Bone Cancer - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

ONE ANCER 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

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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., 1960Bone Cancer: 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: 0-597-83797-X 1. Bone Cancer-Popular works. I. Title.

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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.

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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 bone cancer. 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.

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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.

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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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON BONE CANCER .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Bone Cancer .................................................................................. 5 E-Journals: PubMed Central ......................................................................................................... 9 The National Library of Medicine: PubMed .................................................................................. 9 CHAPTER 2. NUTRITION AND BONE CANCER ................................................................................ 17 Overview...................................................................................................................................... 17 Finding Nutrition Studies on Bone Cancer ................................................................................. 17 Federal Resources on Nutrition ................................................................................................... 18 Additional Web Resources ........................................................................................................... 18 CHAPTER 3. ALTERNATIVE MEDICINE AND BONE CANCER .......................................................... 21 Overview...................................................................................................................................... 21 National Center for Complementary and Alternative Medicine.................................................. 21 Additional Web Resources ........................................................................................................... 29 General References ....................................................................................................................... 30 CHAPTER 4. DISSERTATIONS ON BONE CANCER ............................................................................ 33 Overview...................................................................................................................................... 33 Dissertations on Bone Cancer...................................................................................................... 33 Keeping Current .......................................................................................................................... 33 CHAPTER 5. CLINICAL TRIALS AND BONE CANCER ...................................................................... 35 Overview...................................................................................................................................... 35 Recent Trials on Bone Cancer ...................................................................................................... 35 Keeping Current on Clinical Trials ............................................................................................. 55 CHAPTER 6. PATENTS ON BONE CANCER ....................................................................................... 57 Overview...................................................................................................................................... 57 Patents on Bone Cancer ............................................................................................................... 57 Patent Applications on Bone Cancer ........................................................................................... 70 Keeping Current .......................................................................................................................... 77 CHAPTER 7. BOOKS ON BONE CANCER .......................................................................................... 79 Overview...................................................................................................................................... 79 Book Summaries: Online Booksellers........................................................................................... 79 The National Library of Medicine Book Index ............................................................................. 80 Chapters on Bone Cancer ............................................................................................................. 80 CHAPTER 8. MULTIMEDIA ON BONE CANCER................................................................................ 83 Overview...................................................................................................................................... 83 Bibliography: Multimedia on Bone Cancer.................................................................................. 83 CHAPTER 9. PERIODICALS AND NEWS ON BONE CANCER............................................................. 85 Overview...................................................................................................................................... 85 News Services and Press Releases................................................................................................ 85 Academic Periodicals covering Bone Cancer ............................................................................... 87 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................... 89 Overview...................................................................................................................................... 89 U.S. Pharmacopeia....................................................................................................................... 89 Commercial Databases ................................................................................................................. 90 Researching Orphan Drugs ......................................................................................................... 91 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 95 Overview...................................................................................................................................... 95 NIH Guidelines............................................................................................................................ 95 NIH Databases............................................................................................................................. 97

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Other Commercial Databases....................................................................................................... 99 The Genome Project and Bone Cancer ......................................................................................... 99 APPENDIX B. PATIENT RESOURCES ............................................................................................... 103 Overview.................................................................................................................................... 103 Patient Guideline Sources.......................................................................................................... 103 Finding Associations.................................................................................................................. 108 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 111 Overview.................................................................................................................................... 111 Preparation................................................................................................................................. 111 Finding a Local Medical Library................................................................................................ 111 Medical Libraries in the U.S. and Canada ................................................................................. 111 ONLINE GLOSSARIES................................................................................................................ 117 Online Dictionary Directories ................................................................................................... 119 BONE CANCER DICTIONARY ................................................................................................. 121 INDEX .............................................................................................................................................. 169

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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 bone cancer 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 bone cancer, 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 bone cancer, 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 bone cancer. 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 bone cancer, 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 bone cancer. The Editors

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

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CHAPTER 1. STUDIES ON BONE CANCER Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bone cancer.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and bone cancer, 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 “bone cancer” (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: •

Ewing's Sarcoma of the Mandible: Radiologic Features with Emphasis on Magnetic Resonance Appearance Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 91(6): 728-734. June 2001. Contact: Available from Mosby, Inc. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Website: www.harcourthealth.com. Summary: Ewing's sarcoma is an uncommon malignancy that usually occurs in children. This article presents a case of Ewing's sarcoma of the mandible (lower jaw); the authors describe the radiologic appearance of the lesion with an emphasis on the magnetic resonance imaging (MRI) features. A 12 year old girl presented with fever and a 7 day history of facial swelling. On physical examination, the child showed facial

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asymmetry with a tender and swollen mass in the right side of her face. A presumptive diagnosis of acute suppurative inflammation of the right parotid (salivary) gland was made. The patient was given antibiotics, but no change was seen in the swelling. Panoramic radiograph showed a permeative, poorly demarcated destructive lesion in the right ramus (branch) of the mandible; computed tomography (CT) scan was also performed. Biopsy confirmed diagnosis of Ewing's sarcoma (ES). The MRI allowed a better examination of the affected area and revealed the mass invasion of the mandibular condyle and the petrous part of the temporal bone. Once the diagnosis of ES with extension into the surrounding soft tissues was made, a chemotherapy protocol treatment was started. An MRI after the second chemotherapy session showed progression of the tumor; given the poor response of the tumor to chemotherapy, radiation therapy was added to the treatment protocol. After 6 weeks, MRI showed reduction in tumor size. After the 10th chemotherapy cycle, the patient underwent an autologous (using the patient's own tissue) bone marrow transplantation (BMT). Clinical follow up revealed that the patient is alive and symptom free, with no evidence of local recurrence or distant metastases and with normal laboratory parameters 36 months after diagnosis. The authors conclude that MRI is the diagnostic tool of choice in local staging of ES and is an imaging technique of great value in monitoring the effects of chemotherapy. MRI has also shown its superiority over other techniques for evaluating the medullary and soft tissue components of ES. 6 figures. 15 references. •

Mesenchymal Chondrosarcoma of the Maxilla with Diffuse Metastasis: Case Report and Literature Review Source: Journal of Oral and Maxillofacial Surgery. 60(8): 931-935. August 2002. Contact: Available from W.B. Saunders Company. Periodicals Department, P.O. Box 629239, Orlando, FL 32862-8239. (800) 654-2452. Website: www.harcourthealth.com. Summary: Mesenchymal chondrosarcoma (MCS) is a rare variant of chondrosarcoma (cancer), characterized by widespread, late metastasis (spreading). There are 51 cases of maxillofacial MCS reported in the literature. This article reports an additional case of a maxillary (upper jaw) MCS with subsequent diffuse metastasis. 7 figures. 13 references.

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Osteosarcoma of the Mandibular Condyle: Case Report Source: Journal of Oral and Maxillofacial Surgery. 59(5): 574-577. May 2001. Contact: Available from W.B. Saunders Company. Periodicals Department, P.O. Box 629239, Orlando, FL 32862-8239. (800) 654-2452. Website: www.harcourthealth.com. Summary: Osteosarcoma is one of the most frequently occurring malignant bone tumors. However, it is still a rather rare lesion, affecting only one in 100,000 people every year in the United States. Osteosarcoma of the jaws makes up approximately 5 to 6 percent of cases, with the tumor occurring in the mandible (lower jaw) as frequently as in the maxilla (upper jaw). This article reports a rare case of a temporomandibular joint (TMJ) osteosarcoma. The authors analyze the case's radiologic features, clinical and surgical treatment, the histologic findings, and the final outcome. Fifteen months after surgical treatment, no signs of recurrence were observed on a computed tomography (CT) scan. There was a progressive recovery of jaw mobility. The patient underwent postsurgical orthodontic treatment to reestablish a satisfactory occlusion in the sagittal and transverse dimensions by shifting the mandible posteriorly and to the left. The authors note that osteosarcoma of the jaw usually does not metastasize (spread). The most frequently used treatment procedure includes preoperative chemotherapy, radical surgery with reconstruction, and postoperative chemotherapy. Patients with

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osteosarcoma of the jaws have a 5 year survival rate of 15 to 30 percent. 5 figures. 30 references. •

Metastatic Osteosarcoma to the Maxilla: A Case Report and a Review of the Literature Source: Quintessence International. 33(5): 397-399. May 2002. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. Summary: This article reports a case of a patient with a successfully treated primary osteosarcoma (cancer) of the tibia who experienced an isolated maxillary (upper jaw) metastasis (spread of the cancer), an extremely rare entity. Once the jaw tumor was confirmed histologically, a total maxillectomy and adjuvant chemoradiation therapy were carried out. There has been no local recurrence or distant metastasis in this patient for 1 year. The authors stress that a multimodality therapeutic approach is essential when these patients are treated. Surgery is the gold standard of treatment in operable cases. Adjuvant treatment is required to prevent local recurrence and distant metastasis. 3 figures. 15 references.

Federally Funded Research on Bone Cancer The U.S. Government supports a variety of research studies relating to bone cancer. 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 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 bone cancer. 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 bone cancer. The following is typical of the type of information found when searching the CRISP database for bone cancer: •

Project Title: BONE CANCER AND SKELETAL PAIN Principal Investigator & Institution: Clohisy, Denis R.; Professor; Orthopedic Surgery; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 20-MAR-2001; Project End 28-FEB-2006 Summary: (Verbatim from the Applicant): Bone cancer pain decreases the quality of life of millions of patients each year in the United States. Because there has not been an experimental model appropriate for studying osteolytic bone cancer pain, very little is known about its etiology, and current treatments can be ineffective or have unwanted side effects. We have very recently developed an experimental model for studying bone

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

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cancer pain. Features of this model are that it allows simultaneous quantitative evaluation of tumor growth, bone destruction, bone cell biology, painful behaviors, cellular biology of pain and neurochemistry of pain. Based on our unique capability to study bone cancer pain, we now propose to determine the cause of bone cancer pain in two types of bone cancers: those that stimulate bone destruction (osteolytic), and those that stimulate bone formation (osteoblastic). The long-range goal of our laboratories is to understand the pathophysiology of bone cancer and its sequelae and to use this knowledge to develop new treatments. The objective of this application is to determine the cause of bone cancer's most devastating sequalae: pain. To accomplish this, we will develop an experimental model for studying osteoblastic bone cancer pain and then use that model and our established osteolytic bone cancer model to determine the cause of bone cancer pain. The central hypothesis of this proposal is that bone cancer pain is caused by both the cancer itself and by cancer-induced bone loss. To test this hypothesis, the following Aims will be pursued: (1) establish the role of osteoclasts in the development of osteoblastic cancers; (2) define the characteristics of osteoblastic bone cancer pain; (3) determine if osteoblastic and/or osteolytic bone cancer tumors cause pain; and (4) determine if cancer-induced bone loss (osteoblastic and/or osteolytic) causes pain. At the completion of these Aims we expect to define the bone cell biology and neurochemical basis of pain from osteoblastic bone cancer (Aims 1 & 2), and we expect to prove for the first time that pain from osteoblastic and osteolytic bone cancers is caused both by tumors themselves, and by cancer-induced skeletal destruction (Aims 3 & 4). The results will be significant because they will provide rationale and direction for developing novel, mechanistically based treatments of bone cancer pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF ACUPUNCTURE ON BONE CANCER PAIN IN MICE Principal Investigator & Institution: Zhang, Ruixin; Family Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Cancer pain, particularly bone cancer pain, is a major symptom that significantly affects the quality of life of cancer patients. Clinical trials have demonstrated that acupuncture can alleviate cancer pain, but as yet evidence from basic scientific research is absent. An animal model of femur bone cancer pain, which mimics clinical cancer pain, has been established in our lab. We propose to use this model to evaluate the effects and mechanisms of electroacupuncture (EA) at acupoint G30 (Huan Tiao) on femoral cancer pain. The proposed hypotheses are: 1) EA of acupoint G30 at the optimal sets of parameters will significantly inhibit femur bone cancer-induced hyperalgesia. 2) Activity of the central neurons during cancer pain will be modulated by EA. The specific aims of this proposal are: Aim I: Evaluate the effects of EA on cancer-induced thermal hyperalgesia by measuring hindpaw withdrawal latency. Various combinations of frequencies (10 and 100 Hz) and stimulation durations (10, 15, 20 min) at the maximum tolerable electrical current of 1 mA will be administered to study the anti-hyperalgesic effects of EA in a mouse model of bone cancer pain. Aim II- Determine the optimal treatment protocol. With the optimal sets of parameters determined in Aim I, various EA treatment regimens will be conducted to establish how often treatments should be administered to achieve the greatest anti-hyperalgesic effects. Aim lll: Investigate the central mechanisms of action of EA on cancer pain. The modulation of EA on the activities of central neurons in the spinal cord will be investigated by characterizing Fos protein and dynorphin peptide expression with immunohistochemical staining. These studies will advance our knowledge of EA in

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control and management of cancer pain and provide useful information for designing future clinical trials using optimal EA parameters for patients with cancer pain. These studies will set a stage for further studying the mechanisms of EA in the control and management of cancer pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDIVIDUAL PREDOCTORAL DENTAL SCIENTIST FELLOWSHIP Principal Investigator & Institution: Mach, David B.; Restorative Sciences; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 13-JUN-2003 Summary: (provided by applicant): The proposal that David Mach is submitting will help define the origin of bone cancer pain and begin to dissect out mechanism that are involved in the generation and maintenance of this pain. The experiments that David presented in the Research Training Proposal employ cutting-edge technologies and will position David to be a leader in the field of cancer pain research. A critical feature of David's past and future success has been his ability to closely interact with both basic and clinical scientists and to focus on issues in basic science that will have a direct impact on patient care. Thus, using the first animal model of bone cancer pain that he was involved in generating David will be examining sensory and sympathetic innervation of bone as tumor growth and bone remodeling occur. He will study the extent to which the C-fiber sensory innervation or sympathetic innervation of bone is involved in the regulation of tumor growth, tumor angiogenesis, osteoclast proliferation, and bone destruction/remodeling. David will define the cellular and neurochemical changes that occur in the spinal cord, dorsal column nuclei, dorsal ganglia, and sympathetic ganglia as the bone is destroyed/remodeling. David will define the cellular and neurochemical changes that occur in the spinal cord, dorsal column nuclei, dorsal root ganglia, and sympathetic ganglia as the bone is destroyed/remodeled. These studies should provide David with both the training and the publications so that at the end of his fellowship he will be recognized as a highly productive and innovative clinical-scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INHIBITORS OF RANK AND RANKL IN OSTEOPOROSIS TREATMENT Principal Investigator & Institution: Singh, Sujay K.; Imgenex 11175 Flintkote Ave Ste E San Diego, Ca 92121 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2004 Summary: (provided by applicant): Osteoporosis is a major health problem affecting nearly 1.5 million people every year. The reduction of sex hormone levels in both men and women increase production of certain factors that lead to osteoporosis. One-third of all post-menopausal Caucasian women experience at least osteoporotic fracture during their lifetime. In addition, more than 70 percent of patients with advanced breast or prostate cancer have skeletal metastases leading to bone degradation due to osteoclastogenesis. Ongoing osteoclast activity appears to be involved in the generation and maintenance of ongoing and movement-evoked pain. Blockade of ongoing osteoclast activity appears to have the potential to reduce bone cancer pain in patients with advanced tumor-induced bone destruction. Recent studies have shown that RANKL, a member of the tumor necrosis factor superfamily, by acting through its receptor RANK can induce osteoclast formation leading to osteoporosis. In the present

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study, we propose to identify peptide inhibitors by screening peptide display libraries. The ability of these peptides to interfere with RANKL induced osteoclast formation will be tested. The inhibitory effect of selected peptides in animal models will be tested in the Phase II study. The selected peptides can be used to design even smaller peptides or small molecule non-peptide mimetics, which can be used as therapeutic drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PERIPHERAL NOCICEPTORS IN PERSISTENT PAIN Principal Investigator & Institution: Mantyh, Patrick W.; Professor; Polymer Science & Engineering; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-1987; Project End 30-NOV-2005 Summary: (Adapted from the Investigator's Abstract) A viable model of bone cancer has been developed in which lytic sarcoma cells are injected into the intramedullary space of the mouse femur. The cells are confined within the bone by an amalgam plug produce extensive bone destruction and pain behaviors similar to that observed in patients with bone cancer. A breast cancer cell line bone pain model will also be developed. With these models the cellular and neurochemical pathophysiology that generates and maintains cancer-induced bone pain can be studied. These studies are proposed to define the distribution and time course of tumor invasion in bone, tumor angiogenesis, osteoclast proliferation, bone destruction, remodeling and bone cancer nociceptive behaviors (Aim 1). The studies will define sensory and sympathetic innervation of bone as the interosseus mass grows and nociceptive state changes assessing tumor growth and bone destruction (Aim 2). Neurochemical changes in the spinal cord, dorsal column nuclei, and sympathetic and dorsal root ganglia will be monitored (Aim 3). Pharmacological manipulation of the generation and maintenance of bone cancer nociceptive events will be attempted (Aim 4). The information generated by these studies should significantly expand our understanding of the cellular and molecular mechanisms involved in the generation of bone cancer pain and may lead to effective therapies for treating bone cancer pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT--CONNECTIVE TISSUE ONCOLOGY Principal Investigator & Institution: Baker, Laurence H.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 31-MAY-2006 Summary: The Connective Tissue Oncology Program (CTOP) studies two populations of patients with cancer of the connective tissues: the skeleton and its supporting soft tissues. It is composed of 26 members from 11 department with more than $3.3 million in annual direct support. The cancers studied are either primary or metastatic to these groups of tissues. Sarcomas, or primary cancers of connective tissues, are uncommon forms of malignancy, particularly in comparison to the epithelial cancers, yet represent a raison d'etre of cancer centers: multi-disciplinary oncology. All current practice guidelines underscore the need to have multi- disciplinary teams of physicians and other professionals to care for patients with these uncommon malignancies. Success has been clearly achieved with the approach of combining the medical or pediatric oncologist with the surgeon to produce markedly improved cure rates for bone cancer (osteosarcoma, Ewing's sarcoma), and to a lesser extent, of soft tissue sarcomas. While cancers of the connective tissue are much more common in soft tissue than in bone, the

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reverse is true when one considers metastatic cancers where metastasis to the skeleton is far more common that metastasis to the soft tissue supporting that skeleton. Metastasis to the skeleton is a very common phenomenon associated with human cancer. The prevalence and predilection of metastasis to the bones, despite its commonality, is one of the more poorly understood processes associated with cancer. Even more devastating are the symptoms caused by the metastasis and the relative ineffectiveness of current treatments. The research areas related to sarcomas and metastatic bone tumors represent a common research foci. For example, the bone microenvironment primarily consists of mesenchymal cells similar to the cells from which sarcomas originates from. Additionally, the biology of sarcomas and metastatic cancers is similar in terms of growth characteristics (e.g. slow growth). Accordingly, we think combining these two areas of concern into a single program makes good sense, and in particular, unifies the strengths at this Cancer Center. 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 “bone cancer” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for bone cancer in the PubMed Central database: •

An activity specified by the osteosarcoma line U2OS can substitute functionally for ICP0, a major regulatory protein of herpes simplex virus type 1. by Yao F, Schaffer PA.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189522

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 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. 6 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.

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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 bone cancer, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “bone cancer” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for bone cancer (hyperlinks lead to article summaries): •

“Systemic radioisotopic therapy of primary and metastatic bone cancer”. Author(s): Robinson RG. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1990 August; 31(8): 1326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2384799&dopt=Abstract

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A case with extraosseous Ewing's sarcoma: a late effect related to bone marrow transplantation for thalassemia or a component of a familial cancer syndrome? Author(s): Mutafoglu Uysal K, Olgun N, Sarialioglu F, Kargi A, Cevik N. Source: Pediatric Hematology and Oncology. 2000 July-August; 17(5): 415-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914053&dopt=Abstract

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A comparative study of samarium-153-ethylenediaminetetramethylene phosphonic acid with pamidronate disodium in the treatment of patients with painful metastatic bone cancer. Author(s): Wang RF, Zhang CL, Zhu SL, Zhu M. Source: Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre. 2003 April-June; 12(2): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634464&dopt=Abstract

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Adolescent bone cancer: is the growth spurt implicated? Author(s): Dix D, McDonald M, Cohen P. Source: Eur J Cancer Clin Oncol. 1983 June; 19(6): 859-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6683652&dopt=Abstract

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Analysis of the human tumour necrosis factor-alpha (TNFalpha) gene promoter polymorphisms in children with bone cancer. Author(s): Patio-Garcia A, Sotillo-Pieiro E, Modesto C, Sierrases-Maga L. Source: Journal of Medical Genetics. 2000 October; 37(10): 789-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11183184&dopt=Abstract

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Analysis of urine samples from metastatic bone cancer patients administered 153SmEDTMP. Author(s): Goeckeler WF, Stoneburner LK, Kasi LP, Fossella FV, Price DR, Fordyce WA. Source: Nuclear Medicine and Biology. 1993 July; 20(5): 657-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8358352&dopt=Abstract

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Bone cancer and limb-sparing surgery. Author(s): Pritchard DJ. Source: Seminars in Surgical Oncology. 1997 January-February; 13(1): 1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9025175&dopt=Abstract

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Bone cancer in Wales overestimated. Author(s): Cotter M. Source: Bmj (Clinical Research Ed.). 1994 March 26; 308(6932): 859. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8167510&dopt=Abstract

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Bone cancer incidence rates in New York State: time trends and fluoridated drinking water. Author(s): Mahoney MC, Nasca PC, Burnett WS, Melius JM. Source: American Journal of Public Health. 1991 April; 81(4): 475-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2003628&dopt=Abstract

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Bone cancer risk estimates. Author(s): Puskin JS, Nelson NS, Nelson CB. Source: Health Physics. 1992 November; 63(5): 579-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1290512&dopt=Abstract

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Bone cancer risk. Author(s): Chadwick KH. Source: Journal of Radiological Protection : Official Journal of the Society for Radiological Protection. 2001 March; 21(1): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281534&dopt=Abstract

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Bone cancer--who are at risk? Author(s): Shah SH. Source: J Pak Med Assoc. 1999 May; 49(5): 109. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10555424&dopt=Abstract

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Cellular and neurochemical remodeling of the spinal cord in bone cancer pain. Author(s): Honore P, Schwei J, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML, Clohisy DR, Mantyh PW. Source: Prog Brain Res. 2000; 129: 389-97. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098706&dopt=Abstract

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Clinico-morphological pattern and frequency of bone cancer. Author(s): Shah SH, Muzaffar S, Soomro IN, Pervez S, Hasan SH. Source: J Pak Med Assoc. 1999 May; 49(5): 110-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10555425&dopt=Abstract

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Descriptive epidemiology of bone cancer in greater Bombay. Author(s): Yeole BB, Jussawalla DJ. Source: Indian Journal of Cancer. 1998 September; 35(3): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10226399&dopt=Abstract

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Distant metastases from ear and temporal bone cancer. Author(s): Sasaki CT. Source: Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 2001 JulyAugust; 63(4): 250-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408822&dopt=Abstract

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Double-blind evaluation of short-term analgesic efficacy of orally administered dexketoprofen trometamol and ketorolac in bone cancer pain. Author(s): Rodriguez MJ, Contreras D, Galvez R, Castro A, Camba MA, Busquets C, Herrera J. Source: Pain. 2003 July; 104(1-2): 103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855319&dopt=Abstract

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Epidemiology of bone cancer in children. Author(s): Glass AG, Fraumeni JF Jr. Source: Journal of the National Cancer Institute. 1970 January; 44(1): 187-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515030&dopt=Abstract

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Ethics in action. A woman with terminal bone cancer has asked her physician to help her end her life. Author(s): Haddad A. Source: Rn. 1997 March; 60(3): 17-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9122588&dopt=Abstract

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Herpes vector-mediated expression of proenkephalin reduces bone cancer pain. Author(s): Goss JR, Harley CF, Mata M, O'Malley ME, Goins WF, Hu X, Glorioso JC, Fink DJ. Source: Annals of Neurology. 2002 November; 52(5): 662-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402268&dopt=Abstract

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Hypercalcemia induced by metastatic bone cancer in a patient with chronic renal failure. Author(s): Kajiyama H, Kuroiwa T, Ueki K, Kanai H, Maezawa A, Yano S, Nojima Y, Naruse T. Source: Clinical Nephrology. 2000 October; 54(4): 347-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076112&dopt=Abstract

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Imaging in bone cancer. Author(s): Edeiken J, Karasick D. Source: Ca: a Cancer Journal for Clinicians. 1987 July-August; 37(4): 239-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3111652&dopt=Abstract

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International trends in the incidence of bone cancer are not related to drinking water fluoridation. Author(s): Freni SC, Gaylor DW. Source: Cancer. 1992 August 1; 70(3): 611-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1623476&dopt=Abstract

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Interspecies scaling of risk for radiation-induced bone cancer. Author(s): Raabe OG, Rosenblatt LS, Schlenker RA. Source: International Journal of Radiation Biology. 1990 May; 57(5): 1047-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1970992&dopt=Abstract

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Lifetime bone cancer dose-response relationships in beagles and people from skeletal burdens of 226Ra and 90Sr. Author(s): Raabe OG, Book SA, Parks NJ. Source: Health Physics. 1983; 44 Suppl 1: 33-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6862910&dopt=Abstract

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Management of extremity metastatic bone cancer. Author(s): Schmidt RG. Source: Current Problems in Cancer. 1995 May-June; 19(3): 166-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7545570&dopt=Abstract

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Marrow-sparing effects of 117mSn(4+)diethylenetriaminepentaacetic acid for radionuclide therapy of bone cancer. Author(s): Bishayee A, Rao DV, Srivastava SC, Bouchet LG, Bolch WE, Howell RW. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2000 December; 41(12): 2043-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11138691&dopt=Abstract

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Metastatic bone cancer. Author(s): Welch-McCaffrey D. Source: Cancer Nursing. 1988 April; 11(2): 103-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3383185&dopt=Abstract

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Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. Author(s): Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, Bertrand A, Ahmann FR, Orihuela E, Reid RH, Lerski RA, Collier BD, McKillop JH, Purnell GL, Pecking AP, Thomas FD, Harrison KA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 April; 16(4): 1574-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9552068&dopt=Abstract

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Parental cancer as a risk factor for bone cancer: a nation-wide study from Sweden. Author(s): Li X, Hemminki K. Source: Journal of Clinical Epidemiology. 2002 February; 55(2): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809347&dopt=Abstract

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Phase II study of low-dose methotrexate in advanced osteosarcoma followed by escalation after disease progression: a study of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research on Treatment of Cancer. Author(s): Wagener DJ, van Oosterom AT, Mulder JH, Somers R, Mouridsen HT, Cortes Funes H, Thomas D, Sylvester R. Source: Cancer Treat Rep. 1986 May; 70(5): 615-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3458532&dopt=Abstract

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Primary bone cancer incidence in black and white residents of New York State. Author(s): Polednak AP. Source: Cancer. 1985 June 15; 55(12): 2883-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3857961&dopt=Abstract

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Prostheses in the management of bone cancer. Author(s): Scales JT. Source: British Medical Journal (Clinical Research Ed.). 1983 September 10; 287(6394): 761-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6412815&dopt=Abstract

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Prostheses in the management of bone cancer. Author(s): Nixon JE. Source: British Medical Journal (Clinical Research Ed.). 1983 July 23; 287(6387): 245-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6409266&dopt=Abstract

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Quality of life and psychosocial adjustment of young patients after treatment of bone cancer. Author(s): Felder-Puig R, Formann AK, Mildner A, Bretschneider W, Bucher B, Windhager R, Zoubek A, Puig S, Topf R. Source: Cancer. 1998 July 1; 83(1): 69-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9655295&dopt=Abstract

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Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. Author(s): Hawkins MM, Wilson LM, Burton HS, Potok MH, Winter DL, Marsden HB, Stovall MA. Source: Journal of the National Cancer Institute. 1996 March 6; 88(5): 270-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8614005&dopt=Abstract

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Radium in drinking water and risk of bone cancer in Ontario youths: a second study and combined analysis. Author(s): Finkelstein MM, Kreiger N. Source: Occupational and Environmental Medicine. 1996 May; 53(5): 305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8673177&dopt=Abstract

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Radium in drinking water and the risk of death from bone cancer among Ontario youths. Author(s): Finkelstein MM. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1994 September 1; 151(5): 565-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8069801&dopt=Abstract

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Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer. Author(s): Farhanghi M, Holmes RA, Volkert WA, Logan KW, Singh A. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1992 August; 33(8): 1451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1378887&dopt=Abstract

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Simultaneous presentation of malignant external otitis and temporal bone cancer. Author(s): Grandis JR, Hirsch BE, Yu VL. Source: Archives of Otolaryngology--Head & Neck Surgery. 1993 June; 119(6): 687-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8499104&dopt=Abstract

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Temporal bone cancer. Author(s): Koriwchak M. Source: The American Journal of Otology. 1993 November; 14(6): 623-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8296870&dopt=Abstract

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The relationship between parental occupation and bone cancer risk in offspring. Author(s): Hum L, Kreiger N, Finkelstein MM. Source: International Journal of Epidemiology. 1998 October; 27(5): 766-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839731&dopt=Abstract

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Transforming growth factor-beta-induced mitogenesis of human bone cancer cells. Author(s): Datta HK, Zaidi M, Champaneri JB, MacIntyre I. Source: Biochemical and Biophysical Research Communications. 1989 June 15; 161(2): 672-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2735916&dopt=Abstract

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CHAPTER 2. NUTRITION AND BONE CANCER Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and bone cancer.

Finding Nutrition Studies on Bone Cancer 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 “bone cancer” (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.

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

Circadian optimisation of irinotecan and oxaliplatin efficacy in mice with Glasgow osteosarcoma. Author(s): INSERM E-0118 Chronotherapeutique des cancers and Universite Paris XI, Institut du Cancer et d'Immunogenetique, Hopital Paul Brousse, 14, av. Paul Vaillant Couturier, 94800 Villejuif, France. Source: Granda, T G D'Attino, R M Filipski, E Vrignaud, P Garufi, C Terzoli, E Bissery, M C Levi, F Br-J-Cancer. 2002 March 18; 86(6): 999-1005 0007-0920

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

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

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

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

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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/

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

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

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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

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

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

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

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

Nutrition

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

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND BONE CANCER Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to bone cancer. 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 bone cancer 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 “bone cancer” (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 bone cancer: •

A link between basic fibroblast growth factor (bFGF) and EWS/FLI-1 in Ewing's sarcoma cells. Author(s): Girnita L, Girnita A, Wang M, Meis-Kindblom JM, Kindblom LG, Larsson O. Source: Oncogene. 2000 August 31; 19(37): 4298-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10980604&dopt=Abstract

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A multidisciplinary study investigating radiotherapy in Ewing's sarcoma: end results of POG #8346. Pediatric Oncology Group. Author(s): Donaldson SS, Torrey M, Link MP, Glicksman A, Gilula L, Laurie F, Manning J, Neff J, Reinus W, Thompson E, Shuster JJ. Source: International Journal of Radiation Oncology, Biology, Physics. 1998 August 1; 42(1): 125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9747829&dopt=Abstract

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A randomized controlled trial of octreotide pamoate long-acting release and carboplatin versus carboplatin alone in dogs with naturally occurring osteosarcoma: evaluation of insulin-like growth factor suppression and chemotherapy. Author(s): Khanna C, Prehn J, Hayden D, Cassaday RD, Caylor J, Jacob S, Bose SM, Hong SH, Hewitt SM, Helman LJ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 July; 8(7): 2406-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114446&dopt=Abstract

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Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. Author(s): Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Miser JS. Source: The New England Journal of Medicine. 2003 February 20; 348(8): 694-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594313&dopt=Abstract

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Chemotherapy and P-glycoprotein expression in chondrosarcoma. Author(s): Terek RM, Schwartz GK, Devaney K, Glantz L, Mak S, Healey JH, Albino AP. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 1998 September; 16(5): 585-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9820282&dopt=Abstract

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Chondrosarcoma and myositis ossificans. Author(s): Le Roux DA. Source: Journal of Manipulative and Physiological Therapeutics. 1998 NovemberDecember; 21(9): 640-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9868636&dopt=Abstract

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Circadian optimisation of irinotecan and oxaliplatin efficacy in mice with Glasgow osteosarcoma. Author(s): Granda TG, D'Attino RM, Filipski E, Vrignaud P, Garufi C, Terzoli E, Bissery MC, Levi F. Source: British Journal of Cancer. 2002 March 18; 86(6): 999-1005. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953836&dopt=Abstract

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Ewing's sarcoma of the mandible: a combined approach to treatment. Author(s): Fielding AF, Lindemeyer R, Wood-Harris J, Hartman MJ. Source: J Clin Pediatr Dent. 2002 Summer; 26(4): 409-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175138&dopt=Abstract

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Ewing's sarcoma treatment in Scandinavia 1984-1990--ten-year results of the Scandinavian Sarcoma Group Protocol SSGIV. Author(s): Nilbert M, Saeter G, Elomaa I, Monge OR, Wiebe T, Alvegard TA.

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Source: Acta Oncologica (Stockholm, Sweden). 1998; 37(4): 375-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743460&dopt=Abstract •

Fertility in male patients treated with neoadjuvant chemotherapy for osteosarcoma. Author(s): Longhi A, Macchiagodena M, Vitali G, Bacci G. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 April; 25(4): 292-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679642&dopt=Abstract

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Five-year results in Ewing's sarcoma. The Scandinavian Sarcoma Group experience with the SSG IX protocol. Author(s): Elomaa I, Blomqvist CP, Saeter G, Akerman M, Stenwig E, Wiebe T, Bjork O, Alvegard TA. Source: European Journal of Cancer (Oxford, England : 1990). 2000 May; 36(7): 875-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10785592&dopt=Abstract

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Granulocyte colony stimulating factor permits dose intensification by interval compression in the treatment of Ewing's sarcomas and soft tissue sarcomas in children. Author(s): Womer RB, Daller RT, Fenton JG, Miser JS. Source: European Journal of Cancer (Oxford, England : 1990). 2000 January; 36(1): 87-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741300&dopt=Abstract

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High-dose chemotherapy in the treatment of relapsed osteosarcoma: an Italian sarcoma group study. Author(s): Fagioli F, Aglietta M, Tienghi A, Ferrari S, Brach del Prever A, Vassallo E, Palmero A, Biasin E, Bacci G, Picci P, Madon E. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 April 15; 20(8): 2150-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956277&dopt=Abstract

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High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing's sarcoma does not improve prognosis. Author(s): Meyers PA, Krailo MD, Ladanyi M, Chan KW, Sailer SL, Dickman PS, Baker DL, Davis JH, Gerbing RB, Grovas A, Herzog CE, Lindsley KL, Liu-Mares W, Nachman JB, Sieger L, Wadman J, Gorlick RG. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 June 1; 19(11): 2812-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11387352&dopt=Abstract

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How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The

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Memorial Sloan-Kettering experience and a literature review. Author(s): Kushner BH, Meyers PA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 February 1; 19(3): 870-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157041&dopt=Abstract •

Ifosfamide and actinomycin-D, added in the induction phase to vincristine, cyclophosphamide and doxorubicin, improve histologic response and prognosis in patients with non metastatic Ewing's sarcoma of the extremity. Author(s): Ferrari S, Mercuri M, Rosito P, Mancini A, Barbieri E, Longhi A, Rimondini S, Cesari M, Ruggieri P, Di Liddo M, Bacci G. Source: Journal of Chemotherapy (Florence, Italy). 1998 December; 10(6): 484-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9876058&dopt=Abstract

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Ifosfamide and etoposide plus vincristine, doxorubicin, and cyclophosphamide for newly diagnosed Ewing's sarcoma family of tumors. Author(s): Wexler LH, DeLaney TF, Tsokos M, Avila N, Steinberg SM, Weaver-McClure L, Jacobson J, Jarosinski P, Hijazi YM, Balis FM, Horowitz ME. Source: Cancer. 1996 August 15; 78(4): 901-11. Erratum In: Cancer 1997 February 15; 79(4): 867. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8756388&dopt=Abstract

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In vitro test-system for chemo- and thermosensitivity: an analysis of survival fractions and cell-cycle distributions in human Ewing's sarcomas as a modelfor tumors in pediatric oncology. Author(s): Debes A, Rommel F, Breise M, Willers R, Gobel U, Wessalowski R. Source: Klinische Padiatrie. 2002 July-August; 214(4): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165906&dopt=Abstract

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Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing's sarcoma cells. Author(s): Benini S, Manara MC, Baldini N, Cerisano V, Massimo Serra, Mercuri M, Lollini PL, Nanni P, Picci P, Scotlandi K. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 June; 7(6): 1790-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410521&dopt=Abstract

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Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571. Author(s): McGary EC, Weber K, Mills L, Doucet M, Lewis V, Lev DC, Fidler IJ, Bar-Eli M. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 November; 8(11): 3584-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429650&dopt=Abstract

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Inhibition of poly(ADP-ribose) polymerase activation attenuates beta-lapachoneinduced necrotic cell death in human osteosarcoma cells. Author(s): Liu TJ, Lin SY, Chau YP. Source: Toxicology and Applied Pharmacology. 2002 July 15; 182(2): 116-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140175&dopt=Abstract

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Intensive combined modality therapy including low-dose TBI in high-risk Ewing's Sarcoma Patients. Author(s): Kinsella TJ, Glaubiger D, Diesseroth A, Makuch R, Waller B, Pizzo P, Glatstein E. Source: International Journal of Radiation Oncology, Biology, Physics. 1983 December; 9(12): 1955-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9463099&dopt=Abstract

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Involvement of caspase-3 in epigallocatechin-3-gallate-mediated apoptosis of human chondrosarcoma cells. Author(s): Islam S, Islam N, Kermode T, Johnstone B, Mukhtar H, Moskowitz RW, Goldberg VM, Malemud CJ, Haqqi TM. Source: Biochemical and Biophysical Research Communications. 2000 April 21; 270(3): 793-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772904&dopt=Abstract

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Local therapy and other factors influencing site of relapse in patients with localised Ewing's sarcoma. United Kingdom Children's Cancer Study Group (UKCCSG). Author(s): Shankar AG, Pinkerton CR, Atra A, Ashley S, Lewis I, Spooner D, Cannon S, Grimer R, Cotterill SJ, Craft AW. Source: European Journal of Cancer (Oxford, England : 1990). 1999 November; 35(12): 1698-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674016&dopt=Abstract

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Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86. Author(s): Paulussen M, Ahrens S, Dunst J, Winkelmann W, Exner GU, Kotz R, Amann G, Dockhorn-Dworniczak B, Harms D, Muller-Weihrich S, Welte K, Kornhuber B, JankaSchaub G, Gobel U, Treuner J, Voute PA, Zoubek A, Gadner H, Jurgens H. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 March 15; 19(6): 1818-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251014&dopt=Abstract

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Maffucci's syndrome associated with a cranial base chondrosarcoma: case report and literature review. Author(s): Ramina R, Coelho Neto M, Meneses MS, Pedrozo AA.

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Source: Neurosurgery. 1997 July; 41(1): 269-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9218317&dopt=Abstract •

Neoadjuvant chemotherapy for Ewing's sarcoma of bone: no benefit observed after adding ifosfamide and etoposide to vincristine, actinomycin, cyclophosphamide, and doxorubicin in the maintenance phase--results of two sequential studies. Author(s): Bacci G, Picci P, Ferrari S, Mercuri M, Brach del Prever A, Rosito P, Barbieri E, Tienghi A, Forni C. Source: Cancer. 1998 March 15; 82(6): 1174-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9506366&dopt=Abstract

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Paravertebral extraosseous Ewing's sarcoma. Author(s): Yadav TP, Singh RP, Gupta VK, Chaturvedi NK, Prasad CV. Source: Indian Pediatrics. 1998 June; 35(6): 557-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10216655&dopt=Abstract

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Pelvic girdle chondrosarcoma and inferior vena cava thrombosis. Author(s): Hoekstra HJ, Pras B, Mooyaart EL, van Ginkel R, Molenaar WM. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 1997 December; 23(6): 577-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484938&dopt=Abstract

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PET imaging of osteosarcoma. Author(s): Brenner W, Bohuslavizki KH, Eary JF. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 June; 44(6): 930-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791822&dopt=Abstract

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Predictive factors of histological response to primary chemotherapy in Ewing's sarcoma. Author(s): Bacci G, Picci P, Mercuri M, Ferrari S, Longhi A, Cesari M, Rosito P, Mancini AF, Barbieri E, Baldini N. Source: Acta Oncologica (Stockholm, Sweden). 1998; 37(7-8): 671-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10050985&dopt=Abstract

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Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. Author(s): Goorin AM, Schwartzentruber DJ, Devidas M, Gebhardt MC, Ayala AG, Harris MB, Helman LJ, Grier HE, Link MP; Pediatric Oncology Group.

Alternative Medicine 27

Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 April 15; 21(8): 1574-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697883&dopt=Abstract •

Prognostic factors in nonmetastatic Ewing's sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedico Rizzoli. Author(s): Bacci G, Ferrari S, Bertoni F, Rimondini S, Longhi A, Bacchini P, Forni C, Manfrini M, Donati D, Picci P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 January; 18(1): 4-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10623687&dopt=Abstract

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Prognostic factors in patients with localized Ewing's sarcoma: the effect on survival of actual received drug dose intensity and of histologic response to induction therapy. Author(s): Delepine N, Delepine G, Cornille H, Voisin MC, Brun B, Desbois JC. Source: Journal of Chemotherapy (Florence, Italy). 1997 October; 9(5): 352-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9373791&dopt=Abstract

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Radiotherapy in Ewing's sarcoma and PNET of the chest wall: results of the trials CESS 81, CESS 86 and EICESS 92. Author(s): Schuck A, Hofmann J, Rube C, Hillmann A, Ahrens S, Paulussen M, Jurgens H, Dunst J, Willich N. Source: International Journal of Radiation Oncology, Biology, Physics. 1998 December 1; 42(5): 1001-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9869222&dopt=Abstract

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Regional drug delivery with radiation for the treatment of Ewing's sarcoma. In vitro development of a taxol release system. Author(s): Attawia MA, Borden MD, Herbert KM, Katti DS, Asrari F, Uhrich KE, Laurencin CT. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2001 April 2; 71(2): 193-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274751&dopt=Abstract

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RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing's sarcoma and alveolar rhabdomyosarcoma. Author(s): Thomson B, Hawkins D, Felgenhauer J, Radich J. Source: Bone Marrow Transplantation. 1999 September; 24(5): 527-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10482938&dopt=Abstract

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Second malignancies after treatment for Ewing's sarcoma: a report of the CESSstudies.

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Author(s): Dunst J, Ahrens S, Paulussen M, Rube C, Winkelmann W, Zoubek A, Harms D, Jurgens H. Source: International Journal of Radiation Oncology, Biology, Physics. 1998 September 1; 42(2): 379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9788419&dopt=Abstract •

STEALTH liposome-encapsulated cisplatin (SPI-77) versus carboplatin as adjuvant therapy for spontaneously arising osteosarcoma (OSA) in the dog: a randomized multicenter clinical trial. Author(s): Vail DM, Kurzman ID, Glawe PC, O'Brien MG, Chun R, Garrett LD, Obradovich JE, Fred RM 3rd, Khanna C, Colbern GT, Working PK. Source: Cancer Chemotherapy and Pharmacology. 2002 August; 50(2): 131-6. Epub 2002 June 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172978&dopt=Abstract

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Suppression of centromere dynamics by Taxol in living osteosarcoma cells. Author(s): Kelling J, Sullivan K, Wilson L, Jordan MA. Source: Cancer Research. 2003 June 1; 63(11): 2794-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782584&dopt=Abstract

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The effects of genistein on the synthesis and distribution of glycosaminoglycans/proteoglycans by two osteosarcoma cell lines depends on tyrosine kinase and the estrogen receptor density. Author(s): Nikitovic D, Tsatsakis AM, Karamanos NK, Tzanakakis GN. Source: Anticancer Res. 2003 January-February; 23(1A): 459-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680249&dopt=Abstract

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The Poly(ADP-ribose) polymerase-1-regulated endonuclease DNAS1L3 is required for etoposide-induced internucleosomal DNA fragmentation and increases etoposide cytotoxicity in transfected osteosarcoma cells. Author(s): Boulares AH, Zoltoski AJ, Sherif ZA, Yakovlev AG, Smulson ME. Source: Cancer Research. 2002 August 1; 62(15): 4439-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154052&dopt=Abstract

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Treatment of refractory osteosarcoma with fractionated cyclophosphamide and etoposide. Author(s): Rodriguez-Galindo C, Daw NC, Kaste SC, Meyer WH, Dome JS, Pappo AS, Rao BN, Pratt CB. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 May; 24(4): 250-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972091&dopt=Abstract

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Triggering of p73-dependent apoptosis in osteosarcoma is under the control of E2FspRb2/p130 complexes. Author(s): La Sala D, Macaluso M, Trimarchi C, Giordano A, Cinti C. Source: Oncogene. 2003 June 5; 22(23): 3518-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789260&dopt=Abstract

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Unstratified chemotherapy for non-metastatic osteosarcoma of the extremities in children. Author(s): Lin MT, Lin KH, Lin DT, Yang RS, Wu CT, Lu MY, Hung IJ, Yang CP, Chang TT, Shu SG, Chen RL, Hsiao TC, Chang WH, Lin KS. Source: J Formos Med Assoc. 2003 June; 102(6): 387-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923591&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/

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to bone cancer; 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 Anemia Source: Integrative Medicine Communications; www.drkoop.com

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Bone Cancer Source: Integrative Medicine Communications; www.drkoop.com Cold Intolerance Source: Integrative Medicine Communications; www.drkoop.com Fatigue Source: Integrative Medicine Communications; www.drkoop.com Headache Source: Integrative Medicine Communications; www.drkoop.com Neurologic Complications Source: Integrative Medicine Communications; www.drkoop.com Renal Failure Source: Integrative Medicine Communications; www.drkoop.com Retinopathy Source: Integrative Medicine Communications; www.drkoop.com Swelling Source: Integrative Medicine Communications; www.drkoop.com Tenderness Source: Integrative Medicine Communications; www.drkoop.com Vision Disturbances Source: Integrative Medicine Communications; www.drkoop.com Weakness Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Osteopathy Source: Integrative Medicine Communications; www.drkoop.com Osteopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,724,00.html

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.

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This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON BONE CANCER Overview In this chapter, we will give you a bibliography on recent dissertations relating to bone cancer. 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 “bone cancer” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bone cancer, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Bone Cancer 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 bone cancer. 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: •

Mechanisms of Bone Cancer Pain by Sabino, Mary Ann Chiuten; Phd from University of Minnesota, 2002, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3056352

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The Psychosocial Adaptation to Bone Cancer Diagnosed during Adolescence: a Longterm Follow-up Study by Christ, Grace Constance, Dsw from Columbia University, 1992, 334 pages http://wwwlib.umi.com/dissertations/fullcit/9231981

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.

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CHAPTER 5. CLINICAL TRIALS AND BONE CANCER Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning bone cancer.

Recent Trials on Bone Cancer The following is a list of recent trials dedicated to bone cancer.8 Further information on a trial is available at the Web site indicated. •

A Pilot Study of Autologous T-Cell Transplantation with Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas Condition(s): Ewing's Sarcoma; Rhabdomyosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This is a single arm study. The tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo T cell harvest 10 days after an initial priming peptide-pulsed antigen presenting cell (APC) vaccine is performed. Fresh APCs are utilized for initial priming vaccination. All subsequent vaccinations will use cryopreserved APCs. Minimum number of APCs administered per vaccination is 100,000/kg and maximum is 100,000,000/kg. Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This therapy usually consists of multiagent chemotherapy in the context of a separate protocol. Following chemotherapy, infusion of harvested T cells followed by infusion of peptide-pulsed APC vaccinations occurs every 6 weeks for a total of 3 post-priming vaccinations. Influenza vaccine is administered by intramuscular injection concurrent to peptide-pulsed APC vaccines. IL-2 is administered as a continuous IV infusion for 4 days/week for 3 successive weeks starting on the same day as T cell /peptide-pulsed infusions. Phase(s): Phase II

8

These are listed at www.ClinicalTrials.gov.

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Bone Cancer

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001566 •

Alanosine in Treating Patients With Cancer Condition(s): Gastrointestinal Cancer; musculoskeletal cancer; Osteosarcoma; thorax and respiratory cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as alanosine use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of alanosine in treating patients who have soft tissue sarcoma, sarcoma of the bone, mesothelioma, non-small cell lung cancer, or pancreatic cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062283

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Antineoplaston Therapy in Treating Patients With Malignant Fibrous Histiocytoma Condition(s): childhood soft tissue sarcoma; Muscle Cancer; Osteosarcoma 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 malignant fibrous histiocytoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003510

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Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors Condition(s): childhood soft tissue sarcoma; childhood solid tumor; Melanoma; Neuroblastoma; Osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I trial to study the effectiveness of hu14.18-interleukin2 fusion protein in treating children who have refractory or recurrent neuroblastoma or other tumors.

Clinical Trials 37

Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003750 •

Bone Cancer: Treatment Outcome Based on Tumor Response Condition(s): Osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Standard treatment for patients with non-metastatic bone cancer (cancer that has not spread beyond the bone) includes chemotherapy, then surgery to remove the tumor, and then another course of chemotherapy. Sixty to 70 percent of patients do well with this treatment. However, some of the drugs are highly toxic, causing serious side effects, and still, 30 to 40% of patients' tumors do not respond. In this study, patients will be separated into two different courses of treatment to try to: 1) reduce treatment time, number of medicines, and adverse side effects in patients whose tumors are largely destroyed by the first round of chemotherapy, and 2) improve survival in patients whose tumors do respond well to standard treatment. All patients will receive three doses of the drugs doxorubicin and cisplatin three weeks apart before surgery. Patients whose disease is confined to the bone and whose tumor responds well to the first round of chemotherapy (more than 90% destroyed) will be given another three courses of the same drugs after the tumor is removed. Other patients will be given three courses of the drugs melphalan and cyclophosphamide after surgery. These are patients whose tumor: is confined to the bone but did not respond well to the chemotherapy administered before surgery; had spread beyond the bone at the time of diagnosis; and could not be removed surgically. All patients will have blood tests and imaging studies, including PET scans and DEMRI-a type of magnetic resonance imaging-to evaluate their tumors before and during the study. Patients who receive melphalan and cyclophosphamide will also undergo a procedure to collect special cells called stem cells. These drugs destroy certain blood cells that fight infection and stop bleeding, and stem cells help the bone marrow replace them more quickly. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001821

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Bortezomib in Treating Patients With Advanced or Metastatic Sarcoma Condition(s): adult soft tissue sarcoma; gastrointestinal stromal tumor; metastatic osteosarcoma; metastatic tumors of the Ewing's family; Osteosarcoma; tumors of the Ewing's family Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bortezomib may stop the growth of cancer by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have advanced or metastatic sarcoma.

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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027716 •

Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma Condition(s): metastatic osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; 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. Monoclonal antibodies such as trastuzumab can locate tumor cells and kill them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy with or without trastuzumab in treating patients who have metastatic osteosarcoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023998

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Combination Chemotherapy and Peripheral Stem Cell Transplantation With or Without Radiation Therapy and/or Surgery in Treating Patients With Ewing's Sarcoma Condition(s): localized tumors of the Ewing's family; metastatic tumors of the Ewing's family Study Status: This study is currently recruiting patients. Sponsor(s): European Ewing Tumour Working Initiative of National Groups; National Cancer Institute (NCI); United Kingdom Children's Cancer Study Group; Societe Francaise Oncologie Pediatrique; EORTC Soft Tissue and Bone Sarcoma Cooperative Group; Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany; Gesellschaft fur Padiatrische Onkologie und Hamatologie - Austria; Swiss Institute for Applied Cancer Research; EBMT Solid Tumors Working Party; Children's Oncology Group; EORTC Children's Leukemia Cooperative Group 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. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without radiation therapy and/or surgery in treating Ewing's sarcoma. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy and peripheral stem cell transplantation with or without radiation therapy and/or surgery in treating patients who have a Ewing's sarcoma. Phase(s): Phase III Study Type: Interventional

Clinical Trials 39

Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00020566 •

Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia, Osteosarcoma, or Non-Hodgkin's Lymphoma Condition(s): recurrent childhood acute lymphoblastic leukemia; recurrent childhood lymphoblastic lymphoma; recurrent osteosarcoma; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy consisting of trimetrexate glucuronate plus leucovorin in treating children who have recurrent acute lymphoblastic leukemia, recurrent osteosarcoma, or refractory non-Hodgkin's lymphoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002738

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Combination Chemotherapy in Treating Children Rhabdomyosarcoma or Other Malignant Mesenchymal Tumors

With

Metastatic

Condition(s): childhood rhabdomyosarcoma; childhood soft tissue sarcoma; female reproductive cancer; Gastrointestinal Cancer; musculoskeletal cancer; Osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Societe Internationale d'Oncologie Pediatrique; United Kingdom Children's Cancer Study Group; Societe Francaise Oncologie Pediatrique Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating children with metastatic rhabdomyosarcoma or other malignant mesenchymal tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025441 •

Comparison of Combination Chemotherapy Regimens in Treating Patients With Ewing's Sarcoma or Neuroectodermal Tumor Condition(s): localized tumors of the Ewing's family Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI)

40

Bone Cancer

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. It is not yet known which chemotherapy regimen combined with radiation therapy and/or surgery is more effective for Ewing's sarcoma or primitive neuroectodermal tumor. PURPOSE: Randomized phase III trial to compare different regimens of chemotherapy combined with radiation therapy and/or surgery in treating patients who have Ewing's sarcoma or primitive neuroectodermal tumor. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006734 •

Comparison of Filgrastim and Filgrastim SD/01in Boosting White Cell Counts after Intensive Chemotherapy Condition(s): Ewing's Sarcoma; Rhabdomyosarcoma; Sarcoma; Synovial Sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Filgrastim (granulocyte colony-stimulating factor), which is administered by daily subcutaneous injection after cytotoxic chemotherapy, shortens the duration of chemotherapy-induced neutropenia and lowers the risk of infection. In children treated with dose-intensive chemotherapy, filgrastim reduces the duration of severe neutropenia and, as a result, has become a standard component of the treatment regimen. Filgrastim-SD/01 (AMGEN), which is produced by PEGylation of the aminoterminus of filgrastim, is a sustained duration form of granulocyte colony-stimulating factor. In phase I and phase II trials in adults, a single dose of Filgrastim-SD/01 appears to be equivalent to daily dosing of filgrastim in enhancing neutrophil recovery and has a comparable adverse event profile. Dose-intensive vincristine/cyclophosphamide/doxorubicin (VDoxC) alternating with ifosfamide/etoposide (IE) has become standard therapy for children and adolescents with Ewing's sarcoma and other sarcomas treated at the POB/NCI and other cancer centers within the US. Supportive care measures used in children who are treated with this regimen include mesna to prevent oxazaphosphorine urotoxicity, dexrazoxane to reduce doxorubicin cardiotoxicity, and filgrastim to shorten the duration of neutropenia. The purpose of this randomized open label trial is to compare the tolerance, toxicity, and therapeutic effects of Filgrastim-SD/01 given as a single injection after chemotherapy to daily subcutaneous filgrastim in patients with newly diagnosed sarcoma. The pharmacokinetics of Filgrastim-SD/01 will also be compared to the pharmacokinetics of filgrastim. This trial will also be a platform for performing biological studies of these tumors and for detailed cardiac studies. High-risk patients who are treated on this front line trial and respond will also be candidates for a planned transplant protocol. A total of 34 patients (17 patients per treatment arm) will be entered onto the trial. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004853

Clinical Trials 41

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Diagnostic Study of Patients With Ewing's Sarcoma Condition(s): localized tumors of the Ewing's family; metastatic tumors of the Ewing's family Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Genetic testing may help predict how cancer will respond to treatment and allow doctors to plan more effective therapy. PURPOSE: Diagnostic trial to study genetic differences in patients who have Ewing's sarcoma. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048984

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Evaluation, Treatment, and Natural History of Children with Cancer Condition(s): Ewing's Sarcoma; Leukemia; Lymphoma; Neoplasm; Sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This protocol is designed to evaluate children with cancer who appear to be probable candidates for future protocol entry or have disease manifestations that are of unique scientific importance or educational value. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001686

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Exatecan Mesylate in Treating Patients With Ewing's Sarcoma, Neuroectodermal Tumor, or Desmoplastic Small Round Cell Tumor

Primitive

Condition(s): Ewing's family of tumors; childhood soft tissue sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Daiichi Pharmaceuticals 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 exatecan mesylate in treating patients who have relapsed or refractory Ewing's sarcoma or peripheral primitive neuroectodermal tumor or desmoplastic small round cell tumor. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055952 •

Genetic Study of Children With Soft Tissue Sarcoma or Rhabdomyosarcoma Condition(s): Ewing's family of tumors; childhood rhabdomyosarcoma; childhood soft tissue sarcoma; hematopoietic and lymphoid cancer; Osteosarcoma Study Status: This study is currently recruiting patients.

42

Bone Cancer

Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Determination of genetic markers for soft tissue sarcoma or rhabdomyosarcoma may help doctors identify patients who are at risk for therapy-related leukemia. PURPOSE: Clinical trial to study genetic testing of children with soft tissue sarcoma or rhabdomyosarcoma to identify children who are at risk of developing leukemia from the chemotherapy used to treat sarcoma. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003793 •

Imatinib Mesylate in Treating Patients With Advanced Soft Tissue Sarcoma or Bone Sarcoma Condition(s): Ewing's family of tumors; childhood rhabdomyosarcoma; childhood soft tissue sarcoma; Osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have metastatic or unresectable locally advanced soft tissue sarcoma or bone sarcoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031915

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Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood Condition(s): Ewing's family of tumors; childhood soft tissue sarcoma; Gastrointestinal Cancer; metastatic cancer; Neuroblastoma; Osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have relapsed or refractory solid tumors of childhood. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030667

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Irinotecan in Treating Children With Refractory Solid Tumors Condition(s): Ewing's family of tumors; childhood brain tumor; rhabdomyosarcoma; childhood solid tumor; Neuroblastoma; Osteosarcoma

childhood

Clinical Trials 43

Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; 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 II trial to study the effectiveness of irinotecan in treating children who have refractory solid tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004078 •

Monoclonal Antibody A1G4 Plus BCG in Treating Patients With Cancer Condition(s): childhood Osteosarcoma

soft

tissue

sarcoma; Muscle Cancer; Neuroblastoma;

Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody A1G4 with BCG may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody A1G4 plus BCG in treating patients with cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003023 •

Neoadjuvant and Adjuvant Pamidronate With Induction and Maintenance Chemotherapy in Treating Patients With Osteosarcoma Condition(s): localized osteosarcoma; metastatic osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as cisplatin, doxorubicin, and methotrexate, use different ways to stop cancer cells from dividing so they stop growing or die. Pamidronate given with chemotherapy for osteosarcoma may slow the growth of cancer cells and strengthen bones. PURPOSE: Phase II trial to study the effectiveness of combining adjuvant and neoadjuvant pamidronate with induction and maintenance chemotherapy in treating patients who have newly diagnosed osteosarcoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072306

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Bone Cancer

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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 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

Clinical Trials 45

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011414 •

Phase II Study of Sequential Gemcitabine Plus Docetaxel for Recurrent Ewing's Sarcoma, Osteosarcoma, or Unresectable or Locally Recurrent Chondrosarcoma Condition(s): Osteosarcoma; Sarcoma, Ewing's; Chondrosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Gemcitabine and docetaxel are active antineoplastic agents with a broad spectrum of clinical activity. In single agent phase I trials, gemcitabine and docetaxel have shown some activity in patients with Ewing's sarcoma and osteosarcoma. Chondrosarcomas are known to be refractory to standard chemotherapeutic regimens. A variety of schedules and doses of gemcitabine in combination with docetaxel have been studied in clinical trials. Recently, two clinical trials have reported response rates of approximately 50% when the drugs are given sequentially with gemcitabine followed by docetaxel. Most recently, in vitro data supports the synergy of sequential gemcitabine-docetaxel therapy. The primary objective of this study is to determine the objective response rate of sequential gemcitabine-docetaxel in patients with recurrent Ewing's Sarcoma, recurrent osteosarcoma, and unresectable or locally recurrent chondrosarcomas. Additionally, the pharmacokinetics of gemcitabine and docetaxel will be studied in this patient population and when available, tumor samples for cDNA microarray analysis of gene expression and development of cell lines and xenotransplantation models will be obtained. The study will be conducted with the North American Sarcoma Study Group of the Connective Tissue Oncology Society. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070772

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Studying Genetic Changes in Ewing Sarcoma Tumors Condition(s): Ewing's Sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Ewing sarcoma is a type of cancer usually found in children and young adults. Researchers use tissue samples of Ewing sarcoma tumors to conduct research with the goal of improving the treatments for this disease. The purpose of this study is to maintain a tissue bank from tumor biopsies donated by patients with Ewing Sarcoma to learn about genetic changes seen in these tumors. When Ewing sarcoma is suspected, doctors diagnose the disease by taking a sample of a patient's tumor for evaluation. Some of the tissue from this procedure is usually discarded. Study participants will donate the unused tissue from this diagnostic procedure. Study Type: Observational Contact(s): see Web site below

46

Bone Cancer

Web Site: http://clinicaltrials.gov/ct/show/NCT00063271 •

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 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

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Trastuzumab in Treating Patients With Recurrent Osteosarcoma Condition(s): recurrent osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase II trial to study the effectiveness of trastuzumab in treating patients who have recurrent osteosarcoma. Phase(s): Phase II

Clinical Trials 47

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005033 •

Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) With or Without ImmTher for Newly Diagnosed High Risk Ewing's Sarcoma Condition(s): Ewing's Sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: The goal of this study is to see if treatment with vincristine, doxorubicin, cyclophosphamide and dexrazoxane (VACdxr) given in high doses with or without ImmTher will help patients with Ewing's Sarcoma live longer. The safety of these treatments will also be studied. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038142

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A Pilot Study of Tumor-Specific Peptide Vaccination and IL-2 with or without Autologous T Cell Transplantation in Recurrent Pediatric Sarcomas Condition(s): Ewing's Sarcoma; Rhabdomyosarcoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Arm A: Peripheral blood apheresis by harvesting chemotherapynaive T cells and populations enriched for professional APCs. T cells and APCs are separated from the apheresis product using countercurrent centrifugal elutriation and a monocyte rich fraction is collected. Autologous T cell transplantation during immunotherapy. Arm B: Cell harvesting is performed as soon as possible. Both Arm A and B: Patients receive intravenous infusion of irradiated peptide-pulsed antigen presenting cell vaccination (APC) products as well as intramuscular injection of influenza vaccine on the same day. Recombinant human IL-2 is administered within 4 hours of the peptide pulsed vaccine by continuous intravenous infusion for 4 days per week for 3 successive weeks. Primary toxic effect of this therapy is expected to be related to the IL-2 therapy. Patients with Grade 2 neurologic or cardiac or any Grade 3 or 4 toxic effects will discontinued IL-2 therapy. If toxic effect is not resolved in 72-hours, the patient may remain on study but will not receive any further IL-2. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001564

48

Bone Cancer

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Amifostine to Protect From the Side Effects of Peripheral Stem Cell Transplantation in Treating Patients With High-Risk or Relapsed Solid Tumors Condition(s): childhood soft tissue sarcoma; childhood liver cancer; adult soft tissue sarcoma; Bone Cancer; ovarian sarcoma; Testicular Cancer; Brain Tumor; Eye Cancer; kidney tumor Study Status: This study is no longer recruiting patients. Sponsor(s): University of Minnesota Cancer Center 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. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of high-dose chemotherapy. PURPOSE: Phase I trial to study the effectiveness of amifostine in protecting from the side effects of peripheral stem cell transplantation in treating patients who have highrisk or relapsed solid tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003926

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Chemotherapy in Treating Patients With Metastatic Ewing's Sarcoma or Primitive Neuroectodermal Tumor Condition(s): metastatic tumors of the Ewing's family Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Soft Tissue and Bone Sarcoma Cooperative Group 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 II trial to study the effectiveness of combination chemotherapy in treating patients who have metastatic Ewing's sarcoma or primitive neuroectodermal tumor. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014313

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Combination Chemotherapy and Surgery With or Without G-CSF in Treating Patients With Osteosarcoma Condition(s): localized osteosarcoma Study Status: This study is no longer recruiting patients. Sponsor(s): European Osteosarcoma Intergroup; Medical Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as G-CSF may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects

Clinical Trials 49

of chemotherapy. It is not yet known whether chemotherapy and surgery plus G-CSF is more effective than chemotherapy and surgery alone in treating patients with osteosarcoma. PURPOSE: Randomized phase III trial to compare the effectiveness combination chemotherapy and surgery with or without G-CSF in treating patients who have newly diagnosed osteosarcoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002539 •

Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas Condition(s): childhood bone cancer; childhood brain cancer; childhood eye cancer; childhood kidney tumors; childhood non-Hodgkin's lymphoma; childhood soft tissue sarcoma Study Status: This study is no longer recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of flavopiridol in treating children who have relapsed or refractory solid tumors or lymphoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012181

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Holmium Ho 166 DOTMP Followed by Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Ewing's Sarcoma or Rhabdomyosarcoma That Has Spread to the Bone Condition(s): recurrent childhood rhabdomyosarcoma; recurrent adult soft tissue sarcoma; adult rhabdomyosarcoma; stage IVB adult soft tissue sarcoma; stage IVA adult soft tissue sarcoma; bone metastases; previously treated childhood rhabdomyosarcoma; metastatic tumors of the Ewing's family; recurrent tumors of the Ewing's family Study Status: This study is no longer recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radioactive drugs such as holmium Ho 166 DOTMP can kill cancer cells without harming healthy cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by radiation therapy. PURPOSE: Phase I/II trial to study the effectiveness of holmium Ho 166 DOTMP followed by peripheral stem cell transplantation in treating patients who have metastatic Ewing's sarcoma or rhabdomyosarcoma that has spread to the bone. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below

50

Bone Cancer

Web Site: http://clinicaltrials.gov/ct/show/NCT00006234 •

Interferon alfa and Thalidomide in Treating Patients With Soft Tissue Sarcoma or Bone Sarcoma Condition(s): stage III adult soft tissue sarcoma; stage IVB adult soft tissue sarcoma; stage IVA adult soft tissue sarcoma; stage IIC adult soft tissue sarcoma; localized osteosarcoma; metastatic osteosarcoma Study Status: This study is no longer recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Interferon alfa may interfere with the growth of cancer cells. Combining interferon alfa and thalidomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining interferon alfa and thalidomide in treating patients who have undergone surgery for soft tissue sarcoma or bone sarcoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026416

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A Phase I Study of OncoLAR(r) (Registered Trademark) (NSC 685403) with/without Tamoxifen in Patients with Osteosarcoma Condition(s): Neoplasm Metastasis; Osteosarcoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The suppression of IGF-I and growth hormone may significantly alter the pathobiology of osteosarcoma. SMS 201-955 pa LAR is a long acting analog of Somatostatin which inhibits the pituitary release of growth hormone, reducing levels of circulating IGF-I. Additional data on tamoxifen usage has also demonstrated a reduction in circulating IGF-I levels. The degree of suppression of IGF-I and growth hormone will be determined at two dose levels of SMS 291-955 pa LAR. Tamoxifen will be added to two of the cohorts to determine if the additive effects of tamoxifen and SMS 201-955 pa LAR will lead to additional reduction of circulating IGF-I and growth hormone levels. Arginine-stimulated GH tests to assess levels of growth hormone in the blood will be administered pre-treatment evaluation up to three times, one time on weeks 2, 8, 16, 28, 40, 52, and one month post last dose of SMS 201-955 pa LAR. The four cohorts for this study will receive 60 or 90 mg SMS 201-955 pa LAR injectable every four weeks for up to 52 weeks. Two of the cohorts will receive 10 mg Tamoxifen on a daily basis. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001436

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A Pilot Study for the Treatment of Patients with Metastatic and High Risk Sarcomas and Primitive Neuroectodermal Tumors Condition(s): Neuroectodermal Tumor, Primitive; Neuroepithelioma; Osteosarcoma; Sarcoma; Sarcoma, Ewing's Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This protocol is designed to test the feasibility of the administration of vincristine, adriamycin and cytoxan, alternating with the newly developed regimen ifosfamide VP-16 as well as the efficacy of this therapy in addition to radiotherapy in producing complete responses and disease-free survival in patients with Ewing's sarcoma, primitive sarcoma of bone, peripheral neuroepithelioma, and soft tissue sarcoma. This will not be a randomized study but will be comparable to the large data base of similar patients treated on successive Pediatric Branch studies. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001209

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Chemotherapy in Treating Children With Recurrent or Refractory Sarcomas Condition(s): recurrent childhood rhabdomyosarcoma; recurrent osteosarcoma; embryonal childhood rhabdomyosarcoma; alveolar childhood rhabdomyosarcoma; recurrent childhood soft tissue sarcoma; extraosseous Ewing's sarcoma/primitive neuroectodermal tumor; recurrent tumors of the Ewing's family Study Status: This study is completed. Sponsor(s): Children's Oncology Group; 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 II trial to study the effectiveness of topotecan in treating children who have recurrent, relapsed, or refractory sarcoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003745

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Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Ewing's Sarcoma or Primitive Neuroectodermal Tumor Condition(s): metastatic tumors of the Ewing's family; Neutropenia Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Children's Cancer Group; Pediatric Oncology Group 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 II trial to study the effectiveness of

52

Bone Cancer

combination chemotherapy in treating patients with newly diagnosed metastatic Ewing's sarcoma or primitive neuroectodermal tumor. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002643 •

Combination Chemotherapy Plus Vinblastine and Celecoxib in Treating Patients With Newly Diagnosed Metastatic Ewing's Sarcoma Condition(s): metastatic tumors of the Ewing's family Study Status: This study is not yet open for patient recruitment. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as vinblastine use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of Ewing's sarcoma by stopping blood flow to the tumor. Combining more than one chemotherapy drug with celecoxib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining low-dose vinblastine and celecoxib with standard regimens of combination chemotherapy in treating patients who have newly diagnosed metastatic Ewing's sarcoma Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061893

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Inhaled Sargramostim in Treating Patients With First Pulmonary (Lung) Recurrence of Osteosarcoma Condition(s): metastatic osteosarcoma; recurrent osteosarcoma; lung metastases Study Status: This study is not yet open for patient recruitment. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Inhaling aerosolized sargramostim before and after surgery may interfere with the growth of tumor cells and shrink the tumor so that it can be removed during surgery. Sargramostim may then kill any tumor cells remaining after surgery. This may be an effective treatment for osteosarcoma that has spread to the lung. PURPOSE: Phase II trial to study the effectiveness of inhaled sargramostim in treating patients who are undergoing surgery for the first recurrence of osteosarcoma that has spread to the lung. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066365

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New Therapeutic Strategies for Patients with Ewing's Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma Condition(s): Ewing's Sarcoma; Neuroblastoma; Rhabdomyosarcoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The prognosis for patients with metastatic Ewing's sarcoma family of tumors (ESF), rhabdomyosarcoma (RMS), and neuroblastoma (NBL) remains dismal, with less than 25% long-term disease-free survival. Though less grave, the prognosis for cure for other high-risk patients is approximately 50%. New treatment strategies, including the identification of highly active new agents, maximizing the dose intensity of the most active standard drugs, and the development of improved methods of consolidation to eradicate microscopic residual disease, are clearly needed to improve the outcome of these patients. This protocol will address these issues by commencing with a Phase II window, for the highest risk patients, to evaluate a series of promising drugs with novel mechanisms of action. All patients will then receive 5 cycles of doseintensive "best standard therapy" with doxorubicin (adriamycin), vincristine, and cyclophosphamide (VAdriaC). Patients at high risk of relapse will continue onto a phase I consolidation regimen consisting of three cycles of dose-escalated Melphalan, Ifosfamide, Mesna, and Etoposide (MIME). Peripheral blood stem cell transfusions (PBSCT) and recombinant human G-CSF will be used as supportive care measures to allow maximal dose-escalation of this combination regimen. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001335

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Osteosarcoma Study #2: A Randomized Trial of Pre-Surgical Chemotherapy vs. Immediate Surgery and Adjuvant Chemotherapy in the Treatment of Non-Metastatic Osteosarcoma. A Pediatric Oncology Group Phase III Study Condition(s): Osteosarcoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The study is designed to determine if the administration of multidrug adjuvant chemotherapy for patients with primary non-metastatic osteogenic sarcoma, both prior to and after the definitive surgical procedure for their primary tumor is superior as a treatment strategy to the current approach of giving drugs only after the definitive surgical procedure has been performed. An effort will be made as well to determine if the administration of pre-definitive surgery, chemotherapy leads to an increase in the proportion of the patients suitable for a limb salvage primary surgical procedure. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001217

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Phase II Trial of Gleevec (STI571) in Patients with Advanced Soft Tissue or Bone Cancer Condition(s): Sarcoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will evaluate the safety and effectiveness of the experimental drug Gleevec in patients with soft tissue or bone cancers that have spread or recurred after standard treatment. Gleevec has stopped tumor cell growth and eventually led to tumor cell death with minimal side effects in other forms of cancer. Laboratory and clinical studies suggest that Gleevec may be able to induce remissions in sarcomas as well. Patients 10 years of age and older with advanced soft tissue or bone cancer may be eligible for this study. These cancers may include Ewing's sarcoma, osteosarcoma, synovial sarcoma, leiomyosarcoma, rhabdomyosarcoma, liposarcoma, malignant fibrous histiocytoma, peripheral nerve sheath, fibrosarcoma, and angiosarcoma. Pregnant and nursing women may not participate. Participants will take Gleevec by mouth twice a day for up to 12 months. They will record the doses of Gleevec and any drug side effects. Routine blood tests will be done every 2 weeks for the first 16 weeks of the study, and at least every 4 weeks after that. Scans will be taken to monitor the status of the tumor before starting Gleevec and after 8 weeks of treatment. If the tumor has remained stable in size or gotten smaller, treatment and evaluations will continue on the same schedule in 8-week cycles for a maximum of 12 months. Patients who develop signs or symptoms that the drug is either not controlling the tumor or that it is no longer safe will be taken off the study. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029094

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Rebeccamycin Analogue in Treating Children With Solid Tumors or Non-Hodgkin's Lymphoma Condition(s): Ewing's family of tumors; childhood brain tumor; childhood meningioma; childhood non-Hodgkin's lymphoma; childhood rhabdomyosarcoma; Neuroblastoma; Osteosarcoma; Retinoblastoma; unspecified childhood solid tumor, protocol specific Study Status: This study is suspended. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of rebeccamycin analogue in treating children who have solid tumors or non-Hodgkin's lymphoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006102

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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 “bone cancer” (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/

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

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

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

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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

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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

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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

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

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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/

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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

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

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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

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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

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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

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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

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CHAPTER 6. PATENTS ON BONE CANCER 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 “bone cancer” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bone cancer, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Bone Cancer By performing a patent search focusing on bone cancer, 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.

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

Bone inducing agent from a human osteosarcoma cell line Inventor(s): Anderson; H. Clarke (Shawnee Mission, KS), Sugamoto; Kazuomi (Oyodoku Osaka, JP) Assignee(s): University of Kansas (Kansas City, KS) Patent Number: 5,035,901 Date filed: October 9, 1987 Abstract: Human osteosarcoma Saos-2 cell extracts as for example in the form of a killed-cell, defatted cell residue are found to retain bone inducing-agent(s) after freezedrying. Pellets of this material were found to promote new bone formation. This material is useful therefore for healing bone defects, bone tumors, bone fractures and in promoting bone graft assimilation. Excerpt(s): The invention concerns production of a bone-inducing agent (BIA) from a human osteosarcoma cell line (Saos-2). It has been known for a long time that devitalized and decalcified mammalian bone contains bone morphogenetic factor(s), commonly referred to in the art as bone morphogenetic protein (BMP), with the ability not only to stimulate proliferation of preosseous mesenchymal cells of skeletal muscle, but also to promote their differentiation into ectopic new cartilage, bone and bone marrow (Urist, M. R. (1965) Science 150:893; Van de Putte, K. A., et al. (1965) Clin. Orthop. and Rel. Res. 43:257). A bone-inducing agent (BIA) appears to exist in certain strains of transformed human epithelial cells carried in culture, including FL transformed amnion cells (Anderson, H. C., et al. in (1964) Am. J. Path. 44:507-519 and in (1967) J. Cell. Biol. 33:165-177), HeLa cells (Anderson, H. C. et al. (1968) Fed. Proc. 27:475), WISH amnion cells (Wlodarski, K. (1969) Exp. Cell Res. 57:446-448), and other cell lines (such as neoplastic cells) (Wlodarski, K., et al. (1971) Calcif. Tiss. Res. 7:345-352; Wlodarski, K. (1985) Clin. Orthop. and Rel. Res. 200:248-265), in Dunn mouse osteosarcoma cells of the BFO strain (Amitani, K., et al. (1975) Gann 66:327-329; Hanamura, H. Y., et al. (1980) Clin. Orthop. and Rel. Res. 148:281-290; Takaoka, K., et al. (1980) Clin. Orthop. and Rel. Res. 148:274-280) and in Nagusa cultured human osteosarcoma cells wherein a brief Abstract indicates these cells supposedly can be devitalized and implanted as pellets with retention of BMP activity (Takaoka, K., et al. (1986) 1st International Workshop on Cells and cytokines in Bone and Cartilage). However the Nagusa cells are not available and therefore this finding cannot be confirmed. Web site: http://www.delphion.com/details?pn=US05035901__

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Cancer treatment with Go 6976 Inventor(s): Lu; Zhimin (10172 Black Mountain Rd., Apt. 103, San Diego, CA 92126), Wang; Keming (79 East Ximei Street, Apt. 303, Suzhou, CN) Assignee(s): none reported Patent Number: 6,303,646 Date filed: August 9, 1999

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Abstract: A chemotheraputic cancer treatment in which Go6976 or one of its derivatives is administered to a mammal for the treatment of the cancer. The Go6976 or its derivative is directed to PKC.alpha. activity. Experiments have shown Go6976 to be effective for the treatment of breast cancer, leukemia, lung cancer, bone cancer and skin cancer. These treatments may be accomplished utilizing Go6976 or its derivatives alone or in combination with other prior art chemotherapy agents or in combination with radiation therapy. In a preferred embodiment Go6976 is used for the treatment of cancer as a preventative drug by preventing cancer cell formation. Excerpt(s): This invention relates to cancer treatments and especially to cancer treatments directed to protein kinase C.alpha. enzyme. Researchers have recognized that a family of enzymes known as protein kinase C enzymes is associated with a large number of cancers. This family includes at least eleven isoenzymes. A particular member of this family is identified as the protein kinase C alpha enzyme, abbreviated: PKC.alpha. Researches have reported increases in PKC.alpha. activity in human breast tumors (NG et al., Science. 283:2085-2089) and significant increases in PKC.alpha. expression in prostate cancers (Cornford et al., Am. J. Pathol. 154: 137-144). Researchers have reported that PKC.alpha. is required for the metastasis of human melanoma (Dennis et al., Cancer Lett. 128:65-70) and that PKC.alpha. is related to the progression of brain tumors (Shen et al., Mol. Pharmacol. 55:396-402). There is general agreement among many cancer researchers that some of the most dangerous cancers can be treated with chemotheraputic agents or specially designed oligonuclotides targeted to PKC.alpha. Web site: http://www.delphion.com/details?pn=US06303646__ •

Composition and method for the palliation of pain associated with diseases of the bone and bone joints Inventor(s): Jia; Wei (Columbia, MO) Assignee(s): Mitreoak, Ltd. (Columbia, MO) Patent Number: 5,902,825 Date filed: January 7, 1997 Abstract: A therapeutic composition and method of using the same for the palliation or relief of pain in patients having diseases which affect the bone and bone joints including metastatic bone cancer, arthritis, and other inflammatory arthropathies. The therapeutic composition comprises as the active agent a complex formed of non-radioactive metal ions and organic phosphonic acid ligands, or pharmaceutically acceptable salts thereof. Excerpt(s): The present invention relates generally to the field of therapeutic pharmaceuticals, and is more specifically directed to a composition and method of using the same for the palliation of pain in patients having diseases affecting the bone and bone joints including metastatic bone cancer, rheumatic diseases such as rheumatoid arthritis, osteoarthritis and other inflammatory arthropathies. Various forms and types of disease are known to negatively affect and damage the bones and bone joints of humans and animals. Typically these diseases cause severe and often chronic pain which increases over time eventually progressing to result in loss of function and/or destruction of the joints of the body. The source of this pain and joint damage varies depending upon the disease. For instance, osteoarthritis is a common degenerative joint disorder which normally affects older persons. Osteoarthritis is marked by inflammation of the joint causing swelling, pain and stiffness reducing the mobility and

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activity of the patient. These symptoms increase in intensity and regularity with advancing age. The constant inflammation can eventually lead to complete or partial loss of function and damage to the larger weight-bearing joints of the body. Web site: http://www.delphion.com/details?pn=US05902825__ •

Conjugates for bone imaging and bone cancer therapy Inventor(s): Fitzner; Jeffrey N. (Seattle, WA), Fritzberg; Alan R. (Edmonds, WA), Kasina; Sudhakar (Kirkland, WA), Vanderheyden; Jean-Luc E. (Seattle, WA) Assignee(s): NeoRx Corporation (Seattle, WA) Patent Number: 5,089,249 Date filed: June 16, 1988 Abstract: The present invention provides conjugates formed from calcified tissues targeting agents and radiolabeled compounds. One such conjugate comprises a chelate and a targeting agent that is capable of associating with calcified tissue, wherein the chelate contains at least one nitrogen atom or at least one sulfur atom or combinations thereof as the donor atoms.Another aspect of the invention provides methods for using the conjugates for diagnostic and therapeutic purposes, including those related to bone cancer. Excerpt(s): The present invention relates generally to conjugates formed from calcified tissue targeting agents and radiolabeled compounds such as chelates, and methods of using these compositions. This invention is more particularly related to conjugates which are useful for bone matrix imaging and bone cancer therapy. The invasive growth of cancer cells into bone tissues often results in severe pain syndromes and may ultimately result in death. Ionizing radiation has been used to achieve a reduction in pain. In particular, external radiation therapy has been applied in cases where bone pain is restricted to focal areas. For disseminated bone metastases, however, a treatment which focuses the radiation dose to bone tissue and particularly to bone metastases is desirable. Prior to therapy it is necessary to obtain reliable diagnostic information and to this end several approaches have been tried. An approach that has been the subject of a number of patents, for example, U.S. Pat. No. 3,974,268 to Subramanian et al., involves the use of a technetium-99m (.sup.99m Tc) diphosphonate complex as a skeletal-imaging agent. This approach utilizes a diphosphonate as both the bone-seeking agent and the complexing agent for the radionuclide. Such an approach has at least three major disadvantages. First, by involving the bone-seeking agent in the complexation of the metal radionuclide, the ability of the agent to direct, or "target," the radionuclide to the desired site may be diminished. Second, because diphosphonates are known to form polymers, a preparation of diphosphonates and radionuclides typically includes multiple forms of diphosphonate-radionuclide complexes which have differing charge and uptake properties. Third, the complex formed between a diphosphonate and a radionuclide is not of optimal stability which may necessitate purification of the diphosphonate complex prior to use. Further, even a purified diphosphonate complex may lose the radionuclide during its use. Web site: http://www.delphion.com/details?pn=US05089249__

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In vivo suppression of osteosarcoma pulmonary metastasis with intravenous osteocalcin promoter-based toxic gene therapy Inventor(s): Cheon; Jun (Sung Bu ku Sol, KR), Chung; Leland W. K. (Lovingston, VA), Kao; Chinghai (Charlottesville, VA), Ko; Song-Chu (Charlottesville, VA), Sikes; Robert A. (Charlottesville, VA) Assignee(s): The University of Virginia Patent Foundation (Charlottesville, VA) Patent Number: 6,159,467 Date filed: January 21, 1998 Abstract: A therapeutic agent based on a recombinant adenovirus which employs an osteocalcin promoter for the expression of thymidine kinase can be administered intravascularly to treat metastatic cancer, including osteosarcoma, breast cancer, prostate cancer, ocular melanoma or brain cancer. Systemic administration of this agent provides a preferred route over previous disclosure of local direct administration. The same therapeutic agent can be effectively employed in the treatment of benign conditions, including benign prostatic hypertrophy and arteriosclerosis. Excerpt(s): This invention pertains to the systemic administration of an active agent, a recombinant gene comprising an adenovirus (Ad) which contains an osteocalcin promoter (OC) which drives the expression of thymidine kinase (TK). The agent itself is fully disclosed in the parent application. This invention pertains to the discovery that Ad-OC-TK may be administered systemically, both to treat tumors, and to treat certain benign conditions such as benign prostatic hypertrophy and certain forms of arteriosclerosis. Toxic gene therapy for the treatment of cancer continues to gain prominence in basic research, but remains limited in clinical application because of an inability to deliver the toxic gene to the tumor cells with specificity. Many vectors (e.g. retroviruses, retroviral producing cells, adenoviruses, liposomes, and others) can deliver genes (therapeutic or toxic) to target cells. Localized delivery and restricted gene expression to the primary tumor have been accomplished via direct injection of therapeutic viruses in animal models.sup.1-4 and clinical trails.sup.5.6 This approach is not feasible for the treatment of metastatic disease because of the presence of multiple lesions that would each require separate injection and manipulation. Therefore, alternative approaches to the treatment of metastatic disease with gene therapy must be developed. Systemic delivery of therapeutic genes is attractive for targeting metastatic disease, pulmonary metastases in particular. Because the pulmonary vascular system would be the first encountered, the adenovirus would be trapped in the lung parenchyma, allowing for higher infectivity. Lesoon-Wood et al.sup.7 reported the systemic delivery of wild type p53 complexed with liposomes, targeting the p53 mutated breast cancer cell line (MDA-MB435), inhibiting primary tumor growth by 60%, and decreasing pulmonary metastases in nude mice. Vile et al.sup.8 demonstrated inhibition of B-16 melanoma pulmonary metastases in syngeneic immunocompetent mice by a systemic delivery of retrovirus using a tyrosinase promoter to drive the expression of the toxic gene thymidine kinase (TK) gene. Web site: http://www.delphion.com/details?pn=US06159467__

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Method for palliation of pain in human bone cancer using therapeutic tin-117m compositions Inventor(s): Atkins; Harold L. (Setauket, NY), Mausner; Leonard F. (Stony Brook, NY), Meinken; George E. (Middle Island, NY), Srivastava; Suresh C. (Setauket, NY) Assignee(s): Brookhaven Science Associates LLC (Upton, NY) Patent Number: 5,853,695 Date filed: November 4, 1996 Abstract: The invention provides a method for the palliation of bone pain due to cancer by the administration of a unique dosage of a tin-117m (Sn-117m) stannic chelate complex in a pharmaceutically acceptable composition. In addition, the invention provides a method for simultaneous palliation of bone pain and radiotherapy in cancer patients using compositions containing Sn-117m chelates. The invention also provides a method for palliating bone pain in cancer patients using Sn-117m-containing compositions and monitoring patient status by imaging the distribution of the Sn-117m in the patients. Also provided are pharmaceutically acceptable compositions containing Sn-117m chelate complexes for the palliation of bone pain in cancer patients. Excerpt(s): This invention relates to pharmaceutical compositions comprising tin-117m (Sn-117m) stannic complexes in a defined dose range and methods of using said compositions to alleviate bone pain and to treat osseous metastatic disease. The preparation of tin-117m-labeled stannic (Sn.sup.4+) chelates which localize to bone, and their use as diagnostic radiopharmaceuticals, is described by Srivastava et al., U.S. Pat. No. 4,533,541 (Reference 1) which is incorporated herein by reference. In addition to a description of preparation of Sn-117m stannic complexes of methylene diphosphonate (MDP), pyrophosphate (PYP), ethylidenehydroxydisodium phosphonate (EHDP), and diethylenetriaminepentaacetic acid (DTPA), Srivastava et al. describe the preferential localization of Sn-117m stannic complexes in bone to the substantial exclusion of uptake by blood, muscle, kidney, or liver. (Reference 2.) Autoradiographic studies have shown that the Sn-117m stannic complexes localize to cortical bone but not bone marrow. (Reference 3.) There is no indication, however, of a composition or treatment with Sn117m stannic complexes to alleviate pain associated with cancer in human skeletal bone, or to treat cancer in human skeletal bone. Cancer of the bone and osseous metastases derived from tumors elsewhere (e.g. prostate, breast, and other cancers) can result in substantial pain. The alleviation of such bone pain is highly desirable. A number of radiopharmaceutical agents have been used for the palliation of bone pain from metastatic lesions, primarily originating in breast and prostate cancers. Among these are phosphorus-32 (Reference 4), strontium-89 chloride (Reference 5), samarium-153 EDTMP (Reference 6), rhenium-186 HEDP (Reference 7), and iodine-131 hydroxybenzylidene diphosphonate (HBDP) (Reference 8). One of these, strontium-89 chloride, was approved by the FDA for commercial distribution in June, 1993. Treatment with known radiopharmaceutical agents is limited because of undesirable side effects resulting from uncontrolled irradiation. For example, a limiting factor has been amount of radiation absorbed by red marrow. This results from a lower than desired bone tumor to bone marrow ratio which causes bone marrow toxicity at therapeutic dosages. Web site: http://www.delphion.com/details?pn=US05853695__

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Method to ameliorate osteolysis and metastasis Inventor(s): Guise; Theresa A. (San Antonio, TX), Mundy; Gregory R. (San Antonio, TX), Yoneda; Toshiyuki (San Antonio, TX) Assignee(s): Xenotech (Foster City, CA) Patent Number: 5,993,817 Date filed: February 9, 1995 Abstract: Materials immunoreactive with parathyroid hormone-related protein (PTH-rp) are used in the invention method to prevent and treat cancer metastasis to bone and cancer cell growth in bone as well as osteolysis and symptomatic sequelae thereof. Antibodies with human characteristics are included in the invention for application of the invention method to human subjects. Excerpt(s): The invention relates to the prevention and treatment of cancer metastasis to bone and bone cancer growth and to associated osteolysis, some of the most problematic aspects of cancers of many origins. More specifically, the invention concerns use of antibodies to parathyroid hormone-related protein (PTH-rp) and other forms of anti-PTH-rp to alleviate these conditions. It has long been understood that morbidity and mortality caused by cancer, especially in view of the fact that surgical techniques are readily available, are due to more-or-less systemic sequelae of the original multiplication of the cancer cells. Metastasis of an original tumor to additional locations, the destruction of target locations as a direct or indirect result of this metastasis, cachexia, hypercalcemia, and other symptomologies characterize the course of the malignancy. The mechanisms whereby these sequelae occur are believed to involve a variety of cytokines, growth factors, and cell adhesion molecules, among other factors. It is entirely unknown, however, how cancers dissolve bone in bone metastases since at present, the only cells known to be able to dissolve bone are osteoclasts. It is not known how metastasized cancer dissolves bone in order to accommodate the growth of the cancer. One of many factors which is known to play a role in at least some of these processes is parathyroid hormone-related protein (PTH-rp). Due to its similarity to PTH, it has been recognized as a mediator of humoral hypercalcemia of malignancy (HHM). In this role, PTH-rp secreted by the tumor is circulated through the blood and is associated with hypercalcemia, an index of bone resorption. PTH-rp has been shown to be the cause of systemic bone resorption and calcium reabsorption from urine at the tubule. Both of these result in a systemic elevation of blood calcium levels. This factor has been described in connection with HHM in U.S. Pat. No. 5,116,952. This patent also describes preparation of anti-PTH-rp antibodies using peptide subunits of the partially sequenced protein. This protein has also been called adenylate cyclase stimulating factor (ACSF) in U.S. Pat. No. 5,312,810 and humoral hypercalcemic factor (hHCF) in U.S. Pat. No. 5,114,843. The association of PTH-rp with HHM is also described by Yates, A. J. P. et al., J Clin Invest (1988) 81:932-938. Japanese application A4-228089, published Aug. 18, 1992 describes recombinant production of anti-PTH-rp antibodies, including murine/human chimeras. This application also discloses animal studies demonstrating that either murine or chimeric monoclonal antibodies directed to PTH-rp ameliorate the effects of HHM in a model system where HHM is caused by either systemically infusing PTH-rp into mice peritoneally or by implanting PTH-rp-producing prostate cancer cell lines in nude mice. Web site: http://www.delphion.com/details?pn=US05993817__

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Osteometrin related peptides and nucleic acids and diagnosis and therapies using them Inventor(s): Glimcher; Melvin J. (Boston, MA), Salih; Erdjan (Plymouth, MA), Zhou; HaiYan (Allston, MA) Assignee(s): The Children's Medical Center Corporation (Boston, MA) Patent Number: 6,037,449 Date filed: October 17, 1997 Abstract: Bovine bone cells express osteometrin, a 35 kDA phosphoprotein specifically expressed in bone and dentin tissue. We have found that protein reactive with antiosteometrin antisera is detectable in a wide range of species, and that osteometrin expression is detectable during mineralization of bone tissue. Our findings establish that osteometrin is an indicator of bone metabolism and may be involved in highly conserved aspects of bone and dentin metabolism. Osteometrin is used as a marker for osteoporosis and bone cancer. Excerpt(s): Various proteinaceous components of bone and dentin have been identified. Some of those components, such as collagen, are major structural components and are also present in soft tissues of the body. Noncollagenous proteins (10%) may play functional roles specific to bone and dentin, such as initiation of mineralization and control of calcium phosphate crystal growth and degradation (Glimcher, in Disorders of Bone and Mineral Metabolism, Coe et al., eds., Raven Press, New York, 1992, p. 265-288; Young et al., in Cellular and Molecular Biology of Bone, Noda, ed., Academic Press, San Diego, 1993, p. 191-234; Heinegard et al., FASEB J. 2:2041-51, 1989; Delmas et al., Calcif. Tissue Int. 36:308-16, 1983). Major noncollagenous extracellular matrix proteins include osteocalcin, osteonectin, osteopontin, bone sialoprotein, decorin, and biglycan (Glimcher, 1992, supra; Young et al., 1993, supra,; Heinegard et al., 1989, FASEB J. 2, 2041-51). Common clinically used bone markers include osteocalcin, type I collagen, pyridinoline, dexoxypyridinoline, and alkaline phosphatase (Delmas, 1993, in Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Favus, ed., 2nd Ed., Lippincott-Raven Publishers, Philadelphia). In some contexts, it is desirable to distinguish bone from soft tissue. Specificity of bone markers may be reduced if the marker is also expressed in soft tissue or if antibodies to it react with moieties found in soft tissue, including fragments or degradation products of a marker specifically expressed in bone. For example, while osteocalcin is bone-specific, some osteocalcin antibodies have been shown to also react to some extent with matrix Gla-containing protein, which is distributed in many soft tissues in addition to bone (Hauschka et al., 1989, Physiol. Rev. 69, 990-1047).sup.1 Osteocalcin protein fragments are also present in blood because of bone resorption. Thus, serum osteocalcin levels may not reflect bone formation. In addition, because most osteocalcin is excreted from kidney, osteocalcin levels in individuals with kidney diseases may not accurately reveal the state of bone metabolism.sup.1 The abbreviations used are: BSA, bovine serum albumin; Fc.alpha.R, Fc receptor for Ig; Gdn, guanidine; Gla, carboxyglutamic acid; HPLC, high performance liquid chromatography; Ig, immunoglobulin; Mab, monoclonal antibody; PAGE, SDSpolyacrylamide gel electrophoresis; PCR, polymerase chain reaction; RT, reverse transcriptase; RP, reversed phase. Web site: http://www.delphion.com/details?pn=US06037449__

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Preparation of rhenium phosphonate therapeutic agents for bone cancer without purification Inventor(s): Pipes; David W. (St. Louis, MO) Assignee(s): Mallinckrodt, Inc. (St. Louis, MO) Patent Number: 5,021,235 Date filed: May 2, 1989 Abstract: The process of the present invention includes preparing a first aqueous solution of rhenium in the form of radioactive perrhenate, wherein the concentration of rhenium in said solution is within the range of about 5.times.10.sup.-6 M to about 2.times.10.sup.-3 M, and then reducing and complexing the radioactive perrhenate by mixing a second solution or lyophilized solid with the first solution. The second solution or lyophilized solid comprises a ligand which complexes with the radioactive perrhenate and a reductant wherein the reductant is present in the second solution at a concentration in the range of about 0.005M to about 0.020M and the ligand is present in the second solution at a concentration in the range of about 0.01M and about 0.15M. The pH of the resultant solution is within the range of about 1.5 to about 5.5. Excerpt(s): The present invention relates to the preparation of therapeutic radiopharmaceuticals. Specifically, the invention relates to the preparation of rhenium therapeutic agents. Therapeutic radiopharmaceuticals generally incorporate a strong beta or alpha emitting radionuclide. Severe chemical damage may be caused by such radionuclides if the radionuclides are not handled properly. Radioactive pharmaceuticals, however, are widely used for diagnosis and treatment of certain illnesses such as cancer and heart disease. For diagnostic purposes, radioactive complexes have been used to provide both negative and positive images of body organs, skeletal images and the like. For most applications of radiopharmaceuticals, the nonradioactive portion of the complex to be used is prepared and stored until time for administration to the patient, at which time the radioactive portion of the complex is added to form the radiopharmaceutical of interest. Examples of this are disclosed in U.S. Pat. Nos. 3,983,227 (1976) and 4,652,440 (1987). Further, in many situations, the radioactive component of the complex must be generated and/or purified at the time the radiopharmaceutical is prepared for administration to the patient. U.S. Pat. No. 4,778,672, assigned to the University of Cincinnati, (1988) describes, for example, a method for purifying pertechnetate and perrhenate for later use in a radiopharmaceutical. EP 250966, also assigned to the University of California (1988) describes a method for obtaining a sterile, purified complexed radioactive perrhenate from a mixture which includes, in addition to the ligand-complexed radioactive perrhenate, uncomplexed ligand, unligated perrhenate, rhenium dioxide and various other compounds. Specifically, the application teaches a method for purifying a complex of rhenium-186 and 1-hydroxyethylidene diphosphonate (HEDP) from a crude solution. In the process of forming the complex, high quantities of reductant are required for the reduction of perrhenate to achieve chelation. This process results in excess ligand and reductant in the crude solution. Partially because of the necessity of removing excess ligand and reductant to avoid high uptake of the radioactive complexes in soft tissue, further purification of the rhenium complex (the rhenium is in the form of radioactive ligand-complexed perrhenate) by a low pressure or gravity flow chromatographic procedure is required. Another reason for purification by anion exchange chromatography of the crude rhenium solution is to remove the unstable species and obtain the more thermodynamically stable product. This purification involves the aseptic collection of several fractions which elute from the separation medium used in

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the particular chromatographic procedure, followed by a determination of exactly which fractions to combine. After combining the selected fractions, the fractions are sterile filtered and diluted prior to injection into the patient. The purified rhenium complex must be injected into the patient within one hour of preparation to avoid the possibility of degradation. Thus, a rhenium complex may have to be purified twice before use, causing inconvenience and possible dangers to the user. Web site: http://www.delphion.com/details?pn=US05021235__ •

Radioactive tagged compounds and method for the treatment of metastatic bone cancer Inventor(s): Bordoni; Maurice (Westtown, NY), Lieberman; Ephraim (Suffern, NY), Thornton; Alfred (New Hampton, NY) Assignee(s): Cadema Medical Products, Inc. (Middleton, NY) Patent Number: 5,006,329 Date filed: January 26, 1989 Abstract: Organophosphonates such as methylene diphosphonates and analogs thereof are tagged with chromium-51 for the treatment of bone cancer without causing damage to bone marrow. The chromium-51 organophosphonates seek out, attach to, and treat bone tumors with high specificity. Excerpt(s): The present invention relates to a compound and a method for the treatment of bone cancer, and more particularly, to a compound and method for the treatment of metastatic bone lesions. At the present time, the treatment of metastatic bone cancer (malignant tumors or lesions) is usually ineffective. Direct radiation therapy is usually ineffective. The patient undergoing radiation therapy suffers excruciating pain and eventually dies. During the disease, morphine injections are continually administered in an attempt to alleviate the pain and suffering. If the treatment involves chemotherapy, there are side effects which are very undesirable. Furthermore, chemotherapy is not often effective. The effects of metastatic bone cancer are particularly devastating when the bone cancer appears after an ostensibly successful treatment of another form of cancer, such as breast cancer or prostate cancer. For as yet unknown reasons, hormonal cancers such as breast and prostate cancer have a tendency to metastasize to bring about bone tumors. It would certainly be desirable to increase the cure rate of breast and prostate cancers by successfully treating metastatic bone cancer. Web site: http://www.delphion.com/details?pn=US05006329__

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Radiopharmaceutical stannic Sn-117m chelate compositions and methods of use Inventor(s): Meinken; George E. (Middle Island, NY), Srivastava; Suresh C. (Setauket, NY) Assignee(s): Brookhaven Science Associates (Upton, NY) Patent Number: 6,231,832 Date filed: March 23, 1998 Abstract: Radiopharmaceutical compositions including.sup.117m Sn labeled stannic (Sn.sup.4+) chelates are provided. The chelates are preferably polyhydroxycarboxylate, such as oxalates, tartrates, citrates, malonates, gluconates, glucoheptonates and the like.

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Methods of making.sup.117m Sn-labeled (Sn.sup.4+) polyhydroxycarboxylic chelates are also provided. The foregoing pharmaceutical compositions can be used in methods of preparing bone for scintigraphical analysis, for radiopharmaceutical skeletal imaging, treatment of pain resulting from metastatic bone involvement, treatment of primary bone cancer, treatment of cancer resulting from metastatic spread to bone from other primary cancers, treatment of pain resulting from rheumatoid arthritis, treatment of bone/joint disorders and to monitor radioactively the skeletal system. Excerpt(s): The radiopharmaceutical reagents of this invention, a class of tin-117m radiopharmaceuticals are therapeutic agents (that also incorporate gamma-emission) that localize predominantly in bone after intravenous injection. Images reflecting bone structure or function can also be obtained by a scintillation camera that detects the distribution of ionizing radiation emitted by the radioactive tin-117m agent. Radiochemical reagents, by virtue of their radioactive emission, have become a most useful diagnostic and therapeutic tool. Some of these reagents incorporate a gammaemitting nuclide and localize in a specific organ or bone after intravenous injection. Images reflecting the organ or bone can then be obtained by means of a scintillation camera that detects the distribution of ionizing radiation emitted by the radioactive reagent. The principal radioactive isotope used in diagnostic procedures is technetium99m. Other clinically important diagnostic isotopes are thallium-201, gallium-67, and iodine- 123. All the above are cyclotron-produced. Examples of therapeutic reagents which localize in pathologic tissue include iodine- 131 and phosphorus-32, both reactorproduced. In order to be an effective radioactive drug--whether for therapeutic or diagnostic use--the reagent must combine four elements: low toxicity, specific biodistribution, low background radiation (non-target) dose, and suitable therapeutic/diagnostic radionuclidic emissions. For example,.sup.99m technetium combines with methylene diphosphonate (MDP) to form.sup.99m Tc-MDP, which localizes in the skeleton in general and in areas of hyperactive bone metabolism in particular. Biodistribution of this agent combines rapid, high concentration by target tissue and low uptake by surrounding tissue with rapid blood clearance and urinary excretion of the non-specifically localized radioactive drug. Thus, the amount of localized reagent to resolve the image on scintillation cameras is obtained with minimal radiation dose to the patient. Web site: http://www.delphion.com/details?pn=US06231832__ •

Rat osteosarcoma cell line OSR9TR1 Inventor(s): Doersen; Claus-Jens W. (Cincinnati, OH), Isfort; Robert J. (Cincinnati, OH) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 5,264,358 Date filed: June 24, 1992 Abstract: The present invention relates to a novel cell line isolated from a rat osteosarcoma wherein the cell line has the following characteristics: a) a mutated p53 gene incapable of expressing p53 protein, b) a normal RB-1 gene, c) a 10-fold amplified c-myc gene, d) a normal c-fos gene, e) a deregulated immediate early gene response, f) a canalicular network MATRIGEL.TM. growth pattern, g) tumorigenic in congenitally athymic mice, h) no alkaline phosphatase activity, i) an ability to produce one or more growth factors selected from the group consisting of: 1) an osteoblastic differentiation growth factor, 2) a non-heparin binding mitogenic growth factor, 3) a first heparin binding mitogenic growth factor, 4) a second heparin binding mitogenic growth factor,

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and 5) a third heparin binding mitogenic growth factor, and j) an ability to be serially propagated greater than sixty population doublings. The present invention also relates to growth factors having the characteristics of growth factors isolated from the rat osteosarcoma cell line. The present invention also relates to a process for producing a growth factor which comprises: a) growing an osteosarcoma cell line in a culture medium, and b) recovering the growth factor from the medium. The present invention also relates to a process for producing a growth factor comprising: a) isolating mRNA from an osteosarcoma cell line which codes for the growth factor, b) making cDNA of the mRNA, c) expressing the cDNA in an expression vector, and d) recovering the growth factor. Excerpt(s): This invention relates generally to a novel cell line, and specifically to a novel rat osteosarcoma cell line, as well as to certain growth factors produced by the cell line. Polypeptide growth factors play a key role in regulating the development of multicellular organisms and in the processes of tissue maintenance and repair. (see Cross and Dexter (1991) Cell, Vol. 64, pp.271-280; and Aaronson (1991) Science, Vol. 254, pp. 1146-1153.) At the cellular level, growth factors are involved in regulating proliferation and the progressive aquisition of the differentiated phenotype. Growth factors are capable of stimulating cellular proliferation as well as inhibiting cellular proliferation and many growth factors have been found to be multifunctional (Sporn and Roberts (1988) Nature, Vol. 332, pp.217-219). The highly coordinated functions of growth factors is perhaps best exemplified in the development of the hematopoiectic cell system (Metcalf (1989) Nature, Vol. 339, pp.27-30) where a limited number of stem cells give rise to a larger population of developmental restricted progenitor cells. These progenitors cells are further stimulated to proliferate and differentiate into the mature lymphoid, erythroid and myeloid cells. A balance between cell types and numbers of cells must be maintained throughout the developmental cascade. This requires the concerted actions of growth factors which commit a cell (now developmentally restricted) along a particular cell lineage, of growth factors which stimulate the proliferation of committed cells, and finally, of growth factors which promote the differentiation of the committed cells and inhibit the proliferation of the mature, fully differentiated cells. Tumor cells represent naturally occurring examples of cells where the processes that control cellular proliferation and differentiation have been uncoupled (Cross and Dexter (1991) Cell, Vol. 64, pp.271-280; Aaronson (1991) Science, Vol. 254, pp.1146-1153). The observation that many types of tumor cells secrete growth factors suggests that these factors can contribute to the tumorigenic process as well as normal cellular processes. Tumor cells have been found to secrete autocrine growth factors which stimulate the proliferation of the tumor cells themselves and paracrine growth factors which stimulate surrounding cells to secret factors promoting the proliferation of the tumor cells. Paracrine factors can also stimulate the surrounding cells to provide a cellular environment promoting the survival of the tumor cells. For example, many types of tumor cells secrete growth factors that recruit endothelial cells and stimulate their proliferation and differentiation resulting in a new vasculature supplying nutrients for the tumor cells (Liotta et al., (1991) Cell, Vol. 64, pp.327-336). Web site: http://www.delphion.com/details?pn=US05264358__

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Somatic element of single crystalline sapphire ceramics Inventor(s): Hirabayashi; Masaya (Yokaichi, JP), Kawahara; Haruyuki (Moriguchi, JP), Taniguchi; Yoshio (Gamo, JP) Assignee(s): Kyoto Ceramic Kabushiki Kaisha (Kyoto, JP) Patent Number: 4,122,605 Date filed: September 22, 1976 Abstract: This disclosure relates to a somatic element of single crystalline sapphire ceramics for use as an implant for dental surgery, orthopedic prosthetic surgery and the like, which element is excellent in mechanical strength, flexibility and affinity with its ambient tissue so much so that it eliminates a fear of development of bone cancer and facilitates the proliferation of uniform bone tissue around the somatic element implanted. Excerpt(s): This invention relates to a somatic element of single crystalline sapphire (.alpha.-Al.sub.2 O.sub.3 :corundum) ceramics used as an implant for dental surgery or an implant for orthopedic surgery and to a method of manufacturing the same. Heretofore, metal (for example, stainless steel, Co--Cr alloy, metallic titanium, metallic tantalum, Ni--Cr alloy, etc.) has been used as a material in a somatic element of the kind described. However, the somatic element of such metal is in most cases inferior in socalled "affinity" with (adhesibility to, wettability with) its ambient tissue and in addition, there is a possibility of the somatic element tending to be ionized by saliva, secretion of the mouth, food, body fluids, blood and the like thereby producing harmful effects as a result of metallic ions in the human body. To cite a positive instance of such a fact, it is reported that in the case of stainless steel most generally used as a somatic element for orthopedic surgery, it is necessary to perform a repeated operation on the affected region to extract the element therefrom in a certain period of time after the operation. On the other hand, in the case of a somatic element of polycrystalline ceramics, the element is excellent in affinity with its ambient tissue and chemically highly stable, thereby having no necessity of extracting the element from the implanted region after the operation, but has the disadvantage of it being inferior in mechanical strength to a metallic member. In view of this fact, the present applicant has provided various inventions for improvements in the mechanical strength of a somatic element of ceramics. The somatic element proposed heretofore by the inventions is dependent upon the structure of the element itself for the postoperational strength of the implanted element. For example, in the previous U.S. patent application, Ser. No. 550,186, 1974, such structural consideration was given to the tightening force produced by threadedly fitting a nut over the top of a screw type implant pin of ceramics embedded in the bone tissue (and if necessary, over the bottom part of the pin that projects through the bone tissue) and used to fix the implant pin to the bone tissue so that the implant pin could cope with outer force such as repeated occlusal impact imparted to the pin after the implantation. Similarly, in the previous U.S. patent application, Ser. No. 674,688, 1975, by the present applicant, structural consideration was given to the manner that a screw type implant pin of ceramics was provided in the circumference with a horizontal flange, the horizontal flange acting as a stabilizing seat since the flange is fitted closely into the counterbore formed in a cortical bone (hard tissue) when the pin is threadedly inserted into the bone so that the pin could withstand the outer force to be later applied thereto. This invention, which is from a viewpoint different from what has conventionally been considered, is intended to provide a somatic element of single crystalline sapphire ceramics (.alpha.-Al.sub.2 O.sub.3) which is better in mechanical

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strength, flexibility and affinity with its ambient tissue (particularly osteoplastic cells) than polycrystalline ceramics out of various ceramics. Web site: http://www.delphion.com/details?pn=US04122605__ •

Therapeutic derivatives of diphosphonates Inventor(s): Farcasiu; Dan (4729 Bayard St., Pittsburgh, PA 15213), Hartmann; John F. (1 Woodmeadow La., Princeton Junction, NJ 08550) Assignee(s): none reported Patent Number: 5,854,227 Date filed: June 7, 1995 Abstract: Novel chemotherapeutic agents having utility in treating infectious diseases such as periodontal disease, certain urinary tract infections, infectious urinary tract stones, and bone cancer, are obtained by combining chemically a diphosphonate compound with a therapeutic agent effective against the foregoing diseases. Excerpt(s): Urinary calculi can develop anywhere in the urinary tract. They are hard, mineralized substances producing pain, obstructions and secondary infections. Basically there are two types of urinary stones: metabolic, originating through metabolic dysfunctions, and infectious, associated with bacterial infections. Infection persists in 40% of patients treated with antibiotics, and a full 60% of those develop recurring stones. Left untreated, infected calculi can result in kidney loss and even death in 25% of such cases. Some metabolic stones become contaminated and bacteria are entrapped within the interstices during its crystallization. Such infected stones are notoriously resistant to eradication. Current treatment of infectious urinary calculi involves surgical removal with concomitant administration of antimicrobial agents. Broadly speaking, there are two categories of periodontal disease: gingivitis and periodontitis, both generated by micro-organisms in dental plaque on the tooth surface. Both conditions are characterized by an inflammation of the gingiva, the gum tissue at the base of the teeth. Periodontitis also involves bone erosion and loss of dentition over a long period of time. Burt (1992) Clin. Geriat. Med. 3:447. Osteosarcoma is an exceedingly malignant tumor that usually occurs in children and young adults. The type and extent of the tumor determines the type of treatment which ranges from variously-administered chemotherapeutic agents to limb amputation in conjunction with chemotherapy. Web site: http://www.delphion.com/details?pn=US05854227__

Patent Applications on Bone Cancer 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 bone cancer:

10

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

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Bisphosphonate conjugates and methods of making and using the same Inventor(s): Dixon, H.B.F.; (Cambridge, GB), Mikhailov, Sergey; (Moscow, RU), Padioukova, Nelly; (Moscow, RU), Tzeitline, Grigorii; (Moscow, RU) Correspondence: Joseph E. Kovarik; SHERIDAN ROSS P.C.; Suite 1200; 1560 Broadway; Denver; CO; 80202-5141; US Patent Application Number: 20010041689 Date filed: December 7, 2000 Abstract: The present invention is directed to particular bisphosphonate compounds, and in particular, to bisphosphonate conjugates that are useful in the treatment of soft tissues surrounding bone and bone-related diseases, such as bone cancer and osteoporosis. Excerpt(s): This application claims priority from U.S. Provisional Patent Application No. 60/080,500 filed Apr. 2, 1998 and is a continuation-in-part application of U.S. patent application Ser. No. 09/283,440 filed on Apr. 1, 1999. The entire disclosure of these applications is considered to be part of the disclosure of the accompanying application and is hereby incorporated by reference. Bisphosphonates are known to be useful in the treatment of degenerative bone disorders. Bone degeneration diseases, including Paget's Disease and osteoporosis, have proven difficult to treat because the mechanisms involved are not well understood. Bisphosphonic acid derivatives are known to be osteoselectively taken up by bone tissue. Moreover, bone scanning agents based on the use of some bisphosphonic acid compounds have been used in the past to achieve desirable high definition bone scans (see e.g., U.S. Pat. No. 4,810,486 to Kelly et. al). Other bisphosphonate derivatives have been used as therapeutic agents for bone diseases such as osteoporosis, rheumatoid arthritis, and osteoarthritis (see e.g., U.S. Pat. No. 5,428,181 to Sugioka et. al). Finally, bisphosphonate compounds are known as being useful in inhibiting bone loss, believed to act in a manner which hinders the activity of osteoclasts, so that bone loss is diminished. Bisphosphonate therapy has, however, in the past, frequently been accompanied by severe side effects, such as severe adverse effects on bone development and overall somatic growth. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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BONE CANCER THERAPY Inventor(s): BALIAN, GARY; (CHARLOTTESVILLE, VA), CHUNG, LELAND W.K.; (LOVINGSTON, VA), CUI, QUANJUN; (CHARLOTTESVILLE, VA), GARDNER, THOMAS A.; (CHARLOTTESVILLE, VA), KAO, CHINGHAI; (CHARLOTTESVILLE, VA) Correspondence: MCGUIRE WOODS; 1750 Tyson's Boulevard Suite 1800; McLean; VA; 22102-4215; US Patent Application Number: 20010038834 Date filed: June 24, 1998 Abstract: Homing bone marrow cells deposited at ATTC CRL-12424 can be transfected with a toxic gene which expresses a compound which alone, or in the company of a triggering agent, kills neighboring cancer cells in the bone marrow of a patient receiving the therapy. Toxic genes include cytotoxin such as thymidine kinase, immune stimulating compounds such as interleuken-2 and radiation repair inhibitors, such as Ku

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protein. The transfected cells can be administered directly to the site of the tumor or systemically, or regionally, intramedullary (into the marrow) through intravascular administration. The latter alternative permits the delivery of very high doses of the effective agent. Excerpt(s): This application is a regular National application claiming priority from Provisional Application, U.S. application Ser. No. 60/072,604 filed Jan. 26, 1998. This application is related to U.S. patent application Ser. No. 08/785,008, allowed, U.S. patent application Ser. No. 08/990,746 (Attorney Docket 494-254-27, filed Dec. 15, 1997) and U.S. patent application Ser. No. 09/010,114 (Attorney Docket 494-280-27, filed Jan. 21, 1998). The disclosure of each of these U.S. Patent Applications is incorporated herein by reference. This invention pertains to a therapeutic agent for the treatment of bone cancer, including osteosarcoma and metastatic bone cancer, particularly including prostate and breast cancer metastases. The invention also pertains to methods of administering the therapeutic agent effective in treatment of bone cancer. This agent is used alone, or together with an activating prodrug. Prostate and certain breast cancer metastases to the skeleton as well as osteosarcoma cause significant mortality and morbidity for patients. While improved technology has facilitated both early diagnosis and prevention of this disease, over 50% of men with prostate cancer already have disseminated disease at the time of diagnosis. Detection of prostate cancer cells in bone marrow by reverse transcriptase-polymerase chain reaction (RT-PCR) of prostatespecific antigen (PSA) has been reported in men with pathologically organ-confined disease Wood et al. Cancer 74:2533, 1994. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cancer treatment with Go6976 and its related compounds Inventor(s): Lu, Zhimin; (San Diego, CA), Wang, Keming; (Suzhuu, CN) Correspondence: John R. Ross; Ross Patent Law Office; P.O. Box 2138; Del Mar; CA; 92014; US Patent Application Number: 20020016352 Date filed: July 24, 2001 Abstract: A chemotheraputic cancer treatment in which Go6976 or a compound chemically similar to Go6976 is administered to a mammal for the treatment of the cancer. The chemical compound is targeted to PKC.alpha. activity. Experiments have shown Go6976 and similar compounds to be effective for the treatment of breast cancer, leukemia, lung cancer, bone cancer, skin cancer, prostate cancer, liver cancer, brain tumor, cervical cancer, and cancers located in the digestive tract including gastric cancer and colorectal cancers. These treatments may be accomplished utilizing Go6976 and compounds similar to it alone or in combination with prior art chemotherapy agents or with radiation therapy. In a preferred embodiment Go6976 is used for the treatment of cancer as a preventative drug by preventing cancer cell formation. Excerpt(s): This application is a continuation-in-part application of Ser. No. 09/370,190 filed Aug. 9, 1999. This invention relates to cancer treatments and especially to cancer treatments directed to protein kinase C.alpha. enzyme. Researchers have recognized that a family of enzymes known as protein kinase C enzymes is associated with a large number of cancers. This family includes at least eleven isoenzymes. A particular member of this family is identified as the protein kinase C alpha enzyme, abbreviated: PKC.alpha. Researches have reported increases in PKC.alpha. activity in human breast

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tumors (NG et al., Science. 283:2085-2089) and significant increases in PKC.alpha.: expression in prostate cancers (Cornford et al., Am. J. Pathol. 154: 137 -144). Researchers have reported that PKC.alpha. is required for the metastasis of human melanoma (Dennis et al., Cancer Lett. 128:65-70) and that PKC.alpha. is related to the progression of brain tumors (Shen et al., Mol. Pharmacol. 55:396-402). Recently, Muller et al were granted a patent, U.S. Pat. No. 5,744,460, which discloses a cancer treatment utilizing an antisense oligonuclotide targeted to PKC.alpha. combined with a chemotherapeutic agent. U.S. Pat. Nos. 5,882,927 and 5,885,970 issued to Bennett et al also disclose antisense oligonuclotides targeted to PKC. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Chondrosarcoma associated genes Inventor(s): Terek, Richard M.; (Providence, RI) Correspondence: MINTZ, LEVIN, COHN, FERRIS,; GLOVSKY and POPEO, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20010016649 Date filed: March 27, 2001 Abstract: The invention features a nucleic acid molecule encoding a chondrosarcoma associated polypeptide and methods for diagnosing patients with chondrosarcoma. the gene. Excerpt(s): The invention relates to bone malignancies. Chondrosarcoma, which usually occurs in late adulthood and old age, is the second most common form of bone malignancy. Conventional chondrosarcoma tumors are graded from stage I through stage III, stage III being the most advanced. In addition to conventional chondrosarcoma, there are other types of chondrosarcoma with distinguishing characteristics: myxoid, mesenchymal, clear cell, and dedifferentiated (spindle cell) chondrosarcoma. Diagnosis and grading of chondrosarcoma has been problematic. For example, the criteria used to distinguish benign enchondroma from low grade chondrosarcoma include parameters which are difficult to quantify such as increased cellularity and more than occasional binucleate cells. The histologic criteria are not absolute, and the diagnosis is frequently made by taking into account clinical features such as pain, rate of growth, location, and radiologic features. Furthermore, the location of the tumor may affect clinical assessment. For example, lesions in the hand can appear aggressive histologically and yet behave benignly. In contrast, lesions occurring in the pelvis are likely to represent a malignancy despite a relatively innocuous histologic appearance. Notwithstanding attempts to integrate clinicopathologic criteria, it has not been possible to predict which tumors will metastasize or recur. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Inhibition of bone tumor formation using antisense cDNA therapy Inventor(s): Gendron, Robert L.; (Cincinnati, OH), Paradis, Helene; (Cincinnati, OH) Correspondence: Frost Brown Todd LLC; 2200 PNC Center; 201 East Fifth Street; Cincinnati; OH; 45202; US Patent Application Number: 20020064783 Date filed: April 17, 2001 Abstract: As described herein, the present invention comprises a method for using tubedown-1 (tbdn-1) antisense reagents as gene therapy agents for the treatment of bone tumors and Ewing's sarcoma family of tumors. Antisense-based reagents, such as tbdn1 antisense construct or biologically stabilized oligonucleotides, or any compound which would elicit the downregulation of tbdn-1 level or activity and the same biological effects as tbdn-1 antisense construct on bone tumor growth in vivo provide valuable alternative or supplemental therapies for bone cancer. Excerpt(s): This application is based on and claims priority from U.S. Provisional Patent Application Ser. No. 60/197,977, Robert L. Gendron, filed Apr. 17, 2000. The present invention relates to the use of antisense cDNA targeting for the inhibition and/or prevention of tumor growth. More specifically, this invention relates to the use of antisense nucleic acid derived from the antisense cDNA sequence of tubedown-1 for the inhibition and/or prevention of bone tumors, especially osteosarcoma and Ewings Sarcoma family of tumors. Cancer is generally treated with cytoreductive therapies that involve administration of ionizing radiation or chemical toxins that kill rapidly dividing cells. Unfortunately, these therapies are highly toxic to non-cancer cells and cause severe side effects, such as bone marrow suppression, hair loss and gastrointestinal disturbances. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Musculoskeletal loading device Inventor(s): Leismer, Jeffrey M.; (Gainesville, FL) Correspondence: AKERMAN SENTERFITT; P.O. BOX 3188; WEST PALM BEACH; FL; 33402-3188; US Patent Application Number: 20030199795 Date filed: April 18, 2003 Abstract: A device for non-invasively mechanically stimulating bone or muscle includes a vibrational energy generator for applying vibrational energy to a first end of a length of a tissue which includes bone and/or muscle. The vibrational energy is for inducing strain in at least one region within the length of tissue. A restraint is disposed opposite the first end of the length to resist translation of the length during operation of the device and to provide loading to the bone or muscle. A connecting structure couples the restraint to the vibrational energy generator. The device does not require gravity to operate and as a result is expected to have applications in space, such as with astronauts, with those having bone ailments such as bed-ridden patients, persons with osteoporosis or disuse atrophy, athletes, recovering bone cancer patients, and persons with muscoskeletal disorders. Excerpt(s): The present application claims the benefit of U.S. provisional patent application No. 60/373,546 filed on Apr. 18, 2002, the entirety of which is incorporated

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herein by reference. This invention relates generally to non-invasive musculoskeletal loading devices which provide adjustable loading. The health of human bones is of enormous importance. Bones provide support and protection for the human body. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue which can seriously impede the ability of osteoporotic bones to provide support and protection for the body. An increased risk of bone fracture is present in individuals with osteoporosis. In 1995 alone, the cost of treatment for osteoporotic bone fractures was $13.8 billion. Around 28 million American's suffer from low bone mass or osteoporosis and are at risk of adding to the yearly cost of treatment for the disease. One in every 2 women and 1 in every 8 men over the age of 50 will develop a fracture in their lifetime due to the disease. With changing demographics and the aging of America, the significance of this national as well as international concern will only increase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Preparation and use of radium-223 to target calcified tissues for pain palliation, bone cancer therapy, and bone surface conditioning Inventor(s): Bruland, Oyvind S.; (Hosle, NO), Henriksen, Gjermund; (Mjondalen, NO), Larsen, Roy H.; (Bekkestua, NO) Correspondence: CLARK & ELBING LLP; 101 FEDERAL STREET; BOSTON; MA; 02110; US Patent Application Number: 20030206857 Date filed: June 12, 2003 Abstract: Processes for the preparation, prepared solutions, and the use of radium-223 for the treatment of calcified tumors, bone tumors, treatment of bones, bone surfaces and soft tissues is described. Excerpt(s): The present invention relates to the preparation and use of the "calcium analogue" alkaline-earth radionuclide radium-223 for the targeting of calcified tissues, e.g., bone and a physiological acceptable solution comprising.sup.223Ra. Biomedical use of radionuclides for pain palliation and/or cancer treatment, including prophylactic treatment of bone surfaces to slow down/inactivate undetectable metastases has previously been based upon.beta.-emitters and conversion electron emitters. A substantial percentage of cancer patients is affected by skeletal metastases. As many as 85% of patients with advanced lung, prostate and breast carcinoma develop bony metastases (Garret, 1993; Nielsen et al., 1991). Established treatments such as hormone therapy, chemotherapy and external radiotherapy often causes temporary responses, but ultimately most bone cancer patients experience relapses (Kanis, 1995). There is thus a strong need for new therapies to relieve pain and slow down tumor progression. Bone targeting radioisotopes has been included in clinical trials for the treatment of cancer to the skeleton (De Klerk et al., 1992, Foss{dot over (a)} et al., 1992, Lee et al., 1996, Silberstein, 1996). These radiopharmaceuticals have been based on.beta.-particle emitters (Atkins, 1998) and lately also a conversion electron ermitter (Atkins et al., 1995). Among these compounds which have so far been approved by US Food and Drug Administration, Le., are strontium-89 (Metastron.TM.) and.sup.153Sm EDTMP (Lexidronam.TM.). The strontium-89 compound can only be administered in amounts sufficient for pain palliation, not for tumor therapy, because a significant myelotoxicity occurs before significant antitumour therapeutic dose levels can be reached (Silberman, 1996).

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for the manufacture of 117Sn diethylenetriaminepentaacetic acids Inventor(s): Li, Zizhong; (Upton, NY), Meinken, George; (Middle Island, NY), Srivastava, Suresh C.; (Setauket, NY) Correspondence: Patent Counsel; Brookhaven Natioanl Laboratory; Bldg. 475D; P.O. Box 5000; Upton; NY; 11973-5000; US Patent Application Number: 20020187975 Date filed: May 2, 2001 Abstract: Novel methods are provided for the manufacture of.sup.117mSn(Sn.sup.4+) DTPA. The method allows the use of DTPA, a toxic chelating agent, in an approximately 1:1 ratio to.sup.117mSn(Sn.sup.4+) via either aqueous conditions, or using various organic solvents, such as methylene chloride. A pharmaceutical composition manufactured by the novel method is also provided, as well as methods for treatment of bone tumors and pain associated with bone cancer using the pharmaceutical composition of the invention. Excerpt(s): Bone metastases are the most common cause of cancer pain, and primary bone cancers may also cause severe chronic pain. Approximately 75-80% of patients with prostate, breast, and lung cancer develop osseous metastases which cause bone pain during the late stages of their illness. Clinical management of cancer-related bone pain through palliation is necessary to improve the quality of life of terminal cancer patients. A number of options are currently available for clinical management of bone pain. Nonsteroidal anti-inflammatory agents, opioids, hormones, and cytotoxic chemotherapy are used in the initial stages of bone metastasis, and external beam radiation can be applied locally when bone pain occurs at a single site. As the patient's skeletal tumor burden increases, pain can increase and become multifocal, tending to move from one site to another. Hemibody external beam radiation can afford rapid pain relief for disseminated skeletal tumors. However, such extensive exposure to radiation may affect noncancerous rapidly dividing tissues in the gastrointestinal tract or bone marrow, and morbidity may result from hemibody radiotherapy for bone pain palliation. Radiation emitted by intravenously administered radionuclides may also be used to treat bone pain palliation. A number of bone-seeking radioisotopes have been studied for their ability to palliate bone pain. For example,.sup.32P, which emits a 1.7 MeV.beta. particle and has a half-life of 14.3 days, exhibits a 3- to 5-fold increase in uptake in bone around osseous metastases as compared to normal bone. The uptake of.sup.32P into bone lesions can be increased by pretreatment with androgen, and patients thus treated frequently experienced pain relief within five to fourteen days of.sup.32P orthophosphate administration, with response duration of two to four months. However, bone marrow receives a disproportionately high dose of.sup.32P from the surrounding inorganic bone matrix and from the cellular component of the bone marrow space, resulting in myelosuppression as a side effect. Pancytopenia resulting from myelosuppression by.sup.32P, though reversible, may necessitate transfusions.sup.32P orthophosphate is not currently used for palliation of metastatic bone pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Stainless steel bone-shaped prosthesis for animals Inventor(s): Kuntz, Charles; (Springfield, VA) Correspondence: Richard C. Litman; LITMAN LAW OFFICES, LTD.; P.O. Box 15035; Arlington; VA; 22215; US Patent Application Number: 20020198600 Date filed: June 5, 2002 Abstract: An artificial bone prosthesis for use in animals which replaces the portion of a bone lost as a result of disease, damage, or surgical removal. Because the life span of animals recovering from bone cancer and other bone diseases is very short, the bone prostheses used in bone replacement surgery in these animals do not have to allow for tissue or bone ingrowth, unlike similar prostheses used in humans. As such, the prosthesis of the present invention has a simple, unique shape that can be made of a conventional artificial material such as stainless steel. This makes the prosthesis relatively inexpensive and eliminates the problems arising in conventional natural bone transplants such as tissue rejection and bacterial infection. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/300,437, filed Jun. 26, 2001. The present invention relates to artificial bone prostheses. More particularly, the present invention relates to artificial bone prostheses useful for animals. The present invention is an artificial bone prosthesis for use in animals which provides a number of benefits over traditional bone prostheses. The two primary therapies available to veterinarians and pet owners deciding on bone reconstruction surgery, namely natural bone transplants or artificial human-style prostheses, present a number of problems that make either of them unsatisfactory for use in bone reconstruction surgery in animals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with bone cancer, 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 “bone cancer” (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 bone cancer. You can also use this procedure to view pending patent applications concerning bone cancer. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON BONE CANCER Overview This chapter provides bibliographic book references relating to bone cancer. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bone cancer 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: 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 “bone cancer” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “bone cancer” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “bone cancer” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

21st Century Complete Medical Guide to Bone Cancer (including Ewing's Tumors and Osteosarcoma) - Authoritative Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment Options by PM Medical Health News; ISBN: 159248011X; http://www.amazon.com/exec/obidos/ASIN/159248011X/icongroupinterna

•

Bone Cancer Therapy (Nuclear Medicine Self-Study Program Iv. Nuclear Medicine Oncology, Unit 5-6) by Gerald L. Radioimmunotherapy Denardo (Editor), Sally J. Denardo (Editor) (2000); ISBN: 0932004636; http://www.amazon.com/exec/obidos/ASIN/0932004636/icongroupinterna

•

Frontiers of Osteosarcoma Research: Interdisciplinary Survey of Clinical and Research Advances by Josef F. Novak, James H. McMaster (Editor); ISBN: 088937113X; http://www.amazon.com/exec/obidos/ASIN/088937113X/icongroupinterna

•

Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies (Cancer Treatment and Research, Vol 62) by G. Bennett Humphrey, et al

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(1993); ISBN: 0792319052; http://www.amazon.com/exec/obidos/ASIN/0792319052/icongroupinterna •

Primary Bone Cancer: The Multidiscipline Disease: Proceedings of the Tenth Annual San Francisco Cancer Symposium, San Francisco, Calif., Se by Jerome M. Vaeth (1975); ISBN: 3805521855; http://www.amazon.com/exec/obidos/ASIN/3805521855/icongroupinterna

•

The Management of Metastatic Bone Cancer by James R., Md. Berenson, et al (2006); ISBN: 0443072736; http://www.amazon.com/exec/obidos/ASIN/0443072736/icongroupinterna

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Understanding Primary Bone Cancer (1999); ISBN: 190127621X; http://www.amazon.com/exec/obidos/ASIN/190127621X/icongroupinterna

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Understanding Secondary Bone Cancer; ISBN: 1870403983; http://www.amazon.com/exec/obidos/ASIN/1870403983/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 “bone cancer” (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 •

Bone cancer and other sarcomas Author: National Cancer Institute (U.S.); Year: 1986; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health; [Washington, D.C.]: U.S. G.P.O., 1986

•

Bone cancers: research report. Author: Sciandra, Eva Anderson.; Year: 1992; Bethesda, Md.: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, [1990]

•

Metastatic bone cancer Author: Wirth, Carl R.,; Year: 1979; Chicago: Year Book Medical Publishers, c1979; ISBN: 081519918X http://www.amazon.com/exec/obidos/ASIN/081519918X/icongroupinterna

Chapters on Bone Cancer In order to find chapters that specifically relate to bone cancer, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and bone cancer 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 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 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.

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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 “bone cancer” (or synonyms) into the “For these words:” box.

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CHAPTER 8. MULTIMEDIA ON BONE CANCER Overview In this chapter, we show you how to keep current on multimedia sources of information on bone cancer. 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.

Bibliography: Multimedia on Bone Cancer 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 bone cancer (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 bone cancer: •

Grand rounds: surgical nursing in place of amputation, total femur replacement for bone cancer [sound recording] Source: Memorial Sloan-Kettering Cancer Center; Year: 1976; Format: Sound recording; [New York]: The Center, c1976

•

Interscapulothoracic amputation for chondrosarcoma [motion picture] Source: Herbert Volk, Jacques Pauporte; Year: 1967; Format: Motion picture; New York: Volk; [Danbury, Conn.: for loan by Davis and Geck, 1967]

•

Thyroid and bone cancer [videorecording] Source: University of Texas, System Cancer Center, M. D. Anderson Hospital and Tumor Institute; [produced by] MDA-TV; Year: 1974; Format: Videorecording; Houston: The Center, 1974

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CHAPTER 9. PERIODICALS AND NEWS ON BONE CANCER Overview In this chapter, we suggest a number of news sources and present various periodicals that cover bone cancer.

News Services and Press Releases One of the simplest ways of tracking press releases on bone cancer 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 “bone cancer” (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 bone cancer. 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 “bone cancer” (or synonyms). The following was recently listed in this archive for bone cancer: •

Cytogen says Quadramet could become a primary bone cancer therapy Source: Reuters Industry Breifing Date: February 21, 2002

•

Novartis bone cancer drug effective in phase III studies Source: Reuters Industry Breifing Date: April 04, 2001

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New bone cancer drug effective, easy to administer Source: Reuters Health eLine Date: April 04, 2001

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More chemo not necessarily better for bone cancer Source: Reuters Health eLine Date: March 02, 2001

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Sex hormones may influence osteosarcoma development Source: Reuters Industry Breifing Date: November 20, 2000

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Dog study suggests hormones linked to bone cancer Source: Reuters Health eLine Date: November 20, 2000

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Enkephalin-expressing vector cuts bone cancer pain in mice Source: Reuters Medical News Date: November 25, 2002

•

Shorter, Simpler Bone Cancer Care Source: Reuters Health eLine Date: September 29, 1997 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 “bone cancer” (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.

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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 “bone cancer” (or synonyms). If you know the name of a company that is relevant to bone cancer, 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/. 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 “bone cancer” (or synonyms).

Academic Periodicals covering Bone Cancer Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to bone cancer. In addition to these sources, you can search for articles covering bone cancer 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.”

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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 bone cancer. 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 bone cancer. 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

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to bone cancer: Bleomycin •

Systemic - U.S. Brands: Blenoxane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202093.html

Cyclophosphamide •

Systemic - U.S. Brands: Cytoxan; Neosar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202174.html

Dactinomycin •

Systemic - U.S. Brands: Cosmegen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202179.html

Doxorubicin •

Systemic - U.S. Brands: Rubex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202209.html

Etoposide •

Systemic - U.S. Brands: Etopophos; Toposar; VePesid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202234.html

Ifosfamide •

Systemic - U.S. Brands: IFEX http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202293.html

Leucovorin •

Systemic - U.S. Brands: Wellcovorin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202321.html

Samarium Sm 153 Lexidronam •

Therapeutic - U.S. Brands: Quadramet http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203683.html

Strontium Chloride Sr 89 •

Therapeutic - U.S. Brands: Metastron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202706.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.

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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 bone cancer 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 “bone cancer” (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 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 bone cancer: •

muramyltripeptide, phosphatidy1-ethanolamine encas (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1182

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•

L-leucovorin (trade name: Isovorin) http://www.rarediseases.org/nord/search/nodd_full?code=192

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Leucovorin (trade name: Leucovorin calcium) http://www.rarediseases.org/nord/search/nodd_full?code=217

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L-leucovorin (trade name: Isovorin) http://www.rarediseases.org/nord/search/nodd_full?code=423

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Liposomal N-Acetylglucosminyl-N-Acetylmurmaly-L-Al (trade name: ImmTher) http://www.rarediseases.org/nord/search/nodd_full?code=924

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Liposomal N-Acetylglucosminyl-N-Acetylmurmaly-L-Al (trade name: ImmTher) http://www.rarediseases.org/nord/search/nodd_full?code=925

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.

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APPENDICES

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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

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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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.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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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/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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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

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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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.

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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 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. Type “bone cancer” (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 65347 361 1452 4 0 67164

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 “bone cancer” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

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.

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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 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 Bone Cancer In the following section, we will discuss databases and references which relate to the Genome Project and bone cancer. 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.

20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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. 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.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “bone cancer” (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 bone cancer: •

V-FOS FBJ Murine Osteosarcoma Viral Oncogene Homolog Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?164810 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 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

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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 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

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drop box next to “Search.” Enter “bone cancer” (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. 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 “bone cancer” (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).

24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 bone cancer 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 bone cancer. 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 bone cancer. 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 “bone cancer”:

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•

Guides on bone cancer Bone Cancer http://www.nlm.nih.gov/medlineplus/bonecancer.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html

•

Other guides Benign Tumors http://www.nlm.nih.gov/medlineplus/benigntumors.html Bone Diseases http://www.nlm.nih.gov/medlineplus/bonediseases.html Breast Cancer http://www.nlm.nih.gov/medlineplus/breastcancer.html Multiple Myeloma http://www.nlm.nih.gov/medlineplus/multiplemyeloma.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Soft Tissue Sarcoma http://www.nlm.nih.gov/medlineplus/softtissuesarcoma.html

Within the health topic page dedicated to bone cancer, the following was listed: •

General/Overviews What Is Bone Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_bone_cancer_2.a sp? What Is Bone Metastasis? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_bone_metastasis _66.asp? What Is Ewing's Family of Tumors? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_ewings_family_ of_tumors_48.asp? What Is Osteosarcoma? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_osteosarcoma_c ancer_52.asp?

•

Diagnosis/Symptoms Bone Density Scan Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/bonedensity.pdf

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Bone Scan Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=CA00020 Bone Scan Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/bonescan.pdf Can Bone Cancer Be Found Early? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_can_bone_cancer_be_fou nd_early_2.asp How Is Bone Cancer Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_bone_cancer_dia gnosed_2.asp? How Is Bone Cancer Staged? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_bone_cancer_ staged_2.asp?sitearea= How Is Bone Metastasis Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_bone_metastasis _diagnosed_66.asp? How Is Ewing's Family of Tumors Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_ewings_family_o f_tumors_diagnosed_48.asp? How Is Osteosarcoma Found? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_3x_how_is_osteosarcoma_fo und_52.asp? •

Treatment Ewing's Family of Tumors (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/ewings/patient/ How Is Bone Metastasis Treated? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_4x_how_is_bone_metastasis _treated_66.asp? How is Osteosarcoma Treated? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_4x_how_is_osteosarcoma_tr eated_52.asp?sitearea=cri Osteosarcoma/Malignant Fibrous Histiocytoma of Bone (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/osteosarcoma/Patient

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What Can You Tell Me About Bone and Tissue Transplantation? Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/brochure/thr_report.cfm?Thread_ID=53&topcategory=A bout%2520Orthopaedics&all=all •

Specific Conditions/Aspects What You Need to Know about. Sarcoma and Other Tumors in Paget's Disease Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=p131i&doctitle=What%2BYou%2BNeed%2 Bto%2BKnow%2BAbout%252E%252E%252ESarcoma%2Band%2BOther%2BTumors %2Bin%2BPaget%2527s%2BDisease&doctype=HTML%2BFact%2BSheet

•

Children Childhood Cancer: Osteosarcoma Source: Nemours Foundation http://kidshealth.org/parent/medical/cancer/cancer_osteosarcoma.html

•

From the National Institutes of Health Questions and Answers About Bone Cancer Source: National Cancer Institute http://cis.nci.nih.gov/fact/6_26.htm

•

Organizations American Cancer Society http://www.cancer.org/ National Cancer Institute http://www.cancer.gov/

•

Pictures/Diagrams Atlas of the Body: The Skeleton -- Side View Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZKBBGBGJC &sub_cat=258

•

Prevention/Screening What Are the Risk Factors for Bone Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_what_are_the_risk_factor s_for_bone_cancer_2.asp? What Causes Osteosarcoma? Can It Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_2x_what_causes_osteosarco ma_can_it_be_prevented_52.asp?

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Research Single-Dose Radiation Cost Effective for Cancer Bone Pain Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_2_1x_SingleDose_Radiation_Cost_Effective_For_Cancer_Bone_Pain.asp What's New in Bone Cancer Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new_in_bone_can cer_research_and_treatment_2.asp? What's New in Bone Metastasis Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new_in_bone_met astasis_research_and_treatment_66.asp? What's New in Osteosarcoma Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new_in_osteosarc oma_research_and_treatment_52.asp?

•

Statistics What Are The Key Statistics About Osteosarcoma? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_the_key_statist ics_for_osteosarcoma_52.asp? What Are the Key Statistics For Bone Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_the_key_statist ics_for_bone_cancer_2.asp? What Are the Key Statistics for Ewing's Family of Tumors? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_the_key_statist ics_for_ewings_family_of_tumors_48.asp?

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. 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:

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•

Bone Cancer: Questions and Answers Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7052 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 bone cancer. 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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to bone cancer. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with bone cancer. 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 bone cancer. 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.

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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 “bone cancer” (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 “bone cancer”. 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 “bone cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. 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 “bone cancer” (or a synonym) into the search box, and click “Submit Query.”

111

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.

112 Bone Cancer

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

113

•

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/

114 Bone Cancer

•

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

115

•

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/

116 Bone Cancer

•

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

117

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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on bone cancer: •

Basic Guidelines for Bone Cancer Ewing's sarcoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001302.htm Osteosarcoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001650.htm

•

Signs & Symptoms for Bone Cancer Bone pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003180.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm

118 Bone Cancer

•

Diagnostics and Tests for Bone Cancer Alkaline phosphatase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003470.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Bone scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003833.htm Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm CT scan of the chest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003788.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

•

Background Topics for Bone Cancer Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Distal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002346.htm Flat bones Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002366.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Long bones Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002249.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.htm Proximal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002287.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm Surgical excision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002305.htm

Online Glossaries 119

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

121

BONE CANCER DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [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] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [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] 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] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adverse Effect: An unwanted side effect of treatment. [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 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

122 Bone Cancer

intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] 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]

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 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] 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] Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [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] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile

Dictionary 123

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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [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] 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] 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] Angiosarcoma: A type of cancer that begins in the lining of blood vessels. [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]

Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [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] Antidote: A remedy for counteracting a poison. [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.

124 Bone Cancer

Abbreviated Ag. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] 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]

Antitumour: Counteracting tumour formation. [EU] Apheresis: Components plateletpheresis. [NIH]

being

separated

out,

as

leukapheresis,

plasmapheresis,

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] Aqueous: Having to do with water. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Articular: Of or pertaining to a joint. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a

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variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Background Radiation: Radiation from sources other than the source of interest. It is due to cosmic rays and natural radioactivity in the environment. [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] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [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]

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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] 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] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] 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] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in

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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, 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] Body Fluids: Liquid components of living organisms. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [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 Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood 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 Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [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] 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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH]

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Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [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] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [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] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [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] Cardiotoxicity: Toxicity that affects the heart. [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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [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 Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [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]

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Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] 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] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [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] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [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] Chondrosarcoma: A type of cancer that forms in cartilage. [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] 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] 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 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

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transplantation to replace the work of the kidneys. [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] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [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] 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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [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] Colloidal: Of the nature of a colloid. [EU] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combined Modality Therapy: The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, radioimmunotherapy, chemoradiotherapy, cryochemotherapy, and salvage therapy are seen most frequently, but their combinations with each other and surgery are also used. [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

130 Bone Cancer

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 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] 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] 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]

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Concomitant: Accompanying; accessory; joined with another. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] 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] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Consolidation therapy: Chemotherapy treatments given after induction chemotherapy to further reduce the number of cancer cells. [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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curative: Tending to overcome disease and promote recovery. [EU] 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] 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] 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]

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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] 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] 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 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]

Decubitus: An act of lying down; also the position assumed in lying down. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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]

Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]

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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 the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Diphosphonates: Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [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] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [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] 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] 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 Interactions: The action of a drug that may affect the activity, metabolism, or toxicity

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of another drug. [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] Duct: A tube through which body fluids pass. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] 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 based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [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]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Enchondroma: A benign (noncancerous) growth of cartilage in bones or in other areas where cartilage is not normally found. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [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] 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] 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]

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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] 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]

Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [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] Exatecan mesylate: An anticancer drug that belongs to the family of drugs called topoisomerase inhibitors. Also called DX-8951f. [NIH] External radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external-beam radiation. [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] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [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] Facial: Of or pertaining to the face. [EU]

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Facial Asymmetry: Congenital or acquired asymmetry of the face. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] 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] 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] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Fluoridation: The addition of fluorine usually as a fluoride to something, as the adding of a fluoride to drinking water or public water supplies for prevention of tooth decay in children. [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] 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] Food Technology: The application of knowledge to the food industry. [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

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those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [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 Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [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] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] 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]

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Germ Layers: The three layers of cells comprising the early embryo. [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] 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] Glucuronate: Salt of glucuronic acid. [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] 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] 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] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH.

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It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [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] 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] 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] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [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] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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 Zoster: Acute vesicular inflammation. [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]

Holmium: An element of the rare earth family of metals. It has the atomic symbol Ho, atomic number 67, and atomic weight 164.93. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to

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remain balanced and stable. [NIH] 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 therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hu14.18-interleukin-2 fusion protein: An anticancer drug in which hu14.18, a monoclonal antibody, is combined with interleukin-2. The monoclonal antibody binds to the cancer cells and delivers IL-2, which stimulates the immune system to destroy the cancer cells. [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] 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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypercalcemia: Abnormally high level of calcium in the blood. [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] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [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] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization

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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] Immunoglobulin: A protein that acts as an antibody. [NIH] 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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [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] 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 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] 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 or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [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]

Inferior vena cava: A large vein that empties into the heart. It carries blood from the legs and feet, and from organs in the abdomen and pelvis. [NIH]

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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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [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] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] 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 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] 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-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] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, 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] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intravascular: Within a vessel or vessels. [EU]

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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]

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] 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] 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] 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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] 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] Kinetic: Pertaining to or producing motion. [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] 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

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colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [NIH] Lesion: An area of abnormal tissue change. [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] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [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] Library Services: Services offered to the library user. They include reference and circulation. [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] Linkage: 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] Liposarcoma: A rare cancer of the fat cells. [NIH] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [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 cancer: A disease in which malignant (cancer) cells are found in the tissues 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] Lung metastases: Cancer that has spread from the original (primary) tumor to the lung. [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

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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] 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] 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] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] 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 mesothelioma: A rare type of cancer in which malignant cells are found in the sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [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] Mandibular Condyle: The posterior process on the ramus of the mandible composed of two parts: a superior part, the articular portion, and an inferior part, the condylar neck. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] 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]

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MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [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] 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] 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] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesna: A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from antineoplastic agents, such as ifosfamide or cyclophosphamide. [NIH] Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of

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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] 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] Mineralization: The action of mineralizing; the state of being mineralized. [EU] 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 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]

Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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] 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] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucositis: A complication of some cancer therapies in which the lining of the digestive

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system becomes inflamed. Often seen as sores in the mouth. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Myositis Ossificans: A disease characterized by bony deposits or the ossification of muscle tissue. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [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] 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] 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] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH]

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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] 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] Neutrophil: A type of white blood cell. [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] Nonmetastatic: Cancer that has not spread from the primary (original) site to other sites in the body. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [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 Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [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] 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] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH]

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Orthostatic: Pertaining to or caused by standing erect. [EU] 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] Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]

Osteolytic: Causing the breakdown of bone. [NIH] Osteonectin: Non-collagenous, calcium-binding glycoprotein of developing bone. It links collagen to mineral in the bone matrix. In the synonym SPARC glycoprotein, the acronym stands for secreted protein, acidic and rich in cysteine. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum

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compounds. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [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] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [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] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Particle: A tiny mass of material. [EU] 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] PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH]

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Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Peripheral blood: Blood circulating throughout the body. [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] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphonic Acids: Inorganic or organic derivatives of phosphonic acid with the general formula ROP(OH)2. This includes phosphonates and phosphonic acid esters. The tautomeric form of this compound (P(OH)3) = phosphorous acids. [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] Phosphorus-32: A radioactive form of phosphorus used in the treatment of cancer. It is also used to help locate areas of DNA damage. [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]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [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 protein: One of the hundreds of different proteins present in blood plasma,

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including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [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]

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] 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] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [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]

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Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [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] 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] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary tumor: The original tumor. [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] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [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] 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] Prophylaxis: An attempt to prevent disease. [NIH] 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] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] 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 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]

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Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] 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] 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] 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]

Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [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] 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 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] 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 of atomic number above 83, and possible of induction in all other known elements. [EU] 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.

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Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [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] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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] Radium: A radioactive element symbol Ra, atomic number 88, disintegration of uranium and is is used clinically as a source brachytherapy. [NIH]

of the alkaline earth series of metals. It has the atomic and atomic weight 226. Radium is the product of the present in pitchblende and all ores containing uranium. It of beta and gamma-rays in radiotherapy, particularly

Ramus: Most commonly used for branches of nerves, but applied also to other structures. [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] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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] 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] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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 blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH]

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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] Relapse: The return of signs and symptoms of cancer after a period of improvement. [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] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of 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] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [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] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue 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] 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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide

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side vision and the ability to see objects in dim light (night vision). [NIH] Sagittal: The line of direction passing through the body from back to front, or any vertical plane parallel to the medial plane of the body and inclusive of that plane; often restricted to the medial plane, the plane of the sagittal suture. [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] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Samarium: An element of the rare earth family of metals. It has the atomic symbol Sm, atomic number 62, and atomic weight 150.36. The oxide is used in the control rods of some nuclear reactors. [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. 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] 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] 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

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elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] 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 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] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [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] 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] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [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,

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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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] 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] Sperm: The fecundating fluid of the male. [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] 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] 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.

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[NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [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] Sterile: Unable to produce children. [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] 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] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Strontium: An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62. [NIH] Strontium-89: A radioactive compound that is absorbed by the bone. It is used to treat bone pain associated with prostate cancer. [NIH] Struvite: A type of kidney stone caused by infection. [NIH] Subacute: Somewhat acute; between acute and chronic. [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] 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

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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]

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 methionine. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [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]

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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synovial: Of pertaining to, or secreting synovia. [EU] Systemic: Affecting the entire body. [NIH] 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] 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 skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic,

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but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [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] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] 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] 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] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [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] 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

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DNA topoisomerase. [NIH] Total-body irradiation: Radiation therapy to the entire body. Usually followed by bone marrow or peripheral stem cell transplantation. [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] 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] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] 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] Trastuzumab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. Trastuzumab blocks the effects of the growth factor protein HER2, which transmits growth signals to breast cancer cells. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trimetrexate: A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against Pneumocystis carinii pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. [NIH] Trimetrexate glucuronate: A drug that belongs to the family of drugs called antimetabolites. It is used in the treatment of pneumocystis carinii pneumonia and is being studied in the treatment of cancer. [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] 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]

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Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [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] 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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [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] Ureters: Tubes that carry urine from the kidneys to the bladder. [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 Calculi: Calculi in any part of the urinary tract. According to their composition or pattern of chemical composition distribution, urinary calculi types may include alternating or combination, cystine, decubitus, encysted, fibrin, hemp seed, matrix, mulberry, oxalate, struvite, urostealith, and xanthic calculi. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [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] 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] Vaccination: Administration of vaccines to stimulate the host's immune response. This 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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [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]

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Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Vertebrae: A bony unit of the segmented spinal column. [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] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [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] 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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [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] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] Wettability: The quality or state of being wettable or the degree to which something can be wet. This is also the ability of any solid surface to be wetted when in contact with a liquid whose surface tension is reduced so that the liquid spreads over the surface of the solid. [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]

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]

Dictionary 167

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] 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] 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]

169

INDEX A Acceptor, 121, 163 Acetylgalactosamine, 121, 138 Acetylglucosamine, 121, 138 Acute lymphoblastic leukemia, 39, 121 Acute lymphocytic leukemia, 121 Adaptability, 121, 127, 128 Adenocarcinoma, 121, 149 Adenosine, 121, 124, 152 Adenovirus, 61, 121 Adenylate Cyclase, 63, 121 Adjustment, 15, 121 Adjuvant, 5, 26, 27, 28, 43, 53, 121 Adjuvant Therapy, 28, 121 Adverse Effect, 71, 121, 159 Affinity, 69, 121, 122, 159 Agonist, 122, 162 Algorithms, 122, 125 Alkaline, 64, 67, 75, 118, 122, 127, 156, 161, 162 Alkaline Phosphatase, 64, 67, 122 Alkaloid, 122, 127, 147 Alkylating Agents, 15, 122, 162 Allogeneic, 122, 138, 152 Alopecia, 122, 131 Alpha Particles, 122, 155 Alternative medicine, 86, 122 Alveolar Process, 122, 157 Alveoli, 122, 132 Amifostine, 48, 122 Amino Acid Sequence, 122, 123, 137 Amino Acids, 122, 137, 151, 153, 155, 157, 159, 162, 164 Amnion, 58, 122 Amniotic Fluid, 122 Amputation, 70, 83, 122 Anaesthesia, 122, 141 Analgesic, 12, 123, 144, 147, 149 Analog, 50, 123, 149 Anatomical, 123, 141, 151, 158 Anemia, 29, 123, 136, 162 Anesthesia, 123, 134 Angiogenesis, 7, 8, 123 Angiosarcoma, 54, 123 Animal model, 6, 7, 8, 61, 123 Anions, 123, 143, 159 Annealing, 123, 153 Anthracycline, 123, 132

Antibacterial, 123, 160 Antibiotic, 123, 132, 133, 160 Antibodies, 63, 64, 123, 139, 145, 147, 152, 155 Antibody, 38, 43, 64, 121, 123, 129, 139, 140, 141, 143, 145, 147, 155, 156, 160, 164, 167 Antibody therapy, 38, 123 Anticoagulant, 123, 154 Antidote, 123, 144 Antigen, 35, 47, 121, 123, 130, 140, 141, 145 Anti-infective, 124, 143 Anti-inflammatory, 76, 124, 127, 143 Anti-Inflammatory Agents, 76, 124, 127, 143 Antimicrobial, 70, 124 Antineoplastic, 45, 122, 124, 127, 131, 133, 137, 146, 153, 163, 164, 166 Antineoplastic Agents, 45, 122, 124, 146, 166 Antitumour, 75, 124 Apheresis, 47, 124 Apoptosis, 25, 29, 124, 127 Aqueous, 65, 76, 124, 125, 132, 144 Arterial, 124, 140, 154 Arteries, 124, 126, 131, 147 Arterioles, 124, 126 Arteriolosclerosis, 124 Arteriosclerosis, 61, 124 Articular, 124, 145, 150 Asbestos, 124, 145, 146 Aseptic, 65, 124, 161 ATP, 121, 124, 133, 137, 152, 155, 163, 164 Atrophy, 74, 124 Autologous, 4, 23, 35, 47, 125, 152 Autonomic, 122, 125 B Background Radiation, 67, 125 Bacteria, 70, 123, 125, 132, 134, 135, 147, 160, 165 Bacterial Infections, 70, 125 Barbiturate, 125, 162 Base, 25, 51, 70, 125, 132, 137, 138, 143, 162 Basement Membrane, 125, 135, 143 Benign, 61, 73, 104, 124, 125, 134, 137, 139, 146, 148, 154, 156 Bile, 125, 137, 140, 144 Biliary, 125, 127

170 Bone Cancer

Biliary Tract, 125, 127 Biochemical, 16, 25, 125, 150 Biological response modifier, 125, 142 Biological therapy, 125, 138 Biopsy, 4, 46, 118, 125 Biotechnology, 9, 80, 86, 97, 125 Bladder, 125, 154, 165 Blood Coagulation, 125, 127, 136, 163 Blood pressure, 126, 140, 147, 160 Blood vessel, 123, 126, 134, 139, 143, 144, 145, 146, 159, 160, 161, 163, 165 Body Fluids, 69, 126, 134, 159 Bone Development, 71, 126 Bone Marrow Cells, 71, 126, 129, 146 Bone Marrow Transplantation, 4, 10, 27, 126 Bone metastases, 49, 60, 63, 76, 126 Bone Remodeling, 7, 126 Bone Resorption, 63, 64, 126, 133 Bone scan, 71, 118, 126, 133, 158 Bowel, 126, 133, 142, 149 Bowel Movement, 126, 133 Brachytherapy, 126, 142, 143, 155, 156, 167 Branch, 4, 51, 115, 126, 145, 151, 160, 163 Breakdown, 126, 132, 137, 150 C Cachexia, 63, 126 Calcification, 124, 127, 133 Calcium, 63, 64, 75, 92, 124, 126, 127, 130, 133, 140, 144, 150, 151, 162 Calculi, 70, 127, 165 Camptothecin, 127, 143 Capsules, 46, 127 Carboplatin, 22, 28, 127 Carcinogen, 127, 146 Carcinogenic, 122, 127, 142, 154, 165 Carcinoma, 75, 127, 149, 160 Cardiac, 40, 47, 127, 134, 148 Cardiotoxicity, 40, 127 Case report, 25, 127, 129 Caspase, 25, 127 Cations, 127, 143 Celecoxib, 52, 127 Cell Adhesion, 63, 127 Cell Adhesion Molecules, 63, 127 Cell Cycle, 127, 129, 135 Cell Death, 25, 54, 124, 127, 135, 148 Cell Division, 125, 127, 128, 135, 138, 147, 152 Cell Extracts, 58, 128 Cell Lineage, 68, 128 Cell proliferation, 124, 128

Cell Survival, 128, 138 Cell Transplantation, 35, 38, 47, 48, 49, 128 Centromere, 28, 128 Cervical, 72, 128 Cervix, 128 Character, 128, 132 Chelation, 65, 128 Chemoprotective, 48, 128, 132 Chest wall, 27, 128 Chimeras, 63, 128 Cholesterol, 125, 128, 162 Chondrosarcoma, 4, 22, 25, 26, 45, 73, 83, 128 Chromatin, 124, 128 Chromium, 66, 128 Chromosomal, 128, 157 Chromosome, 128, 144 Chronic, 12, 59, 76, 126, 128, 131, 133, 134, 141, 143, 161 Chronic Disease, 126, 128 Chronic renal, 12, 128 CIS, 106, 129 Cisplatin, 28, 37, 43, 129 Clear cell carcinoma, 129, 132 Clinical study, 129, 131 Clinical trial, 5, 6, 28, 35, 42, 45, 55, 75, 97, 129, 151, 155, 156 Cloning, 125, 129 Cofactor, 129, 154, 163 Collagen, 64, 125, 129, 135, 150, 154 Colloidal, 129, 134, 159 Colony-Stimulating Factors, 129, 138 Colorectal, 72, 129 Colorectal Cancer, 72, 129 Combination chemotherapy, 38, 39, 48, 49, 52, 129 Combined Modality Therapy, 25, 129 Complement, 129, 130, 153 Complementary and alternative medicine, 21, 30, 130 Complementary medicine, 21, 130 Complete response, 51, 130 Computational Biology, 97, 130 Computed tomography, 4, 130, 158 Computerized axial tomography, 130, 158 Computerized tomography, 130 Concomitant, 70, 131 Concretion, 127, 131 Conjunctiva, 131, 142 Connective Tissue, 8, 45, 126, 129, 131, 137, 144, 146, 157, 158, 161 Connective Tissue Cells, 131

Index 171

Consciousness, 123, 131, 133 Consolidation, 23, 53, 131 Consolidation therapy, 23, 131 Contraindications, ii, 131 Controlled clinical trial, 14, 131 Coronary, 131, 147 Coronary Thrombosis, 131, 147 Cortex, 131 Cortical, 62, 69, 131 Cranial, 25, 131, 136, 139 Crystallization, 70, 131 Curative, 131, 163 Cyclic, 121, 131 Cyclophosphamide, 24, 26, 28, 37, 40, 47, 53, 90, 131, 140, 146 Cysteine, 131, 150, 162 Cystine, 131, 165 Cytokine, 131, 136, 158, 163 Cytoplasm, 124, 132, 138, 157 Cytotoxic, 40, 76, 132, 155, 156 Cytotoxic chemotherapy, 40, 76, 132 Cytotoxicity, 28, 129, 132 D Databases, Bibliographic, 97, 132 Daunorubicin, 132, 133 Decubitus, 132, 165 Degenerative, 59, 71, 132, 150 Deletion, 124, 132 Denaturation, 132, 153 Dendrites, 132, 149 Density, 28, 104, 132, 149 Dental Caries, 132, 136 Dental Plaque, 70, 132 Dentition, 70, 132 DES, 18, 132 Dexrazoxane, 40, 44, 47, 132 Diabetes Mellitus, 132, 139, 149 Diagnostic procedure, 45, 57, 67, 86, 132 Digestion, 125, 126, 132, 142, 144, 161 Digestive system, 55, 133, 148 Digestive tract, 72, 133, 159, 160 Diphosphonates, 60, 66, 70, 133 Direct, iii, 7, 8, 60, 61, 63, 66, 89, 133, 156 Disease Progression, 14, 133 Disease-Free Survival, 51, 53, 133 Dissociation, 121, 133, 143 DNA Topoisomerase, 133, 137 Docetaxel, 44, 45, 133 Dorsal, 7, 8, 133, 153 Dorsum, 133 Dose-limiting, 133, 164

Doxorubicin, 24, 26, 37, 40, 43, 44, 47, 53, 90, 132, 133 Drive, ii, vi, 3, 5, 17, 61, 133 Drug Interactions, 91, 133 Drug Tolerance, 134, 163 Duct, 134, 158 E Ectopic, 58, 133, 134 Efficacy, 12, 18, 22, 51, 134, 164 Elasticity, 124, 134 Elastin, 129, 134, 135 Electroacupuncture, 6, 134 Electrocardiogram, 44, 134 Electrons, 125, 134, 143, 155, 156 Electrophoresis, 64, 134 Embryo, 122, 126, 128, 134, 138, 141, 150 Encapsulated, 28, 134 Enchondroma, 73, 134 Endothelial cell, 68, 134, 136, 163 Endotoxin, 134, 164 End-stage renal, 128, 134 Environmental Health, 96, 98, 134 Enzymatic, 127, 130, 132, 134, 153 Enzyme, 59, 72, 121, 122, 127, 133, 134, 153, 155, 156, 163, 164, 166, 167 Epinephrine, 134, 165 Epithelial, 8, 58, 121, 135, 143, 154 Epithelial Cells, 58, 135, 143, 154 Erythrocytes, 123, 126, 135, 156 Escalation, 14, 53, 135 Esophagus, 133, 135, 152, 161 Estrogen, 28, 135, 159, 162 Estrogen receptor, 28, 135 Ethanolamine, 91, 135 Etoposide, 22, 23, 24, 26, 28, 40, 53, 90, 135 Exatecan mesylate, 41, 135 External radiation, 60, 135 External-beam radiation, 135, 143, 155, 167 Extracellular, 64, 131, 135, 150, 159, 162 Extracellular Matrix, 64, 131, 135, 150 Extracellular Matrix Proteins, 64, 135 Extracellular Space, 135 Extremity, 13, 24, 135 Eye Infections, 121, 135 F Facial, 3, 135, 136, 151 Facial Asymmetry, 4, 136 Facial Nerve, 136, 151 Family Planning, 97, 136 Fat, 126, 136, 144, 157, 160, 162 Femoral, 6, 136

172 Bone Cancer

Femur, 6, 8, 83, 136 Fetus, 126, 136, 165 Fibrin, 126, 136, 163, 165 Fibroblast Growth Factor, 21, 136 Fibronectins, 135, 136 Fibrosarcoma, 54, 136 Filgrastim, 40, 136 Fistula, 136, 149 Flavopiridol, 49, 136 Fluoridation, 13, 136 Fluorine, 136 Fold, 67, 76, 136 Folic Acid, 136, 144, 164 Food Technology, 136, 146 Fungi, 135, 136, 147, 167 G Gallate, 25, 137 Gallbladder, 125, 133, 137 Gallium, 67, 137 Gamma Rays, 137, 155, 156 Ganglia, 7, 8, 122, 137, 148 Gas, 135, 136, 137, 140, 149 Gastric, 72, 137 Gastrin, 137, 140 Gastrointestinal, 36, 37, 39, 42, 74, 76, 124, 134, 137, 160, 162 Gastrointestinal tract, 76, 137, 160 Gemcitabine, 45, 137 Gene, 10, 45, 61, 67, 71, 73, 74, 80, 121, 125, 137, 151 Gene Expression, 45, 61, 137 Generator, 74, 137 Genetic Code, 137, 149 Genetic Markers, 42, 137 Genetic testing, 41, 42, 137, 153 Genetics, 10, 137, 151 Genistein, 28, 137 Genotype, 137, 152 Germ cell tumors, 44, 137 Germ Layers, 126, 138 Gland, 4, 138, 144, 151, 152, 154, 158, 161, 163 Glucose, 128, 132, 138, 139, 142, 156 Glucuronate, 138 Glucuronic Acid, 138, 139 Glycoprotein, 22, 44, 138, 143, 150, 163, 164 Glycosaminoglycans, 28, 135, 138 Governing Board, 138, 154 Grade, 47, 73, 138 Grading, 73, 138 Graft, 58, 138, 140, 141

Graft Rejection, 138, 141 Grafting, 138, 141 Granulocyte Colony-Stimulating Factor, 40, 129, 136, 138 Granulocytes, 129, 138, 148, 166 Growth factors, 63, 67, 68, 138 Guanidine, 64, 138 H Half-Life, 76, 139 Haptens, 121, 139 Headache, 30, 139, 142 Hemoglobin, 123, 135, 139, 162 Hemolytic, 139, 162 Hemorrhage, 139, 161 Heparin, 44, 46, 67, 139 Hereditary, 139, 162 Heredity, 137, 139 Herpes, 9, 12, 139 Herpes Zoster, 139 Heterogeneity, 121, 139 Holmium, 49, 139 Homeostasis, 126, 139 Hormonal, 66, 125, 140 Hormone, 7, 50, 63, 75, 121, 132, 134, 137, 140, 142, 143, 149, 153, 157, 160, 163 Hormone therapy, 75, 121, 140 Host, 140, 141, 157, 165, 166 Hu14.18-interleukin-2 fusion protein, 36, 140 Humoral, 63, 138, 140 Humour, 140 Hydrogen, 121, 125, 132, 135, 140, 147, 149, 155 Hydrolysis, 129, 140, 153 Hydroxylysine, 129, 140 Hydroxyproline, 129, 140 Hyperalgesia, 6, 140 Hypercalcemia, 12, 63, 140 Hypersensitivity, 140, 157 Hypertension, 124, 139, 140, 149, 163 Hypertrophy, 61, 140 Hypnotic, 125, 140, 162 I Id, 18, 29, 105, 108, 114, 116, 140 Ifosfamide, 22, 24, 26, 40, 51, 53, 90, 140, 146 Immune response, 121, 123, 138, 139, 140, 141, 162, 165, 166 Immune system, 36, 44, 48, 123, 125, 140, 141, 145, 148, 165, 166 Immunization, 140, 141 Immunoglobulin, 64, 123, 141, 147

Index 173

Immunologic, 141, 156 Immunology, 121, 141 Immunosuppressant, 122, 141 Immunosuppressive, 131, 140, 141 Immunosuppressive therapy, 141 Immunotherapy, 47, 125, 141 Impairment, 135, 141, 146 Implant radiation, 141, 142, 143, 155, 167 Implantation, 69, 141 In vitro, 24, 27, 45, 141, 153 In vivo, 61, 74, 139, 141 Incision, 141, 143 Indicative, 79, 141, 151, 165 Induction, 24, 27, 43, 131, 141, 155 Induction therapy, 27, 141 Infarction, 131, 141, 146 Infection, 37, 40, 70, 77, 124, 125, 135, 141, 142, 144, 145, 157, 161, 166 Inferior vena cava, 26, 141 Inflammation, 4, 59, 70, 124, 135, 139, 142, 148, 150, 152, 157 Influenza, 35, 47, 142 Infusion, 35, 46, 47, 142 Inhalation, 124, 142, 146 Initiation, 64, 142 Innervation, 7, 8, 136, 142 Inorganic, 76, 129, 142, 152, 153 Insulin, 22, 24, 142 Insulin-dependent diabetes mellitus, 142 Insulin-like, 22, 24, 142 Interferon, 50, 142, 145 Interferon-alpha, 142 Interleukin-2, 36, 140, 142 Internal radiation, 142, 143, 155, 167 Interstitial, 126, 135, 142, 143, 167 Intestine, 126, 129, 142, 143 Intoxication, 142, 166 Intracellular, 141, 142 Intramuscular, 35, 47, 142 Intramuscular injection, 35, 47, 142 Intravascular, 72, 142 Intravenous, 46, 47, 61, 67, 142, 143 Intrinsic, 122, 125, 143 Invasive, 60, 75, 143, 145 Iodine, 62, 67, 143 Iodine-131, 62, 143 Ionization, 143 Ionizing, 60, 67, 74, 122, 143, 156 Ions, 59, 69, 125, 133, 138, 140, 143 Irinotecan, 18, 22, 42, 43, 143 Irradiation, 62, 143, 167 Ischemia, 125, 143

J Joint, 4, 59, 67, 124, 143, 150, 162 K Kb, 96, 143 Ketorolac, 12, 143 Kidney Disease, 55, 64, 96, 143 Kinetic, 143 L Laminin, 125, 135, 143 Large Intestine, 129, 133, 142, 143, 156, 159 Latency, 6, 144 Leiomyosarcoma, 54, 144 Lesion, 3, 4, 144 Leucovorin, 39, 90, 92, 144 Leukapheresis, 124, 144 Leukemia, 38, 39, 41, 42, 59, 72, 133, 144 Leukocytes, 126, 138, 142, 144, 164 Levo, 144, 146 Library Services, 114, 144 Ligament, 144, 154 Ligands, 59, 127, 144 Linkage, 137, 144 Lipid, 124, 142, 144 Liposarcoma, 54, 144 Liposome, 28, 144 Liver, 44, 46, 48, 62, 72, 125, 131, 133, 136, 137, 138, 139, 144, 158 Liver cancer, 48, 72, 144 Liver scan, 144, 158 Localization, 62, 144 Localized, 25, 27, 38, 39, 41, 43, 48, 50, 61, 67, 132, 134, 141, 143, 144, 152 Lung metastases, 52, 144 Lymph, 128, 134, 140, 144, 145 Lymph node, 128, 144, 145 Lymphatic, 141, 144, 145, 146, 160 Lymphatic system, 144, 145, 160 Lymphoblastic, 39, 145 Lymphoblasts, 121, 145 Lymphocyte, 123, 145 Lymphoid, 41, 68, 123, 145 Lymphoma, 39, 41, 49, 54, 145 Lytic, 8, 145 M Magnetic Resonance Imaging, 3, 37, 145, 158 Malignancy, 3, 8, 35, 63, 73, 145 Malignant, 4, 15, 36, 39, 54, 66, 70, 105, 121, 124, 137, 144, 145, 146, 148, 150, 154, 156, 157, 158 Malignant mesothelioma, 145, 146 Malignant tumor, 66, 70, 145, 150, 157

174 Bone Cancer

Malnutrition, 125, 126, 145 Mammary, 145, 162 Mandible, 3, 4, 22, 122, 145, 157 Mandibular Condyle, 4, 145 Maxillary, 4, 5, 145 Medial, 124, 145, 158 Mediate, 24, 127, 145 Mediator, 63, 142, 145 MEDLINE, 97, 146 Medullary, 4, 146 Megakaryocytes, 126, 146 Melanin, 146, 152, 165 Melanocytes, 146 Melanoma, 36, 59, 61, 73, 146 Melphalan, 23, 37, 53, 146 Membrane, 122, 130, 131, 143, 146, 148, 150, 152, 153 Meninges, 146 Meningioma, 54, 146 Mental Disorders, 56, 146 Mesenchymal, 4, 9, 39, 58, 73, 146 Mesna, 40, 53, 146 Mesothelioma, 36, 145, 146 Metabolite, 144, 146, 154 Metastasis, 4, 5, 9, 50, 59, 61, 63, 73, 76, 104, 105, 107, 118, 127, 146 Metastasize, 4, 66, 73, 146, 158 Metastatic cancer, 9, 42, 61, 146 Methionine, 146, 162 Methylene Chloride, 76, 146 MI, 119, 146 Microbe, 147, 164 Microorganism, 129, 147, 166 Micro-organism, 70, 132, 147 Mineralization, 64, 147 Mitochondrial Swelling, 147, 148 Mitosis, 124, 147 Mitotic, 133, 135, 147, 166 Mitotic inhibitors, 133, 147 Mobility, 4, 59, 147 Modification, 147, 155 Molecular, 8, 64, 97, 99, 125, 130, 139, 147, 164 Molecule, 8, 73, 123, 125, 130, 133, 140, 147, 156, 164, 165 Monitor, 44, 54, 67, 147, 149 Monoclonal, 38, 43, 46, 63, 64, 140, 143, 147, 155, 164, 167 Monoclonal antibodies, 38, 43, 46, 63, 147, 164 Monocyte, 47, 147 Mononuclear, 147, 164

Morphine, 66, 147, 148, 149 Morphological, 11, 134, 146, 147 Mucins, 132, 147, 158 Mucositis, 147, 163 Mutagenic, 122, 148 Myalgia, 142, 148 Myasthenia, 139, 148 Myeloid Cells, 68, 148 Myelosuppression, 76, 148, 164 Myocardium, 146, 148 Myositis, 22, 148 Myositis Ossificans, 22, 148 N Naive, 47, 148 Narcotic, 146, 147, 148 Nasal Mucosa, 142, 148 Necrosis, 10, 124, 141, 146, 148 Need, 3, 8, 75, 80, 91, 106, 109, 128, 148, 163 Neoplasia, 148 Neoplasm, 41, 46, 50, 148, 158, 165 Neoplastic, 58, 145, 148, 158 Nephropathy, 143, 148 Nerve, 54, 123, 132, 136, 142, 145, 148, 158, 161, 163, 164 Nervous System, 137, 139, 145, 147, 148, 149, 160, 162 Neural, 140, 148 Neuroblastoma, 36, 42, 43, 44, 53, 54, 148 Neurologic, 30, 47, 148 Neurons, 6, 132, 137, 149 Neutrons, 122, 143, 149, 155 Neutropenia, 40, 51, 149 Neutrophil, 40, 149 Nitrogen, 60, 122, 131, 135, 146, 149, 164 Nonmetastatic, 26, 27, 149 Non-small cell lung cancer, 36, 149 Nuclear, 10, 13, 15, 26, 44, 79, 127, 134, 137, 148, 149, 155, 158, 165 Nuclear Medicine, 10, 13, 15, 26, 44, 79, 149 Nuclei, 7, 8, 122, 134, 145, 147, 149, 155 Nucleic acid, 64, 73, 74, 137, 149 Nucleus, 124, 128, 131, 132, 137, 147, 149, 155, 161 O Octreotide, 22, 149 Ocular, 61, 149 Oncologist, 8, 149 Opacity, 132, 149 Opium, 147, 149 Orthostatic, 149, 150

Index 175

Osmotic, 147, 150, 159 Osseointegration, 126, 150 Ossification, 148, 150 Osteoarthritis, 59, 71, 150 Osteoblasts, 150 Osteocalcin, 61, 64, 150 Osteoclasts, 6, 63, 71, 150 Osteogenesis, 126, 150 Osteogenic sarcoma, 53, 150 Osteolysis, 63, 150 Osteolytic, 5, 150 Osteonectin, 64, 150 Osteoporosis, 7, 64, 71, 74, 75, 104, 106, 126, 150 Otitis, 15, 150 Oxalate, 150, 165 Oxalic Acid, 150 Oxaliplatin, 18, 22, 150 P P53 gene, 67, 151 Palliative, 151, 163 Pamidronate, 10, 43, 151 Pancreas, 133, 142, 151, 160 Pancreatic, 36, 151 Pancreatic cancer, 36, 151 Parathyroid, 63, 151, 162 Parathyroid Glands, 151 Parathyroid hormone, 63, 151 Parenchyma, 61, 151 Parotid, 4, 151 Particle, 75, 76, 144, 151 Pathologic, 67, 124, 125, 131, 140, 151, 157, 165 Pathologic Processes, 124, 151 Pathophysiology, 6, 8, 151 PDQ, 105, 151 Pelvic, 26, 151, 154 Peptide, 6, 8, 35, 47, 63, 136, 151, 153, 155 Periodontal disease, 70, 151 Periodontitis, 70, 152 Peripheral blood, 27, 47, 48, 53, 142, 152 Peripheral stem cell transplantation, 38, 48, 49, 152, 164 Pharmacokinetic, 15, 152 Pharmacologic, 123, 139, 152, 164 Pharynx, 142, 152 Phenotype, 68, 152 Phenylalanine, 152, 165 Phosphonic Acids, 133, 152 Phosphorus, 62, 67, 127, 151, 152 Phosphorus-32, 62, 67, 152 Physical Examination, 3, 152

Physiologic, 122, 139, 152, 156, 157 Pigment, 146, 152 Pituitary Gland, 136, 152 Plants, 122, 138, 150, 152, 164 Plasma, 123, 129, 136, 139, 144, 152, 153, 156, 159 Plasma cells, 123, 152 Plasma protein, 152, 159 Plasmapheresis, 124, 153 Platelet-Derived Growth Factor, 24, 153 Plateletpheresis, 124, 153 Platelets, 146, 148, 153, 158 Platinum, 129, 150, 153 Platinum Compounds, 151, 153 Podophyllotoxin, 135, 153 Polymerase, 25, 28, 64, 72, 153 Polymerase Chain Reaction, 64, 72, 153 Polymers, 60, 153, 155 Polypeptide, 68, 73, 122, 129, 153, 160, 162, 167 Polyposis, 129, 153 Polysaccharide, 123, 153, 155 Posterior, 133, 145, 151, 153 Postmenopausal, 150, 154 Postnatal, 154, 161 Postoperative, 4, 154 Practice Guidelines, 8, 98, 154 Precursor, 131, 134, 138, 152, 154, 164, 165 Presumptive, 4, 154 Prevalence, 9, 154 Primary tumor, 53, 61, 154 Probe, 139, 154 Prodrug, 72, 154 Progression, 4, 59, 73, 75, 123, 154 Progressive, 4, 68, 124, 128, 134, 135, 138, 148, 150, 154, 165 Proline, 129, 140, 154 Promoter, 10, 61, 154 Prophylaxis, 154, 165 Prostate, 7, 59, 61, 62, 63, 66, 72, 73, 75, 76, 154, 161 Prostate-Specific Antigen, 72, 154 Prosthesis, 77, 154 Protein C, 46, 122, 150, 154 Protein S, 80, 125, 137, 150, 154, 157 Proteins, 64, 122, 123, 127, 128, 129, 130, 135, 136, 147, 149, 151, 152, 153, 155, 156, 159, 164 Protein-Tyrosine Kinase, 137, 155 Proteoglycans, 28, 125, 135, 155 Protocol, 4, 6, 22, 23, 35, 40, 41, 51, 53, 54, 155

176 Bone Cancer

Protons, 122, 140, 143, 155 Public Policy, 97, 155 Publishing, 5, 9, 155 Pulmonary, 52, 61, 126, 155, 162 Pulse, 147, 155 Purifying, 65, 155 Q Quality of Life, 5, 6, 46, 76, 155, 162 R Race, 146, 155 Radiation, 4, 13, 21, 25, 27, 28, 38, 40, 49, 59, 60, 62, 66, 67, 71, 72, 74, 76, 107, 118, 121, 122, 125, 135, 137, 142, 143, 149, 155, 156, 158, 164, 167 Radiation oncologist, 149, 155 Radiation therapy, 4, 38, 40, 49, 59, 66, 72, 118, 121, 135, 142, 143, 155, 158, 164, 167 Radioactivity, 44, 125, 155 Radioimmunotherapy, 79, 129, 155, 156 Radiolabeled, 60, 143, 155, 156, 167 Radiology, 3, 149, 156 Radiopharmaceutical, 62, 65, 66, 67, 137, 156 Radiotherapy, 15, 21, 27, 51, 62, 75, 76, 126, 143, 155, 156, 167 Radium, 15, 75, 156 Ramus, 4, 145, 156 Randomized, 22, 28, 38, 40, 49, 51, 53, 134, 156 Reabsorption, 63, 156 Reagent, 67, 135, 150, 156 Receptor, 7, 24, 64, 123, 156 Recombinant, 47, 53, 61, 63, 156, 165 Recombination, 137, 156 Reconstitution, 23, 156 Rectum, 126, 129, 133, 137, 143, 154, 156 Recur, 73, 156 Recurrence, 4, 5, 52, 156 Red blood cells, 135, 139, 148, 156 Reductase, 156, 164 Refer, 1, 129, 136, 139, 144, 148, 149, 156 Refraction, 157, 160 Refractory, 28, 36, 39, 41, 42, 43, 45, 49, 51, 157 Regeneration, 136, 156, 157 Regimen, 40, 44, 51, 53, 134, 157 Relapse, 25, 53, 157 Remission, 156, 157 Residual disease, 53, 157 Resorption, 63, 126, 150, 156, 157 Respiration, 147, 157 Response rate, 45, 157

Restoration, 156, 157, 167 Retrovirus, 61, 157 Rhabdomyosarcoma, 27, 35, 39, 40, 41, 42, 44, 46, 47, 49, 51, 53, 54, 157 Rheumatic Diseases, 59, 157 Rheumatism, 157 Rheumatoid, 59, 67, 71, 157 Rheumatoid arthritis, 59, 67, 71, 157 Ribose, 25, 28, 121, 157 Ribosome, 157, 164 Risk factor, 14, 157 Risk patient, 40, 53, 157 Rods, 157, 158 S Sagittal, 4, 158 Saliva, 69, 158 Salivary, 4, 132, 133, 136, 151, 158 Salivary glands, 132, 133, 136, 158 Salvage Therapy, 129, 158 Samarium, 10, 14, 15, 62, 90, 158 Sargramostim, 52, 158 Scans, 37, 44, 46, 54, 71, 158 Schizoid, 158, 166 Schizophrenia, 158, 166 Schizotypal Personality Disorder, 158, 166 Sclerosis, 124, 158 Screening, 8, 129, 151, 158 Secondary tumor, 146, 158 Secretion, 69, 140, 142, 147, 149, 158, 159 Selective estrogen receptor modulator, 159, 162 Semen, 154, 159 Semisynthetic, 127, 135, 159 Senile, 150, 159 Sensibility, 123, 140, 159 Septic, 124, 159 Sequencing, 153, 159 Serine, 154, 159 Serum, 64, 129, 150, 156, 159, 164 Serum Albumin, 64, 159 Side effect, 5, 37, 44, 48, 54, 62, 66, 71, 74, 76, 89, 91, 121, 125, 131, 133, 148, 159, 162, 164 Signs and Symptoms, 157, 159 Skeletal, 6, 7, 13, 58, 60, 62, 65, 67, 75, 76, 159 Skeleton, 8, 67, 72, 75, 106, 126, 136, 143, 159 Skull, 159, 162 Small cell lung cancer, 159 Small intestine, 140, 142, 159 Smooth muscle, 131, 147, 159, 162

Index 177

Social Environment, 155, 159 Sodium, 156, 159 Soft tissue sarcoma, 8, 23, 36, 37, 39, 41, 42, 43, 44, 48, 49, 50, 51, 136, 160 Solid tumor, 36, 42, 43, 44, 48, 49, 54, 123, 133, 160 Solvent, 146, 150, 160 Soma, 160 Somatic, 69, 71, 140, 147, 160 Somatostatin, 50, 149, 160 Specialist, 108, 160 Species, 64, 65, 122, 128, 134, 147, 155, 160, 161, 164, 166, 167 Specificity, 61, 64, 66, 121, 160 Spectrum, 45, 160 Sperm, 128, 137, 160 Spinal cord, 6, 7, 8, 11, 128, 146, 148, 160 Squamous, 149, 160 Squamous cell carcinoma, 149, 160 Staging, 4, 158, 160 Standard therapy, 40, 53, 161 Steel, 69, 77, 161 Stem cell transplantation, 38, 48, 49, 161 Stem Cells, 27, 37, 68, 152, 161 Sterile, 65, 124, 151, 161 Sterility, 131, 161 Stimulus, 133, 142, 144, 161 Stomach, 133, 135, 137, 140, 152, 159, 161 Strand, 153, 161 Stress, 5, 157, 161 Stroke, 56, 96, 161 Stroma, 151, 161 Stromal, 37, 126, 161 Stromal Cells, 126, 161 Strontium, 62, 75, 90, 161 Strontium-89, 62, 75, 161 Struvite, 161, 165 Subacute, 141, 161 Subclinical, 141, 161 Subcutaneous, 40, 161 Subspecies, 160, 161 Substance P, 146, 156, 159, 161 Sulfur, 60, 135, 146, 162 Supportive care, 40, 53, 151, 162 Suppression, 22, 28, 50, 61, 74, 162 Suppurative, 4, 162 Surfactant, 135, 162 Survival Rate, 5, 162 Symphysis, 154, 162 Symptomatic, 63, 162 Synovial, 40, 54, 162

Systemic, 10, 61, 63, 90, 126, 134, 141, 143, 155, 162, 167 T Tamoxifen, 50, 159, 162 Technetium, 60, 67, 133, 162 Temozolomide, 46, 162 Temporal, 4, 12, 15, 162 Teratogenic, 122, 162 Tetany, 151, 162 Thalassemia, 10, 162 Thalidomide, 50, 162 Therapeutics, 22, 91, 163 Thermal, 6, 124, 133, 149, 153, 163 Thigh, 136, 163 Thorax, 36, 163 Thrombin, 136, 154, 163 Thrombomodulin, 154, 163 Thrombosis, 26, 154, 161, 163 Thymidine, 61, 71, 163 Thymidine Kinase, 61, 71, 163 Thyroid, 83, 143, 151, 163, 165 Thyroid Gland, 151, 163 Tin, 62, 67, 153, 163 Tinnitus, 150, 163 Tissue, 4, 8, 14, 38, 41, 42, 45, 46, 48, 49, 50, 54, 60, 64, 65, 67, 68, 69, 70, 71, 74, 75, 77, 104, 106, 123, 124, 125, 126, 127, 128, 131, 134, 135, 136, 138, 141, 142, 144, 145, 146, 148, 149, 150, 152, 153, 154, 157, 159, 160, 161, 162, 163, 164, 165, 167 Tolerance, 40, 121, 163 Tomography, 163 Topoisomerase inhibitors, 135, 143, 163 Topotecan, 51, 163 Total-body irradiation, 23, 164 Toxic, iv, 37, 47, 61, 71, 74, 76, 122, 128, 132, 146, 153, 164 Toxicity, 15, 40, 62, 67, 127, 133, 146, 164 Toxicology, 25, 98, 164 Toxins, 74, 123, 138, 141, 147, 155, 164 Trace element, 128, 136, 163, 164 Transcriptase, 64, 72, 157, 164 Transfection, 125, 164 Translation, 74, 164 Transmitter, 145, 164 Transplantation, 106, 129, 141, 152, 164 Trastuzumab, 38, 46, 164 Trauma, 139, 148, 163, 164 Trimetrexate, 39, 164 Trimetrexate glucuronate, 39, 164 Tryptophan, 129, 164 Tumor Necrosis Factor, 7, 163, 164

178 Bone Cancer

Tumor suppressor gene, 151, 165 Tumorigenic, 67, 68, 165 Tumour, 10, 38, 124, 165 Tyrosine, 24, 28, 155, 165 U Unconscious, 140, 165 Unresectable, 42, 45, 165 Uranium, 156, 162, 165 Ureters, 165 Urethra, 154, 165 Urinary, 67, 70, 127, 165 Urinary Calculi, 70, 165 Urinary tract, 70, 165 Urinary tract infection, 70, 165 Urine, 10, 36, 44, 63, 125, 129, 139, 150, 165 Uterus, 128, 144, 165 V Vaccination, 35, 47, 165 Vaccine, 35, 47, 121, 155, 165 Vagina, 128, 132, 165 Vascular, 61, 141, 163, 165 Vasodilation, 122, 165 Vector, 12, 68, 86, 165 Vein, 44, 46, 141, 143, 149, 151, 165 Vena, 166 Venous, 154, 166 Vertebrae, 160, 166 Vertigo, 150, 166

Veterinarians, 77, 166 Veterinary Medicine, 97, 166 Vinblastine, 52, 166 Vinca Alkaloids, 166 Vincristine, 24, 26, 40, 47, 51, 53, 166 Vinorelbine, 44, 166 Viral, 136, 142, 157, 165, 166 Virulence, 164, 166 Virus, 9, 142, 166 Viscera, 160, 166 Vitro, 139, 166 Vivo, 166 W Weight-Bearing, 60, 166 Wettability, 69, 166 White blood cell, 121, 123, 136, 144, 145, 147, 148, 149, 152, 166 Withdrawal, 6, 166 Wound Healing, 127, 136, 167 X Xenograft, 123, 167 X-ray, 38, 40, 44, 118, 130, 137, 143, 149, 155, 156, 158, 167 X-ray therapy, 143, 167 Y Yeasts, 136, 152, 167 Z Zymogen, 154, 167

Index 179

180 Bone Cancer