug regimen. In addition, for the first treatment cycle only, 17 blood samples of less than one-half teaspoon each are drawn to study the pharmacology of tariquidar (i.e., how the drug works in the body), and another 17 samples are taken to study the pharmacology of the chemotherapy drug. A device, such as a heparin lock, is put in place to avoid having multiple needlesticks for these blood draws. Routine blood tests are done twice a week and various tests, such as X-rays, CT and MRI scans are done periodically to follow the progress of the cancer throughout the treatment period. Patients taking doxorubicin will also have an echocardiogram or MUGA to evaluate heart function. Patients are examined by a doctor at least once a week. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011414 •

Photodynamic Therapy With Porfimer Sodium in Treating Patients With Refractory Brain Tumors Condition(s): adult brain tumor; brain metastases; childhood brain stem glioma; childhood brain tumor; childhood cerebellar astrocytoma; childhood visual pathway and hypothalamic glioma Study Status: This study is currently recruiting patients. Sponsor(s): Medical College of Wisconsin Purpose - Excerpt: RATIONALE: Photodynamic therapy uses light and photosensitizing drugs to kill tumor cells and may be an effective treatment for refractory brain tumors. PURPOSE: Phase I trial to study the effectiveness of photodynamic therapy using porfimer sodium in treating patients who have refractory brain tumors, including astrocytoma, ependymoma, and medulloblastoma. Phase(s): Phase I

Clinical Trials 151

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002647 •

Poly-ICLC in Treating Patients With Recurrent or Progressive Anaplastic Glioma Condition(s): adult anaplastic astrocytoma; Mixed Gliomas; adult anaplastic oligodendroglioma; adult well-differentiated mildly and moderately anaplastic astrocytoma; recurrent adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Biological therapies such as poly-ICLC use different ways to stimulate the immune system and stop tumor cells from growing. PURPOSE: Phase II trial to study the effectiveness of poly-ICLC in treating patients who have recurrent, progressive, or relapsed anaplastic glioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058123

•

Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Primary Brain Tumors Condition(s): adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances such as radioactive iodine to them without harming normal cells. PURPOSE: Randomized phase I/II trial to compare two methods of delivering radiolabeled monoclonal antibody therapy to patients with primary brain tumors. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003478

•

Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Primary or Metastatic Brain Tumors Condition(s): adult brain tumor; brain metastases; localized resectable neuroblastoma; Neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. This may be effective treatment for primary or metastatic brain tumors. PURPOSE:

152 Brain Tumors

Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients with primary or metastatic brain tumors. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003461 •

Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors Condition(s): Ewing's family of tumors; childhood brain tumor; childhood meningioma; childhood solid tumor; Neuroblastoma; Pheochromocytoma Study Status: This study is currently recruiting patients. Sponsor(s): Holden Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiolabeled octreotide can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of radiolabeled octreotide in treating children who have advanced or refractory solid tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049023

•

SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors Condition(s): childhood brain tumor; childhood meningioma; childhood rhabdoid tumor of the central nervous system; childhood spinal cord tumors Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: SCH 66336 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase I trial to study the effectiveness of SCH 66336 in treating children who have recurrent or progressive brain tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015899

•

STI571 to Treat Malignant Brain Tumors Condition(s): Glioma; Astrocytoma; Meningioma; Gliosarcoma; Oligodendroglioma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study has two phases. Phase I will determine the highest dose of the experimental drug STI571 that can be given to patients with brain tumors without

Clinical Trials 153

causing severe side effects. Phase II will evaluate whether this drug can prevent tumor growth in these patients. STI571 has slowed the growth of cancerous brain tumors in animals and has killed cancerous blood cells in patients with leukemia. The drug may work by 1) blocking signals that stimulate cells to grow, and 2) inhibiting the formation of new blood vessels that carry nourishment to the tumor. Patients with recurrent brain tumors whose disease does not respond to standard treatment may be eligible for this study. Both patients who are taking anti-seizure medicines and those who are not will be recruited for the study, since these medicines may influence the way the body handles, or metabolizes, STI571. Candidates must have evidence by magnetic resonance imaging (MRI) or computed tomography (CT) that their tumor is growing. Patients enrolled in the study will undergo a repeat MRI and will have physical and neurological examinations and blood tests within 2 weeks of starting treatment. Participants in both study phases will take STI571 capsules once or twice a day, depending on the dose. This may consist of a total of 4 to 12 capsules per day. The first group of patients in phase I will be given a low dose of STI571. The dose will be increased with subsequent groups of patients as long as the drug is well tolerated. All patients will have physical and neurologic examinations every 4 weeks for as long as treatment continues. Routine blood tests will be taken at regular intervals throughout the course of treatment, as will special blood tests to measure blood levels of STI571, to analyze serum proteins, and to test for substances that stimulate growth of new blood vessels. The intervals of these tests vary for participants in the two different study phases. After the 8th week of treatment, patients in both study phases will have a repeat MRI or CT scan to assess treatment response. Patients whose tumor has increased by less than 50%, remained stable or shrunk may continue to receive STI571. Patients whose tumor has doubled in size or who experience unacceptable drug side effects will be taken off the study. Patients may be requested to undergo additional tests, including dynamic MR with spectroscopy and positron emission tomography (PET) scanning, which can help distinguish live tumor from dying tumor. The procedure for MR with spectroscopy is identical to MRI and will be done at the same time as the standard MRI scan. The procedure for PET is similar to that for CT, but involves injection of a small amount of radioactive tracer material. Patients may continue treatment until STI571 no longer shows benefit or unacceptable side effects appear. Continuation of treatment will be reassessed after 1 year, for those still taking the drug at that time. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023179 •

Study of Karenitecin (BNP1350) in patients with brain tumors Condition(s): Brain Neoplasms; Malignant Neoplasms, Brain; Brain Tumors Study Status: This study is currently recruiting patients. Sponsor(s): BioNumerik Pharmaceuticals, Inc. Purpose - Excerpt: The purpose of this study is to determine if Karenitecin (BNP1350) is effective in the treatment of Brain Tumors Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

154 Brain Tumors

Web Site: http://clinicaltrials.gov/ct/show/NCT00062478 •

Study of Neurologic Progression with Motexafin Gadolinium and Radiation Therapy (SMART) Condition(s): Neoplasm

Brain

Neoplasms;

Carcinoma,

Non-Small-Cell

Lung;

Metastases,

Study Status: This study is currently recruiting patients. Sponsor(s): Pharmacyclics Purpose - Excerpt: The primary purpose of the study is to determine if patients with brain metastases from non-small cell lung cancer treated with Motexafin Gadolinium and whole brain radiation therapy retain their neurologic function and ability to think for a longer time compared to patients treated with whole brain radiation therapy alone. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054795 •

Study of Systemic and Spinal Chemotherapy Followed by Radiation for Infants with Brain Tumors Condition(s): Brain Tumors Study Status: This study is currently recruiting patients. Sponsor(s): Baylor College of Medicine; Texas Children's Hospital; Duke University; Hospital St. Justine; St. Jude Children's Research Hospital Purpose - Excerpt: The purposes of this study are to find the highest dose of mafosfamide that can be given without causing severe side effects, to see how well the combination of these chemotherapy drugs and lower doses of radiation work to delay or stop the growth of the tumor, and to evaluate the pharmacokinetics (how the body handles) of Mafosfamide. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042367

•

Temozolomide and O6-Benzylguanine for Treating Childhood Cancers Condition(s): Brain Neoplasm; Embryonal Neoplasm; Ewing's Sarcoma; Germ Gell Neoplasm; Liver Neoplasm; Nephroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will investigate the combined use of temozolomide (TMZ) and O6-benzylguanine (O6BG) for treating cancer. TMZ is an anti-cancer drug approved to treat certain brain tumors in adults. TMZ loses its effectiveness over time because a protein called AGT makes the tumor resistant to the drug. O6BG inactivates AGT and, therefore, may prolong TMZ's effectiveness. Children and young adults under age 21 with various types of cancer (brain, liver, bone and others) for whom standard treatment

Clinical Trials 155

was not successful may be eligible for this study. Participants will receive TMZ capsules by mouth and an intravenous (through a vein) infusion of O6BG 5 days in a row every month for up to 12 months. Blood will be drawn on days 3 and 5 of the first course of treatment to measure AGT levels. Also on day 5 of the first treatment course, 16 blood samples (1 teaspoon each) will be taken over a 48-hour period to study how the two drugs work in the body. If possible, a heparin lock will be placed in the vein to avoid having multiple needle sticks. A tissue biopsy (removal of a small piece of tumor) may be taken if the tumor is close to the skin and not near a vital organ. The sample will be used to evaluate the effect of O6BG on AGT levels. A doctor will see the patients weekly. Routine blood tests will be done twice a week. MRI or CT scans will be done before treatment begins and every 1 to 2 months during treatment to measure the size of the tumor. Patients with a brain tumor will also have a magnetic resonance spectroscopic test (similar to MRI) every 1 to 2 months to measure chemicals in the tumor. Patients will complete a Quality of Life Assessment questionnaire about the effect of the illness on the patient's behavior and everyday activities. Potential benefits to patients in this study are tumor shrinkage and symptom improvement, such as pain relief. Because this is an experimental therapy, however, the likelihood of tumor shrinkage cannot be predicted. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005019 •

Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors Condition(s): childhood brain tumor; childhood meningioma; childhood spinal cord tumors Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug. PURPOSE: Phase I trial to study the effectiveness of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052780

•

Temozolomide in Treating Patients With Progressive Low-Grade Glioma Condition(s): adult brain tumor; childhood brain stem glioma; childhood brain tumor; childhood cerebral astrocytoma and malignant glioma; Childhood Oligodendroglioma; childhood visual pathway and hypothalamic glioma Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI)

156 Brain Tumors

Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients with progressive low-grade glioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003466 •

Temozolomide Plus Irinotecan in Treating Patients With Recurrent Malignant Glioma Condition(s): recurrent adult brain tumor; adult glioblastoma multiforme; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; Mixed Gliomas Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of temozolomide plus irinotecan in treating patients who have recurrent malignant glioma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006025

•

The Role of Gene Changes in Brain Tumor Formation and Growth Condition(s): Glioma Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will examine tissue from gliomas (a type of brain tumor) removed during surgery for gene mutations, or changes, thought to be involved in tumor formation and growth. One common gene mutation causes the receptor for a protein called epidermal growth factor (EGF) to be in an active state all of the time, allowing uncontrolled cell growth that can lead to tumor formation. This study will analyze blood and tumor tissue samples from patients with gliomas for: - Changes in the EGF gene in the tumor - Changes in other genes, such as that for the EGF receptor (EGFR) - Changes in levels of EGF and EGFR, and in other proteins and genes that respond to changes in the levels of these proteins in the tumor - Changes in the EGF gene and protein in the blood The study will also determine if production of EGF and EGFR obtained from glioma and from blood cells derived from the tumor can be altered in the laboratory to grow indefinitely in culture. Patients between 18 and 75 years of age with a brain tumor that requires surgical treatment may be eligible for this study. Participants will be admitted to the NIH Clinical Center for about 3 to 10 days. They will have a physical and neurological examination, blood and urine tests, other tests, if medically necessary, and will be evaluated and prepared for surgery. During surgery, as much of the tumor as possible will be removed. A small amount of the tumor tissue will

Clinical Trials 157

be collected for this study. No tissue will be removed for this study that would not otherwise have been removed. Some of the tissue will be used to culture glioma cells and the rest will be frozen and stored for examination, as described above. If any normal-appearing brain tissue is removed during surgery in order to enhance safety in removing the tumor, the normal tissue will be studied as well. Brain tissue that appears normal will not be removed strictly for research. During surgery and the day after surgery, a blood sample will be drawn from a catheter (plastic tube) that was placed in an artery or vein for surgery. If catheters are no longer in place, blood will be drawn through a needle in a vein. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059020 •

Thiotepa Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Malignant Glioma Condition(s): adult brain tumor; childhood brain tumor; childhood cerebellar astrocytoma; childhood cerebral astrocytoma and malignant glioma; childhood ependymoma; Childhood Oligodendroglioma Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of thiotepa followed by peripheral stem cell or bone marrow transplantation in treating patients who have malignant glioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008008

•

Vaccine Therapy and Sargramostim in Treating Patients With Sarcoma or Brain Tumor Condition(s): Brain Tumor; childhood brain tumor; childhood soft tissue sarcoma; gastrointestinal stromal tumor; Muscle Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Dana-Farber/Harvard Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may cause a stronger immune response and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining vaccine therapy with sargramostim in treating patients who have advanced sarcoma or brain tumor.

158 Brain Tumors

Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069940 •

Vaccine Therapy in Treating Patients With Gastric Cancer, Non-Small Cell Lung Cancer, Prostate, or Ovarian Cancer Condition(s): adult brain tumor; Gastric Cancer; Non-small cell lung cancer; ovarian epithelial cancer; Prostate Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from a peptide may make the body build an immune response to kill cancer cells. PURPOSE: Phase I trial to compare two different vaccines in treating patients who have gastric cancer, non-small cell lung cancer, prostate, or ovarian cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023634

•

Donepezil and EGb761 in Improving Neurocognitive Function in Patients Who Have Previously Undergone Radiation Therapy for Primary Brain Tumor or Brain Metastases Condition(s): adult brain tumor; brain metastases; radiation toxicity Study Status: This study is not yet open for patient recruitment. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Donepezil and EGb761 may be effective in improving neurocognitive function (such as thinking, attention, concentration, and memory) and may improve quality of life in patients who have undergone radiation therapy to the brain. PURPOSE: Phase II trial to study the effectiveness of donepezil and EGb761 in improving neurocognitive function in patients who have undergone radiation therapy for primary brain tumor or brain metastases. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070161

•

Immunotoxin Therapy in Treating Children With Recurrent Malignant Gliomas Condition(s): recurrent childhood brain tumor Study Status: This study is not yet open for patient recruitment. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI)

Clinical Trials 159

Purpose - Excerpt: RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. PURPOSE: Phase I/II trial to study the effectiveness of immunotoxin therapy in treating children who have recurrent or progressive malignant glioma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053040

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “brain tumors” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

•

For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

•

For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

•

For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

•

For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

160 Brain Tumors

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

•

For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

•

For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

161

CHAPTER 6. PATENTS ON BRAIN TUMORS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “brain tumors” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on brain tumors, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Brain Tumors By performing a patent search focusing on brain tumors, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

162 Brain Tumors

example of the type of information that you can expect to obtain from a patent search on brain tumors: •

Adaptive focusing and nulling hyperthermia annular and monopole phased array applicators Inventor(s): Fenn; Alan J. (Wayland, MA) Assignee(s): Massachusetts Institute of Technology (Cambridge, MA) Patent Number: 5,441,532 Date filed: March 4, 1992 Abstract: An R.F. hyperthermia phased array applicator uses adaptive nulling and focusing with non-invasive electric field probes to control the electric field intensity at selected positions in and around a target body to provide improved heating of solid tumors during hyperthermia treatment. A gradient search or matrix inversion algorithm is used to control the amplitude and phase weighting for the phased array transmit elements of the hyperthermia applicator. A 915 MHz monopole phased array hyperthermia applicator for heating brain tumors has an enclosed vessel including a plurality of monopole transmit antenna elements disposed as a circular arc array on a ground plane which has an aperture for positioning the tumor in proximity to the monopole antenna elements. Adaptive focusing with non-invasive electric field probes is used to maximize the electric field at the tumor site. Parallel plate microwave waveguides are used to direct R.F. energy from the monopole phased array to the tumor site. A microwave transmit and receive module generates amplitude and phase controlled transmit signals for exciting the monopole antenna elements, and receives passive microwave signals from the monopole antenna elements for taking non-invasive radiomerry temperature measurements of the tumor site. Excerpt(s): Appendices A-D of the disclosure of this patent document contain material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever. The successful treatment of deep-seated malignant tumors within a patient is often a difficult task. The objective of the treatment is to reduce in size or completely remove the tumor mass by one or more modalities available at the treatment facility. Common treatment modalities are surgery, chemotherapy, and x-ray therapy. One treatment modality used alone or in conjunction with one of the above modalities is "tissue heating", or hyperthermia. Hyperthermia can be considered as a form of high fever localized within the body. A controlled thermal dose distribution is required for hyperthermia to have a therapeutic value. Typical localized-hyperthermia temperatures required for therapeutic treatment of cancer are in the 43.degree.-45.degree. C. range. Normal tissue should be kept at temperatures below 43.degree. C. during the treatment. Typically, hyperthermia is induced in the body by radio-frequency (RF) waves, acoustic (ultrasound) waves, or a combination of both. One of the most difficult aspects of implementing hyperthermia, with either RF or ultrasound waves, is producing sufficient heating at depth. Multiple-applicator RF hyperthermia arrays are commonly used to provide a focused near-field main beam at the tumor position. Ideally, a focal region should be concentrated at the tumor site with minimal energy delivered to surrounding normal tissue. In RF hyperthermia systems, the hyperthermia antenna beamwidth is proportional to the RF wavelength in the body. A small focal region suggests that the RF wavelength be as small as possible. However, due to propagation losses in tissue, the RF depth of penetration decreases with

Patents 163

increasing transmit frequency. One of the major side-effects in heating a deep-seated tumor with a hyperthermia antenna is the formation of undesired "hot spots" in surrounding tissue. This additional undesired heating often produces pain, burns, and blistering in the patient, which requires terminating the treatment immediately. The patient does not receive anesthetics during the hyperthermia treatment in order to provide direct verbal feedback of any pain. Thus, techniques for reducing hot spots while maximizing energy delivered to the tumor site are desired in hyperthermia treatment. Web site: http://www.delphion.com/details?pn=US05441532__ •

Adenovirus-mediated gene therapy Inventor(s): Loimas; Sami (Kuopio, FI), Sandmair; Anu-Maaria (Kuopio, FI), Vapalahti; Matti (Kuopio, FI), Yla-Herttuala; Seppo (Kuopio, FI) Assignee(s): Ark Therapeutics, Ltd. (GB) Patent Number: 6,579,855 Date filed: June 25, 2001 Abstract: An adenovirus having a functional thymidine kinase gene is useful in the treatment of brain tumors. Excerpt(s): This invention relates to the treatment of brain tumours using gene therapy. The treatment of malignant glioma continues to challenge physicians and scientists. Thymidine kinase gene therapy, using the Herpes Simplex virus thymidine kinase (HSVtk) gene, is one of the most promising treatment modalities, in attempts to change the survival of malignant glioma patients. HSVtk gene therapy is based on the ability of thymidine kinase to catalyze the phosphorylation of ganciclovir (GCV). Phosphorylated GCV acts as a toxic nucleotide analogue, leading to the death of the target cells. This phenomenon is further enhanced by a bystander effect, where neighbouring cells are also destroyed even without transfection. This effect is thought to be due to the release of toxic nucleotide analogues from the transfected cells to neighbouring cells via gap junctions. Retroviruses and adenoviruses have been used as vectors for gene therapy. Both vectors have certain advantages and limitations. Brain tumours are especially suitable for retrovirus-mediated gene transfer, since retroviruses can only infect proliferating cells while normal, non-dividing brain tissue remains intact. The gene transfer efficiency of retroviruses is relatively low, but could be improved by using retrovirus packaging cells instead of isolated viruses. The transduction time can theoretically be prolonged and the number of transfected cells increased. With retroviruses, the transfected gene incorporates into the genome of the target cell and therefore long-term gene expression can be achieved. Web site: http://www.delphion.com/details?pn=US06579855__

164 Brain Tumors

•

Antitumor composition containing a synergistic combination of an anthracycline derivative with a camptothecin derivate Inventor(s): Caruso; Michele (Milan, IT), Geroni; Cristina (Milan, IT), Ripamonti; Marina (Milan, IT), Suarato; Antonino (Milan, IT) Assignee(s): Pharmacia & Upjohn S.p.A. (Milan, IT) Patent Number: 6,403,563 Date filed: September 20, 2000 Abstract: The combination of 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methansulfonyl daunorubicin or 4-demethoxy-N,N-bis(2-chloroethyl)-4'-methansulfonyl daunorubicin together with an antineoplastic topoisomerase I inhibitor yields preparations exhibiting anti-cancer effects. These preparations can be used in the treatment of tumors and especially 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methansulfonyl daunorubicin in the treatment of brain tumors. Excerpt(s): This application claims priority to PCT Application EP 99/01897 filed Mar. 19, 1999 and Application No. GB 9806324.1 filed Mar. 24, 1998. The present invention relates in general to the field of cancer treatment and, more particularly, provides an antitumor composition comprising an alkylating anthracycline and a topoisomerase I inhibitor, having a synergetic antineoplastic effect. an antineoplastic topoisomerase I inhibitor, and a pharmaceutically acceptable carrier or excipient. Web site: http://www.delphion.com/details?pn=US06403563__

•

Apparatus for directing the movement of an endoscopic surgical laser especially for use in vaporizing brain tumors Inventor(s): Shaunnessey; Jerome (910 Southbridge Dr., Aurora, IL 60506) Assignee(s): none reported Patent Number: 5,823,941 Date filed: October 23, 1995 Abstract: An apparatus for removing brain tumors by vaporizing the tumor tissue with a laser beam in select scan planes of the tumor. A cored hole through the tumor is made by the laser beam, and an endoscope is inserted through the cored hole, which has a mirror mounted at a 45 degree angle near the end of it and mounted within it, that is capable of reflecting the laser beam at a 90 degree angle. The endoscope is inserted all the way through the cored hole, and sucessive scans of the brain tumor are taken perpendicular to the endoscope. The endoscope is then moved axially to position the 45 degree mirror at each scan plane, and the reflected laser beam is then rotated and also oscillated between calculated angles to vaporize the tumor tissue in each scan plane, until the entire brain tumor is vaporized by the laser beam. During this procedure the gas being produced by vaporization of the tumor tissue is suctioned out through the interior of the endoscope. Excerpt(s): Many brain tumors are inoperable because of their location in the brain, and therefore, can not be removed without causing the death of the patient or resulting in unacceptable neurological damage. As a result, the prognosis for such patients is poor. Presently, approaching such tumurs is risky, and if they are tried to be reached by present day techniques, the operation is usually quite long and very complicated. And if the surgeon is sucessful in removing the tumor, the patient has went thru a massive

Patents 165

operation on his or her brain, which often times leaves them with considerable neurological damage. Accordingly, it is a general object of this invention to propose a inovative mechanism and technique to eliminate the foregoing disadvantages. Another object is to provide a method for removing brain tumors without actually performing a crainiotomy. Another object is to provide a method for reaching brain tumors that were previously un-reachable. Another objective is to simplify and reduce the time it takes to perform a brain operation. A particular objective is to reduce the risk of brain surgery and the neurological damage it can cause to patients. These and other objectives will become apparent from the following detailed description and accompanying sheets of drawings. Briefly described, the present invention contemplates a novel and unique mechanism for irradicating brain tumors situated deep within the brain. The mechanism is relatively simple, it is comprised of essentially two elements; a slim tube or endoscope for probing into the brain, and a slim guide tube that the endoscope fits inside of. The guide tube is of sufficient length to be inserted into the brain up to the tumor in question, and also project above the skull a suitable distance. The endoscope has a distal end and a caudal end. At the caudal end is a source for producing a thin beam of Laser light capable of destroying living tissue, which is aligned thru the center of the slim tube or Endoscope. Also at the caudal end, separate means are provided for both moving the endoscope axially within the guide tube and rotating the endoscope within the guide tube. At the distal end of the Endoscope, and suitably mounted within the Endoscope is a 45 degree corner reflector capable of reflecting the Laser beam at a 90 degree angle. Destruction of the tumor is accomplished by taking CAT or MRI scans of the tumor in planes perpendicular to the endoscope, and positioning the 45 degree corner reflector in one of the CAT or MRI scan planes, then rotating the reflected Laser beam to destroy the tumor tissue in that particular plane. The reflected Laser beam can be rotated continually or be instructed to only oscillate between some angle. Complete destruction of the tumor is accomplished by moving the corner reflector to successive planes. The entire process is accomplished by digital computer analysis of the profile of each individual CAT or MRI scan, then using this information to direct the positioning and rotation or oscillation of the 90 degree reflected Laser beam to destroy the tumor tissue in that particular scan plane. Web site: http://www.delphion.com/details?pn=US05823941__ •

Apparatus for irradiating living cells Inventor(s): Ignatius; Ronald W. (Dodgeville, WI), Martin; Todd S. (Dodgeville, WI) Assignee(s): Quantum Devices, Inc. (Barneveld, WI) Patent Number: 5,728,090 Date filed: February 9, 1995 Abstract: Apparatus for use in photodynamic therapy (PDT) is provided having a substantially cylindrical support to which is attached a removable, multi-sided head. Each side of the head has an array of light-emitting diodes that provide monochromatic light to activate a photosensitive dye. The apparatus may be used in invasive surgery to treat brain tumors and the like. The apparatus may be used for topical treatments by providing a removable reflector over the light-emitting head. The temperature of the head is controlled, and the head is cooled by circulating cooling fluid through the head. The use of the cooling fluid allows the LEDs to be driven beyond their rated capacity. The catheter may also include an expandable light diffuser that is affixed over the lightemitting head and that is filled with a diffuser fluid such as a lipid solution. The

166 Brain Tumors

apparatus may also be used to provide radiant energy to plants or to patients in nonPDT applications. Excerpt(s): This invention relates to devices used for irradiating a patient or other living cells. More particularly, this invention relates to a catheter for photodynamic therapy used to treat tumors and to destroy microbes. Photodynamic therapy (PDT) is being increasingly used to treat tumors, skin lesions and the like. When PDT is used to treat malignant tumors, a photosensitive dye is injected into the patient at least 24 hours before the planned therapy. The photosensitive dye is typically a hematoporphyrin derivative that is retained in malignant tissue. These dyes absorb light at wavelengths which penetrate cancerous tissue to produce singlet oxygen in vivo that destroys microbes and malignant cells. It is necessary to deliver a large amount of light radiation to the tumor at specific wavelengths to activate the photosensitive dye. Most photosensitive dyes are activated at wavelengths between about 300 nanometers and 800 nanometers. However, it is know that greater penetration of the tumor occurs at higher wavelengths, up to about 1300 nanometers. Web site: http://www.delphion.com/details?pn=US05728090__ •

Aqua-stream and aspirator for brain surgery Inventor(s): Ito; Haruhide (Kanazawa, JP), Kitamura; Akihiro (Ishikawa, JP) Assignee(s): Marui Ika Company, Limited (Tokyo, JP) Patent Number: 4,913,698 Date filed: September 7, 1988 Abstract: An aqua-stream and aspirator for crushing and removing brain tumors in cerbral surgery comprises a pressure chamber, a soft bottle filled with a sterilized saline solution and mounted within the pressure chamber, an irrigation tube connected at one end to an outlet of the soft bottle, an ejection needle removably connected to the other end of the irrigation tube via a swtich for controlling passage of the solution through the irrigation tube, and a suction tube extending parallel to the ejection needle. The pressure chamber is adapted to be pressurized with a harmless gas so as to compress the soft bottle to eject the solution in the soft bottle from the ejection needle. The ejection needle has a nozzle which is bent in such a manner that the solution ejected from the nozzle is directed toward a confronting inside wall of the tip of the suction tube. Excerpt(s): The present invention relates to an aqua-stream and aspirator (AS and A) which is useful in crushing and removing brain tumors during the brain surgery. Conventionally, a variety of surgical instruments, such as an electric knife, a laser knife, and a CAVITRON ultrasonic surgical aspirator (CUSA), for removing brain tumors has been developed and put to practical use. A problem in using a laser knife is that injuries due to local heat are inevitable in and around the incision line, thus producing a nasty smell and smoke, which would screen the operator's visual field. Further, the use of a laser knife necessitates the operator and nurse to wear glasses to protect their eyes from laser light. An electric knife is available for only a limited use. Partly because its handpiece is large in size and heavy in weight, and partly because the action of ultrasonic wave would be spread to even adjacent normal tissue, a CUSA is not suitable for a delicate operation. In addition, an aqua-stream and aspirator (AS and A) utilizing a water stream is known for hepatic surgery. However, in this prior apparatus, partly because its entire structure is large-sized, and partly because pressurized water is ejected perpendicularly to the surface the affected part, there is a fear that even normal

Patents 167

tissue could be crushed. Consequently the prior apparatus cannot be used for a delicate and precise operation which is required such as in cerebral surgery. Web site: http://www.delphion.com/details?pn=US04913698__ •

Carborane containing cholesterol, a new type of molecule for targeted boron drug delivery Inventor(s): Ji; Bing Qing (Athens, GA), Lu; Donghao Robert (Athens, GA) Assignee(s): The University of Georgia Research Foundation, Inc. (Athens, GA) Patent Number: 6,392,068 Date filed: July 5, 2000 Abstract: The present invention relates to novel carborane cholesterol analogs and their use in the treatment of tumor and cancers in humans, and in particular to the treatment of human brain tumors. Pharmaceutical compositions and methods of using these compositions in the treatment of tumors and cancer are other aspects of the present invention. Excerpt(s): Cancer continues to be a major cause of death in humans. Conventional treatment such as surgery, radiation therapy and chemotherapy have been extremely successful in certain cases. In other instances, alternative forms of cancer therapy involving the use of boron have been investigated. For example, Boron Neutron Capture Therapy ("BNCT") has been used to treat certain tumors for which conventional therapies have failed. Such therapies have helped treat Glioblastoma multiforme, a highly malignant, invasive form of brain cancer in Japan. BNCT is a two-step radiotherapy in which selective radioactive effect on tumor cells is achieved by targeting the tumor with non-radioactive.sup.10 B and subsequently exposing it to neutrons. The nuclear reaction between.sup.10 B and low energy neutrons creates high energy and particles, destroying those cells which contain.sup.10 B-containing agent. Various boron-containing compounds have been investigated for the clinical use of BNCT. Boronated analogs of compounds such as amino acids, thiouracils, chlorpromazine, nucleosides, antibodies, etc. have been the focus of compound development. Web site: http://www.delphion.com/details?pn=US06392068__

•

Edelfosin for the treatment of brain tumors Inventor(s): Nagler; Apollonia (Grunwald, DE) Assignee(s): Med-Mark Pharma GmbH (Oberhaching, DE) Patent Number: 6,514,519 Date filed: January 25, 2001 Abstract: Octadecyl-2-methyl-sn-glycero-3-phosphocholine (edelfosine) is suitable for the treatment of brain tumors and can therefore be used to produce a drug for the treatment of brain tumors which can also be administered orally. Excerpt(s): The invention relates to edelfosine (INN; 1-octadecyl-2-methyl-sn-glycero-3phosphocholine, frequently also referred to as ET180CH3) for the treatment of primary and secondary brain tumors originating from solid and nonsolid tumors. Permanent cure of a malignant brain tumor is, according to the present state of knowledge,

168 Brain Tumors

impossible, i.e. there are at present no curative therapeutic approaches to malignant gliomas. The aim is always individual treatment taking account of any losses of function by surgical procedures and a prolongation of the survival time with the best possible quality of life. The incidence of brain tumors is continuing to increase and becomes more marked as people age. Thus, for example, the average incidence is 1.8/100,000 people 15-24 years of age but about 18.4/100,000 of those 65-79 years of age. The age peak is between 55 and 73 years, although increasing numbers of young patients with glioblastomas have been recorded in recent years. The annual incidence of a primary brain tumor in Germany is about 7000 people, of whom most die within the first year. Despite surgery and irradiation, the people survive on average for only 11 months. The tumor has by then become so large, and such large amounts of fluids have escaped that the brainstem is crushed and functions important to life fail. Web site: http://www.delphion.com/details?pn=US06514519__ •

Enhancing delivery of large neutral amino acid drugs Inventor(s): Bigner; Darell D. (Mebane, NC), Friedman; Henry S. (Durham, NC), Griffith; Owen W. (Milwaukee, WI) Assignee(s): Cornell Research Foundation, Inc. (Ithaca, NY), Duke University (Durham, NC) Patent Number: 5,695,751 Date filed: September 21, 1995 Abstract: L-amino acid oxidase is utilized to reduce the plasma level of large neutral amino acids to allow the opportunity of increased large neutral amino acid drug transport across the blood brain barrier. Preferably anti L-amino acid oxidase antibody is administered intermediate to the L-amino acid oxidase and large neutral amino acid drug administrations to deplete L-amino acid oxidase activity once the L-amino acid oxidase has caused the large neutral amino acid drug transport improving level plasma reduction of large neutral amino acids thereby to reduce or eliminate degrading of large neutral amino acid drugs by L-amino acid oxidase. The large neutral amino acid drugs include levodopa, melphalan, L-DON, azaserine, acivicin, L-alanosine and 3(phosphonomethyl)phenylalanines. For treatment of brain tumors, the drug administration is preferably preceded by the administration of a large neutral amino acid glutathione depleting agent, e.g., L-buthionine-SR-sulfoximine. L-Amino acid oxidase is also utilized to enhance the transport of large neutral amino acid glutathione depleting agent across the blood brain barrier as an adjunct to radiation therapy of brain tumors. Excerpt(s): The invention herein is directed to enhancing the delivery of large neutral amino acid drugs and large neutral amino acid glutathione depleting agents in the treatment of diseases where crossing the blood-brain barrier by the drugs and/or agents is necessary. Melphalan, (4-›bis(2-chloroethyl)amino!-L-phenylalanine), is a nitrogen mustard that is useful as a chemotherapeutic agent. Goodman and Gilman's The Pharmaceutical Basis of Therapeutics, 8th edition, pages 1202-1208 (1990) classifies melphalan as an alkylating agent type of chemotherapeutic action and indicates a mechanism of action of cross-linking DNA. Sarosy, G., et al, Journal of Clinical Oncology, Vol. 6, No. 11 (November), pp. 1768-1782 (1988) indicates that melphalan effects cytotoxicity by forming either interstrand, intrastrand, or DNA-protein cross links. The wide spectrum of melphalan's anti-neoplastic activity against tumors, in vivo, is reported in the literature. Goodman and Gilman's The Pharmaceutical Basis of

Patents 169

Therapeutics, 8th edition, pages 1202-1208 (1990) indicates that melphalan is currently used in the treatment of multiple myeloma, breast cancer and ovarian cancer. Sarosy, G., et al, Journal of Clinical Oncology, Vol. 6, No. 11 (November), pp. 1768-1782 (1988), a review article on intravenous melphalan usage, at page 1772 in Table 1 indicates that at lower doses intravenous melphalan demonstrated at least some activity against pancreatic cancer, colon carcinoma, medulloblastoma, rhabdomyosarcoma, osteosarcoma, and ovarian cancer; at page 1774 in Table 3 indicates that at higher dosages intravenous melphalan demonstrated at least some activity against breast cancer, non-small-cell lung cancer, small-cell lung cancer, colon cancer, melanoma, testicular cancer, ovarian cancer, soft tissue sarcoma, Ewing's sarcoma, synovial cell sarcoma, bone (giant cell) sarcoma, Wilms' sarcoma, Wilms' osteogenic sarcoma, rhabdomyosarcoma, multiple myeloma, neuroblastoma, Hodgkin's lymphoma, nonHodgkin's lymphoma, acute lymphocytic leukemia, acute nonlymphoblastic leukemia, chronic granulocytic leukemia and renal cancer and characterizes the response rate for melanoma and colon carcinoma as extraordinarily high; at page 1773, Table 2 indicates that drug combinations including low dosages of intravenous melphalan demonstrated at least some activity against ovarian cancer, testicular cancer, non-small-cell lung cancer, melanoma and multiple myeloma; and at pages 1776-177, Table 4 indicates that drug combinations including higher dosages of intravenous melphalan demonstrated at least some activity against neuroblastoma, melanoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, Burkett's lymphoma, CML-blast crises, multiple myeloma, colonic cancer, breast cancer, sarcoma and gastric cancer. Barlogie, B., et al, Blood, Vol. 67, No. 5 (May), 1298-1301 (1986), indicates that large doses of melphalan demonstrated activity against advanced multiple myeloma. Horowitz, M. E., et al, Journal of Clinical Oncology, Vol. 6, No. 2 (February), 308-314 (1988), indicates that melphalan demonstrated partial responses in 10 of 13 patients having newly diagnosed, poor-risk rhabdomyosarcoma. Houghton, J. A., et al, Cancer Treatment Reports, Vol. 69, No. 1, 9196 (January 1985), indicates that melphalan demonstrated complete regressions in 6 of 7 lines of childhood rhabdomyosarcomas. Leff, R. S., et al, Journal of Clinical Oncology, Vol. 4, No. 11 (November), pp. 1586-1591 (1986), indicates that high-dose melphalan demonstrated complete responses in 15% of cases of metastatic colon cancer and partial responses in 30% of cases of metastatic colon cancer. Pritchard, J., et al, Br. J. Cancer, 45, 86-94 (1982), indicates that high dose melphalan demonstrated complete response in 6 of 11 of certain patients with advanced neuroblastoma. Web site: http://www.delphion.com/details?pn=US05695751__ •

GM-CSF administration for the treatment and prevention of recurrence of brain tumors Inventor(s): Low; Walter C. (Shorewood, MN), Wallenfriedman; Margaret A. (Edina, MN) Assignee(s): Regents of the University of Minnesota (Minneapolis, MN) Patent Number: 5,837,231 Date filed: June 27, 1996 Abstract: A method for inhibiting the growth of brain tumors comprising peripheral administration of GM-CSF in combination with brain tumor antigen. Excerpt(s): This invention relates to a therapeutic method effective for inhibiting the growth of brain tumors and preventing their reoccurrence. Specifically, the invention demonstrates that the peripheral administration of GM-CSF in combination with brain

170 Brain Tumors

tumor antigens effectively inhibits growth of tumor cells in the brain. After such treatment, animals are resistant to further tumor challenges. Brain tumors are a leading cause of death from neurological disease. It has been estimated that approximately 11,000 people in the United States alone die each year from primary tumors of the central nervous system. The most malignant form of primary intracranial tumors is glioblastoma multiforme. The mean survival time for patients with this type of tumor in the absence of any therapy is 14 weeks with a 1-year survival rate of 3%. With surgery, radiation therapy, and chemotherapy, the survival times are not dramatically prolonged. A key problem in dealing with glioblastoma is the inability of the immune system to recognize and destroy these tumor cells. Glial derived brain tumors represent a population of tumors with the capacity to evade and ultimately inhibit the body's mechanism for tumor defense. Clinical observations of patients with glioblastoma suggest that both cell mediated and humoral immunity are suppressed. These patients display cutaneous anergy, decreased numbers of T-cells and diminished responses to mitogens and antigens. Their peripheral blood lymphocytes fail to produce.gamma.interferon (IFN-.gamma.) , granulocyte/macrophage colony stimulating factor (GMCSF) and tumor necrosis factor-.alpha. (TNF-.alpha.) upon stimulation in vitro. When stimulated, T-cells from glioma patients express abnormally low levels of p55, the subunit which confers high affinity to the interleukin-2 (IL-2) receptor. Web site: http://www.delphion.com/details?pn=US05837231__ •

hNT-neuron human neuronal cells to replace ganglion cells Inventor(s): Snable; Gary L. (Atherton, CA) Assignee(s): Layton Bioscience, Inc. (Sunnyvale, CA) Patent Number: 6,162,428 Date filed: February 12, 1997 Abstract: Disclosed herein is the treatment of vision loss in a mammal by transplanting an effective amount of hNT-Neuron cells. The treatment can be accomplished by injecting the cells into the retinal area of the eye. Additionally, the cells can be injected into the visual cortex of the brain. Conditions to be treated are vision loss due to optic nerve damage, including glaucoma, optic nerve sheath meningioma and glioma, Graves' ophthalmopathy, benign or malignant orbital tumors, metastatic lesions, tumors arising from the adjacent paranasal sinuses or middle cranial fossa, giant pituitary adenomas, brain tumors or abscesses, cerebral trauma or hemorrhage, meningitis, arachnoidal adhesions, pseudotumor cerebri, cavernous sinus thrombosis, dural sinus thrombosis, encephalitis, space-occupying brain lesions, severe hypertensive disease or pulmonary emphysema. Excerpt(s): The present invention is in the field of human transplantation and more particularly in the field of intraocular and intracranial transplantation of specially treated human cells which reestablish neuronal connections between the retina and the ocular cortex, which neurons having been damaged by glaucoma or other compressioncausing injuries and diseases. Glaucoma is the occurrence of elevated intraocular pressure which causes progressive blindness in the form of gradual loss of peripheral fields of vision. It is an important cause of blindness and occurs in 1-2% of individuals over the age of 60. Often the disease is asymptomatic, as the patient painlessly and gradually loses vision. Before a diagnosis is made, the patient may have lost half of the one million optic nerve fibers in one eye. Today, intervention is focused on early detection, which depends on a routine eye examination which includes intraocular

Patents 171

pressure measurement (tonometry), funduscropy with attention to the optic disc appearance, and visual field testing. In the normal eye, the optic cups are symmetric and the neural rim is pink. In glaucoma, either localized notching or generalized enlargement of the optic cup can be seen. The rim, although thinned, remains pink until late in the disease. The central optic cup diameter can be compared with the diameter of the disc. The ratio of the horizontal and vertical dimensions can be recorded. The normal cup-disc ratio is less than 0.2 to 0.3. Vertical disparity in one or both eyes is an early sign of glaucoma. Glaucoma is often asymmetric. The finding of asymmetry of the cup-disc ratio implies glaucoma. Early in the disease, visual field loss may include nonspecific constriction and small paracentral scotomas. Eventually, the arcuate nerve fiber bundle defects develop with a characteristic nasal step: The arcuate bundle defect extends to the nasal horizontal raphe to form a step-like configuration on kinetic visual field testing. The papillomacular bundle and vision are spared until late in the disease (HARRISON'S PRINCIPLES OF INTERNAL MEDICINE, 13.sup.th ed. Ed. By Isselbacher, Braunwald, Wilson, Martin, Fauci and Kasper. McGraw-Hill, New York City, 1996. Pp. 104-6). Intraocular pressure reflects the balance between the production and outflow of aqueous humor. The normal range for measurements by applanation tonometry (the tonometer applanates the corneal surface) is 2.09.+-.2.5 mmHg. Another method of measuring intraocular pressure is briefly indenting the cornea with a Schiotz tonometer. Web site: http://www.delphion.com/details?pn=US06162428__ •

Immobilization system for repeated use in imaging and treating of brain tumors Inventor(s): McLaurin, Jr.; Robert L. (1528 Iredell Dr., Raleigh, NC 27608) Assignee(s): none reported Patent Number: 5,370,117 Date filed: January 3, 1994 Abstract: There is disclosed a patient immobilization system for repeated use in imaging and radiation therapy of a patient, the system comprising an immobilization plate, side rails mounted on the plate with mask studs outwardly projecting therefrom engaging a thermoplastic immobilization mask with at least two anchor bars holding the mask on said studs, wherein the improvement comprises a relatively rigid plastic arch having two ventricle leg portions and an apex, the lower ends of each of the leg portions being mounted on a respective one of the anchor bars; a flap of material outwardly projecting from the mask to a point adjacent the arch; a fixation member for mounting the outwardly projecting flap of material to the arch whereby the mask can be tightly held between the bars and the side rails on the studs and at a third point to the arch. Contrast material is provided at the apex of the arch and in each of the leg portions such that the x, y, and z axes can be shown in three-dimensional images of the patient. Excerpt(s): This invention relates to immobilization devices and more particularly to immobilization system for repeated use in imaging and treating of brain tumors. Radiation therapy is the treatment of malignant tissue through the use of radiation. The guiding principle is that malignant tissue has diminished ability to repair the radiation damage; whereas normal, healthy tissue retains the ability to recover from radiation exposure. Therefore, if a tumor is exposed repeatedly to radiation, it should shrink in size or disappear and, as long as the neighboring healthy tissue is given adequate time to recover between treatments, there should not be excessive permanent damage. The goal of radiation therapy is to deliver the radiation to the tumor itself while minimizing exposure of surrounding normal, healthy tissue. One important step in this process is

172 Brain Tumors

treatment planning. Fractionated treatment, i.e. treatment involving the division of total radiation dose into twenty or thirty subparts, has been used for decades in an effort to maximize recovery time for healthy tissue, as well as to minimize side effects and complications from overexposure to radiation. Stereotactic techniques have been developed which employ accurate positioning of the patient during radiographic studies so as to improve the precision in locating tumors and the delivery of radiation. Over the years, the use of radiographic devices such as x-rays and CT scanners in this process has become common, and now the use of Magnetic Resonance Imagery technology (MRI) is being actively investigated. These imaging techniques enable the radiation oncologist to look inside the body and avoid invasive surgery which might otherwise be necessary to locate and describe the lesions. Web site: http://www.delphion.com/details?pn=US05370117__ •

Immunotoxins for treatment of intracranial lesions and as adjunct to chemotherapy Inventor(s): Johnson; Virginia (College Park, MD), Youle; Richard J. (Garrett Park, MD) Assignee(s): The United States of America as represented by the Secretary of the (Washington, DC) Patent Number: 5,352,447 Date filed: August 10, 1992 Abstract: A potent and specific immunotoxin is prepared by coupling a binding-site inactivated diphtheria toxin (CRM 107) to a new binding moiety consisting of transferrin or a monoclonal antibody against the human transferrin receptor. These immunotoxins are tumor specific and lack the nonspecific toxicity produced by the binding activity of the native toxin. The immunotoxin is useful in treating primary brain tumors, metastatic tumors to the brain, CSF-borne tumors, leptomeningeal leukemia and leptomeningeal carcinomatosis. Excerpt(s): The invention claimed in the instant application relates to treatment of malignancies and to use of immunotoxins as an adjunct to chemotherapy for malignancies occurring in any part of the body to prevent development of metastatic lesions in the body which are usually not responsive to conventional chemotherapeutic agents. The use of the invention in treatment of central nervous system malignancies is particularly valuable. The use of systemic chemotherapy and radiation therapy for treatment of malignancies has failed to effectively alter the progress of malignant tumors of the central nervous system. The fatal outcome resulting from malignancies such as prostatic and mammary malignancies is often due to inability of current chemotherapy to effectively reach malignant growths in the central nervous system. The use of cytotoxic products in the treatment of cancer is well known. The difficulties associated with such treatment are also well known. Of these difficulties, the lack of cancer-specific cytotoxicity has received considerable attention, albeit resolution of these difficulties has met with marginal success. Cytotoxic products kill normal cells as well as cancer cells. Such non-specificity results in a number of undesirable side effects for patients undergoing cancer chemotherapy with cytotoxic products, including nausea, vomiting, diarrhea, hemorrhagic gastroenteritis, and hepatic and renal damage. Due to normal cell toxicity, the therapeutic dosage of cytotoxic products has been limited such that cancerous cells are not killed to a sufficient level that subsequently prevents or delays new cancerous growth. Web site: http://www.delphion.com/details?pn=US05352447__

Patents 173

•

Instrument for tumor therapy Inventor(s): Pettus; William G. (194 Crane Dr., Monroe, VA 24574) Assignee(s): none reported Patent Number: 5,722,985 Date filed: December 27, 1996 Abstract: An instrument for treating deep malignant brain tumors. A slender conicallytipped yttrium tubular instrument is provided for simultaneous intra-tumor surgery, aspiration, and brachytherapy. Features include: minimally disruptive stereotactic access to the tumor, incremental rotary surgical excision from the center of the tumor, vacuum aspiration of excised matter and fluids through the tubular instrument, intense tumor-confined yttrium-90 beta radiation, and progressive suction collapsing of the tumor. Potential benefits include: tumor bulk reduction, relief of intracranial pressure, confined radiation of marginal tumor extensions, radiation sterilization of the instrument, prevention of seeding, and avoidance of radiation necrosis complications. Excerpt(s): The present invention is generally related to medical instruments and particularly to surgical, radiation, and aspiration instruments. Deep malignant brain tumors are frequently inaccessible for conventional surgery and impossible to eradicate with safe doses of conventional radiation or with other conventional therapies. These tumors tend to become progressively debilitating due to the buildup of intracranial pressure and other complications, and most are fatal within a few years of detection. There is a need, therefore, for means of accessing deep brain tumors and eradicating or more effectively controlling these tumors. The present invention addresses the above need in a unique manner that provides, in a single instrument, the simultaneous and synergistic benefits of stereotactic surgery, high energy beta brachytherapy, and aspiration, all administered from the center of the tumor. The instrument consists of a slender cone-tipped yttrium tube having a short activated section near the tip that provides an intense, highly localized radiation field in conjunction with surgical excision of tumor matter through longitudinal slots as the tube is reciprocally rotated. The open end of the tube is connected by a hose to a vacuum aspiration system that tends to decompress the cranium as it removes fluids and excised tumor fragments and collapses outlying tumor matter inward into the intense radiation field and into the surgical slots. Peripheral tumor extensions in normal brain tissue may also be extirpated by suction and eradicated as they are drawn inward into the radiation field. The progress of this operation is monitored by imaging techniques and analysis of aspirated tissue, and aspirator suction is reduced at the appropriate stage of tumor collapse to prevent significant radiation damage beyond the tumor margin and to control intracranial stress and the resulting strain in surrounding normal brain structures. Web site: http://www.delphion.com/details?pn=US05722985__

•

Method for diagnosing malignant gliol brain tumors Inventor(s): Bogoch; Samuel (46 E. 91st St., New York, NY 10028) Assignee(s): none reported Patent Number: 4,196,186 Date filed: November 17, 1977

174 Brain Tumors

Abstract: Malignant brain tumors may be diagnosed by comparing the amounts of certain proteins bound to a product, Malignin, derived from brain tumor cells, complexed to an inert carrier, such as bromacetylcellulose. Excerpt(s): This invention is directed to a novel group of compounds, herein termed Recognins. Recognins are made by treating normal or diseased cells or tissues, e.g. tumor cells or artificial cancer cells and separating the desired products. The Recognins may be used to prepare their Chemoreciprocals, i.e., by contacting the Recognins or the Recognins on a support with body fluids. These Chemoreciprocals are useful for diagnostic and therapeutic purposes, i.e., for diagnosing and treating cancers. The Chemoreciprocals are substances which react with immunochemical-like specificity with a Recognin in vivo or in vitro, e.g., in a quantitative precipite in test, in Ouchterlony double diffusion or in immunofluorescence. One of the Recognins of the present invention is Astrocytin. Astrocytin is produced from brain tumor tissue, preferably brain glioma tumor tissue. Protein fractions containing the Astrocytin precursor are first extracted from the tissue. A preferred method of accomplishing the extraction is to treat the tissue with a neutral buffer under conditions of homogenization or other techniques to disrupt the cells and tissues in order to solubilize protein fractions which contain the Astrocytin precursor. At this point, the Astrocytin precursor is still bound to many large molecular weight substances including protein, glycoproteins, lipoproteins, nucleic acids, nucleoproteins, etc. The solubilized proteins are then separated from the resultant tissue extract. The extract solution from the tissue is then clarified to remove insoluble particles. The low molecular weight contaminants are then removed from the resultant solution, by a perevaporation concentration technique. The solution which is obtained is then treated to cleave Astrocytin precursor from other contaminants in order to obtain the protein fraction having a pK range between 1 to 4. Thus, for example, the solution is placed on a chromatographic column and eluted with increasingly acidic solvents. All of the fractions which are eluted in the neutral or acid range down to pK 4 are discarded and those fractions with pK range 1-4 are collected. The eluate is then treated to obtain a product having a molecular weight of about 8,000. This is accomplished, for example, by first filtering the material to remove low molecular weight substances, i.e., those below 1,000 molecular weight, and filtering again to remove those above 25,000. The fraction having a molecular weight between 1,000 and 25,000 is then further treated, i.e., by thin layer gel (TLG) chromatography, to obtain Astrocytin. Web site: http://www.delphion.com/details?pn=US04196186__ •

Method for selective opening of abnormal brain tissue capillaries Inventor(s): Black; Keith L. (1233 Roberto La., Los Angeles, CA 90077) Assignee(s): none reported Patent Number: 5,434,137 Date filed: May 10, 1993 Abstract: A method for selectively opening abnormal brain tissue capillaries of a mammal in order to allow selective passage of both low and high molecular weight neuropharmaceutical agents into abnormal brain tissue. The method utilizes direct infusion of bradykinin into the carotid artery. The dose of bradykinin is maintained at levels which provide opening of abnormal brain tissue capillaries without opening normal brain capillaries. The method is useful for introducing a wide variety of

Patents 175

neuropharmaceutical agents selectively to brain tumors and other abnormal brain tissue. Excerpt(s): The present invention relates generally to methods for increasing the permeability of the blood brain barrier in order to introduce neuropharmaceutical agents into the brain. More particularly, the present invention is directed to a method which selectively increases permeability of the blood brain barrier in abnormal brain tissue. The publications and other reference materials referred to herein to describe the background of the invention and to provide additional detail regarding its practice are hereby incorporated by reference. For convenience, the reference materials are numerically referenced and grouped in the appended bibliography. Capillaries within the brain include a barrier which prevents the delivery of many pharmaceutical agents to the brain. This blood-brain barrier (BBB) is present in both normal and abnormal brain tissue. The treatment of brain tissue abnormalities, such as tumors, require that the neuropharmaceutical agent be preferentially directed to the abnormal tissue. Accordingly, there has been a great deal of interest in developing techniques which are capable of opening the blood-brain barrier to allow transport of neuropharmaceutical agents to the brain (1, 2, 3, 4 and 5). None of these methods, however, are capable of selectively opening the blood-brain barrier only in the abnormal brain while leaving the blood-brain barrier in the normal brain intact. Web site: http://www.delphion.com/details?pn=US05434137__ •

Method for treating brain tumors Inventor(s): Beatty; John F. (Watertown, MA), Biggs; Peter J. (Winchester, MA), Harte; Kenneth J. (Carlisle, MA), Sliski; Alan P. (Lincoln, MA), Smith; Donald O. (Lexington, MA) Assignee(s): Photoelectron Corporation (Waltham, MA) Patent Number: 5,452,720 Date filed: August 9, 1993 Abstract: A method of treating brain tumors in a patient, comprising the steps of: identifying and locating a brain tumor in vivo by affixing a stereotactic frame to the head of the patient, performing a computer tomographic (CT) scan of the skull of the patient to determine the location, size, and shape of the tumor with respect to the stereotactic frame, performing a biopsy by inserting an extraction tool along a path measured with respect to the frame to the tumor location, extracting a tissue from the location, removing the needle and the extracted tissue and analyzing the tissue; implanting at least a portion of an adjustable x-ray radiation source in the patient proximate the tumor, the adjustable radiation source including an electron beam source outside the head of the patient, and directing an electron beam produced by the source outside the head of the patient along the path to the location; and controlling the source to generate an x-ray radiation pattern characterized by a spatial and temporal distribution, to selectively irradiate the tumor. Excerpt(s): The present invention relates to methods of treating brain tumors, particularly using a low power, programmable x-ray source for use in delivering lowlevels of substantially constant or intermittent x-rays to a specified region. Conventional medical x-ray sources are large, fixed position machines. Generally, the head of the x-ray tube is placed in one room and the control console in an adjoining area, with a protective wall, equipped with a viewing window, separating the two. The x-ray tube

176 Brain Tumors

typically is approximately 20 to 35 centimeters (cm) long, and approximately 15 cm in diameter. A high voltage power supply is housed within a container located in a corner of the room containing the x-ray tube. Patients are brought to the machine for diagnostic, therapeutic, or palliative treatment. Diagnostic x-ray machines are typically operated at voltages below 150 kilovolts (kV), and at currents from approximately 25 to 1200 milliamps (mA). By contrast, the currents in therapeutic units typically do not exceed 20 mA at voltages which may range above 150 kV. When an x-ray machine is operated at nominal voltages of 10 to 140 kV, the emitted x-rays provide limited penetration of tissue, and are thus useful in treating skin lesions. At higher voltages (approximately 250 kV), deep x-ray penetration is achieved, which is useful in the treatment of major body tumors. Super voltage machines, operable in the 4 to 8 megavolt (MV) region, are used to ablate or destroy all types of tumors, except superficial skin lesions. Web site: http://www.delphion.com/details?pn=US05452720__ •

Method of cancer tumor treatment by slow release delivery of 1,2,4-benzotriazine oxides to tumor site Inventor(s): Cardinale; Robert M. (11829 Chase Wellesley Dr., #621, Richmond, VA 23233) Assignee(s): none reported Patent Number: 5,637,085 Date filed: November 20, 1995 Abstract: Disclosed are a method and composition for intralesional therapy of solid cancer tumors, and especially brain tumors, comprising, delivering a compound of a 1,2,4-benzotriazine oxide contained in a biodegradable, slow release polymer and subjecting the cancer tumors to irradiation therapy. Excerpt(s): The present invention relates to the field of treatments for cancer tumors. More particularly, the present invention relates to interstitial therapy for brain tumors by delivering a compound of the 1,2,4-benzotriazine oxides family contained in a biodegradable polymer slowly released to the site of the tumor. Glioblastoma multiforme (GBM) patient management remains a formidable task. Radiation therapy improves median survival, and the addition of chemotherapy with nitrosources adds a modest gain for selected patients (See, for example: Kornblith, P. L. et al, Chemotherapy for malignant gliomas. J. Neurosurg. 68: 1-17 (1988); and Walker, M. D. et al, Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery, N. Eng. J. Med., 303: 1323-1329 (1980)). The benefit of radiotherapy, however, is limited by several factors. Although intrinsic radioresistance and rapid cellular proliferation may contribute to therapeutic inefficacy, dose escalation has not yet yielded superior results and is limited by the radiation tolerance of normal brain as reported by Solazar, O. M. et at, High dose radiation therapy in the treatment of malignant gliomas: final report, Int. J. Radial. Oncol. Biol. Phys., 3: 1733-1740 (1979). Hypoxic radioresistance has been demonstrated in several tumor types, including GBM, and oxygen measurements document regional hypoxia in a high percentage of patients with GBM, as reported by, inter alia: Gatenby, R. A. et al, Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int. J. Radial. Oncol. Biol. Phys. 14: 831-838; (1988); Kayama, T. et al, Intratumoral oxygen pressure in malignant brain tumors, J. Neurosurg., 74: 55-59 (1991); Rampling, R. et al, Direct measurement of pO2 distribution and bioreductive enzymes in

Patents 177

human malignant brain tumors, Int. J. Radiat. Oncol. Biol. Phys. 29: 427-431 (1994); and Valk, P. E. et at, Hypoxia in human gliomas: demonstration by PET with fluorine-18fluoromisonidazole, J. Nucl. Med. 33: 2133-2137 (1992)). A treatment that kills radioresistant hypoxic tumor cells should improve the efficacy of radiation therapy. When given as multiple injections in conjunction with fractionated irradiation, tirapazamine (SR-4233), a bioreductive agent that preferentially kills hypoxic dells, increases tumor cell kill while sparing normal tissue in mouse SCCVII and other tumors as reported by: Brown, J. M. et al, Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors, Cancer Res. 50: 7745-7749 (1990) and Brown, J. M. et al, SR 4233: a tumor specific radiosensitizer active in fractionated radiation regimens, Radiother. and Oncol., 20: 151-156 (1991). Brown has considered that tumor hypoxia may actually be of a therapeutic advantage when combining a hypoxic cytotoxin such as tirapazamine with fractionareal irradiation: Brown, J. M. et al, Tumor hypoxia: the picture has changed in the 1990s., Int. J. Radiat. Biol., 65: 95-102 (1994); and Brown, J. M. et al, Therapeutic advantage of hypoxic cells in tumors: a theoretical study, J. Nat. Can. Inst., 83: 178-185 (1991). Web site: http://www.delphion.com/details?pn=US05637085__ •

Method of treating brain tumors expressing tenascin Inventor(s): Bigner; Darell D. (Chapel Hill, NC), Zalutsky; Michael R. (Chapel Hill, NC) Assignee(s): Duke University (Durham, NC) Patent Number: 5,624,659 Date filed: February 22, 1995 Abstract: Methods of treating solid and cystic tumors are disclosed. The method comprises administering to a subject afflicted with a cystic tumor an antibody which binds to tenascin in a therapeutically effective amount. The administering step is carried out by depositing the antibody in the cyst cavity of the cystic tumor. For solid tumors, disclosed is a method involving first, removing a solid tumor from a solid tissue organ of an afflicted subject; then forming an enclosed resection cavity in the organ of the subject at the location from which the solid tumor was removed; and then administering to the subject an antineoplastic agent by depositing the antineoplastic agent in the resection cavity. Particularly preferred for carrying out the foregoing is the monoclonal antibody 81C6 and antibodies which bind to the epitope bound by monoclonal antibody 81C6. Excerpt(s): The present invention relates to the treatment of cancer, and particularly relates to the treatment of cystic brain tumors and cystic brain tumor resection cavities with anti-tenascin antibodies such as 81C6. Despite years of intensive investigation, the prognosis for most patients with primary anaplastic central nervous system (CNS) tumors remains poor. Median survival for adults with the most common form of CNS tumor, the glioblastoma multiforme, is 8-12 months. The outlook is somewhat better for less common tumors such as anaplastic astrocytoma and medulloblastoma, but most primary anaplastic CNS tumors are highly resistant to currently available therapy. Only radiotherapy has been shown to prolong survival in patients with anaplastic gliomas. Following conventional therapy with surgery and external beam radiotherapy, malignant gliomas tend to recur at or near the original tumor site. Temporarily implanted radioactive iodine sources (interstitial brachytherapy) have recently been used to deliver high dose focal radiotherapy to locally recurrent malignant gliomas.

178 Brain Tumors

Web site: http://www.delphion.com/details?pn=US05624659__ •

Methods for inhibiting brain tumor growth Inventor(s): Laug; Walter E. (La Crescenta, CA) Assignee(s): Childrens Hospital Los Angeles (Los Angeles, CA) Patent Number: 6,521,593 Date filed: January 21, 2000 Abstract: The present invention describes methods for inhibition of tumor growth in the brain, using antagonists of integrins such as.alpha.sub.v.beta.sub.3 and.alpha.sub.v.beta.sub.5. Antagonists of the present invention can inhibit angiogenesis in brain tumor tissue. They can also inhibit vitronectin and tenascinmediated cell adhesion and migration in brain tumor cells. They can further induce direct brain tumor cell death. Excerpt(s): The invention relates generally to inhibition of tumor growth and specifically to inhibition of brain tumor growth. Throughout this application various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims. Brain tumors, like other solid tumors, require a perpetually increasing blood supply to maintain continuous growth beyond 1-2 mm.sup.3 (1,2). This is accomplished through angiogenosis, a process which occurs in response to endothelial growth factors released by tumor cells. Angiogenesis involves the induction of endothelial cell proliferation from quiescent microvasculature, migration of neoendothelium toward the tumor bed and, finally, maturation into a new capillary network (3). Brain tumors are the most angiogenic of all human neoplasias. The principal angiogenic factors demonstrated by either in situ hybridization or specific antibodies in tissue sections of patients with glioblastoma and medulloblastoma, the most common malignant brain tumors, are vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) (47). In fact, VEGF expression and microvessel density in glial tumors directly correlate with the degree of malignant characteristics and overall outcome (8-9). Web site: http://www.delphion.com/details?pn=US06521593__

•

No-carrier-added [1.sup.11 c]putrescine Inventor(s): Fowler; Joanna S. (Bellport, NY), McPherson; Daniel W. (Baltimore, MD), Wolf; Alfred P. (Setauket, NY) Assignee(s): The United States of America as Represented by the United States (Washington, DC) Patent Number: 4,874,600 Date filed: April 17, 1986 Abstract: The invention relates to a new radiolabeled imaging agent, no-carrier-added [1-.sup.11 C]putrescine, and to the use of this very pure material as a radiotracer with positron emission tomography for imaging brain tumors. The invention further relates to the synthesis of no-carrier-added [1-.sup.11 C]putrescine based on the Michael

Patents 179

addition of potassium.sup.11 C-labeled cyanide to acrylonitrile followed by reduction of the.sup.11 C-labeled dinitrile. The new method is rapid and efficient and provides radiotracer with a specific activity greater than 1.4 curies per millimol and in a purity greater than 95%. Excerpt(s): The application of positron emission tomography (PET) to the study of human tumors and to the study of the response of such tumors to different therapeutic approaches continues to be of interest. Of particular interest are studies where valid tracer kinetic models exist and physiological quantitation is possible. Such kinetic models are the result of a thorough understanding of the biochemistry of the tracer in the tumor and in the surrounding tissue. Polyamines have been investigated for use as biochemical markers for malignancy, including brain tumors. Since adult brain parenchyma does not normally divide, a polyamine that marks cell growth and proliferation should be taken up and metabolized solely by the brain tumor. Volkow, et al. [Science, 221, 673 (1983)] tested the feasibility of using the polyamine putrescine, labeled with [.sup.3 H] and [.sup.14 C], as a PET tracer for brain tumors. They found that in vivo uptake into transplanted rat glioma was 35 times greater than in normal brain tissue and that metabolism to spermine by the tumor was rapid, in contrast to adjacent normal brain tissue. Winstead, et al. [Eur. J. Nucl Med., 5, 165 (1980)] synthesized carbon-11 labeled putrescine, but the synthesis yielded only carrier contaminated material that had too low a specific activity to be acceptable for human studies. Studies such as the Volkow, et al. study showed the usefulness of the putrescine model but also showed that because of impurities, very low specific activity, inappropriate half-lives, or non-optimum radiation emission, the carrier-added-[.sup.11 C], the [.sup.3 H] and the [.sup.14 C] radiolabels were not suitable for the preparation of a tracer for human studies of brain tumors using PET. Web site: http://www.delphion.com/details?pn=US04874600__ •

Nucleotide and amino acid sequences of a D2-2 gene associated with brain tumors and methods based thereon Inventor(s): Boynton; Alton L. (Redmond, WA), Murphy; Gerald P. (Seattle, WA), Sehgal; Anil (Seattle, WA) Assignee(s): Northwest Biotherapeutics, LLC (Seattle, WA) Patent Number: 5,874,290 Date filed: November 8, 1996 Abstract: Nucleotide sequences of D2-2 genes (human D2-2 and D2-2 homologs of other species), and amino acid sequences of their encoded proteins, as well as derivatives (e.g., fragments) and analogs thereof are disclosed. Nucleic acids hybridizable to or complementary to the nucleotide sequences are also disclosed. D2-2 is a gene expressed at high levels in glioblastoma multiforme tissue as well as certain other forms of tumors and cancers. Therapeutic and diagnostic methods and compositions based on D2-2 proteins fragments and analogs, anti-D2-2 antibodies and nucleic acids for treatment of disorders of overproliferation (e.g., tumors, cancer and hyperproliferative disorders are disclosed. Excerpt(s): The present invention relates t o a novel D2-2 gene and its encoded protein product(s), as well as derivatives and analogs thereof. Production of D2-2 proteins, derivatives, and antibodies is also provided. The invention further relates to therapeutic compositions and methods of diagnosis and therapy. Brain tumors are among the

180 Brain Tumors

leading cause of death among young children and adults. A survey by the American Cancer Society has documented that 13,300 people died of brain tumors in 1995 and over 17,900 will die in 1996 (Parker et al., 1996, CA Cancer J. Clin., 46:5-28). The number of deaths due to brain tumors has been increasing at a significant rate each year. On average, 25,000 Americans are diagnosed with brain cancer yearly. Brain tumors claim the lives of more children than any other form of cancer except leukemia. The increased incidence of brain tumors is not only evident in children but also in adults. It has been documented that a significant increase in mortality has occurred in adult primary malignant tumors between 1982 and 1996 (Parker et al., 1996, CA Cancer J. Clin., 46:528). Glioblastomas, astrocytomas an d meningiomas are the most common brain tumors that affect adults (Thapar and Laws, 1993, CA Cancer J. Clin., 43:263-271). Web site: http://www.delphion.com/details?pn=US05874290__ •

Porphyrins for boron neutron capture therapy Inventor(s): Gabel; Detlef (Bremen, DE), Miura; Michiko (Center Moriches, NY) Assignee(s): The United States of America as represented by the United States (Washington, DC) Patent Number: 4,959,356 Date filed: May 26, 1989 Abstract: Novel compounds for treatment of brain tumors in Boron Neutron Capture Therapy are disclosed. A method for preparing the compounds as well as pharmaceutical compositions containing said compounds are also disclosed. The compounds are water soluble, non-toxic and non-labile boronated porphyrins which show significant uptake and retention in tumors. Excerpt(s): Cancer continues to be one of the foremost health problems. Conventional treatments such as surgery, radiation therapy and chemotherapy have been extremely successful in certain cases; in other instances, much less so. A much less familiar, alternative form of cancer therapy known as Boron Neutron Capture Therapy (BNCT) is being investigated to treat certain tumors for which the conventional methods are to date ineffective. BNCT has been used clinically in Japan to treat Glioblastoma multiforme, a highly malignant, invasive form of brain cancer. In BNCT of malignant brain tumors, the patient is injected with a boron compound highly enriched in boron10. The boronated compound concentrates preferentially in the brain tumor, while the action of the blood-brain barrier prevents its entry into the healthy surrounding tissues. The patient's head is then irradiated with a beam of thermal neutrons that are captured by the boron concentrated in the tumor. The tumor is thus irradiated with high LET alpha and Li particles whose range in tissue is about 10.mu., or the diameter of an average cell. Therefore, a very localized, specific reaction takes place whereby the tumor receives a large radiation dose, compared to that received by the surrounding healthy tissue, from the transit of the thermal neutrons. (3) the boronated drug itself should not be toxic. The second criteria above can usually be satisfied if the boronated drug does not penetrate the normal blood brain barrier. Web site: http://www.delphion.com/details?pn=US04959356__

Patents 181

•

Replication-competent herpes simplex virus Inventor(s): Parysek; Linda Marie (Cincinnati, OH), Pyles; Richard Brent (Cincinnati, OH), Warnick; Ronald E. (Loveland, OH) Assignee(s): The University of Cincinnati (Cincinnati, OH) Patent Number: 6,509,020 Date filed: September 22, 1999 Abstract: A promising approach for the therapeutic treatment of brain tumors utilizes replication-competent, neuroattenuated herpes simplex virus-1 (HSV-1) mutants. This approach requires mutation of HSV-1 to eliminate killing of normal, non-dividing cells of the brain (e.g., neurons). The present invention discloses methods for killing malignant brain tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with defective expression of the gamma 34.5 gene and the uracil DNA glycosylase (UNG) gene, specifically destroys tumor cells, is hypersensitive to anti-viral agents, and is not neurovirulent. Excerpt(s): The present invention relates to recombinant virus strains capable of killing tumor cells. More specifically, the present invention relates to a mutated replicationcompetent viruses which contains mutations in two genes, is hypersensitive to antiviral agents such as ganciclovir, is not neurovirulent and does not replicate in non-dividing cells, yet can kill nervous system tumor cells. The present invention also relates to recombinant herpesvirus strains, vital vaccines incorporating such strains, methods for making such strains and vaccines, and methods for immunizing a human host against herpes simplex virus using the vaccines. Malignant tumors of the nervous system are generally fatal, despite many recent advances in neurosurgical techniques, chemotherapy and radiotherapy. In particular, there is no standard therapeutic modality that has substantially changed the prognosis for patients diagnosed with malignant brain tumors. For example, high mortality rates persist in malignant medulloblastomas, malignant meningiomas and neurofibrosarcomas, as well as in malignant gliomas. Gliomas are the most common primary tumors arising in the human brain. The most malignant glioma, the glioblastoma, represents 29% of all primary brain tumors, some 5,000 new cases per year in the United States alone. Glioblastomas are almost always fatal, with a median survival of less than a year and a 5-year survival of 5.5% or less. Mahaley et al., J. Neurosurg. 71: 826 (1989); Shapiro, et al., J. Neurosurg. 71: 1 (1989): Kim et al., J. Neurosurg. 74: 27 (1991). After glioblastomas are treated with radiotherapy, recurrent disease usually occurs locally; systemic metastases are rare. Hochberg et al., Neurology 30: 907 (1980). Neurologic dysfunction and death in an individual with glioblastoma is due to the local growth of the tumor. Web site: http://www.delphion.com/details?pn=US06509020__

•

Therapy by intrathecal administration of antitumor agent FUDR Inventor(s): Ikenaka; Kazuhiro (Okazaki, JP), Nakagawa; Hidemitsu (Sakai, JP), Yamada; Masanobu (Itami, JP) Assignee(s): Taiho Pharmaceutical Company, Limited (JP) Patent Number: 6,140,311 Date filed: January 27, 1997

182 Brain Tumors

Abstract: The invention relates to a novel method of treating malignant brain tumors and meningeal dissemination of malignant tumors by intrathecally giving FUDR, an antitumor agent, to produce an outstanding therapeutic effect selectively on the tumor cells with safety. Excerpt(s): The present invention relates to a method of treating malignant brain tumors and meningeal dissemination of malignant tumors more effectively with exceedingly higher safety than conventional therapies, using 5-fluoro-deoxyuridine (FUDR), an antitumor agent, which exhibits antitumor activity selectively on the cancer cells. The number of deaths from cancers is ever increasing in the U.S. year by year and-will presumably exceed 600,000 in 1996. About 24% of these deaths are-attributable to brain tumors and the metastases of various primary tumors to the brain. Since the metastasis entails hyper intracranial pressure and dysfunction of the brain, metastatic brain tumors are a major cause of the deaths from cancers (Rev. Neurol. (Paris) 148:477-487, 1992). Especially, approximately 5% of various solid cancers, such as lung cancer, breast cancer and colon cancer, are thought to develop into meningeal carcinomatosis when metastasizing to the brain. Cancer patients tend to develop this disease more frequently in recent years with increases in the survival time. Among other metastatic brain tumors, meningeal carcinomatosis in particular results from meningeal irritation due to tumors, impeded circulation of CSF due to obstruction of the CSF pathway, infiltration of tumors into the cerebrospinal parenchyma, and infiltration of tumors into the cranial nerves or spinal nerves extending through the subarachnoid cavity, therefore presenting a wide variety of seriously aggravated lethal symptoms including headaches, encephalopathies, dyskinesia and sensory disturbances. Web site: http://www.delphion.com/details?pn=US06140311__ •

Tumor demarcation using optical spectroscopy Inventor(s): Jansen; E. Duco (Nashville, TN), Lin; Wei-Chiang (Nashville, TN), Mahadevan-Jansen; Anita (Nashville, TN), Toms; Steven A. (Nashville, TN) Assignee(s): Vanderbilt University (Nashville, TN) Patent Number: 6,377,841 Date filed: April 7, 2000 Abstract: Optical spectroscopy for brain tumor demarcation was investigated in this study. Fluorescence and diffuse reflectance spectra were measured from normal and tumorous human brain tissues in vitro. A fluorescence peak was consistently observed around 460 nm (.+-.10 nm) emission from both normal and tumorous brain tissues using 337 nm excitation. Intensity of this fluorescence peak (F.sub.460) from normal brain tissues was greater than that from primary brain tumorous tissues. In addition, diffuse reflectance (Rd) between 650 nm and 800 nm from white matter was significantly stronger than that from primary and secondary brain tumors. A good separation between gray matter and brain tumors was found using the ratio of F.sub.460 and Rd at 400 nm-600 nm. Two empirical discrimination algorithms based on F (400 nm-600 nm), Rd (600 nm-800 nm), and F (400 nm-600 nm)/Rd (400 nm-600 nm) were developed. These algorithms yielded an average sensitivity and specificity of 96% and 93%, respectively. Excerpt(s): Cancer is a significant cause of illness-related deaths in the United States. It is estimated that approximately 17,000 malignant brain tumors are diagnosed in adults and 1,500 in children every year in the United States. Brain tumors are usually lethal.

Patents 183

Human brain tumors are typically classified as primary tumors and secondary tumors depending on their origin 1. Primary tumors originate in the brain and are classified according to the histological basis from which they are derived; for example, gliomas arise from glial tissue. Secondary tumors arise from metastatic primary cancers originating elsewhere in the body. The two chief sources of secondary brain tumors are lung cancer in the male and breast cancer in the female. The five year survival rate for primary brain tumors is only about thirty-five percent. The most common therapy given to such victims is surgical resection. The normal-tumor boundaries for different primary and secondary brain tumors vary from fingerlike protrusions of tumor cells into normal tissues in glioblastoma multiforme to well-circumscribed nodules with possible surrounding edema in most secondary tumors. The most common initial therapy for primary and secondary brain tumors is surgical resection. Web site: http://www.delphion.com/details?pn=US06377841__ •

Ultrasonic tissue resector for neurosurgery Inventor(s): Acosta; George M. (Long Beach, CA), Daw; Derek J. (Costa Mesa, CA) Assignee(s): Neuro Navigational Corp. (Costa Mesa, CA) Patent Number: 5,772,627 Date filed: July 19, 1996 Abstract: An ultrasonic tissue resector is slidably engaged with a working channel of a flexible neuroendoscope for resecting brain tumors, cysts, hematomas, and herniated spinal discs. The resector includes a piezoelectric transducer for generating ultrasonic energy. The ultrasonic energy is coupled to an ultrasonic probe having a rigid proximal segment for transmitting the energy therealong and a flexible distal segment which can bend to conform to the flexible neuroendoscope. An aspiration channel is provided, and the resector can be endoscopically positioned in the brain through the neuroendoscope and energized to ultrasonically break up tissue such as tumors, cysts, and hematomas and remove the tissue through the aspiration channel. Excerpt(s): The present invention relates generally to neurosurgery, and more particularly to methods and apparatus for removing diseased neurological tissue, such as spinal discs, using ultrasound. Brain tumors, cysts, and neural hematomas pose severe health risks to patients who are afflicted by them. Depending upon the particular circumstances, one treatment is to resect, i.e., to break up and remove, the tumor, cyst, or hematoma from the neurologic system of the patient. For purposes of the present invention, the neurologic system includes the brain and spinal cord. It will be appreciated that the resection of, e.g., a brain tumor, must be precisely accomplished, to avoid damaging healthy brain tissue nearby the tumor. Even slight damage to healthy brain tissue can have grave consequences for the patient. Likewise, it is sometimes necessary to remove a herniated spinal disc, and it is important not to damage healthy spinal cord tissue nearby the disc. Accordingly, the present invention recognizes the need to provide a tissue resector which can be precisely controlled and which advantageously can be used in less invasive neurosurgery, i.e., in conjunction with a neuroendoscope, to minimize the risk of damaging healthy brain or spinal tissue and to minimize patient trauma. Web site: http://www.delphion.com/details?pn=US05772627__

184 Brain Tumors

•

Ultrasound brain lesioning system Inventor(s): Fry; Francis J. (Indianapolis, IN), Sanghvi; Narendra T. (Indianapolis, IN) Assignee(s): Laboratory Equipment, Corp. (Mooresville, IN) Patent Number: 4,951,653 Date filed: March 2, 1988 Abstract: An ultrasound brain lesioning system with ultrasound, CT or MRI site localization includes a skull fixation apparatus, a position data translating fixture and a computer-controlled ultrasound transducer. The skull fixation apparatus is utilized in combination with ultrasound, CT or MRI scan transparencies and with a digitizing tablet in order to transfer transparency data both as to skull fixation benchmarks and tumor locations into a computer. The transducer is cooperatively arranged with the translating system such that the benchmarks of the skull fixation apparatus are utilized to derive X, Y and Z linear coordinates and two rotary coordinates which are at right angles to one another which are also input into the computer such that the computer is then capable of automatically driving the transducer and positioning it at the appropriate location for producing volume lesions in the brain at the site of the identified brain tumors or other selected tissues. Excerpt(s): The present invention relates in general to brain lesioning methods and apparata. More particularly, the present invention relates to a combination system for brain lesioning which initially uses a separate visualization system for site localization. The data from the visualization system is digitized and translated by computer into linear and rotary positioning means for positioning the ultrasound transducer which is used to create volume lesions. The separate visualization system may be a CT or MRI scan or may be ultrasonic imaging. The required output in the depicted configuration is a transparency of the imaged tumor or other volume to be lesioned which can then be translated into a computer by use of a digitizing tablet. Traditionally, the selected method for treatment of brain tumors and related disorders was to first take and process an X-ray film of the brain and from that film roughly determine the size, shape and location of the tumor. The next step was to surgically remove as much of the tumor as possible. As technology has advanced, X-ray usage has yielded to other visualization methods, such as ultrasound, CT scan techniques and MRI utilization. The surgical procedures have expanded to cryoknives and gamma knives. Radon seeds have been implanted and ionizing radiation used. Each of these approaches has met with some success but not without their share of adverse side effects, including incomplete treatment. Any cutting procedure is risky, especially in the area of the brain, in that the procedure may result in the incomplete removal of the tumor tissue, the excess removal of healthy tissue, or both. Ionizing radiation creates a cumulative effect of the dosage to the other, surrounding brain tissue. These concerns and their attendant problems are addressed and solved by the use of ultrasound to produce volume lesions in the brain. As is well known, the noninvasive nature of ultrasound provides a safe and convenient means of treatment by selection of a suitable dosage to produce volume lesions. Web site: http://www.delphion.com/details?pn=US04951653__

Patents 185

•

Use of boswellic acid for treating brain tumors Inventor(s): Ammon; Hermann P. T. (Tubingen, DE), Simmet; Thomas (Hustradtring 63, D-44801 Bochum, DE) Assignee(s): Simmet; Thomas (Bochum, DE) Patent Number: 5,919,821 Date filed: June 10, 1997 Abstract: The present invention relates to the use of pure boswellic acid, a physiologically acceptable salt, a derivative, a salt of said derivative or a vegetable preparation containing boswellic acid for the preparation of a pharmaceutical composition for the treatment of brain tumours. Excerpt(s): The present invention relates to the use of pure boswellic acid, a physiologically acceptable salt, a derivative, a salt of said derivative or a vegetable preparation containing boswellic acid for the production of a pharmaceutical composition for the treatment of brain tumours. The present invention also relates to the use of pure boswellic acid, a physiologically acceptable salt, a derivative, a salt of said derivative or a vegetable preparation containing boswellic acid for the treatment of brain tumours. So far, the possibilities for a treatment of malignant brain tumours are insufficient. Neurosurgical removal of the brain tumours represents severe surgery and, depending on type, size and position of the brain tumours, in many cases does not lead to the complete removal of the malignant tumours. For these reasons, the average survival of the patients suffering from malignant brain tumours is only about 9 months even after a combined treatment including surgery and radiotherapy. An additional chemotherapy using the cytostatics known so far is able to achieve a prolongation of the survival of only about 10% (Lesser, G. J., Grossman S., The chemotherapy of high-grade astrocytomas, Seminars in Oncology, 1994, 21:220-235). Web site: http://www.delphion.com/details?pn=US05919821__

•

Use of phenylglycine derivatives to decrease neuronal death caused by brain tumors and brain lesions Inventor(s): Sontheimer; Harald J. (Birmingham, AL), Ye; Zu-Cheng (Birmingham, AL) Assignee(s): UAB Research Foundation (Birmingham, AL) Patent Number: 6,197,820 Date filed: April 16, 1999 Abstract: The present invention describes impaired glutamate uptake in glioma cells, and further shows that instead of removing glutamate from the extracellular fluid, glioma cells release large amounts of glutamate. The high levels of extracellular glutamate result in elevated [Ca.sup.2+ ].sub.i followed by widespread neuronal death, which could be prevented by treating neurons with the NMDA receptor antagonists, MK-801 or D-AP5, or by depletion of glutamate from the medium. Significantly, several phenylglycine derivatives, including the metabotropic glutamate receptor agonist/antagonist (S)-4-carboxyphenylglycine (S-4CPG), potently and selectively inhibited glutamate release from glioma cells and thereby prevented neurotoxicity. Excerpt(s): The present invention relates generally to the field of neurobiology. More specifically, the present invention relates to compounds, specifically phenylglycine derivatives, that inhibit the release of toxic levels of glutamate from brain tumor cells. L-

186 Brain Tumors

glutamate is an important nutritional amino acid involved in a number of biochemical pathways. Glutamate is also the main excitatory amino acid transmitter in the mammalian central nervous system. Extracellular glutamate concentrations are normally maintained at low micromolar levels to assure proper synaptic function and to prevent excitotoxic injury of neurons (1,2). This is accomplished through the activity of several Na.sup.+ -dependent glutamate transporters expressed by neurons and astrocytes. Of the 5 glutamate transporter subtypes cloned (3-7), two, namely GLAST and GLT-1, appear to be predominantly located on glial cells (8,9). It is believed that astrocytes, which comprise a large portion of the total cell population in the mammalian nervous system, are particularly important in maintaining glutamate homeostasis (1013), since their processes closely encapsulate synapses and they are invulnerable to glutamate challenge. Like neurons, astrocytes maintain a large transmembrane glutamate gradient, with intracellular glutamate concentrations of 2-10 mM (14-16), while the [Glu].sub.o is approximately 1.mu.M (2,17). Since astrocytic glutamate transport is electrogenic and uses the transmembrane electrochemical gradient for Na.sup.+, K.sup.+ and H.sup.+ (18,19), severe disruption of these gradients, or membrane depolarization under conditions of energy failure (ischemia, hypoglycemia), can lead to glutamate release from astrocytes by reversal of glutamate transport (20-22). Web site: http://www.delphion.com/details?pn=US06197820__ •

Use of phosphoprotein patterns for diagnosis of neurological and psychiatric disorders Inventor(s): Gandy; Samuel E. (New York, NY), Greengard; Paul (New York, NY) Assignee(s): The Rockefeller University (New York, NY) Patent Number: 4,874,694 Date filed: April 7, 1987 Abstract: A diagnostic method for neurological and psychiatric disorders utilizes the cerebrospinal fluid incubated in the presence of 32-P labelled ATP and an appropriate protein kinase. After termination of the reaction, a sample is applied to gels for electrophoresis. Subsequent autoradiography results in a disease-specific protein pattern that can be used for diagnosis of disorders such as Alzheimer disease, Huntington disease, Parkinson disease, dystonia ataxia, schizophrenia, epilepsy brain tumors, brain irradiation, head trauma, and acute and chronic encephalitic and vascular disease. Excerpt(s): The present invention relates to medical diagnostic techniques, and particularly to methods for identifying certain neurological and psychiatric disorders. The presence of a great variety of neuron-specific phosphoproteins in nervous tissue supports the view that protein phosphorylation plays many roles in neuronal function. Protein phosphorylation is an important mechanism in neuronal signal transduction. Triggering mechanisms for activation of protein phosphorylation include many established second messengers (cAMP, cGMP, calcium) which are generated by interaction of neurotransmitters with their receptors. The second messengers, in turn, activate protein kinases (protein-phosphorylating enzymes) which transfer phosphate from adenosine triphosphate (ATP) to substrate proteins. These substrate proteins go on to mediate many of the physiological effects attributed to the transmitter-receptor interaction. The protein composition of cerebrospinal fluid is largely derived from serum proteins which leak into the subarachnoid space through imperfections in the blood brain barrier,such as the area postrema, and perhaps across the choroid plexus, the richly vascular structure through which cerebrospinal fluid is generated as an

Patents 187

ultrafiltrate. Some proteins, such as immunoglobulins, may be generated in the subarachnoid space during inflammation. Since the cerebrospinal fluid bathes the surfaces of cerebral and cerebeller cortices, the caudate, brainstem and spinal cord, some contribution of these structures to total cerebrospinal fluid protein might be expected. Indeed, peptide neurotransmitters have been identified in cerebrospinal fluid and are presumably neuron-derived though a serum source has not been excluded. Otherwise, however, cerebrospinal protein chemistry has been notoriously unyielding of neuronspecific information. Web site: http://www.delphion.com/details?pn=US04874694__

Patent Applications on Brain Tumors As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to brain tumors: •

Administration of a thiol-based chemoprotectant compound Inventor(s): Muldoon, Leslie; (Tigard, OR), Neuwelt, Edward A.; (Portland, OR), Pagel, Michael A.; (Milwaukie, OR) Correspondence: Davis Wright Tremaine; Suite 2600; 1501 4th Avenue; Seattle; WA; 98101-1688; US Patent Application Number: 20030176359 Date filed: May 16, 2003 Abstract: A method of administration of a thiol-based chemoprotectant agent including NAC (N-acetylcysteine) and STS (sodium thiosulfate) that markedly affects biodistribution and protects against injury from diagnostic or therapeutic intra-arterial procedures. A method for treating or mitigating the side effects of cytotoxic cancer therapy for tumors located in the head or neck and brain tumors. The thiol-based chemoprotectant agent is administered intra-arterially with rapid and first pass uptake in organs and tissues other than the liver. Excerpt(s): The present application claims the benefit of the filing dates under 35 U.S.C.sctn.119(e) to provisional U.S. Patent Application Serial No. 60/199,936 filed on Apr. 26, 2000 and Provisional U.S. Serial No. 60/229,870 filed on Aug. 30, 2000, which are hereby incorporated by reference. The present invention is based, in part, upon the discovery that a method of administration of N-acetylcysteine (NAC) markedly affects its effective biodistribution. The present invention provides a method for treating or mitigating the side effects, including organ damage, of cytotoxic cancer therapy for tumors located in the head or neck. Additionally, NAC or other thiols can be administered concurrently with, before or after, intra-arterial procedures and provides protective affects to prevent or diminish organ damage. N-acetylcysteine (NAC) is an analog of cysteine. When NAC is administered to a mammal it is deacylated and enters a cellular synthetic pathway for the production of glutathione. Glutathione is involved in the cellular pathways influencing a tumor's resistivity to cytotoxic drugs. The cytotoxic properties of chemotherapeutic drugs can be enhanced by pretreatment with

10

This has been a common practice outside the United States prior to December 2000.

188 Brain Tumors

buthionine sulfoximine (BSO) thereby reducing intracellular glutathione. However, reduction of intracellular gluthionine will potentiate systemic toxicities associated with chemotherapeutic drugs. Thus, this procedure is dose-limiting. For protection, the glutathione levels of "normal" cells have to be reestablished if BSO is used to potentiate the cytotoxic properties of cytotoxic cancer therapies (Kamer et al., Cancer Res. 47:15931597, 1987; Ozols et al., Biochem. Pharm. 36:147-153, 1987; McLellan et al., Carcinogenesis 17:2099-2106, 1995; and Shattuck et al., J. Parenteral Enteral Nutrition 24:228-233, 1998). It may be possible to reduce the bone marrow toxicity of chemotherapeutic drugs by using sulfur-containing chemoprotective agents (thio, thiol, and thioether compounds) to mimic one or many of the activities of glutathione such as conjugation, free radical scavenging, and drug efflux via the multidrug resistance associated proteins. NAC and other thiol agents such as STS have early detoxifying activity not related to the later increase in glutathione levels. These early detoxifying effects occur because the thiols themselves mimic some actions of glutathione such as free radical scavenging, anti-oxidant activity, chemical conjugation, and activation of efflux pumps. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Bisarylamines as potassium channel openers Inventor(s): Andrew McNaughton-Smith, Grant; (Morrisville, NC), Salvatore Amato, George; (Cary, NC) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020193597 Date filed: March 11, 2002 Abstract: Compounds, compositions and methods are provided which are useful in the treatment of diseases through the modulation of potassium ion flux through voltagedependent potassium channels. More particularly, the invention provides bisarylamines, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders (e.g., migraine, ataxia, Parkinson's disease, bipolar disorders, trigeminal neuralgia, spasticity, mood disorders, brain tumors, psychotic disorders, myokymia, seizures, epilepsy, hearing and vision loss, Alzheimer's disease, age-related memory loss, learning deficiencies, anxiety and motor neuron diseases) and as neuroprotective agents (e.g., to prevent stroke and the like) by opening potassium channels associated with the onset or recurrence of the indicated conditions. Excerpt(s): The present application claims priority to U.S. Provisional Patent Application Serial No. 60/277,329, filed on Mar. 19, 2001, the disclosure of which is incorporated herein by reference in its entirety for all purposes. This invention relates to the use of certain bisarylamines as potassium channel openers and to the treatment of diseases modulated by potassium channel opening. Additionally, this invention relates to novel compounds that are useful as potassium channel openers. Ion channels are cellular proteins that regulate the flow of ions, including calcium, potassium, sodium and chloride, into and out of cells. These channels are present in all human cells and affect such processes as nerve transmission, muscle contraction and cellular secretion. Among the ion channels, potassium channels are the most ubiquitous and diverse, being found in a variety of animal cells such as nervous, muscular, glandular, immune, reproductive, and epithelial tissue. These channels allow the flow of potassium in and/or out of the cell under certain conditions. For example, the outward flow of potassium ions upon

Patents 189

opening of these channels makes the interior of the cell more negative, counteracting depolarizing voltages applied to the cell. These channels are regulated, e.g., by calcium sensitivity, voltage-gating, second messengers, extracellular ligands, and ATPsensitivity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Brain tumor diagnosis and outcome prediction Inventor(s): Golub, Todd R.; (Newton, MA), Lander, Eric S.; (Cambridge, MA), Pomeroy, Scott; (Newton, MA), Tamayo, Pablo; (Cambridge, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20020155480 Date filed: January 31, 2002 Abstract: Methods for predicting phenotypic classes of brain tumors, such as brain tumor type or treatment outcome, for brain tumor samples based on gene expression profiles are described. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/265,482, filed on Jan. 31, 2001. The entire teachings of the above application are incorporated herein by reference. Classification of biological samples from individuals is not an exact science. In many instances, accurate diagnoses and safe and effective treatment of a disorder depend on being able to discern biological distinctions among morphologically similar samples, such as tumor samples. The classification of a sample from an individual into particular disease classes has often proven to be difficult, incorrect or equivocal. Typically, using traditional methods such as histochemical analyses, immunophenotyping and cytogenetic analyses, only one or two characteristics of the sample are analyzed to determine the sample's classification, resulting in inconsistent and sometimes inaccurate results. Such results can lead to incorrect diagnoses and potentially ineffective or harmful treatment. Furthermore, important biological distinctions are likely to exist that have yet to be identified due to the lack of systematic and unbiased approaches for identifying or recognizing such classes. Thus, a need exists for an accurate and efficient method for identifying biological classes and classifying samples. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Characterizing a brain tumor Inventor(s): Debinski, Waldemar; (Hershey, PA) Correspondence: Stanley A. Kim; Akerman, Senterfitt & Eidson, P.A.; 222 Lakeview Avenue, Suite 400; P.O. Box 3188; West Palm Beach; FL; 33402-3188; US Patent Application Number: 20020031492 Date filed: June 28, 2001 Abstract: A brain tumor is classified by type or grade includes the steps by quantifying the expression of an IL-13 receptor in a sample of the tumor.

190 Brain Tumors

Excerpt(s): The invention relates generally to the fields of pathology, medicine, and neurooncology. More particularly, the invention relates to the use of interleukin-13 (IL13) binding as a marker for diagnosing the type and/or grade of a brain tumor, and for assessing the prognosis of a patient having a brain tumor. The identification of tumorassociated cellular markers has proven useful for diagnosing various tumors and assessing the prognosis of patients with tumors. Cellular markers that occur on the plasma membrane or in a membrane receptor are particularly useful. Antibodies specific for tumor cell markers or ligands that bind specifically to a tumor cell receptor have been successfully used in diagnostics, including both the characterization of excised tissue samples and in vivo imaging. Numerous different brain tumors are known. For example, several types of brain tumors known as gliomas originate from glial tissue. Within this set of tumors are astrocytomas, brain stem gliomas, ependymomas, and oligodendogliomas. Astrocytomas originate from star-shaped cells termed astrocytes; brain stem gliomas originate in the brain stem; ependymomas originate in the lining of the ventricles or spinal cord; and oligodendrogliomas arise from myelin-producing cells. Brain tumors may also be of non-glial origin. Such non-glial tumors include medulloblastomas, meningiomas, Schwannomas, craniopharyngiomas, germ cell tumors, pineal region tumors, and secondary brain tumors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

CRYSTAL FORM OF N-(4-TRIFLUOROMETHYLPHENYL)-5METHYLISOXAZOLE-4-CARBOXAMID- E Inventor(s): Faasch, Holger; (Hochheim, DE), Hedtmann, Udo; (Frankfurt, DE), Paulus, Erich; (Eppstein, DE), Westenfelder, Uwe; (Frankfurt, DE) Correspondence: Finnegan, Henderson, Farabow, Garrett &; Dunner Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030027851 Date filed: January 19, 2001 Abstract: The invention relates to a crystal modification of the compound of the formula I 1and the processes for the preparation of and use that crystal modifications 1.The invention is used for treating acute immunological episodes, such as sepsis, allergies, graft-versus-host and host-versus-graft-reactions, autoimmune diseases, in particular rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, atopic dermatitis, asthma, urticaria, rhinitis, uveitis, type II diabetes, liver fibrosis, cystic fibrosis, colitis, cancers, such as lung cancer, leukemia, ovarian cancer, sarcomas, Kaposi's sarcoma, meningioma, intestinal cancer, lymphatic cancer, brain tumors, breast cancer, pancreatic cancer, prostate cancer, or skin cancer. Excerpt(s): This case claims benefit under 35 U.S.C.sctn.119 of German priority document 19734438.0 filed on Aug. 8, 1997. This document, as well as German priority document 19756093.8, filed Dec. 17, 1997, are hereby incorporated by reference. The compound of formula I crystallizes in the first crystal modification in the space group P2.sub.1/c with 8 molecules in the unit cell. Molecules of the compound of formula I are present as dimers which originate from the individual molecules by formation of a -C.dbd.O. HN hydrogen bridge bond (2.938.ANG.), the two molecular levels being virtually perpendicular to one another (91.2.degree.). The two molecules have very different conformations. The angles made by the five- and six-membered rings with the central carbonyl group are 5.4.degree. and 2.1.degree. and 23.4.degree. and 23.1.degree., respectively. The latter twist creates the steric preconditions permitting the hydrogen

Patents 191

bridge bond between the two molecules. Lines of strong intensity: 16.70; 18.90; 23.00; 23.65; and 29.05 degrees. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Engraftable neural progenitor & stem cells for brain tumor therapy Inventor(s): Aboody, Karen; (Needham, MA), Breakefield, Xandra O.; (Newton, MA), Lynch, William P.; (Ravenna, OH), Snyder, Evan Y.; (Jamaica Plain, MA) Correspondence: Nixon Peabody Llp; 101 Federal Street; Boston; MA; 02110; US Patent Application Number: 20020115213 Date filed: August 23, 2001 Abstract: One of the impediments to the treatment of some human brain tumors (e.g. gliomas) has been the degree to which they expand, migrate widely, and infiltrate normal tissue. We demonstrate that a clone of multipotent neural progenitor stem cells, when implanted into an experimental glioma, will migrate along with and distribute themselves throughout the tumor in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to express a foreign reporter gene. Furthermore, drawn somewhat by the degenerative environment created just beyond the infiltrating tumor edge, the neural progenitor cells migrate slightly beyond and surround the invading tumor border. When implanted at a distant sight from the tumor bed (e.g., into normal tissue, into the contralateral hemisphere, into the lateral ventricles) the donor neural progenitor/stem cells will migrate through normal tissue and specifically target the tumor cells. These results suggest the adjunctive use of neural progenitor/stem cells as a novel, effective delivery vehicle for helping to target therapeutic genes and vectors to invasive brain tumors that have been refractory to treatment. Excerpt(s): This application is a continuation-in-part of pending U.S. Ser. No. 09/133,873, filed on Aug. 14, 1998, which is incorporated herein by reference. This invention is in the field of gene therapy, more particularly the field of using neuronal cells to treat brain tumors. An effective gene therapy for the treatment of brain tumors has been an elusive goal for many years. Glioblastoma multiforma, which is virtually untreatable, and the less malignant anaplastic astrocytoma account for about onequarter of the 5,000 intracranial gliomas diagnosed yearly in the United States; 75 percent of gliomas in adults are of this category. Because of its profound and uniform morbidity, it contributes more to the cost of cancer on a per capita basis than does any other tumor. The patient, commonly stricken in (lie Fifth decade of life, enters a cycle of repetitive hospitalizations and operations while experiencing the progressive complications associated with relatively ineffective treatments of radiation and chemotherapy ("Harrison's Principles of Internal Medicine," edited by Isselbacher, Braunwald, Wilson, Martin, Fauci and Kasper, 13.sup.th Edition, p.2262, McGraw-Hill, Inc. 1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

192 Brain Tumors

•

Herpes simplex virus type 1 ( HSV-1)-derived vector for selectively inhibiting maligant cells and methods for its use to treat cancer and to express desired traits in maligant and non-miligant mammalian cells Inventor(s): Black, Keith L.; (Los Angeles, CA), Nesburn, Anthony B.; (Malibu, CA), Perng, Guey-Chuen; (Alhambra, CA), Wechsler, Steven L.; (Westlake Village, CA), Yu, John S.; (Los Angeles, CA) Correspondence: Sidley Austin Brown & Wood; 555 West Fifth Street; Los Angeles; CA; 90013-1010; US Patent Application Number: 20020098170 Date filed: November 29, 2001 Abstract: Disclosed is a method of selectively inhibiting the growth of malignant cells in mammals, including humans. The method selectively inhibits the growth of malignant cells of all varieties, and is particularly useful in treating brain tumors and other malignancies of the central nervous system. The method employs HSV-1-derived vectors containing a DNA having a deletion in both copies of the LAT gene and both copies of the ICP34.5 gene of HSV-1. The vectors are delivered to malignant cells either in vivo or in vitro, in accordance with the method. The HSV-1-derived expression vectors are non-neurovirulent and do not spontaneously reactivate from latency, and they optionally contain a functional HSV thymidine kinase gene, which can enhance the effectiveness against cancer of drug treatment with gancyclovir or acyclovir. Alternatively, the HSV-1-derived vectors contain at least one transcriptional unit of a LAT promoter sequence operatively linked to a nucleic acid having a nucleotide sequence encoding a polypeptide toxic for cells expressing the vector, for example, human interferon-.gamma. A method of expressing in a mammalian cell a gene encoding a preselected protein, a method of treating a genetic defect, and a method of detecting an HSV-1 expressing cell also employ vectors of the present invention that contain at least one transcriptional unit of a constitutive LAT promoter operatively linked to and controlling the transcription of a gene encoding a preselected protein. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, useful for practicing the methods, and mammalian cells containing the HSV-derived vectors. Excerpt(s): Throughout this application various publications are referenced within parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. The present invention is related to the medical arts, particularly to the field of gene therapy. Several animal models and animal types of malignant tumor have been used to study oncolysis with wild-type viruses. (Moore, Ann. Rev. Microbiol. 8: 393 [1954]; Moore, Progr. Exp. Tumor Res. 1: 411 [1960]). At least nine viruses have been shown to be capable of inducing some degree of tumor regression of a variety of tumors in animals. A major drawback found in these early studies, however, was systemic infection of the patient by the virus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 193

•

Method for convection enhanced delivery catheter to treat brain and other tumors Inventor(s): Petersen, Daryle Lee; (Eagan, MN) Correspondence: Banner & Witcoff, LTD.; Ten South Wacker Drive; Suite 3000; Chicago; IL; 60606; US Patent Application Number: 20030045866 Date filed: August 30, 2001 Abstract: A method is provided for delivering a therapeutic agent to selected sites within an organism. More particularly, the invention allows for the simultaneous delivery of therapeutics to multiple treatment locations from a single catheter using a single pumping source. The catheter utilizes a microporous membrane that allows for the distribution of therapeutic agents from multiple longitudinal positions. Excerpt(s): The present invention relates generally to improvements in catheter design to administer therapeutic agents to organisms. More particularly, this invention allows for the distribution of therapeutic agents from one or more catheters to selected areas using a single pumping device. Catheters have been used for many years to deliver therapeutic agents to patients. In many instances, catheters are implanted in patients that have been diagnosed with diseases that require long-term therapeutic treatment. Diseases that may require catheter implantation include Alzheimer's, Huntington's, epilepsy, neuro-degenerative disorders, and brain tumors. When treating these types of diseases a need arises to deliver therapeutic drugs to multiple locations simultaneously. For example, the difficulty with treating brain tumors is effectively delivering the therapeutic agent to the tumor and the surrounding tissue that is not located near or in the tumor bed. In the case of a patient with a primary brain tumor such as glioblastoma, the tumor and surrounding tissue that may have been infiltrated by cancer cells should be treated. If these outlying tissues are not treated, the tumor may return. Current technology would require the use of multiple separate catheters and pumps to ensure the equal delivery of therapeutics to the tumor and the outlying tissues. The reduction in the number of catheters and the use of a single pump would make a significant improvement over the current treatment practice. Additionally, in some cases it is optimal to deliver a therapeutic agent through multiple holes rather than through a single hole. Delivery in this manner would promote diffusion of a therapeutic. U.S. Pat. No. 5,720,720 describes convention-enhanced delivery into a brain and other tissue structures using a catheter with a plurality of slit opening symmetrically spaced around the circumference of the catheter. These slit opening function as valves because the slits remain closed until fluid pressure within the catheter forces the slit valves open. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

METHODS FOR TREATING VASCULAR DEMENTIA Inventor(s): Pratt, Raymond; (Leonia, NJ) Correspondence: Edward D. Grieff, ESQ.; Hale And Dorr Llp; 1455 Pennsylvania Avenue, NW; Washington; DC; 20004; US Patent Application Number: 20020040038 Date filed: September 4, 2001 Abstract: The invention describes novel methods for treating and preventing dementia caused by vascular diseases; dementia associated with Parkinson's disease; Lewy Body

194 Brain Tumors

dementia; AIDS dementia; mild cognitive impairments; age-associated memory impairments; cognitive impairments and/or dementia associated with neurologic and/or psychiatric conditions, including epilepsy, brain tumors, brain lesions, multiple sclerosis, Down's syndrome, Rett's syndrome, progressive supranuclear palsy, frontal lobe syndrome, and schizophrenia and related psychiatric disorders; cognitive impairments caused by traumatic brain injury, post coronary artery by-pass graft surgery, electroconvulsive shock therapy, and chemotherapy, administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for treating and preventing delirium, Tourette's syndrome, myasthenia gravis, attention deficit hyperactivity disorder, autism, dyslexia, mania, depression, apathy, and myopathy associated with diabetes by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for delaying the onset of Alzheimer's disease, for enhancing cognitive functions, for treating and preventing sleep apnea, for alleviating tobacco withdrawal syndrome, and for treating the dysfunctions of Huntington's Disease by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. A preferred cholinesterase inhibitor for use in the methods of the invention is donepezil hydrochloride or ARICEPT.RTM. Excerpt(s): This application claims priority to PCT Application No. PCT/US01/07027 filed Mar. 5, 2001, which claims priority to U.S. Provisional Application No. 60/259,226 filed Jan. 3, 2001, U.S. Provisional Application No. 60/220,783 filed Jul. 25, 2000, U.S. Provisional Application No. 60/197,610 filed Apr. 18, 2000, and U.S. Provisional Application No. 60/186,744 filed Mar. 3, 2000. Novel cholinesterase inhibitors are described in U.S. Pat. No. 4,895,841 and WO 98/39000, the disclosures of which are incorporated by reference herein in their entirety. The cholinesterase inhibitors described in U.S. Pat. No. 4,895,841 include donepezil hydrochloride or ARICEPT.RTM., which has proven to be a highly successful drug for the treatment of Alzheimer's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of protecting vasculature from damage by pseudomonas toxin-based immunotoxins during therapy

diphtheria

toxin-and

Inventor(s): Hagihara, Naoshi; (Saga, JP), Youle, Richard J.; (Chevy Chase, MD) Correspondence: Townsend And Townsend And Crew; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020016335 Date filed: June 19, 2001 Abstract: Vascular damage has proven to be dose limiting in administering immunotoxins into the brain to treat brain tumors. Vascular toxicity of immunotoxins which rely in part on exposure to lowered pH in cellular endosomes and lysosomes can be avoided by administering an endosome pH-raising agent systemically during some or all of the time that the immunotoxin is present in the brain of the organism. Suitable endosome pH-raising agents include lysosomotrophic amines, proton ionophores, and vacuolar H+ATPase inhibitors. The invention increases the therapeutic window of the immunotoxins and increases the likelihood the treatment will have an effect on the course of the tumor.

Patents 195

Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60/212,909, filed Jun. 20, 2000, the contents of which are incorporated by reference for all purposes. Not applicable. The prognosis of patients with malignant brain tumors is poor. Standard therapy, including surgery, radiation, and chemotherapy has proven ineffective in the majority of cases. One attempt to improve this grim clinical outlook has resulted from the discovery that many brain tumors over express the transferrin ("Tf") receptor ("Tf-R"). A Tf-targeted immunotoxin known as Tf-CRM107 (Johnson, V. G. et al., J. Biol Chem., 263:1295-1300 (1988)), a conjugate of transferrin ("Tf") and a mutant diphtheria toxin ("DT") lacking receptor-binding function (Greenfield, L. et al., Science, 238:536-539 (1987), can target and kill cells expressing Tf-R, such as tumor cells The potential of Tf-CRM107 for brain tumor therapy has been explored in vitro (Johnson, V. G. et al., J. Biol Chem., 263:1295-1300 (1988), in animal models (Laske, D. W. et al., J. Neurosurg., 80:520-526 (1994)), and in patients with malignant gliomas (Laske, D. W. et al., Nat. Med., 3:1362-1368 (1997) (hereafter, "Laske 1997"). When delivered by high-flow (4-10.mu.l/min) interstitial microinfusion convection-enhanced delivery ("CED") (Bobo, R. H. et al., Proc. Natl. Acad. Sci. USA, 91:2076-2080 (1994)), intratumoral infusion of Tf-CRM107 in patients with malignant brain tumors produces tumor responses (Laske 1997). When CED is used, Tf-CRM107 (140 kDa) is distributed preferentially into the interstitial space of the tumor and the surrounding brain infiltrated by tumor and circumvents the blood-brain barrier ("BBB"). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Quinazolines for treating brain tumor Inventor(s): Liu, Xing-Ping; (Minneapolis, MN), Narla, Rama Krishna; (St. Paul, MN), Uckun, Fatih M.; (White Bear Lake, MN) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20020161226 Date filed: July 11, 2001 Abstract: Novel substituted quinozaline compounds and conjugates useful to inhibit the growth of brain tumor cells and to inhibit adhesion and migration of brain tumor cells. The compounds of the invention include 4-(3'-bromo-4'-hydroxy phenyl)-amino-6,7dimethoxyquinazoline and this compound covalently bound to EGF. Excerpt(s): This invention relates to novel quinazoline derivatives effective to induce apoptosis of brain tumor cells. In particular, the invention includes novel hydroxy quinazoline derivatives having potent cytotoxicity against human brain tumor cells, including glioblastoma. The novel compounds of the invention further inhibit adhesion of brain tumor cells to extracellular matrix proteins and inhibit migration of brain tumor cells through the extracellular matrix, activities required for tumor metastases. As the most malignant primary central nervous systems tumors, high grade anaplastic astrocytoma and glioblastoma multiforme respond poorly to contemporary multimodality treatment programs employing surgical resection, radiation therapy and chemotherapy with a median survival of less than one year after initial diagnosis (Pardos, et al., 1997, Cancer Medicine, 1:1471-1514; Brandes, et al., 1996, Cancer Invest. 14:551-559; Finlay, J. L., 1992, Pediatric Neuro-Oncology, 278-297; Pardos, et al., 1998, Sem. Surgical Oncol., 14:88-95). Consequently, the development of effective new agents and novel treatment modalities against these very poor prognosis brain tumors remains a major focal point in translational oncology research. Glioblastoma multiforme is also a

196 Brain Tumors

highly invasive primary brain tumor with a disappointingly high local recurrence rate and mortality. New agents capable of inhibiting the infiltration of normal brain parenchyma by glioblastoma cells are urgently needed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Reshaped human antibody to human medulloblastoma cells Inventor(s): Ohtomo, Toshihiko; (Gotenba-shi, JP), Sato, Koh; (Gotenba-shi, JP), Tsuchiya, Masayuki; (Gotenba-shi, JP) Correspondence: Harold C. Wegner; Foley & Lardner; Washington Harbour; 3000 K Street, N.W., Suite 500; Washington; DC; 20007-5109; US Patent Application Number: 20030023045 Date filed: December 29, 2000 Abstract: The present invention discloses reshaped antibody to human medulloblastoma cells comprising:(A) an L chair comprising:(1) a human L chain C region, and(2) an L chain V region comprising human L chain FRs and L chain CDRs of mouse monoclonal antibody ONS-M21 to human medulloblastoma cells; and,(B) an H chain containing:(1) a human H chain C region, and(2) an H chain V region comprising human H chain FRs and H chain CDRs of mouse monoclonal antibody ONS-M21 to human medulloblastoma cells.Since the majority of this reshaped human antibody is derived from a human antibody and mouse CDRs have a low level of antigenicity, the reshaped human antibody of the present invention has a low level of antigenicity in humans, and is therefore expected to be useful as a therapeutic agent and diagnostic tool for brain tumors such as medulloblastoma which strongly express antigen that is recognized by this antibody. Excerpt(s): The present invention relates to a human/mouse chimeric antibody comprising variable regions (V regions) of a mouse monoclonal antibody ONS-M21 to human medulloblastoma cells and constant regions (C regions) of human antibody; a reshaped human antibody wherein the complementarity determining regions (CDRs) of human light chain (L chain) V region and hen heavy chain (H chain) V region, are substituted by the CDRs of mouse monoclonal antibody ONS-M21 to human medulloblastoma cells; and the L chain or H chain that composes that antibody. Moreover, the present invention provides a DNA coding for the above-mentioned antibody, and particularly its V region. Moreover, the present invention relates to a vector containing the above-mentioned DNA, and particularly to an Expression vector, along with a host transformed with said vector. Moreover, the present invention provides a process for producing chimeric antibody to human medulloblastoma cells as well as a process for producing a reshaped human antibody to human medulloblastoma cells. In addition, the present invention relates to a single chain Fv composed by linking an H chain V region of a reshaped human antibody to human medulloblastoma cells and an L chain V region of said antibody. In addition, the present invention relates to a process for producing the above-mentioned single chain Fv by using DNA coding for said-single chain Fv, a recombinant vector comprising said DNA, and a host transformed with said recombinant vector. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 197

•

Transgenic animals for screening therapeutic agents for brain tumors Inventor(s): Chiu, Ing-Ming; (Dublin, OH) Correspondence: Calfee Halter & Griswold, Llp; 800 Superior Avenue; Suite 1400; Cleveland; OH; 44114; US Patent Application Number: 20020104114 Date filed: November 21, 2001 Abstract: A transgenic, non-human mammal useful for assessing the effect of candidate chemotherapeutic drugs on the growth of brain tumors in vivo is provided. Incorporated into the genome of the transgenic mammal, which preferably is a rodent, is a transgene which comprises a promoter comprising the nuclear factor binding region of the RR2 cis acting element of a fibroblast growth factor 1B (FGF1B) promoter. Operably linked to the promoter is reporter gene comprising a sequence which encodes the SV40 large T antigen. A transgenic, non-human mammal useful for identifying and isolating FGF1 producing brain cells. Incorporated into the genome of these transgenic animals is a transgene which comprises a promoter comprising the nuclear factor binding region of the RR2 cis acting element of an fibroblast growth factor 1B (FGF1B) promoter. Operably linked to the promoter is reporter gene comprising a sequence which encodes a protein or polypeptide other than an SV40 large T antigen. A method of obtaining neural stem cells from a sample of cells obtained from an animal is also provided. Such method comprises introducing the FGF1B-detector transgene into a sample of cells that have been obtained from the animal, and assaying for expression of the detectable marker in the cells, wherein cells that express the marker are neural stem cells. The cells which express the detectable marker can then be isolated from the population to provide a subpopulation of neural stem cells. Excerpt(s): This application claim priority to U.S. Provisional Application No. 60/252,745 filed Nov. 22, 2000. Animal model systems are useful tools for identifying and characterizing therapeutic agents. Examples of such model systems are transgenic animal models with brain tumors. Currently, there are several transgenic animal models that recapitulate key features of human primitive neuroectodermal tumors (PNET) (Fung, K. M., and Trojanowski, J. Q., (1995) Animal models of medulloblastomas and related primitive neuroectodermal tumors. A review. J. Neuropathol. Exp. Neurol. 54, 285-296). Members of each of these transgenic animal lines develop PNETs arising in different, yet distinct, brain regions. However, the animals in these four transgenic lines also have some features in common, namely the expression of the neuronal cell marker synaptophysin (Fung, K. M., Chikaraishi, D. M., Suri, C., Theuring, F., Messing, A., Albert, D. M., Lee, V. M., Trojanowski, J. Q. (1994). Molecular phenotype of simian virus 40 large T antigen-induced primitive neuroectodermal tumors in four different lines of transgenic mice. Lab. Invest. 70, 114124). The presence of this cell marker indicates that these tumors are derived from cells that have differentiated beyond the earliest stages of neural stem cells. It is desirable to have additional animal models for identifying agents which are effective at preventing, slowing or reversing the growth of brain tumors. It is especially desirable to have an animal whose brain tumor cells are at an early stage of differentiation, i.e., the tumor cells have not yet progressed to the stage where they are expressing markers that are indicative of neurons (synaptophysin and neuron-specific enolase), astrocytes (glial fibrillary acidic protein and S-100), or oligodendrocytes (galactocerebroside). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

198 Brain Tumors

•

USE OF PROTEIN TYROSINE PHOSPHATASE ZETA AS A BIOMOLECULAR TARGET IN THE TREATMENT AND VISUALIZATION OF BRAIN TUMORS Inventor(s): Chin, Daniel J.; (Foster City, CA), Melcher, Thorsten; (San Francisco, CA), Mueller, Sabine; (San Francisco, CA) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20020146370 Date filed: March 23, 2001 Excerpt(s): The present invention relates to the use of proteins which are differentially expressed in primary brain tumor tissues, as compared to normal brain tissues, as biomolecular targets for brain tumor treatment therapies. Specifically, the present invention relates to the use of immunotherapeutic and immunoimaging agents which specifically bind to human protein tyrosine phosphatase-zeta (PTP.xi.) for the treatment and visualization of brain tumors in patients. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention. Brain tumors are considered to have one of the least favorable prognoses for long term survival: the average life expectancy of an individual diagnosed with a central nervous system (CNS) tumor is just eight to twelve months. Several unique characteristics of both the brain and its particular types of neoplastic cells create daunting challenges for the complete treatment and management of brain tumors. Among these are 1) the physical characteristics of the intracranial space, 2) the relative biological isolation of the brain from the rest of the body, 3) the relatively essential and irreplaceable nature of the organ mass, and 4) the unique nature of brain tumor cells. First and foremost, the intracranial space and physical layout of the brain create significant obstacles to treatment and recovery. The brain is made of, primarily, astrocytes (which make up the majority of the brain mass, and serve as a scaffold and support for the neurons), neurons (which carry the actual electrical impulses of the nervous system,) and a minor contingent of other cells such as insulating oligodendrocytes (which produce myelin). These cell types give rise to primary brain tumors (e.g., astrocytomas, neuroblastomas, glioblastomas, oligodendrogliomas, etc.) Although the World Health Organization has recently established standard guidelines, the nomenclature for brain tumors is somewhat imprecise, and the terms astrocytoma and glioblastoma are often used broadly. The brain is encased in the relatively rigid shell of the skull, and is cushioned by the cerebrospinal fluid, much like a fetus in the womb. Because of the relatively small volume of the skull cavity, minor changes in the volume of tissue in the brain can dramatically increase intracranial pressure, causing damage to the entire organ (i.e., "water on the brain"). Thus, even small tumors can have a profound and adverse affect on the brain's function. In contrast, tumors in the relatively distensible abdomen may reach several pounds in size before the patient experiences adverse symptoms. The cramped physical location of the cranium also makes surgery and treatment of the brain a difficult and delicate procedure. However, because of the dangers of increased intracranial pressure from the tumor, surgery is often the first strategy of attack in treating brain tumors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 199

Keeping Current In order to stay informed about patents and patent applications dealing with brain tumors, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “brain tumors” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on brain tumors. You can also use this procedure to view pending patent applications concerning brain tumors. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

201

CHAPTER 7. BOOKS ON BRAIN TUMORS Overview This chapter provides bibliographic book references relating to brain tumors. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on brain tumors include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “brain tumors” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on brain tumors: •

Communication Disorders in Childhood Cancer Source: London, United Kingdom: Whurr Publishers Ltd. 1999. 219 p. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: As the treatments become more effective, an increasing number of children displaying communication deficits as a consequence of treatment for childhood cancer have begun to appear in the caseloads of speech pathologists and other health professionals. This book offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. The treatments offered for these conditions, such as radiotherapy and chemotherapy, may have some long term adverse effects on brain structure and function leading to the development of a number of complications,

202 Brain Tumors

including cognitive deficits as well as speech and language disorders. The book includes nine chapters, that cover the cancers themselves (leukemia and brain tumors), the effects of treatment for pediatric cancer on brain structure and function, language disorders in children treated for brain tumors, language recovery following treatment for pediatric brain tumors, variability in patterns of language impairment in children following treatment for posterior fossa tumor, language disorders in children treated for acute lymphoblastic leukemia, discourse abilities of children treated for neoplastic conditions, motor speech disorders in children treated for brain tumors, and the assessment and treatment of speech and language disorders occurring subsequent to cancer therapy in children. Each chapter includes extensive references and the textbook concludes with a subject index. •

Brain Facts: A Primer on the Brain and Nervous System Source: Washington, DC: Society for Neuroscience. 1993. 52 p. Contact: Society for Neuroscience. 11 Dupont Circle, NW, Suite 500, Washington, DC 20036. (202) 462-6688. PRICE: $6.00. Summary: This book briefly describes what is known about the brain and nervous system, brain disorders, and avenues of research that promise new therapies for many of the most devastating neurological and psychiatric diseases. Topics include brain development; what a neuron is and its function; and the brain's involvement in sensation and perception, learning and memory, movement, sleep, stress, and aging. This book examines advances in research on Parkinson's disease, pain, epilepsy, major depression, and manic-depressive illness in addition to neurological disorders such as addiction, Alzheimer's disease, Down syndrome, Gilles de la Tourette's syndrome, brain tumors, and multiple sclerosis. It explores recent advances in diagnostic methods such as positron emission tomography, magnetic resonance imaging, magnetic source imaging, and gene diagnosis; and discusses potential therapies using drugs and transplants.

•

Effects of Drugs on Communication Disorders. 2nd ed Source: San Diego, CA: Singular Publishing Group. 1999. 238 p. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 347-7707. Fax (800) 774-8398. E-mail: [email protected]. Website: www.singpub.com. PRICE: $49.95 plus shipping and handling. ISBN: 1565939964. Summary: This handbook gives communication specialists information about prescription drugs and their use with patients who suffer neurogenic or psychogenic communication disorders. The book was designed for communication specialists who work in medical centers, rehabilitation clinics, private practice, public schools, or any setting in which drug therapy may influence a client's communication. Chapter 1 is a discussion of why and how drugs work, the scientific basis of neuropharmacology. Chapter 2 contains general information about drug related issues, including how drugs are administered and arrive at their destination in the body, the procedures for drug approval by the Food and Drug Administration (FDA), the influence of age on drug effectiveness, how to evaluate the effectiveness of a drug, and a discussion of dietary supplements and naturally occurring remedies. The authors next discuss the underlying neurologic and psychiatric diseases and conditions most likely to be encountered by speech language pathologists, along with the medicines currently and most commonly used to treat the disorders. Disorders covered include Parkinson disease, myasthenia

Books

203

gravis, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Wilson's disease, cerebral palsy, Huntington's disease, Tourette's syndrome, stroke, epilepsy, neoplasm (brain tumors), dementia, Alzheimer disease, traumatic brain injury (TBI), depression, mania, bipolar disorder, generalized anxiety disorder, schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), stuttering, spasmodic dysphonia, and dysphagia (swallowing disorders). The handbook concludes with a glossary of terms related to medical conditions and management, an appendix of abbreviations and definitions of terms associated with medical management, an appendix of drugs that affect the ear and hearing, and a subject index.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “brain tumors” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “brain tumors” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “brain tumors” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

100 Q&a About Brain Tumors by Virginia, Md. Stark-Vance, M. L. Dubay (2003); ISBN: 0763723088; http://www.amazon.com/exec/obidos/ASIN/0763723088/icongroupinterna

•

21st Century Complete Medical Guide to Brain Tumors including Brain Cancer and Pituitary Tumors - Authoritative Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment Options by PM Medical Health News; ISBN: 1592480128; http://www.amazon.com/exec/obidos/ASIN/1592480128/icongroupinterna

•

Angiogenesis in Brain Tumors by Matthias Kirsch (Editor), Peter McL Black (Editor) (2003); ISBN: 1402077041; http://www.amazon.com/exec/obidos/ASIN/1402077041/icongroupinterna

•

Atlas of Brain Tumors: Light and Electron Microscopic Features: With 257 Figures by Kazuo Tabuchi, A. Nishimoto; ISBN: 0387700242; http://www.amazon.com/exec/obidos/ASIN/0387700242/icongroupinterna

•

Atlas of the histology of brain tumors by K. J. Zülch; ISBN: 0387052747; http://www.amazon.com/exec/obidos/ASIN/0387052747/icongroupinterna

•

Biochemistry of brain tumors by Maria Wollemann; ISBN: 0839107161; http://www.amazon.com/exec/obidos/ASIN/0839107161/icongroupinterna

•

Biological aspects of brain tumors : proceedings of the 8th Nikko Brain Tumor Conference, Karatsu (Saga) 1990; ISBN: 4431700781; http://www.amazon.com/exec/obidos/ASIN/4431700781/icongroupinterna

•

Biological Aspects of Brain Tumors: Proceedings of the 8th Nikko Brain Tumor Conference, Karatsu (Saga 1990) by Japan)/ Tabuchi, Kazuo Nikko Brain Tumor Conference 1990 Karatsu-Shi (Editor), K. Tabuchi; ISBN: 0387700781; http://www.amazon.com/exec/obidos/ASIN/0387700781/icongroupinterna

204 Brain Tumors

•

Biological Effects of Electropollution: Brain Tumors and Experimental Models by S. K. Dutta, Richard M. Millis (1986); ISBN: 0961731419; http://www.amazon.com/exec/obidos/ASIN/0961731419/icongroupinterna

•

Biology of Brain Tumor: Proceedings of the Second International Symposium on Biology of Brain Tumors by M.D. Walker, D.G.T. Thomas (Editor) (1986); ISBN: 0898387752; http://www.amazon.com/exec/obidos/ASIN/0898387752/icongroupinterna

•

Biology of brain tumors; ISBN: 9290180307; http://www.amazon.com/exec/obidos/ASIN/9290180307/icongroupinterna

•

Brain Disorders Sourcebook: Basic Consumer Health Information About Strokes, Epilepsy, Amyotrophic Lateral Sclerosis (Als/Lou Gehrig's Disease) Parkinson's Disease, Brain Tumors by Karen Bellenir (Editor) (1999); ISBN: 0780802292; http://www.amazon.com/exec/obidos/ASIN/0780802292/icongroupinterna

•

Brain Tumor Biology (Progress in Experimental Tumor Research, Vol 27) by C.B. Wilson (Editor), M. L. Rosenblum (Editor) (1984); ISBN: 3805536984; http://www.amazon.com/exec/obidos/ASIN/3805536984/icongroupinterna

•

Brain Tumor Chemotheraphy by Derek Fewer; ISBN: 0398035490; http://www.amazon.com/exec/obidos/ASIN/0398035490/icongroupinterna

•

Brain Tumor Immunotherapy by Linda M. Liau (Editor), et al; ISBN: 0896036383; http://www.amazon.com/exec/obidos/ASIN/0896036383/icongroupinterna

•

Brain Tumor Invasion : Biological, Clinical, and Therapeutic Considerations by Tom Mikkelsen (Editor), et al (1998); ISBN: 0471154520; http://www.amazon.com/exec/obidos/ASIN/0471154520/icongroupinterna

•

Brain Tumor Invasiveness by Ronald H. Goldfarb (Editor) (1994); ISBN: 0792327918; http://www.amazon.com/exec/obidos/ASIN/0792327918/icongroupinterna

•

Brain Tumor Therapy (Progress in Experimental Tumor Research, Vol 28) by C.B. Wilson (Editor), M. L. Rosenblum (Editor) (1984); ISBN: 3805536992; http://www.amazon.com/exec/obidos/ASIN/3805536992/icongroupinterna

•

Brain Tumor: Research and Therapy by M. Nagai (Editor), Japanese Conference on Brain Tumor Research and Therapy 1994 Nasu-Mac (1996); ISBN: 4431701648; http://www.amazon.com/exec/obidos/ASIN/4431701648/icongroupinterna

•

Brain Tumors (1986); ISBN: 3540109331; http://www.amazon.com/exec/obidos/ASIN/3540109331/icongroupinterna

•

Brain Tumors (Contemporary Cancer Research Ser) by Francis Ali-Osman (Editor), Francis Ali Osman (Editor) (2003); ISBN: 1588290425; http://www.amazon.com/exec/obidos/ASIN/1588290425/icongroupinterna

•

Brain Tumors (Contemporary Neurology Series, 54) by William F. Chandler, et al (1999); ISBN: 019512958X; http://www.amazon.com/exec/obidos/ASIN/019512958X/icongroupinterna

•

Brain Tumors in Children: Principles of Diagnosis and Treatment (The International Review of Child Neurology) by Michael E., M.D. Cohen, Patricia K., M.D. Duffner (1994); ISBN: 0781700647; http://www.amazon.com/exec/obidos/ASIN/0781700647/icongroupinterna

•

Brain tumors in the chemical industry; ISBN: 0897661524; http://www.amazon.com/exec/obidos/ASIN/0897661524/icongroupinterna

Books

205

•

Brain Tumors: A Comprehensive Text (Neurological Disease and Therapy, Vol 20) by Robert A. Morantz, John W. Walsh (Editor); ISBN: 0824788265; http://www.amazon.com/exec/obidos/ASIN/0824788265/icongroupinterna

•

Brain Tumors: An Encyclopedia Approach by R.B. Anderson, et al; ISBN: 0838572219; http://www.amazon.com/exec/obidos/ASIN/0838572219/icongroupinterna

•

Brain Tumors: An Encyclopedic Approach by Andrew H. Kaye (Editor), Edward R., Jr. Laws (Editor); ISBN: 0443048401; http://www.amazon.com/exec/obidos/ASIN/0443048401/icongroupinterna

•

Brain Tumors: Biopathology & Therapy by M. Gerosa (Editor); ISBN: 0080320139; http://www.amazon.com/exec/obidos/ASIN/0080320139/icongroupinterna

•

Brain Tumors: Pathology and Its Biological Correlates by D. Schifffer, Davide Schiffer (1997); ISBN: 3540616225; http://www.amazon.com/exec/obidos/ASIN/3540616225/icongroupinterna

•

Brain Tumors: Their Biology and Pathology by Klaus J. Zulch; ISBN: 0387109331; http://www.amazon.com/exec/obidos/ASIN/0387109331/icongroupinterna

•

Cerebral Gliomas: Proceedings of the International Workshop on Brain Tumors, Held in Santa Margherita, Ligure, Italy, 20-22 June 1988 (International by Giovanni Broggi, Massimo A. Gerosa (Editor); ISBN: 0444810811; http://www.amazon.com/exec/obidos/ASIN/0444810811/icongroupinterna

•

Chemotherapy of Brain Tumors (1996); ISBN: 0944093418; http://www.amazon.com/exec/obidos/ASIN/0944093418/icongroupinterna

•

Computed Tomography and Magnetic Resonance Tomography of Intracranial Tumors: A Clinical Perspective by E. Kazner, et al; ISBN: 0387505768; http://www.amazon.com/exec/obidos/ASIN/0387505768/icongroupinterna

•

Computed Tomography in Intracranial Tumors: Differential Diagnosis and Clinical Aspects by E. Kazner (Editor); ISBN: 0387108157; http://www.amazon.com/exec/obidos/ASIN/0387108157/icongroupinterna

•

Damn the Statistics, I Have a Life to Live: Coping With a Brain Tumor My Personal Story by H. Charles Wolf (2003); ISBN: 1410786226; http://www.amazon.com/exec/obidos/ASIN/1410786226/icongroupinterna

•

Diagnosis: Brain Tumor by Rick Jones; ISBN: 1884898149; http://www.amazon.com/exec/obidos/ASIN/1884898149/icongroupinterna

•

Electron Microscopic Atlas of Brain Tumors by Tung P. Poon; ISBN: 0808907409; http://www.amazon.com/exec/obidos/ASIN/0808907409/icongroupinterna

•

Experimental Neurooncology, Brain Tumor and Pain Therapy (1988); ISBN: 3437111604; http://www.amazon.com/exec/obidos/ASIN/3437111604/icongroupinterna

•

Experimental Neurooncology, Brain Tumor and Pain Therapy (Cancer Campaign, Vol 10) by W.J. Bock (Editor) (1988); ISBN: 0895742551; http://www.amazon.com/exec/obidos/ASIN/0895742551/icongroupinterna

•

Eye signs and symptoms in brain tumors by Alfred Huber; ISBN: 0801623022; http://www.amazon.com/exec/obidos/ASIN/0801623022/icongroupinterna

•

Eye symptoms in brain tumors by Alfred Huber; ISBN: 0801623014; http://www.amazon.com/exec/obidos/ASIN/0801623014/icongroupinterna

206 Brain Tumors

•

Familial Brain Tumors by Cornelis C. Tijssen, et al (1982); ISBN: 9024726913; http://www.amazon.com/exec/obidos/ASIN/9024726913/icongroupinterna

•

Gene Therapy for Neurological Disorders & Brain Tumors by E. Antonio, Md. Chiocca (Editor), Xandra O., Ph.D. Breakefield (Editor); ISBN: 0896035077; http://www.amazon.com/exec/obidos/ASIN/0896035077/icongroupinterna

•

Intracranial Tumors in Infancy and Childhood: Basic Research, Diagnosis and Treatment (Progress in Experimental Tumor Research, Vol. 30) by Jap International Symposium on Pediatric Neurooncology 1985 Toba-Shi, et al (1987); ISBN: 3805544367; http://www.amazon.com/exec/obidos/ASIN/3805544367/icongroupinterna

•

Malignant Brain Tumors by David G. Thomas, D.I. Graham (Editor) (1995); ISBN: 0387196897; http://www.amazon.com/exec/obidos/ASIN/0387196897/icongroupinterna

•

Management of Childhood Brain Tumors by Melvin Deutsch (Editor) (1990); ISBN: 0792306694; http://www.amazon.com/exec/obidos/ASIN/0792306694/icongroupinterna

•

Microsurgery of Intracranial Tumors by Wolfgang Seeger, et al; ISBN: 3211826785; http://www.amazon.com/exec/obidos/ASIN/3211826785/icongroupinterna

•

Modern concepts in brain tumor therapy, laboratory and clinical investigations; ISBN: 0719400201; http://www.amazon.com/exec/obidos/ASIN/0719400201/icongroupinterna

•

Molecular neuro-oncology and its impact on the clinical management of brain tumors; ISBN: 3540573518; http://www.amazon.com/exec/obidos/ASIN/3540573518/icongroupinterna

•

Molecular Neuro-Oncology and Its Impact on the Clinical Management of Brain Tumors (Recent Results in Cancer Research, Vol 135) by U. Schlegel, et al; ISBN: 0387573518; http://www.amazon.com/exec/obidos/ASIN/0387573518/icongroupinterna

•

Multidisciplinary aspects of brain tumor therapy : proceedings of the International Symposium on Multidisciplinary Aspects of Brain Tumor Therapy held in Gardone Riviera (Brescia), Italy, June 8-10, 1979; ISBN: 0444801707; http://www.amazon.com/exec/obidos/ASIN/0444801707/icongroupinterna

•

Navigating Through a Strange Land: A Book for Brain Tumor Patients and Their Families by Tricia Ann Roloff (Editor), Stacy Cosgrove (2001); ISBN: 1577491084; http://www.amazon.com/exec/obidos/ASIN/1577491084/icongroupinterna

•

Neurobiology of Brain Tumors (Concepts in Neurosurgery Vol 4) by Michael Salcman (Editor) (1990); ISBN: 0683074962; http://www.amazon.com/exec/obidos/ASIN/0683074962/icongroupinterna

•

Neuro-Oncology: Primary Malignant Brain Tumors (The Johns Hopkins Series in Contemporary Medicine and Public Health) by David G. Thomas (Editor) (1990); ISBN: 0801839246; http://www.amazon.com/exec/obidos/ASIN/0801839246/icongroupinterna

•

Pediatric Cancer Sourcebook: Basic Consumer Health Information About Leukemias, Brain Tumors, Sarcomas (Health Reference Series) by Edward J. Prucha (Editor), Ed Prucha (Editor); ISBN: 0780802454; http://www.amazon.com/exec/obidos/ASIN/0780802454/icongroupinterna

Books

207

•

Primary Brain Tumors (1989); ISBN: 354097055X; http://www.amazon.com/exec/obidos/ASIN/354097055X/icongroupinterna

•

Primary Brain Tumors: A Review of Histologic Classification by William S. Fields (Editor); ISBN: 038797055X; http://www.amazon.com/exec/obidos/ASIN/038797055X/icongroupinterna

•

Raising Health Awareness Through Examining Benign Brain Tumor Cancer, Alpha One, and Breast Implant Issues: Hearing Before the Committee on Energy and Commerce, U.S. House of Representatives by Michael Bilirakis (Editor); ISBN: 0788130862; http://www.amazon.com/exec/obidos/ASIN/0788130862/icongroupinterna

•

Raising Health Awareness Through Examining Benign Brain Tumor Cancer, Alpha One, and Breast Implant: Hearing Before the Subcommittee on Health of the by United States (2002); ISBN: 016066716X; http://www.amazon.com/exec/obidos/ASIN/016066716X/icongroupinterna

•

Stereotactic Biopsy and Brachytherapy of Brain Tumors by Peter Dyck (Editor); ISBN: 0839119267; http://www.amazon.com/exec/obidos/ASIN/0839119267/icongroupinterna

•

That's Unacceptable: Surviving a Brain Tumor - My Personal Story by Rebecca L. Libutti (1997); ISBN: 0967039703; http://www.amazon.com/exec/obidos/ASIN/0967039703/icongroupinterna

•

The Official Patient's Sourcebook on Adult Brain Tumors: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833400; http://www.amazon.com/exec/obidos/ASIN/0597833400/icongroupinterna

•

The Practical Management of Low-Grade Primary Brain Tumors by Jack P. Rock (Editor), et al; ISBN: 0781711010; http://www.amazon.com/exec/obidos/ASIN/0781711010/icongroupinterna

•

Therapy of Malignant Brain Tumors by Kurt Jellinger (Editor); ISBN: 0387819460; http://www.amazon.com/exec/obidos/ASIN/0387819460/icongroupinterna

•

Therapy of Malignant Brain Tumors; ISBN: 3211819460; http://www.amazon.com/exec/obidos/ASIN/3211819460/icongroupinterna

•

Ultrastructure of Brain Tumors and Biopsies by C. L. Dolman (Author) (1984); ISBN: 0275914267; http://www.amazon.com/exec/obidos/ASIN/0275914267/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “brain tumors” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button

208 Brain Tumors

•

Atlas of the histology of brain tumors. Author: Zülch, K. J. (Klaus Joachim),; Year: 1947; Berlin, New York, Springer-Verlag, 1971; ISBN: 3540052747

•

Biopotentials of cerebral hemispheres in brain tumors. Authorized translation from the Russian, by Basil Haigh. Author: Bekhtereva, N. P. (Natal'ia Petrovna); Year: 1961; New York, Consultants Bureau, 1962

•

Brain tumors and chemical injuries to the central nervous system: proceedings of the International Neuropathological Symposium; Year: 1982; Warsaw: Polish Medical Pub., 1978

•

Brain tumors and other space occupying processes. Editor: R. Hess. Author: Hess, Rudolf M.,; Year: 1978; Amsterdam, Elsevier [c1975]; ISBN: 0444413049

•

Brain tumors in children: principles of diagnosis and treatment Author: Cohen, Michael E.,; Year: 1986; New York: Raven, c1984

•

Brain tumors in the chemical industry Author: Selikoff, Irving J.; Year: 1982; New York, N.Y.: New York Academy of Sciences, 1982; ISBN: 0897661516 http://www.amazon.com/exec/obidos/ASIN/0897661516/icongroupinterna

•

Brain tumors in the young Author: Amador, Luis V.; Year: 1984; Springfield, Ill.: Thomas, c1983; ISBN: 0398046972 http://www.amazon.com/exec/obidos/ASIN/0398046972/icongroupinterna

•

Brain tumors of childhood, by Henry M. Cuneo and Carl W. Rand. Author: Cuneo, Henry Michael,; Year: 1953; Springfield, Ill., Thomas [1952]

•

Brain tumors; their biology and pathology. Author: Zülch, K. J. (Klaus Joachim),; Year: 1976; New York, Springer [c1965]

•

Diagnosis and localization of brain tumors; a clinical and experimental study employing fluorescent and radioactive tracer methods. Author: Moore, George Eugene,; Year: 1950; Springfield, Ill., Thomas [c1953]

•

Diagnosis and treatment of brain tumors and care of the neurosurgical patient. Author: Sachs, Ernest,; Year: 1949; St. Louis, Mosby, 1949

•

Erosions, ulcers and postmortem digestion of the stomach and duodenum associated with brain tumors. Author: Mann, Arthur Seldon,; Year: 1952; [Minneapolis, Minn.] 1942

•

Lactate dehydrogenase isoenzymes in the central nervous system: theoretical aspects and practical application in diagnosis of brain tumors. Author: Gerhardt-Hansen, Willie.; Year: 1976; Virum, [Denmark]: Costers Bogtrykkeri, 1968

•

Metastatic brain tumors. Author: Kiefer, Edward Jern,; Year: 1962; [Minneapolis] 1947

•

Pyruvate kinase and brain tumors: its significance for neurosurgical treatment Author: Veelen, Cornelis Willem Martinus van,; Year: 1983; Utrecht: Drukkerij Elinkwijk, [1976]

•

The experimental biology of brain tumors, compiled and edited by Wolff M. Kirsch, Enrica Grossi-Paoletti [and] Pietro Paoletti. Author: Kirsch, Wolff M.,; Year: 1942; Springfield, Ill., Thomas [c1972, i. e. 1971]

•

Ultrastructure of brain tumors and biopsies: a diagnostic atlas Author: Dolman, C. L.; Year: 1987; New York: Praeger, 1984; ISBN: 0030688973

that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

Books

209

http://www.amazon.com/exec/obidos/ASIN/0030688973/icongroupinterna

Chapters on Brain Tumors In order to find chapters that specifically relate to brain tumors, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and brain tumors using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “brain tumors” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on brain tumors: •

Language Disorders in Children Treated for Brain Tumours Source: in Murdoch, B.E. Communication Disorders and Childhood Cancer. London, United Kingdom: Whurr Publishers Ltd. 1999. p. 55-75. Contact: Available from Taylor and Francis, Inc. 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. Fax (800) 248-4724. PRICE: $47.95 plus shipping and handling. ISBN: 1861561156. Summary: As the treatments become more effective, an increasing number of children displaying communication deficits as a consequence of treatment for childhood cancer have begun to appear in the caseloads of speech pathologists and other health professionals. This chapter on language disorders is from a book that offers an overview of the communication impairments that occur in association with the two most common forms of childhood cancer, namely leukemia and brain tumor. The authors discuss a number of factors occurring secondary to the presence and removal of posterior fossa tumors that could conceivably lead to disturbances in language function. The authors review a number of case studies that demonstrate these postoperative complications in language. As yet, no characteristic language pattern has arise that could offer clinicians a starting point for patient management, or alert them to specific areas of language deficit. Rather, the data available to date indicate the presence of variable language abilities within the tumor population thereby necessitating the need for development and implementation of individualized therapy programs. The authors caution that neurological deterioration can occur in these children from months to years after the completion of treatment of brain tumors; postoperative baseline measurements of language abilities are highly recommended. 4 figures. 60 references.

•

Evaluation of Olfactory Deficits by Medical Imaging Source: in Doty, R.L., ed. Handbook of Olfaction and Gustation. New York, NY: Marcel Dekker, Inc. 1995. p. 395-419. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (800) 228-1160 or (212) 696-9000; Fax (212) 685-4540. PRICE: $225.00 plus shipping and handling. ISBN: 0824792521. Summary: In this chapter, from a medical text on olfaction and gustation, the authors review the literature on the evaluation of olfactory deficits by medical imaging. Topics covered include imaging modalities and techniques, including plain radiographs, conventional tomography, computer tomography, magnetic resonance imaging, nuclear

210 Brain Tumors

medicine, and angiography; the basic anatomy and physiology of the olfactory system; peripheral causes of olfactory disturbance, including sinonasal infectious disease, tumors of the nasal cavity and paranasal sinuses, allergic rhinitis, congenital or developmental abnormalities, and substance abuse; and central causes of olfactory diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Korsakoff's psychosis, schizophrenia, congenital anosmia, head trauma, brain tumors, and AIDS. The authors conclude that in assessing the peripheral causes of olfactory deficits, medical imaging studies can reveal anatomical information and structural changes, suggest differential diagnosis, and provide guidelines for surgical intervention. In the evaluation of central causes, imaging studies can provide information elucidating the links between olfactory dysfunction and the structural or functional changes in the living brain. 5 figures. 152 references. (AA-M). •

Alzheimer's Disease and Other Organic Causes of Mental Disorders Source: in Kass, F.I.; et al., eds. Columbia University College of Physicians and Surgeons: Complete Home Guide to Mental Health. New York, NY: Henry Holt and Company, Inc. 1992. p. 206-219. Contact: Available from Henry Holt and Company, Inc. 115 West 18th Street, New York, NY 10011. PRICE: $35.00. ISBN: 0805007245. Summary: Numerous disorders affecting mood, memory, concentration, intellect, and personality arise from physical abnormalities in the brain and often require medical intervention. Psychiatric and psychological treatments may ease some symptoms and may help patients and their families adjust to the diseases and deficits caused by them. However, these treatments often overlook the underlying physical conditions. Consequently, appropriate treatments for some dementias require investigating and addressing the underlying illness or physical problem. As part of a home reference guide, this chapter describes physical conditions that produce mental symptoms. Topics include: Alzheimer's disease (symptoms, progression, diagnosis, medical treatment, care, family caregiver stress, possible causes, and stages); ways of dealing with dementia on a daily basis; other primary dementias (multi-infarct dementia, Huntington's chorea dementia, and Pick's disease dementia); other physical brain disorders (AIDS dementia and other infectious diseases); ways for families to obtain help and information on dementia; medical treatments and medical illnesses that commonly produce organic (physical) mental symptoms (brain tumors and cancer, nutritional deficiencies and toxins, liver disease, endocrine disorders, drug and alcohol use and withdrawal, and trauma); delirium; and financial and legal issues for families caring for patients with Alzheimer's disease or other dementias.

•

Other Dementias and Mental Disorders Due to General Medical Conditions Source: in Sadavoy, J.; et al., eds. Comprehensive Review of Geriatric Psychiatry-II. 2nd ed. Washington, DC: American Psychiatric Press, Inc. 1996. p. 497-528. Contact: American Psychiatric Press, Inc. 1400 K Street, NW, Washington, DC 20005. (202) 682-6262; FAX (202) 789-2648. PRICE: $95.00 plus $7.50 shipping. Internet access: http://www.appi.org. ISBN: 0880487232. Summary: This chapter discusses forms of dementia other than Alzheimer's disease and vascular dementia. The first half of the chapter discusses forms of dementia considered in the differential diagnosis of progressive cognitive impairment. The second part of the chapter describes the secondary mental disorders referred to as 'organic mental disorders' in the 'Diagnostic and Statistical Manual of Mental Disorders, III, Revised'

Books

211

(DSM). The author explains that the term 'organic' was deleted from the DSM IV; thus, experts should specify the actual physical disorder or responsible substance. The dementias discussed include: focal cortical dementias (Pick's disease and others); subcortical dementias (Huntington's disease, dementia in Parkinson's disease, and progressive supranuclear palsy); normal pressure hydrocephalus; dementias caused by an infectious disease (Creutzfeldt-Jakob disease and HIV encephalopathy); dementia associated with metabolic disorders; dementia after head injury; dementia associated with toxic substances; dementia associated with brain tumors; mental disorders due to general medical conditions; amnestic disorders; mood disorders due to a general medical condition; anxiety disorders due to a general medical condition; psychotic disorders due to a general medical condition, with delusions; psychotic disorders due to a general medical condition, with hallucinations; and personality changes due to a general medical condition. 4 tables, 94 references. •

Central and Vascular Vestibular Disorders Source: in Blakley, B.W.; Siegel, M.E. Feeling Dizzy: Understanding and Treating Dizziness, Vertigo, and Other Balancing Disorders. New York, NY: Macmillan Publishing. 1995. p. 117-128. Contact: Available from Macmillan Publishing. 201 West 103rd Street, Indianapolis, IN 46290. (800) 428-5331; Fax (800) 882-8583. PRICE: $21.95 plus shipping and handling. ISBN: 0028600096. Summary: This chapter is from a layperson's guide to vertigo, imbalance, fainting, and other balance disorders. This chapter describes central and vascular vestibular disorders. Topics covered include acoustic neuroma, other brain tumors, cerebral atrophy, disorders of the blood supply, transient ischemic attacks, stroke, migraine, epilepsy, and multiple sclerosis. For each type of vestibular disorder discussed, the authors consider symptoms, diagnosis, etiology, natural course, and treatment options. The authors also share the experiences of patients who have each of these types of disorders.

•

Language-Specific Neurologic Disorders Source: in Vogel, D.; Carter, J.E.; Carter, P.B. Effects of Drugs on Communication Disorders. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1999. p. 103-123. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 347-7707. Fax (800) 774-8398. E-mail: [email protected]. Website: www.singpub.com. PRICE: $49.95 plus shipping and handling. ISBN: 1565939964. Summary: This chapter on language specific neurologic disorders is from a handbook that gives communication specialists information about prescription drugs and their use with patients who suffer neurogenic or psychogenic communication disorders. The book was designed for communication specialists who work in medical centers, rehabilitation clinics, private practice, public schools, or any setting in which drug therapy may influence a client's communication. This chapter covers neurologic disorders that may affect language. For each disorder, the authors provide a definition and cause; discuss the general features, symptoms, and signs; describe the features, symptoms, and signs of language impairment associated with each disorder; list pharmacologic (drug) treatment for each disorder; and discuss the influence that drug treatment may have on communication. Each section also lists references for additional

212 Brain Tumors

information. Disorders covered are stroke, epilepsy (seizure disorder), and neoplasm (brain tumors). 1 table. 21 references. •

Vertigo of Central Origin Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 665-679. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: This chapter on vertigo of central origin is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. Topics include differentiating central and peripheral causes of vertigo; the neurologic complications of ear infections, including epidural abscess and brain abscess; vascular disease, including vertebrobasilar insufficiency, infarction of the brainstem and cerebellum, hemorrhage into the brainstem and cerebellum, and the diagnosis of vascular causes of vertigo; migraine, including the clinical profile, migraine equivalents, and the mechanism of vertigo with migraine; tumors, including tumors of the cerebellopontine angle, and brain tumors; brain trauma, including the mechanism of brain injury, brainstem contusion, postconcussion syndrome, and the diagnosis of persistent dizziness after head trauma; cerebellar degeneration syndromes, including alcohol cerebellar degeneration and familial ataxia syndromes; disorders of the cranial vertebral junction, including the mechanism of brain damage, basilar impression, atlantoaxial dislocation, and Chiari malformation; multiple sclerosis; and vertigo and focal seizure disorders. For each disorder, the author discusses diagnosis, diagnostic tests, and treatment options. 3 figures. 2 tables. 74 references.

213

CHAPTER 8. MULTIMEDIA ON BRAIN TUMORS Overview In this chapter, we show you how to keep current on multimedia sources of information on brain tumors. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on brain tumors is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “brain tumors” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “brain tumors” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on brain tumors: •

Aging Brain Source: Sacramento, CA: Department of Aging. 1987. (videocassette, 6 handouts and 6 page training manual.). Contact: California Department of Aging, Training and Education Section. 1600 K Street, Sacramento, CA 95814. (916) 322-3110. PRICE: $10.00. Summary: This tape contains seven training segments designed for administrators and staff working in residential facilities for the aged. It reviews commonly held beliefs about aging that may negatively influence the care given to aging residents and how these myths developed. According to the tape, many believe that aged people are naturally "senile". Aged people can either accept this belief and act accordingly, creating a self-fulfilling prophecy in which they relinquish their independence to those caring for them, or they can rebel against their caregivers. Several studies related to aging are reviewed that suggest that there are only minor differences between the mental capacities of the young and aged. Treatable diseases that can affect the aged person's

214 Brain Tumors

mental abilities are described including drug overdoses, malnutrition, dehydration, blood clots, brain tumors, depression, alcoholism, liver failure, kidney failure, drastic environmental changes, thyroid problems, heart failure, infections, diabetes, constipation, and emphysema. Organic brain syndromes, incurable diseases that affect mental capability, also are reviewed, including multi-infarct dementia, Pick's disease, Creutzfeldt-Jakob disease, Korsakoff's syndrome, Parkinson's disease, and Alzheimer's disease. Specific attention is given to changes in the brain that occur as the disease progresses, the symptoms, and possible risk factors and causes of the disease. Contact points for the Alzheimer's Association are provided for further information.

Bibliography: Multimedia on Brain Tumors The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in brain tumors (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on brain tumors: •

Brain tumors [videorecording]: new hope, new treatments Source: a presentation of Films for the Humanities & Sciences; ITV, Information Television Network; Year: 2002; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2002

•

Computed tomography of the central nervous system [slide]: brain tumors Source: [by Roger A. Hyman]; Year: 1982; Format: Slide; Chicago, Ill.: Micro X-ray Recorder, Inc., [1982?]

•

Intracarotid chemotherapy for malignant brain tumors [videorecording] Source: Glaxo; produced by Imagination Unlimited; Year: 1991; Format: Videorecording; Research Triangle Park, NC: Glaxo, [1991?]

•

Pathology of brain tumors [slide] Source: John J. Kepes; Year: 1979; Format: Slide; [New York]: Medcom, c1979

•

Pathology of brain tumors [slide] Source: John J. Kepes; Year: 1971; Format: Slide; [New York]: Medcom, c1971

•

Radiologic atlas of brain tumors [videorecording] Source: Mayo; Image Premastering Services, Ltd; Year: 1991; Format: Videorecording; St. Paul, MN: Image PSL; [Rochester, Minn.]: Mayo Foundation, c1991

•

The Basis for therapy of brain tumors [slide] Source: Roswell Park Memorial Institute; Year: 1975; Format: Slide; [Buffalo]: Communications in Learning, 1975

•

Uncommon manifestations of intracranial tumors [sound recording] Source: Department of Continuing Medical Education School of Medicine State University of New York at Buffalo, in cooperation with the Lakes Area Regional Medical Program; Year: 1975; Format: Sound recording; [Buffalo]: Communications in Learning, 1975

215

CHAPTER 9. PERIODICALS AND NEWS ON BRAIN TUMORS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover brain tumors.

News Services and Press Releases One of the simplest ways of tracking press releases on brain tumors is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “brain tumors” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to brain tumors. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “brain tumors” (or synonyms). The following was recently listed in this archive for brain tumors: •

Stereotactic radiotherapy effective for pediatric brain tumors Source: Reuters Medical News Date: October 22, 2003

•

Radiation approach effective for kid's brain tumors Source: Reuters Health eLine Date: October 22, 2003

216 Brain Tumors

•

Inherited BRCA2 mutations linked to pediatric brain tumors Source: Reuters Medical News Date: October 14, 2003

•

Thalidomide with carmustine active against brain tumors Source: Reuters Industry Breifing Date: July 15, 2003

•

Normal mouse embryos can be cloned from reprogrammed brain tumor cells Source: Reuters Medical News Date: June 11, 2003

•

Hypothyroidism a sequela of cranial irradiation of pediatric brain tumor Source: Reuters Medical News Date: February 21, 2003

•

Pediatric brain tumor treatment confers risk for later endocrine, cardiovascular problems Source: Reuters Medical News Date: January 17, 2003

•

Kids' brain tumor Rx tied to later health troubles Source: Reuters Health eLine Date: January 15, 2003

•

Nerve, brain tumor risk higher for A-bomb survivors Source: Reuters Health eLine Date: October 15, 2002

•

Technique could one day treat deadly brain tumors Source: Reuters Health eLine Date: October 04, 2002

•

High-dose measles vaccine could fight brain tumors Source: Reuters Health eLine Date: September 24, 2002

•

Plant compound seen as possible brain tumor therapy Source: Reuters Health eLine Date: August 29, 2002

•

Activating ion channels increases drug delivery to brain tumors Source: Reuters Medical News Date: June 25, 2002

•

FDA to expedite review of NeoPharm cancer drug for treatment of brain tumors Source: Reuters Industry Breifing Date: May 06, 2002

•

Brain tumors safely removed on outpatient basis Source: Reuters Health eLine Date: April 10, 2002

•

Gene therapy slows brain tumor growth in mice Source: Reuters Health eLine Date: February 22, 2002

•

Common virus linked to childhood brain tumor Source: Reuters Health eLine Date: February 19, 2002

Periodicals and News

•

Therapy prolongs life in mice with brain tumors Source: Reuters Health eLine Date: December 31, 2001

•

Gene defect linked to brain tumor Source: Reuters Health eLine Date: December 12, 2001

•

Transplant patients may face brain tumor risk Source: Reuters Health eLine Date: November 09, 2001

•

DNA repair defect may lead to brain tumor Source: Reuters Health eLine Date: October 16, 2001

•

Peregrine Pharmaceuticals gets fast-track designation for brain tumor drug Source: Reuters Industry Breifing Date: October 10, 2001

•

Insight into brain tumor spread may aid treatment Source: Reuters Health eLine Date: September 03, 2001

•

Study suggests new way to fight deadly brain tumor Source: Reuters Health eLine Date: August 30, 2001

•

MRI provides best diagnostic strategy for brain tumor in high-risk children Source: Reuters Medical News Date: August 21, 2001

•

Chickenpox virus tied to lower brain tumor risk Source: Reuters Health eLine Date: July 24, 2001

•

Awake patients are helpful during brain tumor resection Source: Reuters Medical News Date: July 18, 2001

•

Gene may predict speed of brain tumor recurrence Source: Reuters Health eLine Date: July 16, 2001

•

Virus destroys brain tumors in mouse experiment Source: Reuters Health eLine Date: June 19, 2001

•

Polio virus targets, kills brain tumors: study Source: Reuters Health eLine Date: May 21, 2001

•

Women with primary brain tumors are at increased risk for divorce Source: Reuters Medical News Date: May 17, 2001

•

Women with brain tumors at higher risk of divorce Source: Reuters Health eLine Date: May 15, 2001

217

218 Brain Tumors

•

Proxima brain tumor radiation system cleared by FDA Source: Reuters Industry Breifing Date: May 08, 2001

•

Light therapy tested for brain tumors Source: Reuters Health eLine Date: April 26, 2001

•

Compound shrinks brain tumors in mice Source: Reuters Health eLine Date: April 17, 2001

•

Pharmacyclics begins phase II study of Xcytrin for primary brain tumors Source: Reuters Industry Breifing Date: April 10, 2001

•

Therapy on horizon for rare brain tumor in young Source: Reuters Health eLine Date: March 27, 2001

•

First steps taken in development of treatment for rare pediatric brain tumor Source: Reuters Industry Breifing Date: March 27, 2001

•

Genetic discoveries may aid brain tumor treatment Source: Reuters Health eLine Date: March 07, 2001

•

Australian oncologists will treat pediatric brain tumors with novel radiation therapy Source: Reuters Medical News Date: January 30, 2001

•

Brain tumors on the rise in New York Source: Reuters Health eLine Date: January 10, 2001

•

Growth hormone does not increase brain tumor recurrence risk in children Source: Reuters Industry Breifing Date: January 09, 2001

•

Growth hormone safe after brain tumors in children Source: Reuters Health eLine Date: January 02, 2001

•

Mobile phone firms face fresh suits over brain tumors Source: Reuters Medical News Date: December 28, 2000

•

Diffusion MRI allows early assessment of brain tumor treatment Source: Reuters Medical News Date: December 26, 2000

•

FDA clears Vital Images' software upgrade for analyzing heart disease, brain tumors Source: Reuters Industry Breifing Date: November 21, 2000

•

Test helps doctors target brain tumor treatment Source: Reuters Health eLine Date: November 09, 2000

Periodicals and News

•

Stem cells crawl into brain tumors, mouse study shows Source: Reuters Health eLine Date: November 06, 2000

•

Ethypharm's brain tumor drug gets FDA orphan status Source: Reuters Industry Breifing Date: October 10, 2000

•

Targeted radiation therapy controls some brain tumors Source: Reuters Health eLine Date: August 31, 2000

219

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “brain tumors” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “brain tumors” (or synonyms). If you know the name of a company that is relevant to brain tumors, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

220 Brain Tumors

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “brain tumors” (or synonyms).

Academic Periodicals covering Brain Tumors Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to brain tumors. In addition to these sources, you can search for articles covering brain tumors that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

221

CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for brain tumors. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with brain tumors. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

222 Brain Tumors

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to brain tumors: Carmustine •

Systemic - U.S. Brands: BiCNU http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202117.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to brain tumors by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “brain tumors” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From

Researching Medications

223

there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for brain tumors: •

Bromodeoxyuridine http://www.rarediseases.org/nord/search/nodd_full?code=681

•

Microbubble contrast agent (trade name: Filmix Neurosonographic Contrast Agent) http://www.rarediseases.org/nord/search/nodd_full?code=70

•

Herpes simplex virus gene http://www.rarediseases.org/nord/search/nodd_full?code=736

•

Poly-ICLC http://www.rarediseases.org/nord/search/nodd_full?code=835

•

Mitolactol http://www.rarediseases.org/nord/search/nodd_full?code=85

•

Interferon beta (recombinant human) http://www.rarediseases.org/nord/search/nodd_full?code=99

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

225

APPENDICES

227

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

228 Brain Tumors

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

229

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

230 Brain Tumors

•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “brain tumors” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “brain tumors” (or synonyms) into the “For these words:” box. The following is a sample result: •

Progress and Promise, 1992: A Status Report on the NINDS Implementation Plan for the Decade of the Brain Source: Bethesda, MD: National Institute of Neurological Disorders and Stroke. 1992. 50 p. Contact: National Institute of Neurological Disorders and Stroke. Information Office Building 31, 9000 Rockville Pike, Bethesda, MD 20892. (800) 352-9424. Summary: This status report reviews the National Advisory Neurological Disorders and Stroke Council's implementation plan and summarizes progress made in basic and clinical research on neurological disorders. It discusses the major areas of research opportunity, recommendations to the National Institute of Neurological Disorders and Stroke for research objectives in the Decade of the Brain, and resources needed to initiate and fully implement these efforts over the next several years. Future plans and budgets are presented for study in inherited disorders; cerebral palsy and other developmental disorders; epilepsy; traumatic brain and spinal cord injury; stroke and cerebrovascular disease; brain tumors; and various diseases that cause the brain to fail such as Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Other topics include the effects of alcohol and drugs on the brain, pain control, and restoring and repairing brain function. Recommendations for research are presented for each of the areas discussed, including increases in funding and total operating budgets required.

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. 15 16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

Physician Resources

231

Type “brain tumors” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 74454 566 1086 32 0 76138

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “brain tumors” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for

17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

The HSTAT URL is http://hstat.nlm.nih.gov/.

19

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

232 Brain Tumors

general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Brain Tumors In the following section, we will discuss databases and references which relate to the Genome Project and brain tumors. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “brain tumors” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for brain tumors: •

Deleted in Malignant Brain Tumors 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601969 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

Physician Resources

233

http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide

234 Brain Tumors

sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “brain tumors” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form.

24

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

Physician Resources

235

At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “brain tumors” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

25

Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

237

APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on brain tumors can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to brain tumors. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to brain tumors. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “brain tumors”:

238 Brain Tumors

•

Other guides Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Brain Diseases http://www.nlm.nih.gov/medlineplus/braindiseases.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Cancer Alternative Therapy http://www.nlm.nih.gov/medlineplus/canceralternativetherapy.html Eye Cancer http://www.nlm.nih.gov/medlineplus/eyecancer.html Lung Cancer http://www.nlm.nih.gov/medlineplus/lungcancer.html Spinal Cord Diseases http://www.nlm.nih.gov/medlineplus/spinalcorddiseases.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on brain tumors. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Alzheimer's Disease and Related Disorders Fact Sheet (An Overview of the Dementias) Source: Chicago, IL: Alzheimer's Disease and Related Disorders Association, Inc. 1990. [2 p.]. Contact: Alzheimer's Association. 919 North Michigan Avenue, Suite 1000, Chicago, IL 60611-1676. (800) 272-3900; (312) 335-8700; (312) 335-8882 (TDD); FAX (312) 335-1110. PRICE: Single copy free. Summary: Dementia is the loss of intellectual functions of sufficient severity to interfere with a person's daily functioning. It is not a disease in itself, but rather a group of symptoms which may accompany certain diseases or physical conditions. The cause and rate of progression of dementias vary. Some of the more well-known diseases that produce dementia include Alzheimer's disease, multi-infarct dementia, Huntington's

Patient Resources

239

disease, Pick's disease, Creutzfeldt-Jakob disease, and Parkinson's disease. Other conditions which may cause or mimic dementia include depression, brain tumors, nutritional deficiencies, head injuries, hydrocephalus, infections (AIDS, meningitis, syphilis), drug reactions, and thyroid problems. It is imperative that all persons experiencing memory deficits or confusion undergo a thorough diagnostic workup. This requires examination by a physician experienced in the diagnosis of dementing disorders and detailed laboratory testing. The examination should include a reevaluation of all medications. This process will help the patient obtain treatment for reversible conditions, aid the patient and family in planning future care, and provide important medical information for future generations. This fact sheet is also available in Spanish (AZDC01469). •

Neurofibromatosis Type 2: Information for Patients and Families Source: New York, NY: National Neurofibromatosis Foundation, Inc. 1994. 17 p. Contact: Available from National Neurofibromatosis Foundation, Inc. 95 Pine Street, 16th Floor, New York, NY 10005. (800) 323-7938. (212) 344-6633. Fax (212) 747-0004. Email: [email protected]. Website: www.nf.org. PRICE: $1.00 plus shipping and handling. Summary: This booklet describes neurofibromatosis (NF), a genetically determined disorder that causes tumors (mostly benign) to grow on all types of nerves in the body. The booklet defines NF and its two types (NF1 and NF2), then focuses on NF2, which includes a high risk for developing brain tumors; almost all affected individuals develop tumors on both nerves to the ears (also called the eighth cranial nerve). This nerve has two portions: the acoustic (hearing) nerve and the vestibular (balance) nerve which carries information on balance to the brain. The early symptoms of NF2 include hearing loss, ringing in the ears (tinnitus), and problems with balance. Topics include the epidemiology of NF2, the progress of the disease, complications, diagnostic tests (also used to stage the level of disease), and treatment options. The booklet concludes with some frequently asked questions about neurofibromatosis and a glossary of related terms. The contact information for the National Neurofibromatosis Foundation (NNFF) is provided (800-323-7938 or www.nf.org).

•

Positron Emission Tomography: Emerging Research Opportunities in the Neurosciences Source: Bethesda, MD: National Institutes of Health. 1984. 16 p. Contact: Available from National Institute of Neurological and Communicative Disorders and Stroke. National Institutes of Health, Bethesda, MD 20892. (301) 496-4000. PRICE: Call for information. NIH Publication Number 84-2620. Summary: This booklet examines positron emission tomography (PET), the first imaging technique that shows ongoing metabolic activity in various regions of the brain. This technique helps scientists understand how a healthy brain works and what alterations lead to brain diseases, both neurological and psychiatric. This aspect of imaging is especially helpful in studying the effects of Alzheimer's disease on the brain. The basis of PET is a group of radioisotopes that decay and emit positrons, creating imaging capabilities. The booklet discusses PET's use for observing both healthy brains and those affected by neurological diseases, brain tumors, stroke, and dementing disease. Studies at the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) have demonstrated that a decrease in metabolism is greatest in the parietotemporal region of the brain in Alzheimer's patients. PET has many possibilities for new avenues of research into the components of brain function.

240 Brain Tumors

•

Del Oro Caregiver Resource Center for Caregivers of Brain Impaired Adults Source: Carmichael, CA: Del Oro Caregiver Resource Center. 6 p. Contact: Available from Del Oro Caregiver Resource Center. 5713A Marconi Avenue, Suite 300, Carmichael, CA 95608. (800) 635-0220 or (916) 971-0893. PRICE: Free. Summary: This brochure describes the goals, services, and eligibility requirements of a program provided by a California Regional Resource Center to aid adults who suffer from brain impairment due to various causes (Alzheimer's, Parkinson's, Huntington's and other degenerative diseases of the brain; stroke; traumatic brain injury; brain tumors). The Center was founded in 1984 to establish a coordinated resource system to meet the needs of brain impaired adults through assistance to their families, professionals, and other caregivers. The Center supplies information and referral services to caregivers of brain impaired adults, and provides contractual services for legal and financial advice, family counseling, respite care, and diagnostic assessment.

•

Los Angeles Caregiver Resource Center: Part of a Statewide System of Regional Resource Centers Serving Families and Care Givers of Brain Impaired Adults Source: Los Angeles, CA: Los Angeles Caregiver Resource Center. 1991. [6 p.]. Contact: Available from Los Angeles Caregiver Resource Center. 3715 McClintock Avenue, Los Angeles, CA 90089-0191. (213) 740-8711 or (800) 540-4442. PRICE: Free. Summary: This brochure describes the Los Angeles Caregiver Resource Center, a program of the Andrus Older Adult Center at the University of California. The Center is part of a statewide system of regional resource centers serving families and caregivers of adults with permanent brain impairment due to Alzheimer's disease and other dementing illnesses, stroke and other cerebrovascular accidents, traumatic brain injury, brain tumors, and other conditions. The Center assists these caregivers directly by providing the following services: information and community resources, support groups, family consultations, respite care, legal and financial consultations, and workshops on issues related to caregiving. Families who reside in Los Angeles County are eligible for some or all of the services. The brochure describes these services and provides contact information for further inquiries.

•

Fact Sheet: Dementia Source: San Francisco, CA: Family Survival Project. 1989. [4 p.]. Contact: Available from Family Survival Project. 425 Bush Street, Suite 500, San Francisco, CA 94108. (415) 434-3388 or (800) 445-8106 (in California). PRICE: Single copy free, additional copies $1.00 each. Summary: This fact sheet describes dementia as impaired intellectual capacity. An estimated 2.5 million to 6.5 million persons nationwide have dementia. Dementing conditions are caused by abnormal disease processes that can affect younger as well as older persons. It is emphasized that demential is not a normal part of the aging process. Symptoms include memory loss, inability to think problems through, confusion, difficulty concentrating, and inappropriate behavior. Deteriorating intellectual capacity may be caused by a variety of diseases and disorders. Some 100 conditions that mimic serious disorders are actually reversible such as reactions to medications, metabolic disturbances, and brain tumors. To diagnose dementia, a complete medical and neurophysiological evaluation is recommended. Chronic or irreversible dementia requires special care. Arrangements and support must be offered to families who care

Patient Resources

241

for a person with dementia at home. Consultation for long term care, including placement in a skilled nursing facility when indicated, can also be helpful to a family. This fact sheet is also available in Spanish (see AZDCO3305). •

Diagnostic Guide: Cyclic Vomiting Syndrome (CVS) Source: Canal Winchester, OH: Cyclic Vomiting Syndrome Association, USA/Canada. 1999. [1 p]. Contact: Available from Cyclic Vomiting Syndrome Association, USA/Canada. 3585 Cedar Hill Road, NW, Canal Winchester, OH 43110. (614) 837-2586. Fax (614) 837-2586. E-mail: [email protected]. Website: www.cvsaonline.org. PRICE: Single copy free. Summary: This fact sheet offers a diagnostic guide for cyclic vomiting syndrome. Cyclic vomiting refers to discrete and severe episodes of vomiting, nausea, and lethargy (severe tiredness). Episodes are discrete in that the sufferer is free of nausea and vomiting between episodes. Episodes can occur on a routine schedule, be triggered by physical or psychological stress, or appear to come at random. The fact sheet lists the research definition, the current diagnostic criteria, diagnostic studies that can be used to exclude specific diagnoses that mimic CVS, and which tests should be obtained between acute episodes as well as those tests that should be performed during an acute episode. The essential diagnostic criteria for CVS include: recurrent severe episodes of nausea and vomiting, minimum of 3 distinct episodes; more than 4 emeses per hour at the peak; episodes last from hours to days, 24 to 48 hours on average; less than 2 episodes per week; varying intervals of normal health between episodes. Diagnoses that can cause a cyclic vomiting pattern include abdominal migraine, chronic sinus infections, brain tumors, structural abnormalities of the intestinal tract, kidney blockage, metabolic and endocrine disorders, and psychological disturbances. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “brain tumors” (or synonyms). The following was recently posted: •

(1) Best practice evidence-based guideline for the appropriate prescribing of hormone replacement therapy. (2) Guideline update: hormone replacement therapy Source: Effective Practice Institute, University of Auckland - Academic Institution; 2001 May (revised information released on 2002 September 30); 185 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3107&nbr=2333&a mp;string=brain+AND+tumors

•

(1) Botulinum toxin as a biological weapon: medical and public health management. (2) Botulinum toxin as a biological weapon. (Addendum) Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 2001 February 28 (addendum published 2002); 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3619&nbr=2845&a mp;string=brain+AND+neoplasm

242 Brain Tumors

•

2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999 August (updated 2001 November 28); 64 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3080&nbr=2306&a mp;string=intracranial+AND+tumor

•

AACE medical guidelines for clinical practice for management of menopause Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1999 Nov-December; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2138&nbr=1364&a mp;string=brain+AND+neoplasm

•

AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1997 (updated 2001 May-Jun); 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2848&nbr=2074&a mp;string=brain+AND+tumors

•

ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guide Source: American College of Cardiology Foundation - Medical Specialty Society; 2001 October; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2968&nbr=2194&a mp;string=brain+AND+neoplasm

•

ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Source: American College of Cardiology Foundation - Medical Specialty Society; 1998 April (revised 2002 Sep); 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3439&nbr=2665&a mp;string=brain+AND+neoplasm

Patient Resources

•

243

ACR Appropriateness Criteria™ for imaging recommendations for patients with dysphagia Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3259&nbr=2485&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for ataxia Source: American College of Radiology - Medical Specialty Society; 1999; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2449&nbr=1675&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for cerebrovascular disease Source: American College of Radiology - Medical Specialty Society; 1996 (revised 2000); 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2437&nbr=1663&a mp;string=brain+AND+neoplasm

•

ACR Appropriateness Criteriaâ„¢ for dementia Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2445&nbr=1671&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for epilepsy Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2439&nbr=1665&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for follow-up and retreatment of brain metastases Source: American College of Radiology - Medical Specialty Society; 1999; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2505&nbr=1731&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for imaging of intracranial infections Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2446&nbr=1672&a mp;string=brain+AND+tumors

244 Brain Tumors

•

ACR Appropriateness Criteriaâ„¢ for imaging work-up for stage I breast carcinoma Source: American College of Radiology - Medical Specialty Society; 1996 (revised 2002); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3562&nbr=2788&a mp;string=brain+AND+tumor

•

ACR Appropriateness Criteriaâ„¢ for multiple brain metastases Source: American College of Radiology - Medical Specialty Society; 1999; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2504&nbr=1730&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for multiple sclerosis -- when and how to image Source: American College of Radiology - Medical Specialty Society; 1999; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2447&nbr=1673&a mp;string=brain+AND+neoplasms

•

ACR Appropriateness Criteriaâ„¢ for myelopathy Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2443&nbr=1669&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for neuroendocrine imaging Source: American College of Radiology - Medical Specialty Society; 1999; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2448&nbr=1674&a mp;string=intracranial+AND+tumor

•

ACR Appropriateness Criteriaâ„¢ for pre-irradiation evaluation and management of brain metastasis Source: American College of Radiology - Medical Specialty Society; 1999; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2502&nbr=1728&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for progressive neurologic deficit Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2438&nbr=1664&a mp;string=brain+AND+tumors

Patient Resources

•

245

ACR Appropriateness Criteriaâ„¢ for solitary brain metastasis Source: American College of Radiology - Medical Specialty Society; 1999; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2503&nbr=1729&a mp;string=brain+AND+tumors

•

ACR Appropriateness Criteriaâ„¢ for vertigo and hearing loss Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2440&nbr=1666&a mp;string=brain+AND+tumors

•

Acute confusion/delirium Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1998; 41 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1344&nbr=536&am p;string=brain+AND+neoplasm

•

Acute sinusitis in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 July (revised 2002 Dec); 30 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3673&nbr=2899&a mp;string=brain+AND+tumors

•

Adult low back pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 June (revised 2002 Sep); 61 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3498&nbr=2724&a mp;string=brain+AND+tumors

•

Altered mental states Source: American Health Care Association - Professional Association; 1998; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1804&nbr=1030&a mp;string=brain+AND+tumors

•

American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1998 (revised 2003); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3726&nbr=2952&a mp;string=intracranial+AND+tumors

246 Brain Tumors

•

American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1996 (revised 2002); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3525&nbr=2751&a mp;string=brain+AND+tumor

•

American Gastroenterological Association medical position statement: celiac sprue Source: American Gastroenterological Association - Medical Specialty Society; 2000 November 12 (reviewed 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3058&nbr=2284&a mp;string=brain+AND+tumors

•

American Gastroenterological Association medical position statement: parenteral nutrition Source: American Gastroenterological Association - Medical Specialty Society; 2001 May 18; 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3056&nbr=2282&a mp;string=brain+AND+tumors

•

Antithrombotic therapy in atrial fibrillation. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2726&nbr=1952&a mp;string=brain+AND+neoplasm

•

Assessment and management of acute pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 2000 October (revised 2002 Oct); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3500&nbr=2726&a mp;string=brain+AND+neoplasm

•

Behavioral counseling in primary care to promote a healthy diet: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3494&nbr=2720&a mp;string=brain+AND+tumors

Patient Resources

•

247

Cardiovascular disease in women: a guide to risk factor screening, prevention and management Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 2002; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3487&nbr=2713&a mp;string=brain+AND+tumors

•

Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=brain+AND+tumors

•

Clinical practice guideline: management of sinusitis Source: American Academy of Pediatrics - Medical Specialty Society; 2001 September; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2936&nbr=2162&a mp;string=intracranial+AND+tumor

•

Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock Source: American College of Critical Care Medicine - Professional Association; 2002 June; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3433&nbr=2659&a mp;string=brain+AND+neoplasm

•

Driving and heart disease Source: European Society of Cardiology - Medical Specialty Society; 1998 August; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1930&nbr=1156&a mp;string=brain+AND+neoplasm

•

Essential hypertension Source: University of Michigan Health System - Academic Institution; 1997 (revised 2002 Aug); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3539&nbr=2765&a mp;string=brain+AND+neoplasm

•

Evaluation and management of intracranial mass lesions in AIDS. Source: American Academy of Neurology - Medical Specialty Society; 1998; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1446&nbr=654&am p;string=brain+AND+tumors

248 Brain Tumors

•

Evaluation of the newborn with developmental anomalies of the external genitalia Source: American Academy of Pediatrics - Medical Specialty Society; 2000 July; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2770&nbr=1996&a mp;string=brain+AND+tumors

•

Evidence based clinical practice guideline for children with acute bacterial sinusitis in children 1 to 18 years of age Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 2001; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3118&nbr=2344&a mp;string=brain+AND+neoplasm

•

Evidence based clinical practice guideline for medical management of first unprovoked seizure in children 2 to 18 years of age Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 1999 June 28 (revised 2002 July 1); 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3526&nbr=2752&a mp;string=brain+AND+tumors

•

Evidence-based protocol. Individualized music Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1996 (revised 2001 Feb); 35 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3073&nbr=2299&a mp;string=brain+AND+neoplasm

•

Evidence-based protocol. Wandering Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 2002 March; 45 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3250&nbr=2476&a mp;string=brain+AND+neoplasm

•

General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP) Source: American Academy of Family Physicians - Medical Specialty Society; 2002 February 8; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3180&nbr=2406&a mp;string=brain+AND+tumors

Patient Resources

•

249

Genetic counseling for fragile X syndrome: recommendations of the National Society of Genetic Counselors Source: National Society of Genetic Counselors; 2000; 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2546&nbr=1772&a mp;string=brain+AND+tumors

•

Guidelines for detection of thyroid dysfunction Source: American Thyroid Association - Professional Association; 2000 June 12; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2361&nbr=1587&a mp;string=brain+AND+tumors

•

Guidelines for referral to pediatric surgical specialists Source: American Academy of Pediatrics - Medical Specialty Society; 2002 July; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3420&nbr=2646&a mp;string=brain+AND+tumors

•

Identification, referral, and support of elders with genetic conditions Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1999; 31 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1968&nbr=1194&a mp;string=brain+AND+tumors

•

Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3639&nbr=2865&a mp;string=brain+AND+tumors

•

Inpatient management guidelines for people with diabetes Source: American Healthways, Inc - Public For Profit Organization; 1999 (revised 2002 Mar); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3217&nbr=2443&a mp;string=brain+AND+neoplasm

•

Intravenous immunoglobulin preparations Source: University HealthSystem Consortium - Private Nonprofit Organization; 1999 March; 216 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1976&nbr=1202&a mp;string=brain+AND+tumors

250 Brain Tumors

•

K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification Source: National Kidney Foundation - Disease Specific Society; 2002 February; 246 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3192&nbr=2418&a mp;string=brain+AND+neoplasm

•

Laboratory guidelines for screening, diagnosis, and monitoring of hepatic injury Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2000; 42 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3520&nbr=2746&a mp;string=brain+AND+tumors

•

Laboratory support for the diagnosis and monitoring of thyroid disease Source: National Academy of Clinical Biochemistry - Professional Association; 2002; 125 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3522&nbr=2748&a mp;string=brain+AND+tumors

•

Liver transplantation Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2000 January; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3449&nbr=2675&a mp;string=brain+AND+tumors

•

Lung cancer. Palliative care Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3653&nbr=2879&a mp;string=brain+AND+tumors

•

Management of adult testicular germ cell tumours. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1998 September; 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2903&nbr=2129&a mp;string=brain+AND+tumors

Patient Resources

•

251

Management of breastfeeding for healthy full-term infants Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2002 December; 89 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3624&nbr=2850&a mp;string=brain+AND+neoplasm

•

Management of chronic kidney disease and pre-ESRD in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 2000 November; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3099&nbr=2325&a mp;string=brain+AND+tumors

•

Management of lung cancer. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1998 February; 53 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2899&nbr=2125&a mp;string=brain+AND+tumors

•

Management of patients with stroke. Rehabilitation, prevention and management of complications, and discharge planning. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1998 April (revised 2002 Nov); 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3538&nbr=2764&a mp;string=brain+AND+neoplasm

•

Management of type 2 diabetes mellitus Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 March (revised 2002 Sep); 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3499&nbr=2725&a mp;string=brain+AND+neoplasm

•

Manual for radiation oncology nursing practice and education Source: Oncology Nursing Society - Professional Association; 1998; 79 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1687&nbr=913&am p;string=brain+AND+tumors

•

Migraine headache Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 November (revised 2002 Jul); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3441&nbr=2667&a mp;string=intracranial+AND+tumor

252 Brain Tumors

•

Part I. Guidelines for the management of severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000; 165 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3121&nbr=2347&a mp;string=brain+AND+neoplasm

•

Part II. Early indicators of prognosis in severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000; 116 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3122&nbr=2348&a mp;string=brain+AND+neoplasm

•

Pediatric eye and vision examination Source: American Optometric Association - Professional Association; 1994 (revised 2002); 57 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3548&nbr=2774&a mp;string=brain+AND+tumors

•

Pediatric eye evaluations Source: American Academy of Ophthalmology - Medical Specialty Society; 1992 June (revised 2002 Oct); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3543&nbr=2769&a mp;string=brain+AND+tumors

•

Physical activity in the prevention, treatment and rehabilitation of diseases Source: Finnish Medical Society Duodecim - Professional Association; 2002 May 7; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3398&nbr=2624&a mp;string=brain+AND+neoplasm

•

Postmenopausal hormone replacement therapy for the primary prevention of chronic conditions: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3455&nbr=2681&a mp;string=brain+AND+tumors

Patient Resources

•

253

Practice guideline for the treatment of patients with delirium Source: American Psychiatric Association - Medical Specialty Society; 1999 May; 41 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2180&nbr=1406&a mp;string=brain+AND+neoplasm

•

Practice guidelines for psychiatric consultation in the general medical setting Source: Academy of Psychosomatic Medicine - Medical Specialty Society; 1998 JulAugust; 30 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1702&nbr=928&am p;string=brain+AND+neoplasm

•

Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Source: American Academy of Neurology - Medical Specialty Society; 2000 May; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2823&nbr=2049&a mp;string=brain+AND+tumors

•

Practice parameters for the role of actigraphy in the study of sleep and circadian rhythms: an update for 2002 Source: American Academy of Sleep Medicine - Professional Association; 1995 (revised 2003 May 1); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3807&nbr=3033&a mp;string=intracranial+AND+tumor

•

Presentations of lung cancer with special treatment considerations Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3650&nbr=2876&a mp;string=brain+AND+tumors

•

Procedure guideline for somatostatin receptor scintigraphy with In-111 pentetreotide Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 2001 February 11; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2950&nbr=2176&a mp;string=brain+AND+tumors

254 Brain Tumors

•

Prophylactic cranial irradiation in small cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2000 March 22 (updated online 2002 Jul); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3459&nbr=2685&a mp;string=brain+AND+tumors

•

Recommendations on selected interventions to prevent dental caries, oral and pharyngeal cancers, and sports-related craniofacial injuries Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2002 July; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3287&nbr=2513&a mp;string=brain+AND+tumors

•

Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 370 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2720&nbr=1946&a mp;string=brain+AND+neoplasm

•

Small cell lung cancer Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3651&nbr=2877&a mp;string=brain+AND+tumors

•

Specialty referral guidelines for cardiovascular evaluation and management Source: American Healthways, Inc - Public For Profit Organization; 2002; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3168&nbr=2394&a mp;string=brain+AND+tumors

•

The noninvasive staging of non-small cell lung cancer: the guidelines Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3642&nbr=2868&a mp;string=brain+AND+tumors

•

Ultrasonographic examinations: indications and preparation of the patient Source: Finnish Medical Society Duodecim - Professional Association; 2000 April 18 (revised 2001 October 24); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3385&nbr=2611&a mp;string=brain+AND+tumors

Patient Resources

•

255

VHA/DOD clinical practice guideline for the management of major depressive disorder in adults Source: Department of Defense - Federal Government Agency [U.S.]; 1997 (updated 2000); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2585&nbr=1811&a mp;string=brain+AND+neoplasm

•

VHA/DoD clinical practice guideline for the management of substance use disorders Source: Department of Defense - Federal Government Agency [U.S.]; 2001 September; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3169&nbr=2395&a mp;string=brain+AND+neoplasm

•

Wheelchair biking for the treatment of depression Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 2003 February; 53 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3682&nbr=2908&a mp;string=brain+AND+neoplasm Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Adult Brain Tumors (PDQ®): Treatment Information for Patients Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4820

•

Childhood Brain Tumors (PDQ®): Treatment Information for Patients Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4821

•

Dictionary for Brain Tumor Patients Summary: Browse this site for online assistance in finding basic definitions for some general or specific medical and scientific terms, symbols and acronyms related to brain tumors. Source: American Brain Tumor Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1984

256 Brain Tumors

•

Primer of Brain Tumors Summary: The Primer of Brain Tumors is a reference manual for learning about, and better understanding, brain tumors. Source: American Brain Tumor Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6554

•

What You Need To Know About™ Brain Tumors Summary: This booklet describes the symptoms, diagnosis, and treatment of brain tumors. Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7119 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to brain tumors. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Brain Tumors The following is a list of associations that provide information on and resources relating to brain tumors:

Patient Resources

•

257

American Brain Tumor Association Telephone: (847) 827-9910 Toll-free: (800) 886-2282 Fax: (847) 827-9918 Email: [email protected] Web Site: http://www.abta.org Background: The American Brain Tumor Association (ABTA) is an independent, notfor-profit organization founded in 1973. Services include more than 20 publications that address brain tumors, their treatment, and coping with the disease. These publications are written in easy-to-understand language. The materials address brain tumors in all age groups. The Association provides free social service consultations by telephone; a mentorship program for new brain tumor support group leaders; a nationwide database of established support groups; a rescue listing of physicians offering investigative treatments; the 'Connections' pen pal program; and an award-winning Internet site. The American Brain Tumor Association conducts national symposia and sponsors regional Town Hall meetings for patients and their families.

•

Brain Tumor Foundation for Children, Inc Telephone: (770) 458-5554 Fax: (770) 458-5467 Email: [email protected] Web Site: www.braintumorkids.org Background: The Brain Tumor Foundation for Children, Inc. (BTFC) is a national voluntary organization dedicated to providing emotional and informational support to families of children with brain tumors. Established in 1983 and currently consisting of approximately 1,400 members, BTFC is also committed to promoting public awareness of pediatric brain tumors and raising funds to support research that may discover potential cures and improve the treatment and quality of life of those affected by pediatric brain tumor disease. In addition, the Brain Tumor Foundation for Children has support groups, offers family networking services, and engages in patient education. Educational materials includes brochures, pamphlets, and a regular newsletter.

•

Brain Tumor Foundation of Canada Telephone: (519) 642-7755 Toll-free: (800) 265-5106 Fax: (519) 642-7192 Email: [email protected] Web Site: http://www.btfc.org Background: The Brain Tumour Foundation of Canada is a not-for-profit organization dedicated to reaching every person in Canada affected by a brain tumour with support, education and information, and to fund brain tumour research. Established in 1982, the Brain Tumor Foundation of Canada is committed to raising public awareness about the causes, effects, and treatment of brain tumors; working to support and improve the quality of life of those affected by brain tumors; and striving to find a cure for brain tumors. The Foundation s primary educational objective is to meet the information needs of individuals with brain tumors and their families. Educational materials include comprehensive and easy-to-read patient resource handbooks in adult and pediatric

258 Brain Tumors

versions. Other materials include pamphlets designed to alert individuals, parents, educators, and health care professionals to the early warning signs and symptoms of brain tumors; a quarterly newsletter entitled 'Brainstorm'; and many books, publications, videos, and audio cassettes. Program activities include support group meetings; a national telephone support system; home and hospital visits; and an annual Adult and Pediatric Brain Tumor Information Day. Relevant area(s) of interest: Brain Tumors •

Brain Tumor Society Telephone: (617) 924-9997 Toll-free: (800) 770-8287 Fax: (617) 924-9998 Email: [email protected] Web Site: http://www.tbts.org Background: The Brain Tumor Society (TBTS) is a national voluntary not-for-profit organization dedicated to finding a cure for brain tumors, improving affected individuals quality of life, disseminating educational information on brain tumors, and providing psychosocial support to affected individuals and their families. The Society raises funds and makes grants to advance carefully selected scientific research projects, improve clinical care, and find a cure. The Society encourages participation in support groups and offers a wide range of services to help individuals cope with and manage the problems associated with brain tumors. TBTS offers a variety of educational programs to raise public awareness, facilitate early diagnosis and treatment, and to educate professionals about psychosocial issues associated with rare diagnoses. Educational materials include a newsletter entitled 'Heads Up,' a booklet on resources, brochures, and special resources for persons with rare brain tumors.

•

Central Brain Tumor Registry of the United States Telephone: (630) 655-4786 Fax: (630) 655-1756 Email: [email protected] Web Site: www.cbtrus.org Background: The Central Brain Tumor Registry of the United States (CBTRUS) is a voluntary not-for-profit organization dedicated to collecting and disseminating statistical data on all primary benign and malignant brain tumors. Such data collection and dissemination is for the purposes of accurately describing incidence rates and survival patterns, evaluating diagnosis and treatment, facilitating studies concerning causes (etiology), promoting professional and public awareness, and, ultimately, working toward the possible prevention of such brain tumors. CBTRUS was incorporated in 1992 following a two-year study by the American Brain Tumor Association to determine the feasibility of a central registry for all brain tumor cases. In the past, standard data collection in the United States had been limited to malignant brain tumor cases. The Central Brain Tumor Registry has since developed a populationbased brain tumor registry including data on both malignant and non-malignant brain tumors through centralizing and compiling information on newly diagnosed cases from 13 participating state cancer registries. The CBTRUS database summarizes collaborators' data and generates statistics that are published in the form of an Annual Report. The Annual Report is mailed free of charge to over 2,000 members of the neuroscience

Patient Resources

259

community as well as to affected individuals, family members, and businesses upon request. In addition to data collection and dissemination, CBTRUS is dedicated to conducting special studies aimed at broadening the scope of data concerning the incidence and prevalence of brain tumors in certain populations. CBTRUS also encourages and promotes interdisciplinary dialogue with other professional and volunteer organizations, believing that only through collaboration and cooperation will brain tumors be understood and overcome. •

Children's Brain Tumor Foundation Telephone: (212) 448-9494 Toll-free: (866) 228-4673 Fax: (212) 448-1022 Email: [email protected] Web Site: www.cbtf.org Background: The Children's Brain Tumor Foundation (CBTF), founded in 1988, funds scientific research on the causes of, and improved treatments for, pediatric brain and spinal cord tumors and provides support and educational services to families and survivors. CBTF distributes 'A Resource Guide for Parents of Children with Brain and Spinal Cord Tumors' at no charge to families in English and Spanish, co-sponsors educational seminars and teleconferences, and provides online information through its Web site at www.cbtf.org. Each year, CBTF provides information and referrals to critical services to hundreds of families from all over the world. The Parent-to-Parent Network provides support to newly diagnose families from experienced parents who have been trained as volunteers. A newsletter, The Challenge, is published twice a year.

•

National Brain Tumor Foundation Telephone: (510) 839-9777 Toll-free: (800) 934-2873 Fax: (510) 839-9779 Email: [email protected] Web Site: http://www.braintumor.org Background: The National Brain Tumor Foundation is a national not-for-profit voluntary organization that serves as a comprehensive center for information regarding resources and support services for people whose lives are affected by brain tumor disease. Established in 1981, the National Brain Tumor Foundation also provides financial support for investigational studies into the causes, prevention, and treatments of brain tumors. To these ends, the National Brain Tumor Foundation has funded basic and applied laboratory research and clinical trials of new treatments at major institutions in the United States. The organization has also supported research into quality of life issues that regularly confront people with brain tumors. A comprehensive guide is available for affected individuals and their families who want to learn more about brain tumors. The National Brain Tumor Foundation also produces a variety of educational materials including a newsletter entitled 'Search.' Affected individuals and family members may also receive referrals to a network of support groups throughout the United States.

260 Brain Tumors

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to brain tumors. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with brain tumors. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about brain tumors. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “brain tumors” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “brain tumors”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “brain tumors” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

Patient Resources

261

The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “brain tumors” (or a synonym) into the search box, and click “Submit Query.”

263

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

26

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

264 Brain Tumors

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

265

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

266 Brain Tumors

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

267

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

268 Brain Tumors

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

269

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

271

BRAIN TUMORS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH]

272 Brain Tumors

Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the

Dictionary 273

tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as

274 Brain Tumors

standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis Factor: Substance causing proliferation of new blood vessels. It is found in tissues with high metabolic requirements, such as the retina, and in certain cancers. The

Dictionary 275

factor is also released by hypoxic macrophages at the edges or outer surfaces of wounds and initiates revascularization in wound healing. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anosmia: Absence of the sense of smell; called also anosphrasia and olfactory anaesthesia. [EU]

Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiangiogenesis: Prevention of the growth of new blood vessels. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

276 Brain Tumors

Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH]

Dictionary 277

Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU]

278 Brain Tumors

Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous tumor cells: Cancer cells from an individual's own tumor. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the

Dictionary 279

internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azaserine: Antibiotic substance produced by various Streptomyces species. It is an inhibitor of enzymatic activities that involve glutamine and is used as an antineoplastic and immunosuppressive agent. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH]

280 Brain Tumors

Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomedical Engineering: Application of principles and practices of engineering science to biomedical research and health care. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bispecific antibodies: Antibodies developed in the laboratory to recognize more than one protein on the surface of different cells. Examples include bispecific antibodies 2B1, 520C9xH22, mDX-H210, and MDX447. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example,

Dictionary 281

in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH]

282 Brain Tumors

Brain metastases: Cancer that has spread from the original (primary) tumor to the brain. [NIH]

Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain stem glioma: A tumor located in the part of the brain that connects to the spinal cord (the brain stem). It may grow rapidly or slowly, depending on the grade of the tumor. [NIH] Brain Stem Infarctions: Infarctions that occur in the brain stem which is comprised of the midbrain, pons, and medulla. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Buthionine sulfoximine: A drug that may help prevent resistance to some anticancer drugs. [NIH]

Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Butyrylcholinesterase: An aspect of cholinesterase (EC 3.1.1.8). [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadaver: A dead body, usually a human body. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the

Dictionary 283

interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]

Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU]

284 Brain Tumors

Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cavernous Sinus: An irregularly shaped venous space in the dura mater at either side of the sphenoid bone. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular Structures: Components of a cell. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellopontine: Going from the cerebellum (the part of the brain responsible for coordinating movement) to the pons (part of the central nervous system located near the base of the brain.) [NIH] Cerebellopontine Angle: Junction between the cerebellum and the pons. [NIH]

Dictionary 285

Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [NIH] Chemosensitizer: A drug that makes tumor cells more sensitive to the effects of chemotherapy. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Chlorpyrifos: An organothiophosphate cholinesterase inhibitor that is used as an insecticide and as an acaricide. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU]

286 Brain Tumors

Cholinergic Agents: Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of acetylcholine, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of muscarinic agonists, although most modern texts discourage that usage. [NIH] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroid Plexus: A villous structure of tangled masses of blood vessels contained within the third, lateral, and fourth ventricles of the brain. It regulates part of the production and composition of cerebrospinal fluid. [NIH] Choroid plexus tumor: A rare type of cancer that occurs in the ventricles of the brain. It usually occurs in children younger than 2 years. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Abnormalities: Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic granulocytic leukemia: A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myelogenous leukemia or chronic myeloid leukemia. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH]

Dictionary 287

Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins,

288 Brain Tumors

such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the

Dictionary 289

alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementarity Determining Regions: Three regions (CDR1, CDR2 and CDR3) of amino acid sequence in theimmunoglobulin variable region that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (receptors, antigen, T-cell). [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH]

290 Brain Tumors

Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Contusion: A bruise; an injury of a part without a break in the skin. [EU] Conventional therapy: A currently accepted and widely used treatment for a certain type of

Dictionary 291

disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Irradiation: The exposure of the head to roentgen rays or other forms of radioactivity for therapeutic or preventive purposes. [NIH] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] CSF: Cerebrospinal fluid. The fluid flowing around the brain and spinal cord. CSF is produced in the ventricles of the brain. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH]

292 Brain Tumors

Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclic Vomiting Syndrome: Sudden, repeated attacks of severe vomiting (especially in children), nausea, and physical exhaustion with no apparent cause. Can last from a few hours to 10 days. The episodes begin and end suddenly. Loss of fluids in the body and changes in chemicals in the body can require immediate medical attention. Also called abdominal migraine. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyproheptadine: A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of

Dictionary 293

data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]

Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary

294 Brain Tumors

genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dexrazoxane: A drug used to protect the heart from the toxic effects of anthracycline drugs such as doxorubicin. It belongs to the family of drugs called chemoprotective agents. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diagnostic Services: Organized services for the purpose of providing diagnosis to promote and maintain health. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diazinon: A cholinesterase inhibitor that is used as an organothiophosphorus insecticide. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are

Dictionary 295

the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihematoporphyrin Ether: The purified component of hematoporphyrin derivative, it consists of a mixture of oligomeric porphyrins. It is used in photodynamic therapy (hematoporphyrin photoradiation) to treat malignant lesions with visible light and experimentally as an antiviral agent. It is the first drug to be approved in the use of photodynamic therapy in the United States. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]

Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used

296 Brain Tumors

to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage schedule: A scheme set up to determine and regulate size, frequency and number of doses. [EU] Dose Fractionation: Adminstration of the total dose of radiation in parts, at timed intervals. [NIH]

Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is

Dictionary 297

generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]

symptoms

resulting

from

an

absent

or

Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is

298 Brain Tumors

based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromagnetic Fields: Fields representing the joint interplay of electric and magnetic forces. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and

Dictionary 299

other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelial Growth Factors: These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic fibroblast growth factors but have different amino acid sequences. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH]

300 Brain Tumors

Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Ependymal: It lines the cavities of the brain's ventricles and the spinal cord and slowly divides to create a stem cell. [NIH] Ependymal tumors: A type of brain tumor that usually begins in the central canal of the spinal cord. Ependymomas may also develop in the cells lining the ventricles of the brain, which produce and store the special fluid (cerebrospinal fluid) that protects the brain and spinal cord. Also called ependymomas. [NIH] Ependymomas: Brain tumors that usually begin in the central canal of the spinal cord. Ependymomas may also develop in the cells lining the ventricles of the brain, which produce and store the special fluid (cerebrospinal fluid) that protects the brain and spinal cord. Also called ependymal tumors. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH]

Dictionary 301

Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethionine: 2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the

302 Brain Tumors

brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH] Fasciculation: A small local contraction of muscles, visible through the skin, representing a spontaneous discharge of a number of fibres innervated by a single motor nerve filament. [EU]

Fast Neutrons: Neutrons, the energy of which exceeds some arbitrary level, usually around one million electron volts. [NIH]

Dictionary 303

Fat: Total lipids including phospholipids. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU]

304 Brain Tumors

Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Antibody Technique: Test for tissue antigen using either a direct method by conjugation of antibody with fluorescent dye or an indirect method by formation of antigenantibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody. The tissue is then examined by fluorescence microscopy. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluoroimmunoassay: The use of fluorescence spectrometry to obtain quantitative results for the fluorescent antibody technique. One advantage over the other methods (e.g., radioimmunoassay) is its extreme sensitivity, with a detection limit on the order of tenths of microgram/liter. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]

Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungemia: The presence of fungi circulating in the blood. Opportunistic fungal sepsis is

Dictionary 305

seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma knife: Radiation therapy in which high-energy rays are aimed at a tumor from many angles in a single treatment session. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]

Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrectomy: An operation to remove all or part of the stomach. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH]

306 Brain Tumors

Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ cell tumors: Tumors that begin in the cells that give rise to sperm or eggs. They can occur virtually anywhere in the body and can be either benign or malignant. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. [NIH] Glial tumors: A general term for many types of tumors of the central nervous system, including astrocytomas, ependymal tumors, glioblastoma multiforme, and primitive neuroectodermal tumors. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH]

Dictionary 307

Gliosarcoma: A type of glioma. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH]

308 Brain Tumors

Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Handicap: A handicap occurs as a result of disability, but disability does not always constitute a handicap. A handicap may be said to exist when a disability causes a substantial and continuing reduction in a person's capacity to function socially and vocationally. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the

Dictionary 309

sensorineural pathways. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hemangiopericytoma: A type of cancer involving blood vessels and soft tissue. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematoporphyrin Derivative: A complex mixture of monomeric and aggregated porphyrins used in the photodynamic therapy of tumors (hematoporphyrin photoradiation). A purified component of this mixture is known as dihematoporphyrin ether. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring.

310 Brain Tumors

2. The genetic constitution of an individual. [EU] Herniated: Protrusion of a degenerated or fragmented intervertebral disc into the intervertebral foramen compressing the nerve root. [NIH] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic

Dictionary 311

acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic

312 Brain Tumors

chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunoconjugates: Combinations of diagnostic or therapeutic substances linked with specific immune substances such as immunoglobulins, monoclonal antibodies or antigens. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of drugs and radioisotopes in the chemotherapy and radioimmunotherapy of certain cancers. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH]

Dictionary 313

Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort Tlymphocytes into subsets based on CD antigens by the technique of flow cytometry. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators

314 Brain Tumors

or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as

Dictionary 315

a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-13: T-lymphocyte-derived cytokine that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature Blymphocytes. It appears to play a role in regulating inflammatory and immune responses. [NIH]

Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds,

316 Brain Tumors

wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intracranial tumors: Tumors that occur in the brain. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intrathecal chemotherapy: Anticancer drugs that are injected into the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Iodine-131: Radioactive isotope of iodine. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a

Dictionary 317

mechanical deformation. Ion channels which neurotransmitter receptors are not included. [NIH]

are

integral

parts

of

ionotropic

Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ionophores: Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratolytic: An agent that promotes keratolysis. [EU]

318 Brain Tumors

Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]

Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lateral Ventricles: Cavity in each of the cerebral hemispheres derived from the cavity of the embryonic neural tube. They are separated from each other by the septum pellucidum, and each communicates with the third ventricle by the foramen of Monro, through which also the choroid plexuses of the lateral ventricles become continuous with that of the third ventricle. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended

Dictionary 319

between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linear Energy Transfer: Rate of energy dissipation along the path of charged particles. In radiobiology and health physics, exposure is measured in kiloelectron volts per micrometer of tissue (keV/micrometer T). [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between

320 Brain Tumors

linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locoregional: The characteristic of a disease-producing organism to transfer itself, but typically to the same region of the body (a leg, the lungs, .) [EU] Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors. [NIH] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH]

Dictionary 321

Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Mafosfamide: A form of cyclophosphamide that can be administered as an intrathecal infusion. Mafosfamide is being studied as an anticancer drug; it belongs to the family of drugs called alkylating agents. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant meningioma: A rare, quickly growing tumor that occurs in the membranes that cover and protect the brain and spinal cord (meninges). [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet.

322 Brain Tumors

[NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Mechlorethamine: A vesicant and necrotizing irritant destructive to mucous membranes. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkin's disease and lymphomas. It causes severe gastrointestinal and bone marrow damage. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Megestrol: 17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by

Dictionary 323

means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH]

324 Brain Tumors

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei

Dictionary 325

normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]

Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes,

326 Brain Tumors

nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multimodality treatment: Therapy that combines more than one method of treatment. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Hypertonia: Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle

Dictionary 327

known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neoplastic meningitis: Tumor cells that have spread from the original (primary) tumor to the tissue that covers the brain, spinal cord, or both. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU]

328 Brain Tumors

Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroectodermal Tumors: Malignant neoplasms arising in the neuroectoderm, the portion of the ectoderm of the early embryo that gives rise to the central and peripheral nervous systems, including some glial cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuroma: A tumor that arises in nerve cells. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Diseases: A general term encompassing lower motor neuron disease; peripheral nervous system diseases; and certain muscular diseases. Manifestations include muscle weakness; fasciculation; muscle atrophy; spasm; myokymia; muscle hypertonia, myalgias, and musclehypotonia. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurosyphilis: A late form of syphilis that affects the brain and may lead to dementia and death. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are

Dictionary 329

neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutron Capture Therapy: A technique for the treatment of neoplasms in which an isotope is introduced into target cells followed by irradiation with thermal neutrons. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH] Nitrosoureas: A group of anticancer drugs that can cross the blood-brain barrier. Carmustine and lomustine are nitrosoureas. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH]

330 Brain Tumors

Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [NIH] Oligodendroglial: A cell that lays down myelin. [NIH] Oligodendroglioma: A rare, slow-growing tumor that begins in brain cells called oligodendrocytes, which provide support and nourishment for cells that transmit nerve impulses. Also called oligodendroglial tumor. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of meta-

Dictionary 331

rhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic cup: The white, cup-like area in the center of the optic disc. [NIH] Optic disc: The circular area (disc) where the optic nerve connects to the retina. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic Nerve Diseases: Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Otolaryngologist: A doctor who specializes in treating diseases of the ear, nose, and throat. Also called an ENT doctor. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otology: The branch of medicine which deals with the diagnosis and treatment of the disorders and diseases of the ear. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian epithelial cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH]

332 Brain Tumors

Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palliative therapy: Treatment given to relieve symptoms caused by advanced cancer. Palliative therapy does not alter the course of a disease but improves the quality of life. [NIH] Palsies: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH]

Dictionary 333

Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papilledema: Swelling around the optic disk. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Paraneoplastic syndrome: A group of symptoms that may develop when substances released by some cancer cells disrupt the normal function of surrounding cells and tissue. [NIH]

Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediatric Endocrinologist: A doctor who sees and treats children with problems of the endocrine glands; diabetes is an endocrine disorder. [NIH] Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It

334 Brain Tumors

is applied also in evaluating the quality of health care provided to patients. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Pericytes: Smooth muscle cell that wraps around normal blood vessels. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal

Dictionary 335

layer of the bowel wall. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylating: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH]

336 Brain Tumors

Pilot study: The initial study examining a new method or treatment. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pineal region tumors: Types of brain tumors that occur in or around the pineal gland, a tiny organ near the center of the brain. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]

Dictionary 337

Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Poly C: A group of cytosine ribonucleotides in which the phosphate residues of each cytosine ribonucleotide act as bridges in forming diester linkages between the ribose moieties. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Population Density: Number of individuals in a population relative to space. [NIH] Porfimer sodium: An anticancer drug that is also used in cancer prevention. It belongs to the family of drugs called photosensitizing agents. [NIH]

338 Brain Tumors

Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Positron emission tomography scan: PET scan. A computerized image of the metabolic activity of body tissues used to determine the presence of disease. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presumed Consent: An institutional policy of granting authority to health personnel to perform procedures on patients or to remove organs from cadavers for transplantation unless an objection is registered by family members or by the patient prior to death. This also includes emergency care of minors without prior parental consent. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a

Dictionary 339

designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary central nervous system lymphoma: Cancer that arises in the lymphoid tissue found in the central nervous system (CNS). The CNS includes the brain and spinal cord. [NIH]

Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procarbazine: An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH]

340 Brain Tumors

Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH]

Dictionary 341

Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or

342 Brain Tumors

from destruction of their walls. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation Oncology: A subspecialty of medical oncology and radiology concerned with the radiotherapy of cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radiation Tolerance: The ability of some cells or tissues to withstand ionizing radiation without serious injury. Tolerance depends on the species, cell type, and physical and chemical variables, including radiation-protective agents and radiation-sensitizing agents. [NIH]

Radiation-Protective Agents: Drugs used to protect against ionizing radiation. They are usually of interest for use in radiation therapy but have been considered for other, e.g. military, purposes. [NIH] Radiation-Sensitizing Agents: Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements

Dictionary 343

of atomic number above 83, and possible of induction in all other known elements. [EU] Radiobiology: That part of biology which deals with the effects of radiation on living organisms. [NIH] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the diagnosis and treatment of cancer and in pain management of bone metastases. Also called radioactive drugs. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Rationalize: To attribute one's actions to rational and creditable motives without adequate analysis of the true and unconscious motives. [NIH] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH]

344 Brain Tumors

Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative Biological Effectiveness: The ratio of radiation dosages required to produce identical change based on a formula comparing other types of radiation with that of gamma or Roentgen rays. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residential Facilities: Long-term care facilities which provide supervision and assistance in activities of daily living with medical and nursing services when required. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of

Dictionary 345

dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respite Care: Patient care provided in the home or institution intermittently in order to provide temporary relief to the family home care giver. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rhabdoid tumor: A malignant tumor of either the central nervous system (CNS) or the kidney. Malignant rhabdoid tumors of the CNS often have an abnormality of chromosome 22. These tumors usually occur in children younger than 2 years. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue

346 Brain Tumors

structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans.

Dictionary 347

In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains

348 Brain Tumors

spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an

Dictionary 349

ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft tissue sarcoma: A sarcoma that begins in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU]

350 Brain Tumors

Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language. [NIH] Speech pathologist: A specialist who evaluates and treats people with communication and swallowing problems. Also called a speech therapist. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Spermine: A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH]

Dictionary 351

Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotactic radiosurgery: A radiation therapy technique involving a rigid head frame that is attached to the skull; high-dose radiation is administered through openings in the head frame to the tumor while decreasing the amount of radiation given to normal brain tissue. This procedure does not involve surgery. Also called stereotaxic radiosurgery and stereotactic radiation therapy. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU]

352 Brain Tumors

Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and

Dictionary 353

methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Supratentorial: Located in the upper part of the brain. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Surgical Instruments: Hand-held tools or implements used by health professionals for the performance of surgical tasks. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester

354 Brain Tumors

transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptophysin: A 38-kDa integral membrane glycoprotein of the presynaptic vesicles in neuron and neuroendocrine cells. It is expressed by a variety of normal and neoplastic neuroendocrine cells and is therefore used as an immunocytochemical marker for neuroendocrine differentiation in various tumors. In Alzheimer disease and other dementing disorders there is an important synapse loss due in part to a decrease of synaptophysin in the presynaptic vesicles. [NIH] Synchrotron: An accelerator in which the particles are guided by an increasing magnetic field while they are accelerated several times in an approximately circular path by electric fields produced by a high-frequency generator. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]

Telemedicine: Delivery of health services via remote telecommunications. This includes interactive consultative and diagnostic services. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the

Dictionary 355

skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teniposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]

hydroxyethyl)-4-

Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU]

356 Brain Tumors

Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tirapazamine: A drug that makes tumor cells more sensitive to radiation therapy. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] Tonometer: For testing the intra-ocular tension. [NIH]

Dictionary 357

Tonometry: The standard to determine the fluid pressure inside the eye (intraocular pressure). [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] Translating: Conversion from one language to another language. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH]

358 Brain Tumors

Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor infiltrating lymphocytes: White blood cells that have left the bloodstream and migrated into a tumor. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU]

Dictionary 359

Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uncoupling Agents: Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those ionophores that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes. [NIH] Unresectable: Unable to be surgically removed. [NIH] Untranslated Regions: The parts of the messenger RNA sequence that do not code for product, i.e. the 5' untranslated regions and 3' untranslated regions. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]

Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This

360 Brain Tumors

includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertebrobasilar Insufficiency: Localized or diffuse reduction in blood flow through the vertebrobasilar arterial system, which supplies the brain stem; cerebellum; occipital lobe; medial temporal lobe; and thalamus. Characteristic clinical features include syncope; lightheadedness; visual disturbances; and vertigo. brain stem infarctions or other brain infarction may be associated. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU]

Dictionary 361

Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH]

362 Brain Tumors

Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] X-ray tube: Evacuated vessel for the production of X-radiation by the bombardment of a target, contained in an anode, with electrons accelerated by an electric field. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

363

INDEX 3 3-dimensional, 51, 271, 340 A Abdomen, 198, 271, 281, 300, 320, 332, 334, 351, 352, 355 Abdominal, 241, 271, 292, 305, 332, 334 Aberrant, 53, 271 Ablate, 176, 271 Ablation, 271 Abscess, 79, 212, 271 Acceptor, 271, 332, 356 Acetylcholine, 271, 285, 286, 329 Acetylcysteine, 187, 271 Acoustic, 162, 211, 239, 271, 361 Acrylonitrile, 179, 271, 346 Actin, 271, 326, 327 Activities of Daily Living, 271, 344 Acute lymphoblastic leukemia, 46, 60, 202, 271 Acute lymphocytic leukemia, 169, 271 Acute myelogenous leukemia, 47, 271, 272 Acute myeloid leukemia, 271, 272 Acute nonlymphocytic leukemia, 271, 272 Acyclovir, 192, 272, 305 Adaptability, 272, 284 Adaptation, 272, 285, 326, 336 Adenine, 92, 272, 342 Adenocarcinoma, 272, 329 Adenosine, 186, 272, 335 Adenosine Triphosphate, 186, 272, 335 Adenovirus, 24, 59, 65, 67, 163, 272 Adhesions, 170, 272 Adhesives, 271, 272 Adjustment, 108, 272 Adjuvant, 24, 56, 57, 137, 272 Adolescence, 21, 272 Adverse Effect, 30, 201, 272, 297, 348 Aerobic, 9, 272, 340 Afferent, 272, 291, 331 Affinity, 57, 170, 272, 273, 278, 299, 349 Age Groups, 257, 273 Age of Onset, 273, 282, 359 Aged, 80 and Over, 273 Agonist, 17, 185, 273, 296, 354 Airway, 273, 349 Alexia, 273, 297 Algorithms, 11, 182, 273, 280 Alimentary, 273, 316, 333

Alkaline, 273, 282, 332 Alkaloid, 273, 282, 288 Alkylating Agents, 273, 283, 321, 354, 359 Alkylation, 15, 273 Alleles, 273, 320 Allergen, 273, 348 Allergic Rhinitis, 210, 273 Allogeneic, 273, 307, 334 Alopecia, 273, 292 Alpha Particles, 273, 342 Alternative medicine, 219, 273 Aluminum, 274, 362 Alveolar Process, 274, 345 Alveoli, 274, 341 Amino Acid Sequence, 179, 274, 275, 289, 299, 302, 306 Amino Acids, 90, 167, 168, 274, 301, 306, 334, 337, 340, 346, 348, 352, 356, 357 Amnestic, 211, 274 Ampulla, 274, 299 Anaesthesia, 274, 275, 314 Anal, 50, 274, 300, 303 Analog, 187, 272, 274, 305, 330 Analogous, 274, 296, 357 Anaplastic, 6, 19, 21, 25, 30, 56, 106, 140, 143, 144, 146, 147, 151, 156, 177, 191, 195, 274 Anatomical, 14, 50, 57, 210, 274, 278, 298, 313, 320, 333, 347 Anemia, 107, 233, 274, 282, 304, 326 Anergy, 170, 274 Anesthesia, 273, 274 Anesthetics, 163, 274, 300 Angiogenesis, 8, 13, 14, 15, 22, 24, 27, 33, 35, 56, 58, 70, 78, 178, 203, 274, 275, 299, 322 Angiogenesis Factor, 14, 274 Angiogenesis inhibitor, 8, 24, 33, 275, 299 Angiography, 210, 275 Animal model, 49, 192, 195, 197, 275, 358 Anions, 275, 317, 353 Annealing, 275, 337 Anode, 275, 362 Anomalies, 248, 275, 355 Anorexia, 275, 305 Anosmia, 210, 275 Anthracycline, 164, 275, 293, 294 Antiallergic, 275, 292

364 Brain Tumors

Antiangiogenesis, 21, 70, 126, 275 Antiangiogenic, 10, 16, 103, 275 Antibacterial, 275, 350 Antibiotic, 275, 279, 293, 296, 305, 334, 350 Antibodies, 7, 8, 25, 57, 62, 107, 167, 177, 178, 179, 190, 275, 276, 280, 308, 312, 321, 325, 336, 343 Antibody therapy, 151, 152, 275 Anticoagulant, 275, 340 Anticonvulsants, 128, 275 Antidote, 275, 319 Antiemetic, 275, 276, 285 Antiepileptic, 90, 276 Antigen-presenting cell, 61, 276 Anti-infective, 276, 311, 316 Anti-inflammatory, 276, 294, 307, 338 Antimetabolite, 272, 276, 294, 301 Antineoplastic Agents, 16, 273, 276, 361 Antioxidant, 82, 276 Antipruritic, 276, 292 Antipsychotic, 276, 285 Antiserum, 15, 276 Antiviral, 181, 271, 272, 276, 295, 315 Antiviral Agents, 181, 276 Anuria, 277, 318 Anus, 274, 277, 281, 316 Anxiety, 188, 203, 211, 277 Anxiety Disorders, 211, 277 Aorta, 277, 360 Apathy, 194, 277 Aperture, 162, 277, 342 Aphasia, 274, 277 Apnea, 277 Aponeurosis, 277, 305 Apoptosis, 16, 27, 56, 59, 61, 127, 195, 277 Applicability, 24, 28, 33, 40, 277 Aqueous, 171, 277, 279, 287, 292, 298, 311, 319, 320 Aqueous humor, 171, 277, 287 Arachidonate 12-Lipoxygenase, 277, 320 Arachidonate 15-Lipoxygenase, 277, 320 Arachidonate Lipoxygenases, 277, 320 Arginine, 277, 329, 331, 342, 359 Aromatic, 9, 18, 277, 335 Arterial, 95, 103, 128, 187, 277, 278, 281, 283, 285, 311, 340, 354, 357, 360 Arteries, 277, 278, 280, 281, 291, 324 Arteriolar, 278, 281, 344 Arterioles, 278, 281, 282 Arteriovenous, 108, 278 Aspiration, 173, 183, 278 Assay, 26, 278, 343

Astringents, 278, 323 Astrocytes, 16, 52, 186, 190, 197, 198, 278 Asymptomatic, 170, 278 Ataxia, 186, 188, 212, 233, 243, 278, 311, 355 Atopic, 190, 278 Atrial, 242, 246, 278 Atrial Fibrillation, 242, 246, 278 Atrium, 278, 360 Atrophy, 4, 211, 233, 278, 328 Attenuated, 84, 278 Autoimmune disease, 91, 190, 278, 326 Autologous, 57, 90, 119, 278, 334 Autologous tumor cells, 57, 278 Autonomic, 271, 276, 278, 291, 334, 353 Autonomic Nervous System, 278, 334, 353 Autoradiography, 186, 279 Axonal, 51, 279 Axons, 279, 331, 334, 345 Azaserine, 168, 279 B Bactericidal, 279, 301 Bacteriophage, 279, 357 Bacterium, 279, 290 Basal Ganglia, 276, 278, 279, 281, 282, 286, 305, 306, 326 Basal Ganglia Diseases, 278, 279, 286, 326 Base, 35, 39, 47, 53, 56, 272, 279, 284, 292, 293, 306, 317, 318, 354 Basement Membrane, 279, 302, 318 Benign, 25, 170, 207, 239, 258, 279, 282, 305, 306, 308, 327, 343 Bewilderment, 279, 289 Bilateral, 64, 279 Bile, 279, 305, 310, 320, 352 Biochemical, 16, 17, 29, 45, 52, 56, 63, 71, 91, 179, 186, 273, 276, 280, 304, 318, 348 Biological response modifier, 14, 280, 315 Biological therapy, 139, 280, 308 Biological Transport, 280, 294 Biomarkers, 8, 9, 84, 88, 107, 280 Biomedical Engineering, 11, 27, 63, 280 Biomolecular, 198, 280 Biopsy, 17, 155, 175, 207, 280, 301 Biosynthesis, 280, 348 Biotechnology, 66, 68, 207, 219, 229, 232, 233, 234, 280 Biotin, 118, 280 Bipolar Disorder, 188, 203, 280 Bispecific antibodies, 57, 116, 280 Bladder, 29, 142, 280, 286, 313, 326, 328, 340, 359

Index 365

Bleomycin, 96, 280 Blood Coagulation, 280, 282, 303, 356 Blood pressure, 280, 283, 311, 325, 349 Blood Volume, 27, 33, 50, 80, 104, 281 Blood-Brain Barrier, 13, 16, 32, 60, 62, 63, 118, 121, 168, 175, 180, 195, 281, 319, 329 Body Fluids, 174, 280, 281, 297, 349, 358 Bone Marrow Transplantation, 141, 157, 281 Bone metastases, 281, 343 Bone scan, 281, 346 Boron, 32, 66, 69, 71, 72, 76, 116, 167, 180, 281 Boron Neutron Capture Therapy, 32, 66, 69, 76, 116, 167, 180, 281 Bowel, 274, 281, 294, 330, 334 Bowel Movement, 281, 294 Brachytherapy, 41, 44, 106, 116, 173, 177, 207, 281, 316, 317, 342, 362 Bradykinin, 64, 174, 281, 317, 329 Brain Diseases, 238, 239, 281 Brain Infarction, 4, 281, 360 Brain metastases, 79, 147, 150, 151, 154, 158, 243, 244, 282 Brain Neoplasms, 9, 130, 139, 141, 153, 154, 282, 311, 355 Brain Stem, 22, 150, 155, 190, 281, 282, 285, 360 Brain stem glioma, 22, 150, 155, 190, 282 Brain Stem Infarctions, 281, 282, 360 Branch, 267, 282, 321, 328, 331, 333, 341, 350, 355 Breakdown, 50, 282, 294, 305, 330 Bronchioles, 274, 282, 341 Burns, 131, 163, 282 Burns, Electric, 282 Buthionine sulfoximine, 188, 282 Butyric Acid, 282, 301 Butyrylcholinesterase, 69, 282 C Cachexia, 143, 282 Cadaver, 5, 282 Cadmium, 96, 282 Cadmium Poisoning, 282 Calcium, 16, 186, 188, 282, 288, 319, 322, 349 Camptothecin, 164, 282, 317 Capillary, 16, 56, 111, 178, 281, 282, 283, 360 Capillary Permeability, 111, 281, 283 Capsules, 153, 155, 283 Captopril, 8, 283

Carbohydrates, 283, 284 Carbon Dioxide, 283, 293, 303, 345, 360 Carboplatin, 78, 95, 116, 119, 122, 128, 141, 283 Carboxy, 52, 283 Carcinogen, 283, 323, 355 Carcinogenic, 273, 283, 314, 329, 330, 339, 352 Carcinoma, 32, 62, 87, 154, 169, 242, 244, 283, 329 Cardiac, 5, 242, 278, 283, 298, 300, 327, 332, 352 Cardiac arrest, 5, 283 Cardiovascular, 81, 216, 247, 254, 283, 348 Carmustine, 216, 222, 283, 329 Carotene, 283, 345 Case report, 85, 283, 287, 303 Case series, 81, 283, 287 Catheters, 157, 193, 283, 305, 313, 316 Cations, 283, 317 Caudal, 165, 283, 312, 338 Causal, 28, 284, 300 Cause of Death, 24, 167, 170, 180, 284 Cavernous Sinus, 170, 284 Cell Adhesion, 178, 284, 315 Cell Cycle, 21, 32, 98, 284, 287, 301, 340, 355 Cell Death, 26, 28, 178, 277, 284, 301, 327, 355 Cell Differentiation, 284, 349 Cell Division, 233, 279, 284, 301, 308, 322, 324, 325, 336, 339 Cell membrane, 17, 280, 284, 294, 305, 338 Cell proliferation, 12, 53, 58, 66, 83, 284, 315, 349 Cell Survival, 284, 308 Cell Transplantation, 140, 141, 284 Cellular Structures, 284, 325 Cellulose, 283, 284, 336 Central Nervous System Infections, 284, 308, 311 Cerebellar, 39, 150, 157, 212, 278, 284, 344 Cerebellopontine, 212, 284 Cerebellopontine Angle, 212, 284 Cerebellum, 39, 65, 212, 281, 282, 284, 285, 291, 304, 337, 344, 360 Cerebral hemispheres, 208, 279, 281, 282, 285, 306, 318 Cerebral Infarction, 281, 285, 311 Cerebral Palsy, 203, 230, 285 Cerebrospinal, 93, 182, 186, 198, 285, 286, 291, 300, 311

366 Brain Tumors

Cerebrospinal fluid, 93, 186, 198, 285, 286, 291, 300, 311 Cerebrovascular, 5, 230, 240, 243, 279, 285, 355 Cerebrum, 285, 291, 336, 358 Cervical, 94, 128, 285 Cervix, 9, 50, 285 Character, 285, 293 Chelation, 118, 133, 285 Chemoprotective, 188, 285, 294 Chemosensitizer, 8, 285 Chimera, 97, 285 Chlorpromazine, 167, 285 Chlorpyrifos, 18, 285 Cholesterol, 167, 279, 285, 319, 352, 354 Cholinergic, 4, 276, 285, 286, 326 Cholinergic Agents, 4, 286 Cholinesterase Inhibitors, 194, 286, 296 Chorea, 4, 210, 276, 286 Choreatic Disorders, 286 Choroid, 145, 186, 286, 318, 345, 359 Choroid Plexus, 145, 186, 286, 318 Choroid plexus tumor, 145, 286 Chromatin, 277, 286, 329 Chromic, 117, 286 Chromium, 286 Chromosomal, 47, 76, 89, 108, 286, 345 Chromosome, 145, 286, 290, 308, 319, 320, 345 Chromosome Abnormalities, 145, 286 Chronic Disease, 282, 286 Chronic granulocytic leukemia, 169, 286 Chronic myelogenous leukemia, 46, 286 Chronic renal, 287, 337 Ciliary, 277, 287, 326, 359 Ciliary processes, 277, 287 Circadian, 253, 287 Circadian Rhythm, 253, 287 Circulatory system, 287, 299, 316 CIS, 12, 197, 287, 345 Cisplatin, 60, 117, 119, 287 Clathrin, 287, 288, 299 Cleave, 174, 287 Clinical Medicine, 287, 338 Clinical study, 29, 50, 287 Clone, 191, 287 Cloning, 76, 280, 287 Clot Retraction, 287, 336 Coated Vesicles, 287, 299 Cochlear, 288, 356, 361 Cochlear Diseases, 288, 356 Cofactor, 288, 340, 356

Cognition, 51, 64, 288 Cohort Studies, 288, 300 Colchicine, 288, 358 Colitis, 190, 288 Collagen, 7, 109, 272, 279, 288, 302, 322, 336, 339 Collapse, 28, 173, 282, 288, 349 Colloidal, 288, 298 Communication Disorders, 160, 201, 202, 209, 211, 228, 288 Complement, 67, 288, 289, 315, 321, 348 Complementarity Determining Regions, 196, 289 Complementary and alternative medicine, 125, 134, 289 Complementary medicine, 125, 289 Complete response, 169, 289 Compress, 14, 166, 289 Computational Biology, 229, 232, 289 Computed tomography, 80, 131, 153, 214, 289, 346 Computerized axial tomography, 289, 346 Computerized tomography, 85, 289 Conception, 289, 303, 351 Concomitant, 4, 53, 116, 125, 289 Cone, 173, 289 Confusion, 239, 240, 245, 289, 295, 311, 359 Congestive heart failure, 4, 290 Conjugated, 30, 54, 62, 290, 304, 327, 330, 346 Conjugation, 118, 188, 290, 304 Conjunctiva, 290, 358 Connective Tissue, 281, 288, 290, 303, 305, 320, 324, 334, 345, 346, 354 Connexins, 290, 305 Consciousness, 290, 293, 295, 354 Constipation, 214, 276, 290 Constitutional, 290, 326 Constriction, 171, 290, 317, 341 Consultation, 241, 253, 290 Consumption, 102, 290, 305, 345 Continuous infusion, 60, 116, 125, 290 Continuum, 27, 290 Contraindications, ii, 290 Contralateral, 15, 191, 290, 331, 344 Control group, 51, 290 Contusion, 212, 290 Conventional therapy, 29, 177, 290, 291 Conventional treatment, 6, 167, 180, 291 Convulsions, 291, 298, 311, 328 Cooperative group, 44, 60, 291

Index 367

Coordination, 8, 37, 38, 44, 46, 285, 291, 326 Cornea, 171, 277, 291, 347, 352, 359 Coronary, 194, 291, 324 Coronary Thrombosis, 291, 324 Cortex, 170, 278, 281, 291, 339, 344 Cortical, 32, 211, 291, 301, 347, 355 Cortices, 187, 291, 308 Cortisone, 291, 294, 338 Cranial Irradiation, 89, 112, 216, 254, 291 Cranial Nerves, 182, 291 Craniocerebral Trauma, 279, 291, 308, 311, 355, 356 Cross-Sectional Studies, 291, 300 CSF, 16, 57, 169, 172, 182, 285, 291, 316, 346 Curative, 168, 291, 355 Cutaneous, 170, 291, 320 Cyanide, 179, 291 Cyclic, 16, 56, 241, 292, 308, 329, 338, 347 Cyclic Vomiting Syndrome, 241, 292 Cyclophosphamide, 19, 292, 312, 321 Cyproheptadine, 143, 292 Cyst, 177, 183, 292 Cysteine, 187, 271, 292, 352 Cystine, 292 Cytokine, 21, 40, 61, 92, 292, 315, 346 Cytomegalovirus, 292, 305 Cytomegalovirus Infections, 292, 305 Cytoplasm, 277, 284, 292, 308, 325, 346, 354 Cytosine, 65, 292, 337 Cytoskeleton, 292, 315, 324 Cytostatic, 8, 292 Cytotoxic, 8, 19, 42, 58, 59, 97, 105, 109, 172, 187, 292, 313, 343, 349 Cytotoxic chemotherapy, 59, 292 Cytotoxicity, 58, 63, 168, 172, 195, 287, 292, 318 D Data Collection, 258, 292 Databases, Bibliographic, 229, 292 Daunorubicin, 164, 293, 296 De novo, 6, 9, 48, 60, 293 Decarboxylation, 293, 310, 342 Defense Mechanisms, 293, 315 Degenerative, 191, 193, 240, 293 Dehydration, 214, 293 Deletion, 52, 69, 192, 277, 293, 320 Delirium, 4, 194, 210, 245, 253, 276, 293 Delusions, 211, 293, 341

Dementia, 4, 5, 133, 193, 203, 210, 214, 238, 240, 243, 276, 293, 328 Denaturation, 293, 337 Dendrites, 293, 328 Density, 32, 50, 52, 90, 147, 178, 293, 304, 319, 330, 337 Dental Caries, 254, 293, 304 Deoxyguanosine, 15, 69, 293 Deoxyribonucleic, 293, 294, 346 Deoxyribonucleic acid, 294, 346 Deoxyuridine, 182, 294, 356 Depolarization, 186, 294, 349 Depressive Disorder, 76, 255, 294 Dermatitis, 190, 294 Deuterium, 294, 311 Dexamethasone, 33, 79, 294 Dexrazoxane, 119, 150, 294 Dextroamphetamine, 294, 324 Diabetes Mellitus, 294, 309, 330 Diagnostic procedure, 161, 219, 294 Diagnostic Services, 294, 354 Diarrhea, 172, 294 Diarrhoea, 294, 305 Diastolic, 294, 311 Diazinon, 18, 294 Diffusion, 10, 27, 28, 50, 79, 93, 99, 110, 136, 174, 193, 218, 280, 283, 294, 314 Digestion, 208, 273, 279, 281, 294, 320, 352 Digestive system, 160, 294, 326 Digestive tract, 78, 294, 349, 351 Dihematoporphyrin Ether, 295, 309 Dilatation, 295, 339, 341 Dilation, 281, 295, 311 Diphtheria, 172, 194, 195, 295 Diphtheria Toxin, 172, 194, 195, 295 Diploid, 295, 336, 337 Discrimination, 11, 182, 295 Disease Vectors, 295, 314 Disease-Free Survival, 45, 295 Disinfectant, 295, 301 Dislocation, 212, 295, 351 Disorientation, 289, 293, 295 Disparity, 171, 295 Dissociation, 15, 273, 295, 317 Dissociative Disorders, 295 Distal, 165, 183, 279, 295, 298, 340, 341 Dizziness, 211, 212, 296, 360 Docetaxel, 149, 296 Donepezil, 158, 194, 296 Dopa, 84, 296, 319 Dopamine, 276, 285, 294, 296, 319, 335 Dorsal, 296, 338, 351

368 Brain Tumors

Dorsum, 296, 305 Dosage schedule, 48, 296 Dose Fractionation, 95, 296 Dose-dependent, 51, 296 Dose-limiting, 188, 296 Dosimetry, 25, 47, 48, 95, 128, 296 Doxorubicin, 62, 149, 294, 296 Drive, ii, vi, 5, 27, 115, 201, 209, 296 Drug Approval, 202, 221, 296 Drug Design, 19, 222, 223, 296 Drug Interactions, 222, 297 Drug Resistance, 6, 8, 21, 54, 71, 83, 297 Drug Tolerance, 297, 356 Drug Toxicity, 5, 297 Duct, 274, 297, 302, 346 Dumping Syndrome, 292, 297 Duodenum, 208, 279, 297, 299, 352 Dura mater, 284, 297, 323, 332 Dyes, 166, 297, 304 Dyskinesia, 182, 276, 297 Dyslexia, 194, 297 Dysphagia, 203, 243, 297 Dysphonia, 203, 297 Dysphoric, 294, 297 Dysplasia, 233, 297 Dystonia, 186, 276, 297 Dystrophy, 233, 297 E Ectoderm, 297, 328 Edema, 51, 133, 137, 183, 297, 316 Effector, 39, 57, 61, 271, 288, 297, 318, 328 Effector cell, 57, 61, 297, 318, 328 Elastin, 288, 298, 302 Elective, 298 Electrocardiogram, 148, 150, 298 Electroconvulsive Therapy, 4, 298 Electrode, 9, 275, 298 Electrolyte, 293, 298, 318, 338, 349 Electromagnetic Fields, 80, 96, 298 Electrons, 276, 279, 298, 317, 321, 332, 342, 343, 362 Electrophoresis, 186, 298 Elementary Particles, 298, 321, 329, 340 Embolus, 298, 314 Embryo, 284, 297, 298, 313, 328 Emphysema, 214, 298 Empirical, 55, 182, 298 Emulsion, 279, 298, 303 Enamel, 293, 298 Encapsulated, 48, 298 Encephalitis, 170, 298, 299 Encephalitis, Viral, 299

Encephalopathy, 211, 299 Endocrine Glands, 299, 333 Endocrine System, 299, 328 Endoscope, 164, 165, 299 Endoscopic, 164, 299 Endosomes, 194, 299 Endostatin, 22, 299 Endothelial cell, 7, 16, 17, 31, 32, 56, 64, 77, 178, 281, 299, 303, 356 Endothelial Growth Factors, 178, 299 Endothelium, 16, 299, 329, 336 Endothelium, Lymphatic, 299 Endothelium, Vascular, 299 Endothelium-derived, 299, 329 Endotoxin, 299, 358 End-stage renal, 287, 299, 337 Enhancer, 20, 300 Environmental Exposure, 9, 18, 300, 330 Environmental Health, 9, 139, 228, 230, 300 Enzymatic, 80, 279, 282, 283, 288, 293, 300, 310, 337, 345 Ependymal, 300, 306 Ependymal tumors, 300, 306 Ependymomas, 55, 190, 300 Epidemiologic Studies, 18, 300 Epidemiological, 36, 300, 303 Epidermal, 32, 52, 73, 118, 156, 300, 323 Epidermal Growth Factor, 32, 52, 73, 156, 300 Epidermis, 300 Epidermoid carcinoma, 300, 351 Epidural, 212, 300, 316 Epigastric, 300, 332 Epinephrine, 296, 300, 359 Epithelial, 188, 272, 280, 300, 301, 318 Epithelial Cells, 300, 301, 318 Epithelium, 279, 299, 301, 317 Epitope, 177, 301 Erythema, 301, 359 Erythrocyte Volume, 281, 301 Erythrocytes, 274, 281, 301, 348 Escalation, 99, 130, 176, 301 Esophagus, 50, 294, 295, 301, 335, 352 Essential Tremor, 233, 301 Estrogen, 301, 347, 354 Ethanol, 28, 301 Ethionine, 301 Ethmoid, 301, 333 Etoposide, 60, 84, 95, 117, 119, 120, 127, 128, 130, 301 Eukaryotic Cells, 301, 313, 330, 359

Index 369

Evacuation, 290, 301 Excipient, 164, 301 Excisional, 19, 301 Excitation, 182, 301, 304 Excitatory, 186, 301, 307, 328 Excitatory Amino Acids, 301, 328 Excrete, 277, 302, 318 Exhaustion, 292, 302 Exocrine, 302, 332 Exogenous, 24, 283, 302, 359 Exon, 10, 139, 302 Exotoxin, 62, 302 Extensor, 302, 341 External-beam radiation, 302, 317, 342, 362 Extracellular, 7, 26, 47, 50, 54, 98, 185, 186, 189, 195, 278, 290, 302, 315, 322, 349 Extracellular Matrix, 7, 26, 47, 195, 290, 302, 315, 322 Extracellular Matrix Proteins, 195, 302, 322 Extracellular Space, 50, 98, 302 Extraction, 17, 174, 175, 302 Extravasation, 33, 302, 309 Exudate, 58, 302 Eye Infections, 272, 302 F Family Planning, 229, 302 Farnesyl, 8, 302 Fasciculation, 302, 328 Fast Neutrons, 302, 329 Fat, 281, 282, 283, 298, 303, 319, 326, 346, 349, 353 Fatal Outcome, 56, 172, 303 Fatigue, 51, 147, 148, 303, 309 Fatty acids, 303, 320 Febrile, 303, 351 Feces, 290, 303 Fetus, 198, 303, 338, 359 Fibrin, 280, 287, 303, 336, 355, 356 Fibrinogen, 303, 336, 355 Fibroblast Growth Factor, 178, 197, 299, 303 Fibronectins, 302, 303 Fibrosis, 190, 233, 303, 347 Fistula, 303, 330 Fixation, 171, 184, 303, 348 Flatus, 304, 305 Flow Cytometry, 304, 313 Fluorescence, 11, 69, 182, 304 Fluorescent Antibody Technique, 304 Fluorine, 25, 85, 177, 304

Fluoroimmunoassay, 15, 304 Folate, 5, 57, 294, 304 Fold, 7, 9, 16, 31, 304 Folic Acid, 304, 319 Foramen, 304, 310, 318 Fossa, 83, 170, 202, 209, 285, 304 Fourth Ventricle, 286, 304, 355 Fovea, 303, 304 Fractionation, 31, 51, 304 Frontal Lobe, 194, 285, 304, 325 Fructose, 304, 310 Fungemia, 100, 304 Fungi, 290, 302, 304, 305, 324, 362 G Gadolinium, 31, 48, 110, 116, 117, 118, 154, 305 Gait, 4, 305 Gallbladder, 271, 294, 305 Gamma knife, 87, 95, 109, 128, 132, 305 Gamma Rays, 305, 342, 343 Ganciclovir, 163, 181, 305 Ganglia, 271, 279, 305, 327, 334, 353 Ganglion, 170, 305, 345, 361 Ganglioside, 22, 87, 305 Gap Junctions, 163, 290, 305, 353 Gas, 63, 164, 166, 283, 294, 304, 305, 311, 322, 329, 330, 352, 360 Gastrectomy, 292, 305 Gastric, 158, 169, 300, 305, 310 Gastrin, 73, 305, 310 Gastroenteritis, 172, 305 Gastrointestinal, 40, 51, 157, 281, 282, 286, 297, 300, 301, 305, 306, 322, 348, 350, 352, 355, 358 Gastrointestinal tract, 286, 301, 306, 348, 350, 358 Gels, 186, 306 Gene Expression, 12, 19, 20, 22, 28, 39, 44, 65, 66, 79, 163, 189, 234, 306 Generator, 306, 354 Genetic Code, 306, 329 Genetic testing, 306, 337 Genetics, 12, 18, 27, 32, 83, 86, 88, 103, 108, 111, 290, 306, 325 Genital, 306, 359 Genitourinary, 51, 306, 359 Genotype, 10, 21, 306, 335 Germ cell tumors, 149, 190, 306 Germ Cells, 306, 322, 330, 332, 355 Germline mutation, 83, 306, 309 Gland, 72, 291, 306, 320, 332, 336, 340, 347, 352, 356

370 Brain Tumors

Glial Fibrillary Acidic Protein, 197, 306 Glial tumors, 29, 52, 178, 190, 306 Gliosarcoma, 33, 152, 307 Glucocorticoid, 294, 307, 338 Glucokinase, 307, 310 Glucose, 75, 92, 117, 126, 142, 233, 284, 286, 294, 307, 309, 310, 311, 314, 315, 346, 350 Glucuronic Acid, 307, 309 Glutamate, 185, 307, 324 Glutamic Acid, 304, 307, 339 Glutamine, 279, 307 Glycine, 307, 348 Glycoprotein, 64, 80, 82, 132, 149, 303, 307, 318, 326, 354, 356, 358 Glycosaminoglycans, 302, 307 Gonadal, 89, 307, 352 Governing Board, 307, 338 Grade, 7, 12, 17, 19, 25, 32, 33, 36, 37, 40, 51, 53, 55, 57, 58, 77, 78, 82, 101, 102, 104, 111, 145, 155, 156, 185, 189, 190, 195, 207, 282, 306, 307 Grading, 17, 104, 307 Graft, 190, 194, 307, 310, 313 Graft Rejection, 307, 313 Grafting, 307, 313 Gram-negative, 77, 308, 340 Gram-Negative Bacteria, 77, 308 Gram-positive, 77, 308 Granule, 39, 308, 346 Granulocytes, 308, 319, 349, 362 Gravis, 194, 203, 308 Growth factors, 35, 53, 148, 299, 308 Guanylate Cyclase, 308, 329 H Half-Life, 25, 308 Handicap, 97, 129, 308 Haploid, 308, 336, 337 Haptens, 273, 308, 343 Headache, 251, 308, 311 Headache Disorders, 308 Health Services, 308, 354 Health Status, 147, 308 Hearing Disorders, 288, 308 Heart failure, 214, 309 Hemangiopericytoma, 147, 309 Hematologic malignancies, 40, 309, 320 Hematology, 7, 90, 97, 100, 102, 129, 130, 309 Hematoma, 4, 5, 183, 309 Hematoporphyrin Derivative, 166, 295, 309

Heme, 309, 327, 338 Hemodialysis, 309, 318 Hemoglobin, 274, 301, 309, 338 Hemoglobin A, 309, 338 Hemoglobinuria, 233, 309 Hemorrhage, 5, 90, 170, 212, 291, 308, 309, 352 Hemostasis, 309, 315, 348 Heparin, 150, 155, 299, 309 Hepatic, 166, 172, 250, 293, 309 Hereditary, 31, 286, 306, 309, 345 Hereditary mutation, 306, 309 Heredity, 306, 309 Herniated, 183, 310 Herpes, 19, 20, 26, 32, 65, 67, 68, 88, 163, 181, 192, 223, 272, 310 Herpes virus, 19, 310 Herpes Zoster, 310 Heterodimers, 310, 315 Heterogeneity, 12, 19, 26, 55, 62, 107, 273, 310 Hexokinase, 96, 310 Hiccup, 285, 310 Histamine, 276, 292, 310 Histology, 31, 33, 53, 203, 208, 310 Homeostasis, 186, 310 Homogeneous, 29, 104, 290, 310 Homologous, 273, 290, 310, 348, 353 Hormonal, 278, 310 Hormone Replacement Therapy, 241, 252, 310 Hormone therapy, 117, 310 Host, 23, 26, 57, 65, 181, 190, 196, 279, 295, 310, 312, 313, 345, 359, 361 Humoral, 170, 307, 310 Humour, 310 Hybrid, 32, 52, 287, 310 Hybridization, 86, 310, 325 Hydrocephalus, 4, 5, 211, 239, 311, 316 Hydrogel, 48, 311 Hydrogen, 108, 190, 271, 279, 283, 293, 294, 302, 311, 325, 329, 330, 332, 335, 340, 353 Hydrogen Peroxide, 108, 311, 353 Hydrolysis, 287, 311, 335, 337, 340 Hydrophilic, 64, 311 Hydrophobic, 64, 311, 319 Hydroxylysine, 288, 311 Hydroxyproline, 288, 311 Hypersensitivity, 273, 311, 346, 348 Hypertension, 247, 311, 316, 330 Hyperthermia, 53, 162, 311

Index 371

Hyperthyroidism, 5, 246, 311 Hypoglycaemia, 293, 311 Hypoglycemia, 186, 311 Hypothalamic, 150, 155, 311 Hypothalamus, 279, 281, 282, 311, 336, 350, 355 Hypothyroidism, 5, 216, 246, 312 Hypoxia, 9, 20, 24, 53, 92, 94, 176, 293, 312, 355 I Ifosfamide, 60, 312 Illusion, 312, 360 Imaging procedures, 312, 357 Imidazole, 280, 310, 312 Immune function, 312, 313 Immune Sera, 312 Immune system, 26, 139, 150, 151, 170, 275, 276, 280, 297, 312, 313, 321, 326, 360, 362 Immunity, 21, 49, 61, 67, 170, 312, 357 Immunization, 49, 248, 312, 313, 339, 348 Immunocompromised, 24, 312 Immunoconjugates, 62, 312 Immunodeficiency, 233, 242, 312 Immunofluorescence, 174, 312 Immunoglobulin, 249, 275, 289, 304, 312, 315, 325 Immunohistochemistry, 77, 78, 312 Immunologic, 45, 312, 313, 343 Immunology, 60, 77, 272, 273, 313 Immunophenotyping, 189, 313 Immunosuppressive, 21, 279, 292, 307, 312, 313 Immunosuppressive Agents, 21, 313 Immunosuppressive therapy, 313 Immunotherapy, 13, 42, 49, 53, 57, 61, 93, 109, 126, 204, 280, 313 Immunotoxin, 93, 158, 159, 172, 194, 195, 313 Impairment, 5, 27, 36, 52, 202, 210, 211, 240, 278, 279, 293, 297, 302, 313, 323, 341 Implant radiation, 313, 316, 317, 342, 362 Implantation, 193, 242, 289, 313 In situ, 20, 78, 178, 313 In Situ Hybridization, 78, 178, 313 Incision, 166, 313, 316 Incontinence, 311, 313 Incubated, 186, 313 Incubation, 58, 313 Indicative, 50, 197, 203, 313, 333, 360 Induction, 26, 53, 56, 61, 127, 178, 276, 313, 343

Infancy, 83, 206, 314 Infant, Newborn, 273, 314 Infarction, 212, 285, 291, 314, 324 Infiltration, 49, 182, 196, 314 Informed Consent, 46, 314 Infusion, 155, 174, 195, 314, 321 Ingestion, 282, 314, 337 Inhalation, 5, 310, 314, 317, 337 Initiation, 8, 15, 50, 314, 357 Inoperable, 164, 314 Inorganic, 287, 314, 336 Inositol, 314, 324, 347 Insecticides, 18, 314, 335 Insight, 31, 217, 314 Insulator, 314, 326 Insulin, 76, 314, 315, 359 Insulin-dependent diabetes mellitus, 315 Insulin-like, 76, 315 Integrins, 56, 178, 315 Interferon, 49, 58, 170, 192, 223, 315, 321 Interferon-alpha, 315 Interleukin-1, 190, 315 Interleukin-13, 190, 315 Interleukin-2, 107, 170, 315 Interleukin-4, 77, 315 Interleukins, 313, 315 Intermittent, 175, 315 Internal Medicine, 191, 309, 315, 322 Internal radiation, 315, 317, 342, 362 Interstitial, 41, 59, 101, 106, 176, 177, 195, 281, 302, 316, 317, 344, 362 Intervertebral, 310, 316, 320 Intervertebral Disk Displacement, 316, 320 Intestinal, 190, 241, 283, 316, 321 Intestines, 271, 303, 305, 306, 316, 347 Intoxication, 4, 293, 316, 362 Intracellular, 186, 188, 287, 314, 315, 316, 323, 324, 329, 338, 347, 348 Intracellular Membranes, 316, 323 Intracranial Hemorrhages, 311, 316, 355 Intracranial Hypertension, 308, 311, 316, 356 Intracranial Pressure, 108, 173, 182, 198, 316, 341 Intracranial tumors, 21, 48, 117, 119, 170, 214, 316 Intramuscular, 316, 333 Intraocular, 170, 316, 357 Intraocular pressure, 170, 316, 357 Intrathecal, 43, 44, 181, 316, 321 Intrathecal chemotherapy, 44, 316

372 Brain Tumors

Intravascular, 21, 67, 316 Intravenous, 95, 120, 128, 142, 155, 169, 249, 305, 314, 316, 333 Intrinsic, 6, 23, 176, 273, 279, 316 Invasive, 7, 9, 16, 18, 23, 25, 27, 33, 48, 59, 85, 137, 162, 165, 167, 172, 180, 183, 191, 196, 312, 316, 321 Involuntary, 279, 286, 301, 316, 326, 350 Iodine, 85, 104, 126, 151, 177, 316 Iodine-131, 104, 316 Ion Channels, 188, 216, 278, 316, 328 Ionization, 72, 317 Ionizing, 27, 184, 273, 300, 317, 342, 343 Ionophores, 194, 317, 359 Ions, 188, 279, 295, 298, 311, 317, 338 Irinotecan, 19, 108, 120, 128, 130, 132, 156, 317 Iris, 291, 317, 342, 359 Irradiation, 27, 31, 50, 65, 91, 168, 176, 177, 186, 244, 281, 317, 329, 362 Irrigation, 166, 317 Ischemia, 186, 278, 305, 317, 328 Isoenzyme, 310, 317 Isoflurane, 108, 317 J Joint, 34, 298, 317, 320, 351, 353, 354 K Kallidin, 281, 317 Kb, 228, 317 Keratolytic, 293, 317, 337 Kidney Disease, 160, 228, 233, 250, 251, 318 Kidney Failure, 214, 299, 318 Kidney Failure, Acute, 318 Kidney Failure, Chronic, 318 Killer Cells, 318 Kinetic, 27, 96, 116, 129, 171, 179, 317, 318 L Labile, 180, 288, 318 Laminin, 7, 279, 302, 318 Language Disorders, 202, 209, 288, 318 Large Intestine, 294, 295, 316, 318, 343, 349 Latency, 96, 192, 318 Latent, 53, 318 Lateral Ventricles, 191, 318, 348, 355 Lectin, 318, 323 Lens, 277, 318, 362 Lesion, 25, 319, 320, 348 Lethal, 19, 29, 34, 52, 62, 182, 279, 291, 295, 319 Lethargy, 241, 311, 312, 319 Leucocyte, 319, 321

Leucovorin, 120, 319 Leukocytes, 281, 308, 315, 319, 325, 358 Levo, 296, 319, 323 Levodopa, 168, 296, 319 Library Services, 266, 319 Life cycle, 12, 286, 305, 319 Life Expectancy, 198, 319 Ligament, 319, 340, 351 Ligands, 189, 190, 315, 319 Ligation, 57, 319 Linear Energy Transfer, 30, 319 Linkages, 18, 307, 309, 319, 337, 354 Lipid, 165, 283, 314, 317, 319, 326 Lipopolysaccharide, 308, 319 Lipoprotein, 308, 319 Lipoxygenase, 67, 121, 277, 319 Liquor, 102, 320 Liver Neoplasms, 301, 320 Liver scan, 320, 346 Localization, 25, 62, 86, 89, 97, 184, 208, 312, 320 Locomotion, 320, 336 Locoregional, 94, 128, 320 Lomustine, 6, 131, 320, 329 Loss of Heterozygosity, 32, 320 Low Back Pain, 245, 320 Lucida, 318, 320 Lumbar, 316, 320 Lupus, 320, 354 Luxation, 295, 320 Lymph, 57, 285, 287, 299, 310, 320, 321, 352 Lymph node, 57, 285, 320, 321 Lymphatic, 190, 299, 314, 320, 321, 324, 337, 349, 351, 356 Lymphatic system, 320, 321, 349, 351, 356 Lymphoblastic, 321 Lymphoblasts, 46, 271, 321 Lymphocyte, 19, 276, 315, 318, 321, 322 Lymphocytic, 321 Lymphoid, 46, 47, 60, 143, 275, 319, 321, 339 Lymphoma, 49, 60, 62, 143, 144, 169, 233, 309, 321 Lymphoproliferative, 45, 321 Lytic, 12, 321 M Macrophage, 170, 315, 321 Mafosfamide, 84, 127, 154, 321 Magnetic Resonance Spectroscopy, 17, 22, 23, 71, 94, 98, 142, 321

Index 373

Major Histocompatibility Complex, 315, 321 Malabsorption, 233, 321 Malformation, 212, 321 Malignancy, 12, 27, 39, 52, 93, 179, 321 Malignant meningioma, 143, 181, 321 Malignant tumor, 8, 12, 25, 26, 37, 162, 166, 172, 180, 181, 182, 192, 321, 326, 331, 345 Malnutrition, 214, 278, 282, 321, 326 Mammary, 172, 322, 354 Mandible, 274, 322, 345 Mania, 194, 203, 322 Manic, 202, 276, 280, 322, 341 Manic-depressive psychosis, 322, 341 Manifest, 50, 279, 322 Mastication, 322, 358 Matrix metalloproteinase, 7, 80, 92, 322 Maxillary, 322, 333 Mechlorethamine, 322, 339 Medial, 93, 301, 322, 331, 350, 360 Mediate, 7, 186, 296, 318, 322 Mediator, 296, 315, 322, 348 Medical Oncology, 119, 131, 322, 342 Medical Records, 14, 30, 322, 345 MEDLINE, 229, 232, 234, 322 Medulloblastoma, 24, 39, 44, 54, 55, 65, 99, 122, 141, 144, 145, 150, 169, 177, 178, 196, 322 Megaloblastic, 294, 304, 322 Megestrol, 143, 322 Meiosis, 322, 353 Melanin, 317, 323, 335, 359 Melanocytes, 323 Melanoma, 29, 49, 169, 233, 281, 323 Melphalan, 116, 168, 323 Membrane Glycoproteins, 323 Membrane Proteins, 12, 323 Memory, 51, 58, 64, 136, 148, 158, 188, 194, 202, 210, 239, 240, 275, 293, 323 Meningeal, 182, 323 Meninges, 284, 291, 297, 321, 323 Meningioma, 19, 32, 138, 141, 146, 147, 148, 152, 155, 170, 190, 323 Meningitis, 4, 170, 239, 323 Menopause, 242, 323 Menstruation, 323 Mental Disorders, 160, 210, 323, 339, 341 Mental Health, iv, 6, 160, 210, 228, 231, 323, 339, 341 Mental Processes, 295, 323, 341 Mental Retardation, 234, 288, 323

Mercury, 96, 304, 323 Mesenchymal, 300, 324 Metabolic disorder, 23, 211, 324 Metabolite, 105, 319, 324, 335 Metabotropic, 185, 324 Metastasis, 49, 137, 182, 244, 245, 322, 324 Metastasize, 59, 324, 347 Methionine, 25, 117, 119, 122, 125, 129, 301, 324, 353 Methylphenidate, 147, 148, 324 Methyltransferase, 68, 80, 100, 104, 324 MI, 269, 324 Microbe, 324, 357 Microgram, 304, 324 Microorganism, 288, 324, 333, 362 Micro-organism, 293, 324 Microscopy, 17, 279, 304, 324, 330 Microtubules, 324, 332 Migration, 7, 12, 16, 23, 111, 178, 195, 324 Millimeter, 11, 324 Mitochondrial Swelling, 324, 327 Mitosis, 277, 324, 325 Mitotic, 296, 301, 325, 355, 361 Mitotic inhibitors, 296, 325 Mitoxantrone, 97, 325 Mobility, 50, 325 Modeling, 11, 20, 22, 26, 35, 36, 65, 297, 325 Modification, 14, 26, 53, 61, 190, 325, 342 Molecular Probes, 78, 325 Monitor, 41, 44, 63, 150, 325, 329 Monoclonal, 17, 29, 33, 47, 56, 62, 68, 105, 110, 151, 172, 177, 196, 312, 317, 325, 342, 362 Monoclonal antibodies, 17, 29, 47, 151, 312, 325 Monocytes, 315, 319, 325 Mononuclear, 325, 358 Mood Disorders, 188, 211, 325 Morphological, 17, 298, 323, 325 Morphology, 17, 309, 325 Motion Sickness, 325, 327 Motor Cortex, 86, 325, 344 Mucinous, 305, 325 Mucociliary, 325, 349 Mucolytic, 271, 326 Mucosa, 320, 326, 327 Mucositis, 326, 356 Multidrug resistance, 8, 188, 326 Multimodality treatment, 195, 326 Multiple Myeloma, 169, 326

374 Brain Tumors

Multiple sclerosis, 3, 190, 194, 202, 203, 211, 212, 230, 244, 326 Muscarinic Agonists, 286, 326 Muscle Contraction, 188, 326 Muscle Fibers, 326, 327 Muscle Hypertonia, 326, 328 Muscular Atrophy, 233, 326 Muscular Dystrophies, 297, 326 Mutagenic, 273, 326, 329 Myasthenia, 194, 202, 326 Myelin, 190, 198, 326, 330 Myelogenous, 326 Myeloma, 169, 326 Myeloproliferative Disorders, 45, 326 Myocarditis, 295, 326 Myocardium, 99, 324, 326 Myoglobin, 327, 338 Myopathy, 194, 327 Myosin, 326, 327 Myotonic Dystrophy, 233, 327 N Narcolepsy, 96, 106, 294, 324, 327 Nasal Cavity, 140, 210, 327, 333 Nasal Septum, 327 Natural killer cells, 49, 327 Nausea, 172, 241, 275, 276, 292, 305, 327, 341, 359 Necrosis, 29, 50, 129, 137, 173, 277, 281, 285, 306, 314, 324, 327 Neonatal, 247, 327 Neoplasia, 66, 91, 92, 233, 327 Neoplastic, 12, 39, 52, 53, 54, 168, 198, 202, 320, 321, 327, 330, 354 Neoplastic meningitis, 54, 327 Nephropathy, 318, 327 Nervous System, 4, 5, 6, 8, 12, 13, 14, 27, 31, 34, 36, 37, 38, 39, 44, 57, 58, 61, 62, 65, 72, 85, 105, 113, 129, 140, 141, 145, 152, 170, 172, 177, 181, 186, 192, 195, 198, 202, 208, 214, 233, 271, 272, 278, 281, 282, 284, 286, 294, 305, 306, 307, 319, 322, 324, 326, 327, 328, 331, 334, 337, 339, 345, 348, 353 Neural, 23, 28, 31, 64, 66, 88, 131, 171, 183, 191, 197, 272, 310, 318, 327 Neuralgia, 188, 328 Neuroblastoma, 45, 46, 122, 140, 149, 151, 152, 169, 328 Neuroectodermal Tumors, 197, 328 Neuroendocrine, 244, 328, 354 Neurogenic, 99, 202, 211, 328 Neuroma, 211, 328

Neuromuscular, 81, 271, 328 Neuromuscular Diseases, 81, 328 Neuronal, 12, 28, 89, 111, 136, 170, 185, 186, 191, 197, 328, 334 Neuropharmacology, 38, 202, 328 Neurophysiology, 101, 294, 328 Neuroprotective Agents, 188, 328 Neuropsychology, 55, 328 Neurosyphilis, 5, 328 Neurotoxicity, 64, 185, 328 Neurotransmitters, 186, 301, 328 Neutron Capture Therapy, 71, 72, 118, 329 Neutrons, 167, 180, 273, 281, 302, 317, 329, 342 Neutropenia, 305, 329 Nitric Oxide, 93, 329 Nitrogen, 168, 273, 292, 302, 303, 307, 318, 323, 329, 358 Nitrosamines, 18, 329 Nitrosoureas, 6, 18, 176, 329 Non-small cell lung cancer, 154, 158, 254, 329 Nonverbal Communication, 288, 329 Nuclear Matrix, 89, 329 Nuclear Pore, 329 Nuclei, 147, 273, 290, 298, 321, 324, 329, 331, 340, 361 Nucleic acid, 174, 179, 192, 292, 306, 311, 313, 329, 330, 342, 346, 350 Nucleic Acid Hybridization, 311, 330 Nucleolus, 329, 330, 346 Nucleoproteins, 174, 330 O Occipital Lobe, 330, 360, 361 Octreotide, 152, 330 Ocular, 170, 330, 356 Odour, 277, 330 Olfaction, 209, 330 Oligodendroglial, 75, 116, 126, 330 Oligodendroglioma, 30, 131, 139, 140, 143, 144, 146, 151, 152, 155, 156, 157, 330 Oliguria, 318, 330 Oncogene, 35, 81, 98, 109, 233, 330 Oncogenic, 315, 330, 340 Oncologist, 330 Oncolysis, 21, 24, 26, 192, 330 Oncolytic, 12, 21, 24, 65, 330 Oocytes, 39, 330 Opacity, 293, 330 Ophthalmology, 252, 303, 330 Opportunistic Infections, 242, 330 Opsin, 330, 345

Index 375

Optic Chiasm, 312, 331 Optic cup, 171, 331 Optic disc, 171, 331 Optic Nerve, 170, 331, 332, 341, 345, 347 Optic Nerve Diseases, 331, 341 Orbit, 331 Orbital, 170, 331 Ornithine, 331, 342 Orthostatic, 276, 330, 331 Osmosis, 331 Osmotic, 62, 324, 331 Osteogenic sarcoma, 169, 331 Osteosarcoma, 149, 154, 169, 331 Otolaryngologist, 212, 331 Otolaryngology, 212, 331 Otology, 212, 331 Outpatient, 112, 216, 331 Ovarian epithelial cancer, 158, 331 Ovaries, 331, 348 Ovary, 11, 332 Overall survival, 41, 56, 332 Overdose, 5, 332 Ovulation, 322, 332 Ovum, 319, 332, 339, 362, 363 Oxaliplatin, 22, 332 Oxidation, 72, 271, 276, 277, 292, 332, 359 Oxides, 176, 332 Oxygenation, 9, 20, 91, 332 P P53 gene, 46, 332 Pacemaker, 332 Pachymeningitis, 323, 332 Paclitaxel, 64, 103, 112, 116, 121, 125, 130, 131, 132, 332 Palliative, 116, 126, 176, 250, 322, 332, 355 Palliative therapy, 116, 126, 332 Palsies, 72, 332 Palsy, 4, 194, 211, 332 Pancreas, 5, 28, 271, 280, 294, 314, 332, 350, 358 Pancreatic, 169, 190, 233, 332 Pancreatic cancer, 169, 190, 233, 332 Papilla, 333 Papillary, 147, 333 Papilledema, 333, 341 Paranasal Sinuses, 170, 210, 333, 349 Paraneoplastic syndrome, 249, 333 Parenchyma, 179, 182, 196, 333 Parenteral, 188, 246, 333 Parenteral Nutrition, 246, 333 Parkinsonism, 276, 319, 333 Paroxysmal, 233, 308, 333

Partial response, 169, 333 Particle, 333, 357 Partnership Practice, 333, 339 Pathogen, 313, 333 Pathogenesis, 12, 47, 81, 91, 333 Pathologic, 277, 280, 281, 291, 311, 333, 338, 341, 344 Pathologic Processes, 277, 333 Pathophysiology, 9, 333 Patient Education, 238, 257, 264, 266, 269, 333 Pediatric Endocrinologist, 117, 333 Peer Review, 36, 38, 44, 115, 333 Pelvic, 334, 340 Penicillamine, 8, 334 Penicillin, 334, 360 Peptide, 12, 56, 158, 187, 303, 334, 337, 340, 356 Perception, 202, 289, 308, 334, 347 Perforation, 277, 304, 334 Perfusion, 10, 50, 108, 312, 334 Pericardium, 334, 354 Pericytes, 16, 334 Peripheral blood, 157, 170, 315, 334 Peripheral Nerves, 334, 351 Peripheral Nervous System, 188, 328, 332, 334, 350, 352 Peripheral Nervous System Diseases, 328, 334 Peripheral stem cell transplantation, 140, 141, 334 Peripheral vision, 334, 361 Peritoneal, 58, 334 Peritoneum, 334 Pesticides, 18, 314, 335 PH, 79, 80, 92, 112, 126, 131, 335 Phallic, 303, 335 Pharmacodynamic, 58, 335 Pharmacokinetic, 55, 122, 335 Pharmacologic, 34, 45, 58, 211, 274, 308, 335, 357 Pharynx, 327, 335 Phenotype, 35, 197, 335 Phenyl, 195, 335 Phenylalanine, 168, 335, 359 Phospholipases, 335, 349 Phosphorus, 101, 282, 335 Phosphorylating, 186, 335 Phosphorylation, 53, 163, 186, 335, 359 Photodynamic therapy, 69, 101, 150, 165, 166, 295, 309, 335 Photosensitizing Agents, 335, 337

376 Brain Tumors

Physical Examination, 142, 149, 335 Physiologic, 31, 98, 273, 280, 296, 308, 323, 335, 343, 344 Physiology, 11, 27, 210, 272, 309, 328, 335 Pigment, 323, 327, 335 Pilot study, 11, 51, 82, 127, 336 Pineal gland, 336 Pineal region tumors, 190, 336 Pituitary Gland, 303, 336 Plants, 166, 273, 283, 307, 318, 325, 336, 340, 346, 357, 358 Plasma, 12, 47, 168, 190, 275, 281, 284, 299, 303, 309, 318, 326, 336, 344, 348 Plasma cells, 275, 326, 336 Plasma Volume, 281, 336 Plasmin, 7, 336, 356, 359 Plasminogen, 7, 8, 336, 356, 359 Plasminogen Activators, 336 Plasticity, 64, 336 Platelet Activation, 336, 349 Platelet Aggregation, 329, 336 Platelets, 277, 329, 336, 346, 348, 356 Platinum, 287, 332, 336 Platinum Compounds, 332, 336 Plexus, 337 Ploidy, 70, 337 Podophyllotoxin, 301, 337, 355 Poisoning, 282, 293, 297, 305, 316, 323, 327, 337 Poly C, 15, 337 Polycystic, 233, 337 Polyethylene, 118, 337 Polymerase, 30, 276, 337 Polymerase Chain Reaction, 30, 337 Polymorphic, 21, 337 Polymorphism, 21, 337 Polypeptide, 192, 197, 274, 288, 300, 303, 311, 327, 336, 337, 340, 350, 363 Polysaccharide, 276, 284, 337, 340 Pons, 282, 284, 304, 337 Population Density, 9, 337 Porfimer sodium, 150, 337 Porphyrins, 180, 295, 309, 338 Positron emission tomography scan, 85, 338 Posterior, 83, 122, 202, 209, 274, 278, 285, 286, 296, 317, 330, 332, 338, 347, 350 Postnatal, 28, 338, 351 Postoperative, 117, 209, 305, 338 Postoperative Complications, 209, 338 Postsynaptic, 338, 349, 353 Potassium, 16, 179, 188, 338

Potassium Channels, 188, 338 Potentiate, 188, 338, 342 Potentiation, 61, 177, 286, 338, 349 Practicability, 338, 358 Practice Guidelines, 231, 241, 242, 250, 254, 338 Preclinical, 15, 24, 40, 42, 54, 55, 58, 61, 65, 338 Precursor, 174, 292, 296, 297, 300, 302, 319, 335, 336, 338, 350, 358, 359, 360 Prednisone, 338, 339 Prenatal, 18, 120, 298, 338 Presumed Consent, 5, 338 Presynaptic, 338, 353, 354 Prevalence, 259, 338 Primary central nervous system lymphoma, 140, 339 Primary Prevention, 252, 339 Primary tumor, 11, 170, 181, 182, 183, 339 Primitive neuroectodermal tumors, 121, 131, 141, 144, 145, 197, 306, 322, 339 Private Practice, 202, 211, 339 Probe, 128, 183, 339 Procarbazine, 6, 120, 131, 339 Progeny, 290, 339 Progesterone, 322, 339, 352 Prognostic factor, 54, 72, 88, 339 Progression, 18, 19, 21, 31, 35, 36, 58, 61, 154, 210, 238, 275, 339, 358 Projection, 14, 293, 331, 339, 344 Proline, 83, 288, 311, 339 Promoter, 20, 24, 80, 192, 197, 339 Prophase, 330, 339, 353 Prophylaxis, 43, 253, 276, 339, 360 Proportional, 30, 162, 333, 339 Prospective Studies, 55, 339 Prostate, 11, 25, 28, 50, 158, 190, 233, 280, 340, 358 Protease, 340, 356 Protein C, 23, 154, 156, 168, 186, 274, 279, 288, 319, 340 Protein Conformation, 274, 340 Protein Kinases, 186, 340 Protein S, 7, 207, 234, 276, 280, 295, 306, 340, 346 Proteins, 21, 23, 24, 31, 35, 53, 56, 60, 93, 97, 111, 145, 147, 148, 153, 156, 174, 179, 186, 188, 198, 274, 276, 280, 284, 286, 287, 288, 290, 299, 301, 302, 303, 305, 310, 311, 315, 322, 323, 325, 329, 330, 334, 336, 340, 343, 346, 348, 355, 357, 361 Proteinuria, 326, 340

Index 377

Proteoglycans, 279, 302, 340 Proteolytic, 7, 288, 303, 336, 340, 356, 359 Protocol, 8, 35, 38, 46, 51, 248, 339, 340 Protons, 23, 273, 311, 317, 321, 340, 342 Proto-Oncogene Proteins, 332, 340 Proto-Oncogene Proteins c-mos, 332, 340 Protozoa, 290, 324, 340 Proximal, 9, 183, 295, 327, 338, 340 Pseudomonas, 62, 194, 340 Pseudotumor Cerebri, 170, 316, 341 Psoriasis, 190, 335, 341 Psychiatric, 5, 186, 194, 202, 210, 239, 253, 288, 323, 341 Psychiatry, 5, 210, 303, 341, 352 Psychic, 341, 347 Psychogenic, 202, 211, 341 Psychology, 35, 82, 108, 127, 295, 328, 341 Psychomotor, 293, 341 Psychophysiology, 328, 341 Psychosis, 210, 276, 341 Public Health, 9, 10, 54, 121, 139, 206, 231, 241, 341 Public Policy, 229, 341 Publishing, 66, 202, 211, 341 Pulmonary, 170, 280, 290, 318, 341, 353, 360 Pulmonary Artery, 280, 341, 360 Pulmonary Edema, 318, 341 Pulmonary Emphysema, 170, 341 Pulse, 63, 325, 342 Pupil, 291, 295, 342 Purines, 342, 348 Purulent, 110, 271, 342 Putrefaction, 342 Putrescine, 178, 179, 342, 350 Q Quiescent, 178, 342 R Race, 296, 323, 324, 342 Radiation oncologist, 172, 330, 342 Radiation Oncology, 8, 22, 43, 55, 76, 84, 85, 116, 251, 342 Radiation Tolerance, 176, 342 Radiation-Protective Agents, 342 Radiation-Sensitizing Agents, 342 Radioactivity, 150, 291, 342 Radiobiology, 319, 343 Radiofrequency ablation, 127, 343 Radioimmunoassay, 304, 343 Radioimmunotherapy, 312, 343 Radioisotope, 301, 343, 357

Radiolabeled, 7, 47, 54, 151, 152, 178, 317, 342, 343, 362 Radiopharmaceuticals, 118, 343 Radiotherapy, 6, 13, 30, 34, 45, 46, 47, 51, 63, 75, 84, 85, 103, 105, 121, 126, 130, 131, 167, 176, 177, 181, 185, 201, 215, 281, 317, 342, 343, 351, 362 Randomized, 60, 148, 151, 176, 298, 343 Rationalize, 63, 343 Reality Testing, 341, 343 Receptors, Antigen, 289, 343 Recombinant, 12, 21, 24, 60, 62, 105, 181, 196, 223, 343, 360 Recombination, 290, 343 Rectum, 277, 281, 294, 295, 304, 305, 313, 318, 340, 343 Recur, 29, 177, 344 Recurrence, 7, 29, 35, 47, 54, 89, 137, 169, 188, 196, 217, 218, 280, 287, 322, 344 Red Nucleus, 278, 344 Refer, 1, 63, 288, 296, 303, 305, 310, 320, 329, 341, 343, 344, 348, 361 Refraction, 344, 350 Refractory, 24, 44, 59, 141, 150, 152, 155, 191, 344 Regeneration, 63, 303, 344 Regimen, 63, 150, 297, 344, 345 Registries, 258, 344 Relapse, 46, 60, 344 Relative Biological Effectiveness, 30, 344 Remission, 280, 322, 344 Renal failure, 293, 344 Renin, 283, 344 Renin-Angiotensin System, 283, 344 Reproductive cells, 306, 309, 344 Research Design, 13, 344 Research Support, 45, 344 Resected, 17, 57, 117, 344 Resection, 11, 29, 41, 47, 83, 103, 128, 177, 183, 195, 217, 344 Residential Facilities, 213, 344 Resorption, 50, 311, 344 Respiration, 277, 283, 325, 345 Respite Care, 240, 345 Response rate, 169, 345 Retina, 170, 274, 286, 319, 331, 345, 346, 359, 362 Retinal, 170, 289, 295, 331, 345 Retinal Ganglion Cells, 331, 345 Retinoblastoma, 233, 345 Retinol, 345 Retreatment, 243, 345

378 Brain Tumors

Retrospective, 11, 27, 345 Retrospective study, 27, 345 Retrovirus, 65, 105, 163, 345 Rhabdoid tumor, 145, 152, 345 Rhabdomyosarcoma, 60, 149, 154, 169, 345 Rheumatism, 345, 346 Rheumatoid, 190, 346 Rheumatoid arthritis, 190, 346 Rhinitis, 190, 346 Ribonucleic acid, 79, 346 Ribonucleoproteins, 329, 346 Ribose, 272, 337, 346 Ribosome, 346, 357 Rigidity, 316, 333, 336, 346 Risk factor, 74, 94, 106, 120, 214, 247, 300, 346 Rod, 279, 340, 346 Rodenticides, 335, 346 Rubber, 271, 346 S Saline, 166, 346 Saliva, 346 Salivary, 72, 292, 294, 332, 346, 352 Salivary glands, 292, 294, 346 Saponins, 346, 352 Sarcoma, 60, 149, 154, 157, 169, 190, 339, 346, 349 Sargramostim, 157, 346 Scans, 52, 142, 149, 150, 155, 164, 165, 346 Schizoid, 347, 362 Schizophrenia, 186, 194, 203, 210, 298, 347, 362 Schizotypal Personality Disorder, 347, 362 Sclera, 286, 290, 347, 359 Sclerosis, 203, 204, 233, 326, 347 Screening, 18, 197, 247, 250, 287, 347 Second Messenger Systems, 328, 347 Secondary tumor, 11, 183, 324, 347 Secretion, 188, 287, 300, 310, 312, 315, 330, 347 Secretory, 347, 353 Sedative, 58, 347 Segmentation, 71, 347 Seizures, 188, 275, 293, 306, 333, 347 Selective estrogen receptor modulator, 347, 354 Semen, 340, 347 Semisynthetic, 282, 301, 348, 355 Senile, 133, 213, 348 Sensitization, 26, 63, 65, 348 Sepsis, 190, 304, 348 Septic, 247, 348

Septum, 318, 348 Septum Pellucidum, 318, 348 Sequela, 216, 348 Sequencing, 337, 348 Serine, 53, 340, 348, 356 Serotonin, 276, 292, 348, 358 Serous, 299, 348 Serum, 47, 107, 153, 186, 276, 288, 312, 318, 343, 348, 358 Sex Characteristics, 272, 348 Sex Determination, 233, 348 Shock, 194, 247, 348, 358 Signal Transduction, 8, 22, 40, 66, 186, 314, 348 Signs and Symptoms, 4, 205, 258, 344, 349 Sinusitis, 245, 247, 248, 349 Skeletal, 286, 326, 349, 350 Skeleton, 271, 317, 349 Skull, 165, 175, 184, 198, 291, 316, 331, 349, 351, 355 Sleep apnea, 194, 349 Small cell lung cancer, 254, 349 Small intestine, 297, 310, 316, 349, 361 Social Environment, 342, 349 Sodium, 32, 66, 72, 78, 109, 112, 150, 187, 188, 349 Soft tissue, 60, 149, 157, 169, 281, 309, 349 Soft tissue sarcoma, 60, 149, 157, 169, 349 Solvent, 28, 301, 331, 349 Somatic, 272, 291, 310, 323, 325, 334, 349 Somatostatin, 121, 253, 330, 350 Sorbitol, 310, 350 Spasm, 310, 328, 350 Spasmodic, 203, 350 Spasticity, 188, 350 Spatial disorientation, 296, 350 Specialist, 260, 295, 350 Specificity, 11, 12, 18, 26, 51, 60, 62, 172, 174, 182, 273, 277, 350 Spectrum, 44, 168, 350 Speech Disorders, 202, 350 Speech pathologist, 201, 209, 350 Sperm, 286, 306, 309, 344, 350, 358 Spermidine, 350 Spermine, 179, 350 Sphenoid, 284, 333, 350 Spinal Nerves, 182, 334, 351 Spirochete, 351, 354 Spleen, 292, 320, 321, 351 Sporadic, 345, 351 Sprains and Strains, 320, 351 Sprue, 246, 351

Index 379

Squamous, 9, 29, 176, 300, 329, 351 Squamous cell carcinoma, 29, 176, 300, 329, 351 Squamous cells, 351 Staging, 254, 346, 351 Statistically significant, 45, 351 Stem cell transplantation, 140, 141, 351 Stem Cells, 23, 66, 191, 197, 334, 351 Stereotactic radiosurgery, 8, 51, 61, 92, 126, 128, 129, 351 Sterility, 292, 351 Sterilization, 173, 352 Steroid, 33, 291, 346, 352 Stimulant, 292, 294, 310, 317, 324, 352, 360 Stimulus, 296, 297, 298, 301, 316, 318, 352, 355 Stomach, 208, 271, 294, 295, 301, 305, 306, 310, 316, 327, 335, 349, 351, 352 Strand, 337, 352 Stress, 173, 202, 210, 241, 279, 305, 327, 346, 352, 359 Stroke, 4, 23, 42, 54, 147, 156, 160, 188, 203, 211, 212, 228, 230, 239, 240, 251, 328, 352 Stroma, 317, 333, 352 Stromal, 83, 157, 352 Stupor, 319, 352 Subacute, 4, 314, 349, 352 Subarachnoid, 5, 182, 186, 304, 308, 316, 352 Subclinical, 314, 347, 352 Subcutaneous, 24, 297, 333, 352 Submaxillary, 300, 352 Subspecies, 350, 352 Substance P, 279, 324, 347, 352 Substrate, 7, 186, 352 Suction, 166, 173, 352 Sulfur, 188, 302, 324, 352 Superoxide, 93, 353 Superoxide Dismutase, 93, 353 Supplementation, 120, 353 Support group, 132, 240, 257, 258, 259, 353 Suppression, 35, 63, 294, 353 Suppressive, 56, 353 Supratentorial, 9, 17, 51, 108, 121, 131, 141, 144, 145, 353 Surfactant, 77, 353 Surgical Instruments, 166, 353 Survival Rate, 11, 44, 59, 170, 183, 332, 353 Sympathetic Nervous System, 278, 328, 353 Symphysis, 340, 353 Symptomatic, 47, 110, 353

Synapses, 186, 286, 329, 353, 354 Synapsis, 353 Synaptic, 186, 349, 353 Synaptic Vesicles, 353 Synaptophysin, 197, 354 Synchrotron, 31, 354 Syncope, 354, 360 Synergistic, 35, 65, 164, 173, 354 Synovial, 169, 354 Syphilis, 4, 239, 328, 354 Systemic disease, 20, 354 Systemic lupus erythematosus, 190, 354 Systemic therapy, 54, 354 Systolic, 311, 354 T Tamoxifen, 90, 347, 354 Technetium, 80, 354 Teichoic Acids, 308, 354 Telangiectasia, 233, 354 Telecommunications, 354 Telemedicine, 14, 354 Temozolomide, 6, 131, 141, 144, 154, 155, 156, 354 Temporal, 26, 64, 147, 175, 308, 354, 355, 360 Temporal Lobe, 147, 355, 360 Teniposide, 119, 355 Teratogenic, 58, 273, 355 Testicular, 169, 250, 355 Testis, 82, 355 Thalamic, 278, 355 Thalamic Diseases, 278, 355 Thalamus, 281, 282, 355, 360 Therapeutics, 28, 40, 163, 168, 193, 222, 355 Thermal, 162, 180, 281, 295, 329, 337, 355 Thiamine, 4, 355 Thiotepa, 122, 141, 157, 355 Third Ventricle, 312, 318, 355 Thorax, 271, 320, 355 Threonine, 340, 348, 355 Threshold, 311, 355 Thrombin, 303, 336, 340, 355, 356 Thrombolytic, 336, 355 Thrombomodulin, 340, 356 Thrombosis, 7, 170, 315, 340, 352, 356 Thrombus, 291, 314, 336, 355, 356 Thymidine, 67, 129, 163, 192, 356 Thymidine Kinase, 67, 163, 192, 356 Thymus, 312, 320, 321, 356 Thyroid, 4, 106, 214, 239, 242, 249, 250, 311, 312, 316, 356, 359

380 Brain Tumors

Thyroid Gland, 311, 356 Thyrotropin, 312, 356 Thyroxine, 335, 356 Tinnitus, 239, 341, 356, 361 Tirapazamine, 177, 356 Tissue Plasminogen Activator, 7, 356 Tolerance, 9, 272, 342, 356 Tonicity, 297, 356 Tonometer, 171, 356 Tonometry, 171, 357 Topical, 165, 278, 301, 311, 357 Topoisomerase inhibitors, 8, 317, 357 Topotecan, 59, 122, 357 Torsion, 314, 357 Toxicity, 5, 7, 9, 19, 25, 28, 30, 41, 44, 47, 57, 59, 91, 158, 172, 188, 194, 297, 323, 357 Toxicology, 48, 230, 357 Toxins, 18, 210, 276, 298, 307, 314, 325, 343, 357 Trace element, 281, 286, 304, 357 Tracer, 84, 153, 179, 208, 357 Trachea, 335, 356, 357 Transcriptase, 345, 357 Transcription Factors, 53, 357 Transduction, 8, 20, 60, 163, 348, 357 Transfection, 61, 163, 280, 357 Transfer Factor, 312, 357 Transgenes, 23, 357 Transient Ischemic Attacks, 211, 357 Translating, 40, 184, 357 Translation, 12, 24, 28, 36, 63, 208, 357 Translational, 13, 32, 34, 40, 41, 42, 51, 55, 63, 65, 66, 195, 358 Transmitter, 186, 271, 278, 296, 302, 316, 322, 353, 358 Transplantation, 23, 58, 141, 157, 170, 250, 287, 312, 318, 321, 334, 338, 358 Trauma, 170, 183, 186, 210, 212, 293, 327, 328, 358 Treatment Outcome, 189, 358 Trigeminal, 188, 358 Tropism, 67, 81, 358 Tryptophan, 288, 348, 358 Tuberculosis, 290, 320, 358 Tuberous Sclerosis, 31, 233, 358 Tubulin, 47, 324, 358 Tumor infiltrating lymphocytes, 26, 358 Tumor marker, 18, 280, 358 Tumor model, 15, 16, 27, 33, 50, 62, 358 Tumor Necrosis Factor, 78, 117, 170, 358

Tumor suppressor gene, 31, 52, 54, 59, 80, 320, 332, 358 Tumour, 257, 305, 330, 358 Type 2 diabetes, 251, 359 Tyrosine, 73, 77, 126, 198, 296, 359 U Ubiquitin, 63, 359 Unconscious, 274, 293, 312, 343, 359 Uncoupling Agents, 317, 359 Unresectable, 146, 359 Untranslated Regions, 92, 359 Uracil, 65, 181, 359 Uranium, 354, 359 Uremia, 318, 344, 359 Urethra, 340, 359 Urinary, 72, 286, 306, 311, 313, 326, 330, 356, 359 Urinary Plasminogen Activator, 356, 359 Urinate, 142, 359 Urine, 16, 138, 139, 147, 148, 150, 156, 277, 280, 300, 309, 313, 318, 330, 340, 359 Urogenital, 306, 359 Urokinase, 8, 359 Urticaria, 190, 359 Uterus, 285, 323, 331, 339, 359, 360 Uvea, 359 Uveitis, 190, 359 V Vaccination, 49, 61, 359 Vaccine, 49, 61, 157, 158, 216, 272, 340, 360 Vagina, 285, 323, 360 Valine, 334, 359, 360 Valves, 193, 360 Vascular endothelial growth factor, 111, 178, 360 Vasodilator, 281, 296, 310, 360 VE, 91, 360 Vector, 19, 20, 26, 61, 65, 92, 111, 118, 181, 192, 196, 357, 360 Vein, 142, 150, 155, 157, 278, 316, 329, 360 Venereal, 354, 360 Venom, 12, 360 Venous, 278, 281, 284, 285, 340, 360 Venous blood, 281, 285, 360 Ventral, 311, 337, 351, 360 Ventricle, 171, 318, 341, 342, 354, 360 Ventricular, 311, 360 Venules, 281, 282, 299, 360 Vertebrae, 316, 350, 360 Vertebral, 212, 360 Vertebrobasilar Insufficiency, 212, 360 Vertigo, 211, 212, 245, 360, 361

Index 381

Vesicular, 17, 310, 360 Vestibular, 211, 239, 361 Vestibule, 361 Vestibulocochlear Nerve, 356, 361 Vestibulocochlear Nerve Diseases, 356, 361 Veterinary Medicine, 229, 361 Villi, 311, 361 Villous, 286, 361 Vinblastine, 118, 358, 361 Vinca Alkaloids, 361 Vincristine, 120, 131, 339, 358, 361 Vinorelbine, 149, 361 Viral, 12, 24, 26, 35, 60, 65, 88, 107, 181, 271, 276, 299, 303, 330, 345, 357, 361 Viral vector, 24, 35, 65, 88, 361 Virulence, 278, 357, 361 Virus Diseases, 276, 361 Visceral, 279, 291, 334, 361 Viscosity, 271, 361 Visual Cortex, 170, 361 Visual field, 166, 171, 331, 341, 361 Vitreous Body, 345, 362 Vitro, 7, 11, 16, 20, 22, 24, 26, 28, 42, 45, 48, 53, 55, 57, 58, 59, 60, 65, 66, 83, 105, 119, 170, 174, 182, 192, 195, 309, 313, 337, 362

Vivo, 7, 11, 17, 22, 23, 25, 26, 28, 29, 32, 39, 42, 45, 48, 53, 56, 57, 58, 59, 60, 65, 67, 71, 78, 83, 94, 98, 105, 118, 127, 137, 166, 168, 174, 175, 179, 181, 190, 192, 197, 309, 313, 362 W Wakefulness, 293, 362 White blood cell, 271, 275, 286, 313, 319, 321, 326, 327, 329, 336, 358, 362 Windpipe, 335, 356, 362 Withdrawal, 194, 210, 293, 362 Womb, 198, 359, 362 Wound Healing, 275, 303, 315, 322, 362 X Xenograft, 55, 60, 62, 275, 358, 362 X-ray therapy, 162, 317, 362 X-ray tube, 175, 362 Y Yeasts, 305, 335, 362 Yttrium, 173, 362 Z Zygote, 289, 290, 363 Zymogen, 340, 363

382 Brain Tumors

Index 383

384 Brain Tumors

Brain Tumors - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Brain Injuries - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Brain Cancer - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Brain - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Brain Damage - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Traumatic Brain Injury - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Influenza A - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Facial Paralysis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Wine - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Breast Augmentation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lipomas - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Barbiturates - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Cephalexin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lymphedema - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Vaginitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Feet - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Brain Tumors - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Brain Injuries - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Brain Cancer - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Brain - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Brain Damage - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Traumatic Brain Injury - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Influenza A - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Facial Paralysis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Wine - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Breast Augmentation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lipomas - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Barbiturates - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Cephalexin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lymphedema - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Vaginitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Feet - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Recommend Documents