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

BLADDER CANCER A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AME...

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BLADDER CANCER 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., 1960Bladder 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: 0-597-83791-0 1. Bladder 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 bladder 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 BLADDER CANCER .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Bladder Cancer.............................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND BLADDER CANCER ........................................................................ 111 Overview.................................................................................................................................... 111 Finding Nutrition Studies on Bladder Cancer........................................................................... 111 Federal Resources on Nutrition ................................................................................................. 117 Additional Web Resources ......................................................................................................... 118 CHAPTER 3. ALTERNATIVE MEDICINE AND BLADDER CANCER.................................................. 121 Overview.................................................................................................................................... 121 National Center for Complementary and Alternative Medicine................................................ 121 Additional Web Resources ......................................................................................................... 141 General References ..................................................................................................................... 142 CHAPTER 4. DISSERTATIONS ON BLADDER CANCER.................................................................... 143 Overview.................................................................................................................................... 143 Dissertations on Bladder Cancer................................................................................................ 143 Keeping Current ........................................................................................................................ 144 CHAPTER 5. CLINICAL TRIALS AND BLADDER CANCER .............................................................. 145 Overview.................................................................................................................................... 145 Recent Trials on Bladder Cancer................................................................................................ 145 Keeping Current on Clinical Trials ........................................................................................... 164 CHAPTER 6. PATENTS ON BLADDER CANCER .............................................................................. 167 Overview.................................................................................................................................... 167 Patents on Bladder Cancer......................................................................................................... 167 Patent Applications on Bladder Cancer ..................................................................................... 189 Keeping Current ........................................................................................................................ 202 CHAPTER 7. BOOKS ON BLADDER CANCER .................................................................................. 203 Overview.................................................................................................................................... 203 Book Summaries: Federal Agencies............................................................................................ 203 Book Summaries: Online Booksellers......................................................................................... 204 The National Library of Medicine Book Index ........................................................................... 206 Chapters on Bladder Cancer....................................................................................................... 207 CHAPTER 8. MULTIMEDIA ON BLADDER CANCER ....................................................................... 213 Overview.................................................................................................................................... 213 Video Recordings ....................................................................................................................... 213 Bibliography: Multimedia on Bladder Cancer ........................................................................... 214 CHAPTER 9. PERIODICALS AND NEWS ON BLADDER CANCER .................................................... 215 Overview.................................................................................................................................... 215 News Services and Press Releases.............................................................................................. 215 Newsletter Articles .................................................................................................................... 220 Academic Periodicals covering Bladder Cancer ......................................................................... 220 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 223 Overview.................................................................................................................................... 223 U.S. Pharmacopeia..................................................................................................................... 223 Commercial Databases ............................................................................................................... 225 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 229 Overview.................................................................................................................................... 229

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NIH Guidelines.......................................................................................................................... 229 NIH Databases........................................................................................................................... 231 Other Commercial Databases..................................................................................................... 234 The Genome Project and Bladder Cancer................................................................................... 234 APPENDIX B. PATIENT RESOURCES ............................................................................................... 239 Overview.................................................................................................................................... 239 Patient Guideline Sources.......................................................................................................... 239 Finding Associations.................................................................................................................. 246 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 249 Overview.................................................................................................................................... 249 Preparation................................................................................................................................. 249 Finding a Local Medical Library................................................................................................ 249 Medical Libraries in the U.S. and Canada ................................................................................. 249 ONLINE GLOSSARIES................................................................................................................ 255 Online Dictionary Directories ................................................................................................... 259 BLADDER CANCER DICTIONARY......................................................................................... 261 INDEX .............................................................................................................................................. 343

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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 bladder 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 bladder 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 bladder 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 bladder 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 bladder 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 bladder 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 BLADDER CANCER Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bladder 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 bladder 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 “bladder 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: •

Biology and Management of Bladder Cancer Source: Medical Progress. 322(16): 1129-1137. April 1990. Summary: This article reviews current information about the biology and management of bladder cancer. It covers epidemiology, pathology and histogenesis including adverse prognostic factors. It discusses new techniques in the management including diagnosis and staging, intravesical chemotherapy, preemptive intravenous chemotherapy, and monoclonal antibodies, as well as surgery and radiotherapy.

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

Project Title: ANTI MALIGNANCIES

TUMOR

THERAPIES

FOR

GENIOTURINARY

Principal Investigator & Institution: Nanus, David M.; Associate Professor; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 14-SEP-2000; Project End 31-AUG-2005 Summary: Research Plan: The objectives of this proposal are to develop a Genitourinary Oncology Program at NYPH for the treatment of patients with urological tumors involving the activation of state of the art clinical trials, performing laboratory-based studies which will increase our understanding of these diseases leading to improved therapies, and to instruct beginning clinicians in the methodologies of patient-oriented research. The specific aims are 1) to conduct clinical and translational trials for patients with renal cancer, including the study of biologic therapies with liposomal tretinoin plus interferon, and monocloncal antibodies (mAb); 2) To conduct clinical and translational trials for patients with prostate cancer, including the study of mAb muJ591 which recognizes prostate specific membrane antigen (PSMA), and the effects of liposomal tretinoin on biochemical (PSA) relapse; 3) To conduct clinical trials for patients with bladder cancer including chemotherapy for patients with metastatic disease or who are at high-risk for relapse (adjuvant); and 4): To mentor medical oncology fellows and junior faculty in clinical and translational trial design and conduct. This award will allow Dr. Nanus protected time to successfully complete these aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ARSENIC AND HEALTH IN BANGLADESH Principal Investigator & Institution: Christiani, David C.; Professor; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001 Summary: (Taken from application) Exposure to arsenic has been associated with the induction of cancer in humans. It is widely accepted that arsenic can cause non-

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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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melanoma skin cancers (in particular, squamous-cell carcinoma). In addition, arsenic may be an important cause of bladder, lung, lung, and other internal cancers. We propose to study biomarkers of exposure, skin lesions, skin and bladder cancer, and heritable susceptibility in two populations: one in Taiwan, where remediation efforts have resulted in a reduction in arsenic exposure to ranges of one to three-hold in most US communities; and a second population in Bangladesh, an area recently described with extremely high exposures from drinking-water contamination. We propose a population-based approach, incorporating markers of exposure (drinking-water arsenic, toenail arsenic), susceptibility (genetic polymorphisms in metabolizing genes), and outcome (squamous-cell carcinoma of the skin, bladder, cancer, non-malignant skin lesions) in order to test several hypotheses important to advancing our understanding of the human-health consequence of arsenic exposure. We will conduct a repeat-measures study, designed to evaluate biologic markers including toenail concentrations, methylated arsenic compounds in the urine, and genetic traits. We will also conduct two case-control studies of skin and bladder cancer: one an extension of our ongoing work in Taiwan and the other in Bangladesh. These studies are designed to fill important research gaps in our understanding of arsenic and human health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ARSENIC EXPOSURE AND BLADDER CANCER IN MICHIGAN Principal Investigator & Institution: Nriagu, Jerome; Professor; Environmental Health Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The objective of this proposal is to explore the factors that have contributed to the observed geographic co-clustering in bladder cancer mortality and arsenic concentrations in drinking water in Michigan. The focus will be on the spatial and spatio-temporal patterns of arsenic exposure and how these may relate to the incidence of bladder cancer in those areas of Michigan with elevated levels of arsenic in their drinking water. Reported arsenic concentrations in well waters in the study area range from 1 to 1310 mg/I, with most common levels being 5-50 mg/L. The project being proposed will consist of three components: (1) Construction of exposure scenarios with time dimension that will involve development of the novel space-time information system (STIS) model to be validated using a combination of space-and-timedependent concentrations of arsenic measured in the study, supplementary historical information on arsenic levels in water supplies, hydrogeochemistry of the area, and selfreported residence information and water drinking habits; (2) Biomonitoring of arsenic exposure to be based on analysis of toenails (known to indicate average exposure over a relatively long time) for arsenic and a number of confounding trace elements such as selenium, zinc, copper and antimony; (3) A population-based, case-control bladder cancer study which will be used as an outcome measure for exposure to arsenic in drinking water. Bladder cancer cases (700) and controls (700, matched to cases by sex, race, and +/- 5-year age groups) will be recruited from long-term residents of the 11 counties (Genesee, Huron, lngham, Jackson, Lapeer, Livingston, Oakland, Sanilac, Shiawassee, Tuscola and Washtenaw) with elevated levels of arsenic in their groundwater. Structured personal interviews will be administered to obtain information on lifetime residential history, current and past water consumption patterns, life-style risk factors (including cigarette smoking and alcohol use), medical history, occupational history, family history of cancer, and dietary habits. The study is designed to shed some light on the dose-response relations for exposure of the U.S. population to arsenic

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concentrations in the 5-100 mg/L range where no information currently exists. Current efforts by the U.S. Environmental Protection Agency to reduce the maximum contaminant level for arsenic in our drinking water have been bedeviled by contradictory and unvalidated predictions of the risks of chronic exposure to low levels (< 100 mg/L) of arsenic in water. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ARSENIC MODE OF ACTION IN CANCER--MODELS OF EPIGENIC MECHANISM Principal Investigator & Institution: Kelsey, Karl T.; Professor; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001 Summary: Arsenic poses unique problems for environmental health scientists in that it is recognized as a human carcinogenic but is not carcinogenic in animal models. Furthermore, arsenical compounds do not induce gene mutations, although they do potentiate the genotoxic effects of other mutagens and are associated with chromosomal abnormalities. These properties indicate that arsenic has a mode of action different from other well-characterized environmental carcinogens whose actions are mediated by DNA damage. One hypothesis is that arsenic acts through epigenetic mechanisms; arsenic may produce reversible cell alterations that influence the expression of genes involved in growth and differentiation. The purpose of this proposal is to investigate the effects of arsenic exposure in the context of an ongoing population based case control study of bladder cancer. We hypothesize that DNA methylation of genes in the causal pathway for disease will occur with a higher frequency in cases with bladder cancer who are also exposed to high levels of arsenicals. Thus, we propose to investigate methylation and mutation of genes in the causal pathway for the genesis of bladder cancer, with special attention to their association with exposure to arsenic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOMARKERS FOR DETECTION OF BLADDER CANCER Principal Investigator & Institution: Ribeiro-Filho, Leopoldo A.; Federal University of Sao Paulo Rua Pedro De Toledo 78L/15 Andar Sao Paulo, Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant) The main goal of this project is to investigate the whether inactivation of E-cadherin, Beta and gamma-catenins can be used as biomarkers for bladder cancer initiation / progression or metastasis. Also investigate the molecular mechanisms of inactivation of E-cadherin, Beta and gamma-catenins in bladder cancer through mutation / CpG methylation pathways. We will also investigate the functional role of the E-cadherin, Beta, and gamma catenins genes in bladder cancer. Specific Hypotheses: We hypothesize that inactivation of E-cadherin, Beta, and gamma catenins is associated with stage and grades of bladder cancer. The mechanisms of inactivation of the E-cadherin, Beta, and gamma catenins gene are through mutation/hypermethylation pathways. Transfection of E-cadherin, Beta and gamma catenins genes will suppress growth of bladder cancer cells. To test these hypotheses, we will pursue the following specific aims. Specific Aim # 1. To analyze gene and protein expression of E-cadherin, Beta, and gamma catenins in different stages and grades of bladder cancer. This specific aim is based on the hypothesis that inactivation of E-cadherin, Beta, and gamma catenins genes can be detected in early stages of bladder cancer and that the frequency of loss of these genes increases with progression

Studies

7

of the cancer process. Under this specific aim, we will determine the gene and protein expression of E-cadherin, Beta, and gamma catenins in normal and different stages and grades of bladder cancer. RNA expression will be analyzed by RT-PCR (for screening) and northern blot (for quantification). Protein expression will be analyzed by immunohistochemistry (for localization) and western blotting (for quantification). Specific Aim # 2. To investigate the mechanisms of inactivation of E-cadherin, Beta, and gamma catenins genes in bladder cancer. This specific aim is based on the hypothesis that mutation / hypermethylation pathways are involved in inactivation of E-cadherin, Beta, and gamma catenins genes in bladder cancer. Under this specific aim, we will first determine the mutation and CpG methylation of E-cadherin, Beta, and gamma catenins genes in different stages and grades of bladder cancer. CpG methylation will be analyzed by sodium bisulfite methylation techniques and confirm by direct DNA sequencing. Specific Aim # 3. To investigate the functional role of E-cadherin, Beta, and gamma catenins genes in bladder carcinogenesis. Under this specific aim, we will test the hypothesis that transfection of the E-cadherin, Beta, and gamma catenins genes in dominant-negative bladder cancer cells can suppress in vitro growth. Under this specific aim, we will transfect these genes and assess their in vitro growth and in vitro invasion assays. Accomplishment of these experiments will provide us with better biomarkers for detection of bladder cancer Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOMARKERS OF BLADDER CANCER IN SPINAL CORD INJURY INDIVIDIUALS Principal Investigator & Institution: Getzenberg, Robert H.; Director of Urological Research and Asso; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 22-AUG-2001; Project End 30-JUN-2006 Description (provided by applicant): Patients with spinal cord injuries are known to have a significantly increased risk (over 400 fold) for developing bladder tumors. Unfortunately, bladder cancer in these patients often presents late, at an aggressive stage, typically indicating a poor prognosis. The early diagnosis of bladder cancer is central to the effective treatment of the disease. An aggressive regular evaluation schedule with cystoscopy, cytology and bladder biopsies is necessary at the present time to detect these tumors in this high-risk population. A sensitive and non-invasive screening procedure, utilizing a bladder cancer marker, would substantially facilitate the detection of tumors in this population. Recently, various urine-based tests for bladder cancer have become available. They have demonstrated varying degrees of efficacy in identifying patients with bladder cancer in the general population. The efficacy of these markers, specifically in patients with spinal cord injury has not been studied. This is necessary when considering the differences in the disease in these individuals along with the co-existing conditions. In this project, the aim is to evaluate the efficacy of a novel marker for bladder cancer as well as of two commercially available markers in a cohort of patients with spinal cord injury. The markers to be studied are: (l) the BLCA-4 assay - a bladder cancer specific nuclear matrix protein present in elevated levels in the urine of patients with bladder cancer; (2) the BTA assay - a urine-based test to detect presence of a marker derived from the basement membrane of bladder cancer cells which is a tumor antigen reported to be a member of the complement H factor family and (3) NMP22 - a urine-based test which detects elevated levels of a generic nuclear matrix protein in patients with bladder cancer. These tests will also be compared to routine voided urine cytology which is the standard diagnostic

8

Bladder Cancer

test currently used to screen and detect bladder cancer in these patients. Cystoscopy and biopsy of visible lesions will be the definitive method of diagnosis of bladder cancer. Such a comparative analysis will allow to determine the optimal and most effective test that can be used to screen and monitor spinal cord injured patients for bladder cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOMARKERS OF CARCINOGENESIS Principal Investigator & Institution: Smith, Martyn T.; Professor; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2001 Summary: Carcinogenesis is known to involve multiple steps of somatic mutation. During the last two decades various biomarkers have been developed to detect early chromosomal and mutational effects of carcinogenic exposure in humans. Although these biomarkers have been shown to be associated with a wide range of carcinogenic exposures, they are not truly biomarkers of early effect as they are not on the causal pathway of environmentally-induced cancers. These biomarkers should be better predictors of increased cancer risk than those currently available. Specific chromosome rearrangements and altered gene methylation are known to be key factors in the development of leukemia, lymphoma, lung and bladder cancer. We plan to develop novel quantitative real time PCR methods for a number of leukemia/lymphoma-related translocations (e.g. 1 (12;21) and t(14;18)) and methylation-specific PCR methods that allow us to examine the methylation status of various cancer-related genes (e.g.p16/INK4a and p14/ARF. We will then make an initial test of the association of some of these markers with non-Hodgkins lymphoma and examine their prevalence in the general population, including newborns. There is currently considerable debate about the presence of translocations in human blood, especially in newborns. In addition, we will perform in vitro cell culture studies with these new markers to examine the nature of the chromosomal damage and aberrant gene methylation produced in critical target cells by the Superfund chemicals, arsenic and benzene. We also plan to use the real-time PCR methods to backtrack leukemia to birth in newborn blood samples from childhood leukemia cases collected under Project 2. This will determine if the translocations or inversions present in the blood of leukemia cases were present at birth and open up new avenues for potentially predicting childhood leukemia. Finally, we will apply the methylation specific-PCR methods to specific genes in leukemia marrow samples collected under Project 2 and in lung and bladder tumors from arsenic endemic areas collected under Project 3, to determine if chemical-specific gene methylation patterns exist in the tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: BLADDER CANCER AND URINARY SCHISTOSOMIASIS IN GHANA Principal Investigator & Institution: Shiff, Clive J.; Molecular Microbiol and Immun; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Bladder cancer in Africa is frequently associated with infection by the urinary trematode parasite, Schistosoma haematobium and has been the subject of several hospital-based studies. In fact, a recent review of the topic was unable only to quote any data on the epidemiology and associated risk factor

Studies

9

analysis for bladder cancer in Africa. There is a need to establish the role of this condition in endemic areas, and to determine the nature and frequency of various risk factors so that public health authorities can formulate effective control strategies. Recent research has suggested that chronic inflammation due to chronic and repeated insults from microorganisms may increase oxidative stress damage in tissue resulting in genetic changes that set the stage for malignant transformation of tissue. Urinary schistosomiasis is a persistent infection of young people that becomes chronic as they age, providing a nidus in the urothelium, which may attract bacteria, viruses and other inflammation stimulants. These, in their plethora may be the source of the repeated insults that contribute to tissue hyperplasia. However, in order to establish the true public health importance of bladder cancer, it is necessary to collect epidemiological data from an endemic area. This can be done in Ghana where S. haematobium is prevalent. Using appropriate sampling procedures, within the limitation of a small grant, sufficient infected individuals can be examined with noninvasive techniques which will provide data on the prevalence and intensity of infection as well as on the existence of biomarkers of cancer and co-infections detected by urine examination. Ultrasound examination will provide evidence for lesions of the urothelium classified for magnitude. Finally where indicated, and with informed consent, invasive examination by collection of biopsy material may be necessary for verification of the nature of any lesion. Cytological examination of urine sediment and subsequent testing of tissue for proteomics analysis in later studies will provide information on the various insults occurring in the bladder and the extent of local inflammatory responses and their association with developing cancer. The study has the potential to be extended in order to consider the mechanism of genetic change and selection of oncogenes on an epidemiological basis, and to assess the frequencies with which these occur in people living in such endemic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLADDER CANCER BIOMARKERS GUIDES TO SURGERY AND THERAPY Principal Investigator & Institution: Hurst, Robert E.; Professor; Urology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-APR-2004 Summary: (Adapted from the Investigator's Abstract) The Urology Research Group at the University of Oklahoma is a multidisciplinary group of scientists working on a multicenter translational research program in bladder cancer biomarkers. The hypothesis being tested is that metastasis requires several functional phenotypic traits to be simultaneously present in cells, and that these phenotypes can be defined by quantitatively measured biomarkers representing functional phenotypes. This approach depends upon integrating model system studies of bladder cancer cells of defined metastatic potential grown on natural connective tissue matrix and in nude mice with small-scale retrospective studies of known outcome to identify markers for functional phenotypes needed for mestastasis. The model systems allow specific mechanisms of metastasis to be investigated and manipulated in vitro and in animal models to assess the response of selected biomarkers. The small-scale retrospective studies with patient samples identify specific mechanisms to be investigated. The functional phenotypes being evaluated include markers for matrix degradation (matrix metalloproteinases, MMP and their inhibitors, TIMP), motility (autocrine motility factor receptor, AMFR), weak cell adhesion (E-cadherin, integrins), evasion of apoptosis (transglutaminase), cytoskeletal changes (actin), biomarkers associated with angiogenesis (bFGF), and

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biomarkers of modulation of epithelial-stromal interactions (TGF-b). The marker profiles found most useful in these basic mechanistic studies of markers and mechanisms will be evaluated further in retrospective studies of patients with known outcomes to begin to develop a panel of biomarkers to identify metastatic risk. Because the emphasis is on identification of clinically useful markers, these studies will involve 50 or fewer patients because markers that are not clearly useful in a study of this size have minimal potential for use as clinical markers. The objective of these studies is to assess sensitivity and specificity, identify which markers cluster together or provide independent information on metastatic risk. The emphasis will be on Grade 2 tumors because for this group, stage and grade are least useful. The results of this study should generate biomarker profiles that are based in basic, mechanistic understanding of metastasis that can subsequently be tested in controlled clinical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLADDER CANCER PREVENTION BY SILIBININ Principal Investigator & Institution: Agarwal, Rajesh; Professor; Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Bladder cancer is the most common type of cancer linked to occupational and environmental exposure to harmful chemical substances. Such substances are absorbed into bloodstream, filtered by kidneys, and stored in the bladder. Exposure of bladder tissue and lining to harmful substances eventually causes cancer. Standard treatment for bladder cancer includes surgery, chemo and radiation therapy, biological therapy, and combinations of these. However, surgery has undesirable physical and psychological effects, metastases are difficult to treat, and recurrence occurs. One approach to control bladder cancer growth and metastasis could be its prevention by phytochemicals; this approach has had a renewed public and scientific interest for the prevention of different epithelial cancers. Overall, human cancers appear to involve a gradual accumulation of genetic and epigenetic changes over a period of years. For example, alone or in combination, cell signaling, cell cycle and apoptosis regulators, and angiogenesis are identified as critical, perhaps causal, epigenetic events associated with tumor growth, progression and metastasis of several malignancies including bladder cancer. Together, these studies suggest that agents that could modulate these targets/events will be potent cancer preventive agents in general and bladder cancer in particular. Our recent studies in different human cancer cells show that silibinin inhibits cell signaling, modulates cell cycle regulators causing G1/G2-M arrest and leads to differentiation and/or apoptosis, and prevents skin and prostate cancers in mouse models. Together, hypothesis proposed is: silibinin is a novel bladder cancer preventive agent, and anti-cancer effect of silibinin involves inhibition of cell survival signaling leading to anti-proliferative and apoptotic efficacy. Following aims would establish bladder cancer preventive efficacy of silibinin. 1) To assess and define the effect of silibinin on cell survival signaling in normal bladder epithelial and bladder carcinoma HTB2 cells. 2) To assess and establish the efficacy of silibinin in human bladder carcinoma HTB2 xenograft growth and regression in nude mice. As a practical and translational approach, we believe that outcome of proposed studies will form a firm basis for a well-developed R01 grant to further define and establish the efficacy of silibinin against bladder cancer and the molecular mechanisms associated with its effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER RISKS AMONG TEXTILE WORKERS IN CHINA Principal Investigator & Institution: Checkoway, Harvey L.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 10-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): The manufacture of cotton, wool, and synthetic fiber textiles is one of the world's largest industries. Moreover, some specific exposures within the industry are either known or suspected carcinogens. In spite of these considerations, existing knowledge of cancer risks to textile workers is based on fragmentary epidemiologic data. We are proposing an epidemiologic study in a cohort of roughly 267,000 women employees in the textile industry in Shanghai, China. The study cohort has been enumerated previously for a randomized trial of the efficacy of breast self exam, and is well characterized with respect to demographic, reproductive, and lifestyle factors, including cigarette smoking and alcohol use. We will focus on the following exposure/disease associations as primary hypotheses, all of which have been suggested but remain largely inconclusive in the literature: cotton and wool dusts and sinonasal cancer; formaldehyde and nasopharyngeal cancer; cotton dust and lung cancer; textile dyes and urinary bladder cancer; synthetic fibers and colon cancer. In a more exploratory mode, we will investigate textile exposures as potential etiologic factors for breast cancer. The study will consist of two related phases. The first phase will involve comparisons of site-specific cancer risks between the cohort and rates in the general population of Shanghai women during 1989-97. Incidence rates will be compared with city rates for the entire cohort and for the various manufacturing sectors (cotton, wool, synthetics, silk, dyeing, and finished apparel). The second, more in-depth analytic phase will be a case-cohort study nested within the cohort. The case groups will include incident, during 1989-97, cancers of the lung (expected number 1248), sinonasal passage (21), nasopharynx (100), bladder (81), colon (433), and breast (1196). A common referent subcohort (N=2496), will be selected as an age-stratified random sample from the study base of women textile workers. Historical exposure reconstruction will be performed for cotton, wool, silk, and synthetic fiber dusts, dyes, and formaldehyde to support dose-response estimation. The proposed study will be comprised of unquestionably the world's largest, most well characterized cohort of textile workers, and should therefore generate important information that is needed for cancer risk reduction strategies for women in China and elsewhere, including the United States. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER SERO EPIDEMIOLOGY AMONG THE JAPANESE IN HAWAII Principal Investigator & Institution: Nomura, Abraham M.; Director; Kuakini Medical Center 347 N Kuakini St Honolulu, Hi 96817 Timing: Fiscal Year 2001; Project Start 15-SEP-1983; Project End 30-JUN-2003 Summary: (Adapted from the Investigator's Abstract) This is a sero-epidemiologic prospective study to identify biochemical markers related to common cancers occurring among 11,132 American Japanese subjects examined in Hawaii. Their unthawed serum, obtained many years prior to the diagnosis of cancer, will be used in the investigation. The proposal is focused on five specific cancer sites: prostate, colon, breast, stomach and urinary bladder. Eight specific aims will be addressed: 1) to determine whether low serum isoflavonoid levels increase the risk of prostate cancer; 2) to see if low serum selenium levels increase prostate cancer risk; 3) to determine whether high serum insulin level increases the risk of colon cancer risk in men; 4) to find out if low serum

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isoflavonoid levels increase breast cancer risk in women; 5) to determine whether men carrying the Helicobacter pylori Vac-A strains are at increased risk for stomach cancer; 6) to see if the presence of H. pylori serum markers increase the risk of total and causespecific mortality in men; 7) to find out if serum levels of vitamin A and carotenoids are inversely associated with urinary bladder cancer risk in men; 8) to determine whether low serum selenium levels increase urinary bladder cancer risk in men. The population base for aim 4 consists of 1787 women, born from 1900 to 1935 who were interviewed and examined from 1975-1977. The subjects for the rest of the aims are 9345 men born from 1896 to 1935, who were interviewed and examined from 1971 to 1976. A wealth of epidemiologic-based data was collected on these participants, and they have been under continuous hospital surveillance for cancer since their examination. Two types of study design will be used in this proposal: 1) prospective study (aim 6); 2) nested case-control study (the rest of the aims). It is estimated that the number of incident cases will be as follows: 376 prostate, 387 colon, 120 breast, 293 stomach, and 131 urinary bladder cancer cases. The number of cause -specific mortality cases should be at least 870 coronary deaths, 1277 cancer deaths and 4145 deaths among the men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOPREVENTION OF BLADDER CANCER BY SOYBEAN Principal Investigator & Institution: Zhou, Jin-Rong; Assistant Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): This proposal is focused on the chemopreventive activity of soybean bioactive components on bladder cancer. The hypothesis is that increased dietary consumption of soybean bioactive components may serve as an effective nutritional regimen for the prevention of bladder cancer progression and metastasis by modulating bladder tumor angiogenesis, apoptosis and/or proliferation. The rationale for supporting this hypothesis is based on the followings: (1) Soy bioactive components exert their effects on anti-bladder cancer via both blood circulation and direct contact with the mucosa of the bladder, and (2) Our animal studies and in vivo mechanistic studies indicated that soy phytochemicals inhibited bladder tumor progression by inducing tumor cell apoptosis, inhibiting tumor proliferation and inhibiting tumor angiogenesis. In this proposal, three specific aims will be designed to test our hypothesis by using a clinically relevant orthotopic bladder model. Specific Aim 1 is to determine the effect of soybean components on orthotopic growth and/or metastasis of both well-differentiated, low metastatic (RT4) and poorly differentiated, highly metastatic (253J B-V) human bladder tumors. Soybean components (soy isoflavone-depleted soy protein, soy phytochemical concentrate, and soy genistin) will be evaluated for their effects on the growth and metastasis of both RT4 and 253J-B-V tumors in vivo. Specific aim 2 is to determine the effect of soybean components on the expression of tumor biomarkers that are related to tumor cell apoptosis and proliferation and tumor angiogenesis. These apoptotic and proliferation biomarkers include (a) apoptotic index and related apoptosis inducers (p53, p21/wafl, bax, TNFalpha) and apoptosis repressors (bcl-2, bcl-xl), (b) proliferation index and cell cycle related cyclins (A, D, E) and cyclin-dependent kinases (cdks 2, 4, 6). Our in vitro microarray assays have suggested that markers that are related to angiogenesis network are among important genes that are significantly modulated by soy components. These angiogenic biomarkers include tumor angiogenic factors (VEGF, bFGF, angiopoietin-1) and anti-angiogenic factor angiopoietin-2. RT-PCR and immunohistochemistry followed by image analysis will be applied to determine the expression of above molecular

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markers. Specific aim 3 is to further elucidate mechanisms involved in the interactive affect of genes and soy bioactive components on bladder cancer modulation in vitro and in vivo by employing microarrayed cDNA chip technology. By using an oligonucleotide array containing sequences complementary to about 12,000 full-length human cDNAs, both dose-dependent and time-dependent mRNA expression patterns will be determined in both in vitro and in vivo samples. Some of these significantly different gene transcripts will be confirmed by RT-PCR. Results derived from the proposed studies by integrating nutrition, molecular biology and genetics in bladder cancer prevention research will be expected to provide significant insight into the utilization of dietary soy in the prevention of bladder cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOPREVENTION OF CHEMICALLY-INDUCED BLADDER CANCERS Principal Investigator & Institution: Grubbs, Clinton J.; Professor and Director; Nutrition Sciences; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 30-APR-2005 Summary: (provided by applicant): Numerous epidemiological studies have established a strong association between cigarette smoking and urinary bladder cancer. The overall goals of this proposal are to evaluate chemopreventive agents and surrogate markers for future clinical trials to prevent cancers in former smokers. The chemically induced urinary bladder cancer model that will be used will allow the correlation of changes in surrogate endpoints with the ability of the agent(s) to inhibit bladder carcinogenesis. The first specific aim will evaluate three classes of chemopreventive agents (lipoxygenase inhibitor, farnesyl transferase inhibitor (FTI), and COX-2 inhibitor) either alone or in combination for efficacy in the prevention of bladder cancers. The agents are esculetin, R115777, and celecoxib, respectively. The second specific aim will measure the expression of survivin in urinary bladder lesions and in urine of rats treated with the carcinogen OH-BBN and/or chemopreventive agents. The rationale for using survivin as a molecular marker/predictor in these studies is twofold. First, increased expression of survivin in cancer versus normal tissues is contributed by associated Ras and secondly, survivin provides a highly sensitive and specific marker of onset and progression of bladder cancer. This is particularly relevant for the chemopreventive experiments with the farnesyl transferase inhibitor R115777 and suggests that monitoring the modulation of survivin expression during this study may provide a molecular indicator of Ras-dependent transformation. The third specific aim will initially determine the effect of R115777 on gene expression profiles as assessed by Affymetrix gene chip analysis to establish new biomarkers that are involved in urinary bladder carcinogenesis and modulatable by chemopreventive agents. The hypothesis is that farnesyl transferase inhibitors will prevent chemically-induced urinary bladder cancers by modulating the expression of genes associated with apoptosis and cell cycle regulation pathways. Depending on the results in the FTI treated rats, additional profiles can be assessed in the celecoxib and esculetin treated animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMOPREVENTION OF SUPERFICIAL BLADDER CANCER Principal Investigator & Institution: Belldegrun, Arie S.; Associate Professor of Surgery; Urology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024

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Timing: Fiscal Year 2002; Project Start 07-AUG-2002; Project End 31-JUL-2007 Summary: The overall goals of this grant application are to 1) develop an effective chemoprevention strategy to reduce the risk of bladder cancer recurrence and to 2) investigate surrogate biomarkers that can serve as intermediate endpoints of the interventional efficacy of chemoprevention. Bladder cancer represents an important health problem in the United States and it currently ranks as the fourth most common cancer site in men and the eight most leading site in women. Since these tumors have a very high incidence of recurrence, the psychological and economic burden to the health care system of repeated diagnostic evaluations and therapy are substantial. Bladder cancer is an ideal model for studies of risk assessment early detection, chemoprevention and the development of intermediate biomarkers. Cigarette smoking represents the single most significant, preventable cause of bladder cancer and its carcinogenesis has a long latency period of close to twenty years following initial exposure, providing ample opportunities for intervention. Recently several potential surrogate end point markers have been developed for the detection of the clinically occult, premalignant phase of bladder cancer. These markers include the QFIA biomarker profile (DNA/M344/Actin Associated Protein) urinary basic fibroblast growth factor (bFGF) measurement, and Microsatellite Instability (MI) markers. Using the tumor recurrence rate as a primary end point and the biomarkers as secondary end points, we propose to perform a randomized, placebo-controlled, clinical trial using two promising chemoprevention agents targeting specific biochemical pathways on a cohort of high risk individuals who are former smokers with a grater than 30 pack year smoking history. Eligible subjects will have had a previous episode of low grade, low stage cancer of the bladder who are at high risk to develop disease recurrence, but for whom the standard of care would be observation. We will also construct tissue microarrays using specimens obtained during the evaluation of this clinical cohort to perform present and future translational high throughput studies to study the expression of markers associated with genetic susceptibility and tumor progression, and to identify potential therapeutic targets for cancer prevention. This grant application will involve a multi-disciplinary approached based on organization into program cores. An Administrative Core will perform the overall oversight for all aspects of the proposed work. A Clinical Core will run the clinical trial. The development and evaluation of the proposed biomarkers will be performed by the Biomarker and Nutritional Cores. All tissue samples will be collected and stored, and tissue arrays constructed by the Tissue Core. Finally, the Biostatistics Core will help design the clinical trial and evaluate the measured endpoints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOPREVENTION OF TOBACCO RELATED CANCER IN ANIMALS Principal Investigator & Institution: Pereira, Michael A.; Director; Pathology; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): Our overall goal is to develop biomarkers for chemoprevention studies of cigarette smoke-related cancers that can be translated to clinical studies in former smokers. To obtain this aim, we propose: Specific Aim 1: Develop biomarkers for chemoprevention of lung cancer in former smokers using a mouse model for lung cancer and related biological and molecular alterations; and Specific Aim 2: Develop biomarkers for chemoprevention of bladder cancer in exsmokers using a rat model for urinary bladder cancer and associated biological and molecular alterations. Our hypothesis is that chemopreventive agents will decrease

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cancer incidence by modulating and reversing biological and molecular alterations in phenotypically normal tissue, precancerous tissues and tumors. Further, we hypothesize that the modulation of the biological and molecular alterations can be developed as biomarkers for chemoprevention in animal and clinical studies including studies in former smokers. To accomplish Aim 1, lung tumors will be induced in strain A mice by exposure to cigarette smoke, benzo(a)pyrene and 4-(Methyl nitrosamino)-1-(3- pyridyl)1-butanone (NNK) and to accomplish Aim 2, bladder tumors will be induced in F344 rats by N-butyl-N-hydroxybutyl)nitrosamine (OH-BBN). After exposure to the carcinogens including cigarette smoke has ceased the animals will be administered the chemo-preventive agents: budesonide and the farnesyl transferase inhibitor, R115777 in the lung studies and budesonide, ketoprofen and sulindac in the bladder study. Biological and molecular alterations of cell proliferation, apoptosis, methylation of genes (both hypomethylation of protooncogenes and hypermethylation of tumor suppressor genes) and alteration in mRNA and protein expression will be determined in phenotypically normal tissues, precancerous lesions and tumors at different times during the progression to cancer. The ability of the chemopreventive agents to modulate and reverse these biological and molecular alterations in tissue and lesions will be determined in parallel with the ability of the agents to prevent cancer. Thus, biological and molecular alterations that are modulated in parallel with the prevention of cancer by the chemopreventive agents will be indicated as biomarkers for chemoprevention studies including those in former smokers where the agents will similarly be administered after exposure to cigarette smoke had ceased. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CIRCULATING INHIBITORS OF ENDOTHELIAL CELL GROWTH Principal Investigator & Institution: Folkman, M Judah.; Director; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 16-MAY-1995; Project End 31-DEC-2003 Summary: (Adapted from the investigator's abstract) The long term objectives of this grant and its Specific Aims are: 1) To elucidate the molecular mechanisms of action of two endogenous inhibitors of angiogenesis previously identified in this laboratory, and 2) To discover other proteins which make up a family of natural angiogenesis inhibitors in the body. The first Aim will focus on the following questions: 1) What is the effect of angiostatin on endothelial cell cycle progression? 2) How does glycosylation effect angiostatin function? 3) How is collagen XVIII processed to endostatin? And 4) What is the molecular mechanism of the specificity of endostatin as an inhibitor of vascular endothelial cells? The second Aim will involve purification and sequencing of a new angiogenesis inhibitor that has recently been detected. They will employ a double tumor model in mice, also called the "concomitant resistance" model. One of these inhibitors is generated by human bladder cancer cells. Endostatin is already in clinical trial. They believe that these inhibitors along with others, yet to be identified and fully characterized, may eventually be added to conventional chemotherapy or to radiotherapy or to immunotherapy to improve efficacy of anti-cancer therapy, to decrease toxicity, and to reduce the development of acquired drug resistance. A study of mechanism of endogenous inhibitors may enlarge their understanding of the family of proteins which operate to suppress angiogenesis under physiological conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLIN.RELEVANCE OF CIRCULAT.TUMOR CELLS IN BLADDER CANCER Principal Investigator & Institution: Osman, Iman; Assistant Professor; Dermatology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 07-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): The main objective of this proposal is to define the clinical relevance of detecting circulating tumor cells (CTC) in bladder cancer patients. The specific aims are: 1) To compare the detection rates of CTC for uroplakins (I-Ill), keratins (k19 and k20), and Epidermal Growth Factor Receptor (EGFR) in patients with superficial bladder cancer versus those with metastatic bladder cancer, and 2) To examine the relation between the expression of these molecular markers in primary and metastatic tissue deposits and their CTC detection rate. We propose to test blood samples from 50 bladder cancer patients with superficial tumors (expected to have low likelihood of micrometastases) and 50 with grossly metastatic disease (expected to have a high likelihood of micrometastases) using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). All patients will be sampled three times over a four week period to increase the positive CTC detection rate. The CTC RT-PCR will be then correlated with presence of disease at the time of the assay to define the most clinically informative marker(s) that provide the best sensitivity, specificity and overall predictive value for the presence of micrometastases. The tissue expression of the molecular markers will be assessed using immunohistochemistry as well as RT-PCR in specimens obtained from patients outlined in aim 1, and the results will then be correlated with the RT-PCR results for CTC. This analysis will help us to understand changes in the tissue expression of these markers during the progression of bladder cancer and how these changes are related to seeding of CTC in the blood. Our preliminary data clearly demonstrate the feasibility of conducting the proposed work as a collaborative effort between New York University School of Medicine and Memorial Sloan-Kettering Cancer Center. This cooperative work endows the study with the strong laboratory and clinical facilities that are necessary for the successful conduct of this type of translation research. We plan this project as a phase I pilot study, in response to the "Pilot and Feasibility Program in Urology" Program Announcement #02-013; we intend to generate sufficient data in order to pursue the development of CTC in a phase II prospective study that will examine the correlation between CTC detection and recurrence in patients with muscle invasive disease following surgical resection of the tumor. We foresee phase III marker development as a multi-institutional study with the goals of independently verifying and validating this correlation prior to considering an application to the FDA for integrating CTC detection as part of the standard of care management for bladder cancer patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COLLABORATIVE UROLOGICAL RESEARCH IN SPINAL CORD INJURY Principal Investigator & Institution: Chancellor, Michael B.; Professor; Urology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 22-AUG-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Urological complications are one of the most common and devastating health problems for SCI patients. Yet this important field has not received significant research attention. Especially lacking is collaboration among urologists, rehabilitation physicists and basic scientists. The Collaborative Urologic

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Research Program in SCI (CURP-SCI) at the University of Pittsburgh was organized in 1998 to build upon the strengths of the large number of laboratories interested in SCI neurophysiology, cellular biology, tissue mechanics and advanced therapeutics. The goal of the CURP-SCI is to foster collaborative, interdisciplinary research programs with the aim of developing a rational therapy for SCI urologic dysfunction. There are four Projects and three Cores in the Program: Project 1. Mechanisms of detrusor hyperreflexia development after SCI (William de Groat, Pharmacology); Project 2. Alterations in bladder mechanics in SCI (Michael Sacks, Biomechanics); Project 3. Biomarkers of bladder cancer in SCI individuals (Robert Getzenberg, Urology and Pittsburgh Cancer Institute); and Project 4. Novel intervention strategies for neurogenic bladder (Michael Chancellor, Urology). The Cores are: A. Administrative Core (Michael Chancellor); B. Patient and Tissue Banking Core (Rajiv Dhir); and C. SCI Animal Core (William de Groat). Although all four projects will have animal studies, there is also focus on clinical correlation and improvement of care for SCI patients. Project 4 (Dr. Chancellor) will bridge a study of intravesical vanilloids in animal models and concurrent clinical trial of intravesical resiniferatoxin (RTX) in neurogenic bladder patients. Projects 2 and 3 will also have direct clinical correlation with analysis of human bladder tissue and urine (Core B). The program is integrated with the regional SCI and MS programs that serve over 2.5 million people. Dr. John Horton, Department of Rehabilitation Medicine, is the Director of the SCI Clinical Program. Diane BorelloFrance, Ph.D., Department of Physical Therapy and Rehabilitation Medicine, will oversee and direct clinical outcome and data analysis. This Program builds on the commitment of the participants to SCI research and the synergistic and collaborative history of the laboratories. It takes advantage of the considerable resources of the university and will be carried out in the more than 25,000 s.f. of fully equipped laboratory and clinical space. This Program is important for the advancement of patient care and basic understanding of SCI and neurogenic bladder dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--BIOSTATISTICS Principal Investigator & Institution: Goodman, Steven; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: The Biostatistics Core resources has an integral role in the development, execution and analysis of the research efforts of the Johns Hopkins program project in Bladder Cancer Research. The core will provide support for Program investigators in the following areas: (1) structure on the research database and interface for data entry, data retrieval and patient or sample tracking; (2) procedures to ensure data quality, integrity, and confidentiality; (3) interim reports of project progress, patient accrual, processing of specimens, completeness of data gathering, and monitoring of patient drop-out or loss of follow-up; (4) advice on any modifications that might be necessary in study design; (5) development of new statistical methods to for the progression model; (6) data analysis and interpretation; (7) assistance in the writing of reports for publication. The biostatistics core will consist of three experienced members of the division of Biostatistics in the Oncology Center and a member of the faculty of the department of Biostatistics. A working relationship already exists between the director of the core and several principle investigators of program projects. The data coordinator described in the administrative core will work closely with the biostatistics core, coordinating all aspects of data management critical to the program's success. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--BIOSTATISTICS AND BLADDER CANCER DATABASE Principal Investigator & Institution: Groshen, Susan G.; Professor; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 13-SEP-2002; Project End 31-AUG-2007 Summary: Revised Abstract: "Biostatistics and Bladder Cancer Database", provides statistical input for the design, conduct, and interpretation of all laboratory and clinical studies as well as maintenance of the Bladder Cancer Research Database, a resource essential to the translational aspects of the program project. In the previous review, concerns were expressed about suboptimal integration of core biostatistical efforts with those of Project 2 and a lack of innovative statistical approaches to integrate biomarker results. The revised approach shows better integration of Core B activities with the plan for the statistical analyses of data to be collected for this project. It is clarified that Drs. Yu and Groshen have a longstanding collegial relationship and will be meeting regularly for discussions regarding implementation of the research, quality control, and the analytic plan. Methods for exploring the co-expression of COX-2 and DNMTs are elaborated with stratification for smoking status, vitamin C intake, and other variables. Power calculations have been revised to include two-tailed tests of significance, and samples sizes appear sufficient to detect approximate 10 percent differences with sufficient statistical power. Sample size considerations are given in greater detail for not only the univariate comparisons, but also for examination of two-way and three-way interactions. There is also a plan to incorporate multivariate modeling of the data for tumor stage at detection to evaluation impact of the biomarkers on progression of bladder carcinogenesis. Dr. Groshen has proposed to use resampling methods (Westiall and Young, 1993) to address overfitting issues in model selection. Data base activities of the core have been enhanced to include the management of specimen tracking and management of intermediate data. In summary, all of the issues raised in the previous review have been adequately addressed. As a result, Core B is now well-integrated with other components of the program project and provides excellent statistical support crucial to the success of this program. This core was previously rated as satisfactory and is now rated as superior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--MOLECULAR EPIDEMIOLOGY AND ECOGENETICS Principal Investigator & Institution: Spitz, Margaret R.; Professor and Chair; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAR-2006 Summary: The overall goal of this research core is to develop and validate genetic markers for cancer susceptibility. By incorporating molecular genetics and cytogenetics into population studies, the investigators hope to gain insights into the complex interactions between genetic and environmental determinants of cancer. Of particular interest are the low penetrance genes that may modulate one's response to environmental exposures and contribute to the etiology of sporadic cancers. Specific aims include maintaining and expanding communication and scientific interaction among Core and other Center members, as well as non-Center members; strengthen current and promote future research activities in the area of genetic susceptibility to environmental disease; stimulate and facilitate intra- and inter-Core grant renewals and new investigators-initiated grant proposals; and serve in consultative and collaborative roles across research and facility cores to include concept development, study design, human tissue procurement and environmental data collection. Major areas of research

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focus in this Core encompass: 1) the assessment of phenotypic markers of DNA damage and repair as markers of susceptibility to carcinogenesis, 2) the evaluation of polymorphisms in select metabolic and DNA repair genes and DNA adducts in the etiology of lung, bladder, breast, and pancreatic cancers, and 3) the development of statistical models for cancer risk assessment by combining biomarkers and for genotypephenotype and surrogate-tissue marker correlation. Intra-Core 4 and inter-Core collaborative studies being conducted or completed include the following: 1) a casecontrol study of lung cancer examining cytogenetic and molecular determinants of tobacco carcinogenesis, 2) a study of genetic and environmental determinants, including phytoestrogen intake, of prostate cancer progression, 3) a genetic epidemiologic study of gliomas in relation to family history and genetic susceptibility markers, 4) a study of microsatellite instability and the risk of bilateral breast cancer, 5) a study of genetic polymorphisms, epidemiologic risk factors and differences in breast cancer survival among different ethnic groups, 6) a study of DNA adducts, P53 mutation spectrum, oxidative DNA damage and breast cancer risk among premenopausal women, 7) a study of molecular genetics of hereditary nonpolyposis colorectal cancer, 8) a study of modifier genes that influence age-associated risk of colorectal cancer, 9) two studies evaluating environmental and genetic determinants of advanced prostate cancer, 10) studies of second malignancies after treatment for hairy cell leukemia, acute myelocytic leukemia, 11) a study of cutaneous malignant melanoma and non-melanoma skin cancer, 12) a study of linkage and linkage disequilibrium, methods for traits, 13) a study of genetic susceptibility of bladder cancer, 14) a study of mutagen sensitivity and progression in Barrett's esophagus, 15) a study of the genetic, hormonal and behavioral determinants of obesity, 16) a pilot study of breast and colorectal cancers among Egyptians and organochlorine pesticides exposures, and 17) a pilot study to examine associations of mutagen sensitivity, oxidative damage and DNA adducts in lung cancer. The stated long term goal of this Core is to develop a validated risk model for cancer, such as lung cancer, to take into account simultaneously the effects of numerous genetic and environmental factors and the nature of subgroups (women, never-smokers, young subjects, ethnic minorities, etc). Future plans include the use of funds from the Tobacco Settlement for the State of Texas to establish an archival laboratory for the long-term storage and tracking of biological specimens and a centralized genotyping core. It also plans to expand in the area of nutritional epidemiology, and in its molecular epidemiologic studies to include brain and lymphoid malignancies. Future plans also include the development of a genotyping chip, in collaboration with Genometrix, expansion of the CRED website and implementation of multivariate statistical analysis to the large database that will be generated by incorporating chip technologies into studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--TISSUE Principal Investigator & Institution: Westra, William H.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: (Applicant's Description) Over the past decade, knowledge about the pathogenesis of human tumors has been attributed to and limited by the availability of well characterized human tissues. With this in mind, tissue facilities have emerged as a means of overseeing tissue distribution for investigative studies. To facilitate the availability of human tissues for the study of bladder cancer, the Tissue Core will collect tissue in a manner that meets the needs of the individual investigators yet does not

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compromise patient care. The Tissue Core will store these tissues in such a way as to ensure long term security and easy accessibility. The Tissue Core will process tissues so that they are suitable for further analysis. Finally, the Core will distribute tissues to investigators in a timely fashion. Through these activities, the Tissue Core will play a central role in the multidisciplinary approach to the study of bladder neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--TRANSLATIONAL PATHOLOGY Principal Investigator & Institution: Martin, Sue Ellen.; Associate Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-APR-1980; Project End 30-NOV-2005 Summary: The Translational Pathology Core Facility provides normal and tumor tissue specimens necessary for many of the laboratory-based, epidemiologic and clinical studies being conducted by Cancer Center investigators. Since the establishment of this facility four years ago, over 9,000 fresh, frozen, OCT or fixed tissue specimens have been provided to over 45 Cancer Center members located at the USC Health Sciences campus and Childrens Hospital Los Angeles (CHLA) to support their peer-reviewed, funded research. The facility is organized into three arms, each with distinct but related functions; one supplies fresh or frozen adult normal and tumor tissue specimens (supervised by Dr. Andy Sherrod, Department of Pathology), another provides pediatric normal and tumor tissue specimens (supervised by Dr. Timothy Triche, CHLA Department of Pathology), and the third provides population-based, fixed tissue specimens primarily for epidemiologic studies (supervised by Dr. Wendy Cozen, Department of Preventive Medicine). Although each arm operates somewhat independently due to the unique aspects of reach type of service, there is overall coordination under the direction of Dr. Sue Ellen Martin, Associate Professor of Pathology. The request process for tissue has a formal, multi-step protocol to ensure that all studies utilizing tissue are judged to be of sufficient scientific merit and have documented approval from the USC or CHLA Institutional Review Board (IRB). Patient identifying information is not released unless the investigator has IRB approval and a signed informed consent from the patient. Examples of past research supported by the Translational Pathology Core Facility includes studies examining the relationship between exogenous hormones and expression of breast cancer markers, DNA-repair mechanisms and hereditary non-polyposis colon cancer, the effectiveness of antiangiogenesis factors on tumor progression, tobacco smoke exposure and p53 expression in lung and bladder cancer, and the function of the BRCA1 protein. Current research supported by the Translational Pathology Core Facility includes identification of genetic markers that predict prostate cancer progression, characterization of the VEGF repertoire in a variety of tumors for targeting a novel and promising anti- angiogenesis factor, studies of genetic determinants of biologic behavior in neuroblastoma tumors, genetic predisposition to and therapeutic response to retinoblastoma; and gene translocation and microarray gene expression in pediatric sarcoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COX-2 & DNA METHYLTRANSFERASE EXPRESSION AND RISK FACTOR Principal Investigator & Institution: Ross, Ronald K.; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 13-SEP-2002; Project End 31-AUG-2007

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Summary: Revised Abstract: "COX-2 and DNA Methyltransferase Expression and Risk Factors for Bladder Cancer", is directed by Dr. Ronald K. Ross who seeks to identify key factors in human bladder carcinogenesis drawing on the results obtained in previous well-conducted epidemiologic trials. Dr. Ross will evaluate expression of two genes involved in two different pathways, namely COX-2 and DNMTs. Strengths of the project include the availability of a large existing epidemiologic database of confirmed bladder cancer patients with laboratory data on N-acetyltransferase (NAT) and glutathione-S-transferase (GST) genotypes, and access to tumor specimens for immunohistochemistry on the majority of these cases. The project investigators have extensive expertise in epidemiology and molecular and cellular biology. The strengths in combining molecular data with epidemiology are considerable, and there is a high likelihood of success in contributing significant knowledge to the field of bladder carcinogenesis. In the previous review numerous deficiencies were identified which reduced the overall scientific merit of this project. The deficiencies included lack of integration of the statistical analyses with Core B activities, lack of innovative statistical approaches to integrate biomarker results, lack of quality control in immunochemical staining, omission of two-sided power calculations for main effects and interactions, and extrapolation of results to development of a more comprehensive index of bladder cancer progression and risk. The applicants have revised their experimental approach and outline a plan for improved integration with Core B for the statistical analyses of data to be collected for this project. It was emphasized that Drs. Mimi Yu and Susan Groshen have a longstanding collegial relationship and will be meeting regularly for discussions regarding implementation of the research, quality control, and the analytic plan. Methods for exploring the co-expression of COX-2 and DNMTs are elaborated with stratification for smoking status, vitamin C intake, and other variables. A detailed description has been provided on validation of DNMT measurements and quality control issues regarding molecular analyses of the bladder cancer specimens. Dr. Debra Hawes has been added to the project to oversee quality control issues for immunohistochemical analysis in conjunction with Core C activities, which significantly improves the quality control of the project. Power calculations have been revised to include two-tailed tests of significance, and samples sizes appear sufficient to detect approximate 10 percent differences with sufficient statistical power. Sample size considerations are given in greater detail for not only the univariate comparisons, but also for examination of two-way and three-way interactions. There is also a plan to incorporate multivariate modeling of the data for tumor stage at detection to evaluation impact of the biomarkers on progression of bladder carcinogenesis. This project has been considerably improved since the last submission and received an average merit rating of 1.4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEATH RECEPTOR IN BLADDER CANCER PROGRESSION AND THERAPY Principal Investigator & Institution: Mcconkey, David J.; Associate Professor; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: Immunomodulators such as BCG and the interferons display a strong antitumoral activity in bladder cancer, but the mechanisms mediating tumor cell sensitivity or resistance to these therapies remain unclear. Members of a family of cell surface receptors homologous to the type I TNF family and Fas are commonly activated by immunomodulators and cancer chemotherapeutic agents in other solid tumors. Our

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preliminary data demonstrate that variants of a human bladder TCC cell line orthotypically selected for enhanced tumorigenicity are completely resistant to interferon- and death receptor-induced apoptosis, although they are equally sensitive to induction of apoptosis by a variety of pharmacological death stimuli. Our overall hypothesis is that receptors mediate the anti-tumor effects of the interferons in bladder cancer and that acquisition of death of receptors mediate the anti-tumoral effects of the interferons in bladder cancer and that acquisition of death of receptors mediate the antitumoral effects of the interferons in bladder cancer and that acquisition of death of orthotypically-selected cell variants, in our preclinical orthotopic nude mouse model of human bladder cancer, and in a Phase clinical trial that will provide use with primary tissue specimens before and immediately after IFN therapy. Our Specific Aims are, (1) to define the molecular mechanisms involved in cytokine resistance in vitro, (2) To define the role of death receptors in tumor progression and the response to IFN-based therapy in vivo, and (3) To determine the role of death receptors in the response to IFN-based combination chemotherapy in patients with locally invasive bladder cancer. Significant improvements to current therapeutic strategies are dependent on a better understanding of tumor cell biology. Our studies will allow us to test a widely6-held scientific hypothesis in a unique preclinical models and in bladder cancer patients. We expect that the information gained from these studies will not only allow for better stratification of patients to particular existing regiments but also to the design of novel, rational, death receptor-based future strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEOXYGUANOSIN 8 YL N ACETYLBENZIDINE FORMATION BY PEROXIDATIVE METABOLISM Principal Investigator & Institution: Lakshmi, v; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001 Summary: N'-(3'-Monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine (dGp-ABZ) is thought to play an important role in initiation of benzidine-induced bladder cancer in humans. This report assesses the possible formation of this adduct by peroxidatic activation of N-acetylbenzidine (ABZ). Adduct formation was measured by 32Ppostlabeling. Ram seminal vesicle microsomes were used as a source of prostaglandin H synthase (PHS). The peroxidatic activity of PHS was compared to that for horseradish peroxidase. Both peroxidases converted ABZ to dGp-ABZ whether DNA or 2'deoxyguanosine 3'-monophosphate (dGp) was present. Following 32P-postlabeling, the enzymatic and synthetic adduct were extracted from PEI-cellulose plates and shown to have the same HPLC elution profiles for the bisphosphate adduct (32P-dpGp-ABZ). Treatment of the enzymatic and synthetic bisphosphate adduct with nuclease P1 yielded a product which eluted at the same time from the HPLC (32P-dpG-ABZ). Additional experiment s demonstrated that the PHS-derived 5'-monophosphate (dpG-ABZ ) and 3'monophosphate (dGp-ABZ) adducts were also identical to their corresponding synthetic standard. With comparable amounts of total ABZ metabolism, PHS produced about 40fold more dGp-ABZ than horseradish peroxidase (1943 + 339 vs 49 + 7.8 fmol/mg dGp). Adduct formation was dependent upon the presence of peroxidase and the specific substrate, i.e., arachidonic acid or H2O2. Adduct formation by PHS was inhibited by indomethacin (0.1 mM), ascorbic acid (1 mM) and glutathione (10 mM), but not by DMPO (100 mM), a radical scavenger. Horseradish peroxidase adduct formation was also inhibited by ascorbic acid and glutathione. In addition, DMPO elicited greater than a 96% inhibition. Results demonstrate peroxidatic metabolism of ABZ to form dGp-ABZ.

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The mechanism of dGp-ABZ formation by PHS and horseradish peroxidase may be different. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT AND EVALUATION OF EXPOSURE BIOMARKERS PAHS, PHIP AND AROMATIC AMINES Principal Investigator & Institution: Tannenbaum, Steven R.; Professor/ Director; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 07-APR-1993; Project End 31-MAY-2007 Summary: (provided by applicant): The long-term objective of this Project is to develop molecular biomarker strategies that are based on DNA and protein adducts and reveal exposure to carcinogens and their biologically effective dose in people. The hypothesis driving the research in this Project is that levels of specific biomarkers define exposure and biologically effective dose in susceptible individuals. The strategies will employ laser-induced fluorescence (LIF) for high performance liquid chromatography (HPLC) detection, with and without derivatization labeling, and mass spectrometric technologies, including electrospray HPLC-tandem mass spectroscopy (HPLC-MS-MS). Accelerator mass spectrometry (AMS) will be an important new technology introduced into the Program Project to facilitate the early-stage tracer experiments necessary for adduct identification and structure elucidation. This Project is designed to develop the advanced exposure assessment methods needed to discern hazards for human populations where ambient exposure levels are low, but the toxicologic hazards of these exposures remain high. The classes of agents under investigation include PAHs, heterocyclic aromatic amines (HAAs) associated with cooked foods, and aromatic amines. Serum albumin adducts of benzo[a]pyrene, B[a]P, one of the hydrocarbons, will be determined in human population studies using advanced HPLC-LIF methods to assess its role in human cancer. The structure of albumin adducts of PhIP, a prominent cooked-food carcinogen, will be determined and the adducts will be validated as exposure biomarkers. HPLC-LIF and MS methods for PhIP and aromatic amine DNA adducts will be developed and validated. Biomarker investigations of specific alkylanilines associated epidemiologically with bladder cancer will be undertaken to confirm their biological role. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DISCOVERY OF GENOTOXIC BIOMARKERS IN URINE FOR CANCER Principal Investigator & Institution: Giese, Roger W.; Professor; Pharmaceutical Sciences; Northeastern University 360 Huntington Ave Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): This project seeks to develop a new methological procedure that has the potential for improving the quality of cancer epidemiological research. The new procedure involves the use of mass spectrometry (MS) to analyze DNA adducts inherent to or derived from urine. The "inherent DNA adducts" will be analyzed for two purposes: (1) as potential biomarkers for human exposure to carcinogens, and (2) as potential biomarkers for the presence and tissue location of cancer. This latter hypothesis is suggested by bringing together the following observations by others: (1) each tissue has a unique pattern of lipophilic, apparently endogenous DNA adducts (as detected by 32P-post-labeling/HPLC); (2) some tissue DNA is spilled into the blood (increasingly so in cancer), and (3) some of the free DNA

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in the blood ends up in the urine. The "derived DNA adducts" will be obtained by following a published method in which genotoxic chemicals are extracted from smoker's urine and reacted in the presence of an S9 metabolic activation system with calf thymus DNA. Previous investigators have considered the genotoxic chemicals in smoker's urine to be the same as the mutagens, which are present. Detection in this project of the three types of DNA adducts (inherentexogenous, inherent-endogenous and derived) will be accomplished by using a method that we have recently developed in which the adducts, after isolation, are labeled with an imidazole substituted mass tag followed by use of matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDITOFMS). Our new technique is very sensitive and measures the exact masses of a broad range of known and unknown DNA adducts simultaneously, unlike any prior analytical method for DNA adducts. Along with urine samples from control subjects and smokers, urine from patients with renal and bladder cancer will be tested. Urine is an attractive sample for epidemiological studies. The project initiates a collaboration between an analytical chemist and a molecular biologist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNA REPAIR AND BLADDER CANCER Principal Investigator & Institution: Andrew, Angeline S.; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Each year, 51,200 people in the United States are diagnosed with bladder cancer and 10,600 die of the disease. Exposure to environmental chemicals as well as genetic factors play a significant role in initiation of bladder cancer. Epidemiologic investigations have clearly shown an increased risk of bladder and other cancers associated with arsenic exposure, but the level at which it poses a measurable health risk has been the topic of considerable debate, and its precise mechanism of action remains unknown. Furthermore, a number of studies have reported an interaction between smoking, genetic polymorphisms and cancer risk. We will test the hypothesis that polymorphisms in the nucleotide excision repair pathway are associated with increased bladder cancer risk. We will address this hypothesis using exposure data and blood samples collected in a large population-based study of bladder cancer in the New Hampshire (850 cases, 1,365 controls). The specific aims of the project will be to 1) test the hypothesis that genetic variants in the nucleotide excision repair pathway genes (XPD, XPC, XPA, and ERCC1), are associated with increased risk of bladder cancer, and 2) determine whether environmental exposures (arsenic, smoking) and nucleotide excision repair polymorphisms interact to increase bladder cancer risk. This study presents a unique opportunity to clarify how genetic and environmental factors affect DNA repair and contribute to bladder cancer susceptibility. Through our study, we hope to contribute to both our mechanistic understanding of bladder cancer and to identify subgroups of the population that may be at greater risk of environmentallyinduced cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DOSIMETRY OF RISK FOR LUNG AND BLADDER CANCER AMONG CIGA Principal Investigator & Institution: Djordjevic, Mirjana V.; Institute for Cancer Prevention 1 Dana Rd Valhalla, Ny 10595 Timing: Fiscal Year 2001

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Summary: During the past four decades the cigarette consumption in the U.S.A. gradually changed from high-nicotine, high-"tar" to low-nicotine, low- "tar" brands. Concurrently, there was also a gradual shift observed in the major types of cancer and sites within the lung in cigarette smokers. These changes went from predominance of squamous cell carcinoma, located primarily in the bronchi, to adenocarcinoma in the peripheral lung. It is our working hypothesis that the reduction of the smoke yields of U.S. cigarettes and especially that of the addicting nicotine (sales weighted average changed from 2.7 mg in 1955 to 0.85 mg in 1993) resulted in deeper inhalation of the smoke and thus greater exposure of the peripheral lung to cigarette smoke carcinogens. Increased exposure is also to be considered since more intense smoking of low-nicotine cigarettes leads to higher yields of nicotine and certain carcinogens. Four groups of white and African-American male and female smokers of low- (1.2) nicotine cigarettes will be studied to assess the relationship between their smoking habits and their actual exposure to nicotine, "airborne", and "bloodborne" carcinogens. Currently, the exposure to nicotine and "tar" is assessed on the basis of FTC data. These are established with standard machine-smoking parameters which were developed in 1936. This method does not reflect the smoking habits of today's cigarette smokers. This project together with the risk estimates established in Project 1 for the major types of lung cancer among smokers of cigarettes with low-, medium-, and high-nicotine content, will result, for the first time, in meaningful estimates of exposure to nicotine and to nicotine-derived carcinogens for each of the three classes of cigarettes. The study will also clarify if the low-nicotine cigarette is indeed less "harmful" than the medium- and high-nicotine cigarette. This study has major public health implications. Lung cancer remains the leading cause of cancer death in the U.S.A, while the overall mortality rate from lung cancer continues to rise. Currently, cigarette smoking contributes to more than 90% of the lung cancer deaths in American men and to more than 75% in American women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DRUG METABOLIZING ENZYMES-RISK FACTORS IN BLADDER CANCER Principal Investigator & Institution: Branch, Robert A.; Professor/Director; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-JUL-1994; Project End 30-JUN-2005 Summary: This molecular epidemiology proposal is to continue applying knowledge of pharmacogenomic implications of gene expression of individual drug metabolizing enzymes to assess their role as risk markers for bladder cancer. We propose to use measures of whole body activity for drug metabolizing enzymes using the Pittsburgh cocktail that comprises CYP1A2 (caffeine), CYP2C19 (S-mephenytoin), CYP2D6 (debrisoquine), CYP2E1 (chlorzoxazone) and CYP3A4 (dapsone), as well as mRNA concentrations for each of these CYP enzymes in leukocytes and genotypic identification of known polymorphisms of CYP metabolizing enzymes to include CYP2D6 and CYP2E1. We will assess acetylation using a phenotypic trait measure (dapsone), supplemented by genotyping as well as GSTMI, and GSSTI using genotyping. Our initial work has provided evidence that high activity for CYPD6, low activity of CYP3A4, mutant alleles for acetylation and the null genotype for GSTMI are risk factors for bladder cancer, but to different extent for various forms of this cancer. We have also shown that high CYP2D6 activity is associated with mutations of the retinoblastoma (Rb) gene and low activity of CYP3A4 is independently associated with p53 mutations. Furthermore, different groups of risk factors relate to different mutational spectra of p53. We now propose to extend these observations. Our specific aim is to test the

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hypothesis that bladder cancer is comprised of a heterogeneous group of diseases in which different groups of associated risk factors relate to disease states that not only vary in etiology, but also in histopathological expression and natural history of the disease. This hypothesis will be evaluated in a case-control study of over 200 patients with incidence presentation of bladder cancer and over 200 controls matched for age, gender and ethnicity, in which environmental and constitutive variables will be related to the disease process. This study will involve a protocol that incorporates an exposure questionnaire, the Pittsburgh cocktail and blood sampling for mRNA quantitation and DNA genotyping. The disease process will be evaluated by clinical assessment and staging, identification of mutations of p53 and Rb genes, blinded histopathological review with grading and following the natural history for the disease. Collectively, these molecular epidemiology studies will improve our understanding of pathogenic mechanisms involved in different forms of bladder cancer and will expand our understanding of the regulation of the gene products that are responsible for drug metabolism in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY CANCER DETECTION AND SUSCEPTIBILITY BIOMAKERS Principal Investigator & Institution: Bigbee, William L.; Professor; Environ & Occupational Health; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: This proposal, in response to the RFA CA-98-028 Early Detection Research Network/Biomarkers Developmental Laboratories (EDRN/BDL), is an integrated multi-disciplinary project of the University of Pittsburgh Cancer Institute (UPCI) bringing together faculty with relevant expertise in key disease sites including bladder, colorectal, lung/aerodigestive tract, and ovarian cancer. For each site, a lead CoInvestigator and research group, with ongoing interactions among basic cancer researchers, biostatisticians, clinicians, surgeons, and pathologists, have proposed innovative approaches to the discovery of new early cancer detection/susceptibility biomarkers and refinement and initial validation of panels of recently described biomarkers. In addition, two research groups with molecular genetics expertise in the characterization of cancer gene mutations and metabolic enzyme/DNA repair gene polymorphisms will apply these endpoints in collaborative studies in several organ sites. These studies utilize the extensive UPCI clinical infrastructure and pathology resources necessary for the collection, histopathological characterization, and processing of tissue/biological fluid samples built, in part, upon UPCI's participation in the initial EDR Network. Specific biomarkers to be investigated in this project include a unique BLCA-4 protein immunoassay in urine for early detection of bladder cancer; LOH for 5q, mutation in K-ras and exon 15 of APC, and expression of iNOS and COX-2 as early detection markers of colorectal carcinoma; SAGE analysis of ovarian tumors for discovery of peripheral blood-based immunoassay markers; ras and p53 gene mutations in lung/airway biopsy samples and EGF and GRP receptor expression in buccal mucosa and peripheral blood as early detection biomarkers of HNSCC and NSCLC; and application of genotyping assays for CYP1A1, GSTM1, GSTT1, MPO, and NAT2 together with the development and validation of new assays for the recently-described polymorphisms in the DNA nucleotide excision repair (NER) genes XPD and XPF as risk susceptibility markers for bladder, colorectal, and/or lung/aerodigestive cancer. These research activities will be conducted in the context of an active integrated UPCI EDRN/BDL program, facilitated by the Principal Investigator who brings extensive

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experience and UPCI programmatic leadership in research and molecular epidemiological application of biomarkers, in an environment focused on a collaborative process of cancer biomarkers discovery, evaluation, and validation to support the broader research and clinical goals of the EDRN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY DETECTION OF URINARY BLADDER CANCER Principal Investigator & Institution: Czerniak, Bogdan A.; Pathology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The overall goal of this project is to develop markers for early detection of occult urinary bladder neoplasia and its imminent progression to invasive clinically aggressive urinary bladder cancer. The core preliminary data for this proposal is provided by our genome-wide model of urinary bladder cancer progression from occult in situ preneoplastic conditions to invasive cancer. The data was generated by a strategy of whole organ histologic and genetic mapping developed in our laboratory. Using this approach we matched the patterns of genetic and molecular alterations with the natural history of disease, i.e its progression from preneoplastic conditions to invasive cancer. Our model provides data on over 30 putative tumor supressor gene loci involved in the development and progression of urinary bladder cancer. From this data, the most promising putative tumors supressor gene loci were selected for the development of markers to detect early occult urinary bladder neoplasia and its aggressive variants. In addition we hypothesize that there is a molecular mechanism of bladder cancer progression based on the amplification and overexpression of novel oncogenic kinase STK 15/BTAK responsible for genomic stability. Overexpression of this enzyme appears to be responsible for genomic instability causing abnormal segregation of chromosomes. We plan to use allelic losses in several target suppressor gene loci of chromosomes 3, 9, 10, and 13 as well as amplification/over expression of STK15/BTAK as markers for early detection of urinary bladder neoplasia and its progression to invasive clinically aggressive bladder cancer. This project should provide two major products: (1) Public repository of shared data base on all tested markers and their performance as diagnostic probes, that can be used for the development of diagnostic markers and identification of target genes not only in the urinary cancer, but in other cancer types. This data will compliment our genome wide model of bladder cancer progression and will serve as a guide for targeting tumor suppressor genes involved in bladder cancer and other cancer types. In addition, information on minimal amplified regions involving 20q amplicon will provide valuable information for markers development and for identification of dominantly activated transforming genes involved in progression of bladder cancer and possibly other cancers. (2) Diagnostically relevant panel of approximately ten FISH and ten hypervariable DNA probes for early detection of occult preneoplastic changes in the urinary bladder and their aggressive variants progressing to invasive cancer for major clinical validation trial. If this project is funded, it is the intent of our commercial partner Urocor to submit a supplemental SBIR application (letter of support from Dr. Robert W. Veltri, Vice President and General Manager of the UroSciences Group, is attached). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EASTERN COOPERATIVE ONCOLOGY GROUP Principal Investigator & Institution: Loehrer, Patrick J.; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167

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Timing: Fiscal Year 2001; Project Start 01-MAY-1989; Project End 30-APR-2004 Summary: Indiana University (IUMC) has made major administrative and scientific contributions to ECOG. During the past grant period, the principal investigator was changed from Dr. Lawrence Einhorn to Dr. Patrick Loehrer. Dr. Loehrer was elected to serve on the Executive Committee, Nominating Committee, and the Research Foundation Board of Directors for ECOG. In addition, Dr. Loehrer served as Chairman of the Genitourinary Committee. Several other IUMC investigators have served as subcommittee chairs of co-chairs including Dr. George Sledge (Breast Cancer Committee: Co-chair), Dr. Michael Gordon (Leukemia Committee: Co-chair), Dr. Worta McCaskill-Stevens (Underserved Populations Committee: Chair, Health Practices and Outcome Committee: Co-chair), Drs. Craig Nichols and Richard Foster (Testicular Cancer Subcommittee: Co-chairs), Dr. Bruce Roth (Prostate Cancer Subcommittee: Cochair), and Drs. Scott Saxman and Anne Greist (Toxicity Monitoring Committee). Susan Fox has served as the GU Nursing co-chair from 1995-1997 and was nice chair and chair of the Nursing Committee for 1997. Major contributions of IUMC have been that of scientific leadership of innovative trials. Several ECOG trials designed by IUMC investigators have been presented at the American Society of Clinical Oncology meetings including the Plenary session. In addition, several pilot studies conducted by IUMC and selected ECOG institutions have led to groupwide trials. Selective examples include defining the comparable activity of VIP and BEP in Poor Risk Testicular Cancer (EE3887), evaluations of a five drug regimen in Advanced Testis Cancer (E1893), and Trials in Refractory Germ Cell Tumors (ES5888, PB887, PB889). In bladder cancer, we have looked at escalated dosages of M-VAC, vinblastine, ifosfamide, gallium nitrate (E5892) and proved that Taxol has major activity in previously untreated bladder cancer (E1892). Dr. George Sledge piloted a trial with paclitaxel and Adriamycin which later led to a multi-institutional prospective randomized trial which was presented in 1997 at the Plenary Session at ASCO (E1183), Dr. Loehrer has also chaired three prospective trials in thymoma which have been completed within ECOG (E4587, E4589, and E1C93). Dr. Gordon is study chair or co-chair of two trials in leukemia including a phase III trial in elderly patients (E7996) and a phase II study in relapsed or refractory AML (E5995). With the scientific and administrative leadership of IUMC within ECOG firmly established, the focus of our institution within the next grant period will be to enhance patient accrual. This will be accomplished by broadening our affiliate network and expanding our efforts in the multi-disciplinary program. The recent affiliation of Rush Presbyterian St. Luke's Medical Center (and its active affiliates) will have a major impact upon accrual from the IUMC network. In addition, several investigators from the affiliate network including Rush and the Indiana Regional Cancer Center already have administrative and scientific leadership positions within ECOG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF ARSENIC Principal Investigator & Institution: Karagas, Margaret R.; Professor; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001 Summary: Overall objectives of the proposed study are to quantify carcinogenesis risks due to arsenic exposure at levels commonly found in the US. This research project shares the goals of the program of the program project of furthering our understanding of the environmental and health effects of arsenic has been identified as a potent skin carcinogen in highly exposed in rural regions of the northeastern US. Arsenic has been identified as a potent skin carcinogen in highly exposed human populations, but it is

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uncertain whether these effects occur at low levels. We propose to extend our epidemiological case-control study of bladder and skin of bladder and skin cancers in a US population: (1) to further resolve the dose-response relationship between low to moderate levels of arsenic exposure and risk of bladder cancer, (2) to test the hypothesis that arsenic is related specifically to intraepidermal carcinomas (including Bowen's disease) and multiple concomitant basal cell carcinomas (BCC) of the skin, and (3) to identify subgroups of individuals who may be at high risk of arsenic-associated cancers due to co-carcinogen exposure (e.g., low selenium). We will expand our investigations of individual biomarkers of arsenic exposure by testing the reliability of existing measures (drinking water, urine, and toenails) and exploring new molecular-genetic markers (i.e., based on cDNA arrays). New Hampshire is ideally suited to study the effects of low-dose arsenic exposure since it is one of the few regions of the country with a population-based surveillance system for non- melanoma skin cancer and over 20% of the private wells in the region contain levels of arsenic suspected of being carcinogenic. New Hampshire has unusually high bladder cancer mortality rates which are as yet unexplained, and there is accumulating evidence that these malignancies may result from arsenic ingestion. Thus, our study provides a unique opportunity to obtain results directly applicable to the US population and to help identify those at greater risk for arsenic-induced malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDERMAL GROWTH FACTOR RECEPTOR IN BLADDER CANCER Principal Investigator & Institution: Bar-Eli, Menashe; Professor; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: Epidermal growth factor receptor (EGF-R) regulates the growth of human transitional cell carcinoma (TCC) of the bladder in part, by regulating the expression of the matrix metalloproteinase MMP-9. We observed that therapy of human TCC growing within the bladders of athymic nude mice with the EGF-R inhibitor C225 downregulated the expression of MMP-9 and inhibited tumor growth and metastasis. The goal of this proposal is to delineate the cellular and molecular mechanisms by which EGF-R directed therapy inhibits MMP-9 expression. Four Specific aims will be pursued. Four specific aims will be pursued. First, we propose to establish that the downregulation of MMP-9 by EGF-R blockade is common the interruption of signaling and not selective to the type of therapy. We will use alternative strategies of EGF-R selective tyrosine kinase inhibitors and the enforced expression of dominant negative mutant EGF-Rs (mitogenically-active or -inactive). Second, we will analyze rates of transcription, promoter activity, and the cis-trans elements regulating transcription to determine the mechanism for the down-regulation of MMP-9 gene expression following EGF-R blockade therapies. Third, to determine a causal effect of EGF-R signaling on MMP9 production and TCC angiogenesis, we will test the in vitro and in vivo effect of EGF-R blockade on TCC cells engineered to constitutively express MMP-9 as well as strategies designed to specifically block the expression/function of these factors. Finally, we propose to evaluate whether the therapeutic efficacy of cytoreductive chemotherapy is enhanced in combination with EGF-R blockade therapy and whether this therapy will down-regulate MMP-9 expression. We hypothesize that MMP-9 is a relevant target for novel therapy since it is over-expressed by human TCC which resists conventional therapy. The knowledge gained from this research will extend our understanding of the cellular and molecular mechanisms by which EGF-R directed therapy inhibits tumor growth and lead to novel therapies for the advanced TCC by combining conventional

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cytoreductive chemotherapy with EGF-R inhibitors that will ultimately by translated into clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL ANALYSIS OF RAD24-CLASS CHECKPOINT PROTEINS. Principal Investigator & Institution: Walther, Andre P.; None; Brandeis University 415 South Street Waltham, Ma 024549110 Timing: Fiscal Year 2001; Project Start 01-JUL-2000 Summary: Eukaryotic cells have developed a series of cellular "checkpoints" that sense the presence of damaged DNA and cause a delay in cell cycle progression to ensure that genetic information is faithfully transferred to progeny cells. Failure of checkpoint genes to halt cell cycle progression can lead to improper chromosomal segregation, segregation of damaged chromosomes, and replication of damaged chromosomes. Several human checkpoint genes map to chromosomal regions implicated m the etiology of a variety of cancers including small cell lung carcinoma, duodenal adenocarcinoma, head and neck squamous cell carcinoma, bladder cancer, and colon cancer. An understanding of checkpoint function will shed light on the mechanism of tumor formation and cancer predisposition and may provide insights into new therapeutic targets for cancer treatment. The high level of conservation between human and yeast checkpoint genes makes the budding yeast, Saccharomyces cerevisiae, an ideal organism for studying checkpoints. In budding yeast, RAD17, RAD24, MEC3, and DDC1 are required for detecting damaged DNA and activating the checkpoint response. It is currently not known how this is accomplished. The proposed studies will determine how these sensor genes recognize damaged DNA and generate the checkpoint signal with biochemical and genetic studies that define protein-DNA interactions and proteinprotein interactions among sensor proteins. Identifying direct interactions among the sensor proteins and determining whether these interactions are important for recognizing specific DNA structures or modulating the structure of damaged DNA will be crucial to understand how sensor genes function in establishing the checkpoint. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE-ENVIRONMENT INTERACTIONS: THE ODYSSEY COHORT Principal Investigator & Institution: Helzlsouer, Kathy J.; Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: Polymorphisms of many genes controlling metabolism of xenobiotic compounds and DNA repair processes are associated with susceptibility to cancer as well as other chronic diseases. We need studies that are more holistic in design and provide insights into the net effect on health of having specific genotypes. We propose a population-based cohort study to examine the broad impact of genetic variation in candidate genes and their interaction with environmental exposures on cancer incidence and survival specifically, and health and aging more generally. Participants (N=8395) of two blood and data specimen banks (CLUE I (1974) and CLUE II (1989)) comprise the study cohort (Odyssey Cohort). The cohort has been followed prospectively for 24 years and information on environmental factors such as smoking, education and housing are available as far back as 1963. DNA will be extracted from buffy coat specimens obtained from participants in 1989 and stored at - 70 C. We will investigate polymorphisms in genes coding for enzymes that:1) metabolize nutrients and hormones (MTHFR, VDR,

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CYP17, CYP1B1, COMT, CYP3A4 ); 2) metabolize carcinogens (ADH, GSTM1, GSTT1, GSTP1, NAT1 and NAT2, NOS, CYP1A1, CYP1B1, EH); and 3) control DNA repair processes (XRCC1, XRCC3, XPD). In this cohort, power is greater than 90 percent to detect a relative risk of 2 for main effects of genotypes on mortality and cancer incidence and at least 80 percent to detect gene-environment and gene-gene interactions of twofold for the major cancer sites (such as breast, prostate and colorectal) and 3- to 5-fold for less common cancers such as endometrial and bladder cancer. As additional polymorphisms in candidate genes with potential relevance to the major health outcomes are identified we will be able to investigate their impact on health and survival, providing a valuable resource. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC MARKERS OF BLADDER CANCER PROGRESSION Principal Investigator & Institution: Waldman, Frederic M.; Professor; Cancer Center; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 05-JUL-2001; Project End 31-JAN-2006 Summary: The goal is to identify and validate tumor markers, which predict the outcome of patients with bladder cancer. Analyses of tumor material will be done to define genetic and expression alterations in each tumor, to associate these alterations with the tumor stage, with other clinical characteristics of the tumor, and with the patient's clinical course. High throughput analyses using genomic slide-based arrays comprised of human BAC genomic probes at 1 mb density, and gene expression arrays comprised of more than 7,000 human cDNA clones, will be applied to human bladder tumor samples. Tumor will be grouped by stage in order to identify correlated sets of genes for each group. These gene sets will then be used for testing of prognostic utility in separate sets of patient samples. The Specific Aims are: Aim 1. Genetic Alterations During Bladder Cancer Progression. We will test the hypothesis that pathways of tumor progression are genetically defined. DNA copy number and RNA expression alterations will be identified in groups of tumor according to stage of bladder tumor progression. A. Low Grade Superficial Disease (150 pTa tumors). B. High Grade Superficial Disease (100pT1 tumors and 50 pTis). C. Muscle Invasive Disease (150) tumors will be used to identify patterns of genetic alterations and expression changes according to stage. D. Stromal changes in superficial and invasive cancer: Tumor fibroblasts prepared by collaborators (Drs. Hayward) will be used to define altered gene expression patterns in the tumor stroma (compared to fibroblasts away from the tumor). Candidates genes identified in these studies will then be tested for association with tumor stage. Aim 2. Genetic Alterations as Predictors of Clinical Outcome. Candidate gene alterations identified in Aim 1 will be tested for association with clinical outcome. A. High risk superficial tumor. We will test the utility of candidate gene markers will be tested in separate patient groups for association with outcome after treatment with intravesicle BCG and Gemcitibine. A. High risk muscle invasive tumors. Molecular markers will be tested in patients with node positive tumors who receive no further treatment, and in separate patient groups, as markers of response to MVAC therapy, and as markers of response to taxanes. C. Validation of Candidate Markers with Tissue Arrays. We will use tissue arrays to validate markers which are identified in Aim 1 and tested in Aims 2A-B. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIGH THROUGHPUT GENETIC ANALYSIS OF BLADDER CANCER Principal Investigator & Institution: Sidransky, David; Associate Professor; Otolaryn & Head & Neck Surgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 05-JAN-1999; Project End 30-NOV-2003 Summary: A program project is proposed by researchers at the John Hopkins Medical Institutions and the University of California at Berkeley entitled "High Throughput Genetic analysis of Primary Bladder Cancer and Urine Sediment"> The goals of this proposal are to improve our understanding of the molecular genetic changes that drive bladder cancer progression as we develop and integrate novel high throughput approaches for the detection of these genetic alterations. These approaches will be used to translated our findings into the clinical setting where we will evaluate genetic alterations as predictors of disease outcome and targets for molecular detection. We intend to accomplish these goals by addressing the following specific aims in project #1; 1) to identify and characterize key genetic alterations in primary bladder cancer 2) to place these genetic changes in a molecular progression model 3) to identify microsatellite loci susceptible to instability and 4) to integrate the aforementioned genetic targets into molecular detection strategies. In project #2, we will develop high throughput platforms by 1) building a monster-capillary array electrophoresis (MCAE) scanner at Berkeley 2) transferring this technology to Hopkins initially at 256 lane capacity and then to 3) 1024 lane capacity 4) Synthesis and evaluation of Energy transfer (ET) primers and 5) building and transferring CAE on glass (chip) substrates. In project #3, we will use established genetic changes form projects #1 and 2 to 1) test these alterations as predictors of prognosis and disease outcome 2) validate early detection strategies based on microsattelite analysis in urine and 3) test new molecular approaches in serum as markers of disease burden. Unlike traditional methods of isolated investigators, this program emphasizes sharing of subjects, tissue samples, resources, technical expertise and data analysis strategies. Our program will not only offer clinical direction for basic research efforts, but will also facilitate the direct translation of stateof-the-art high throughput technology into the basic laboratory and clinical area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE MEDIATED BLADDER INFLAMMATION Principal Investigator & Institution: Ratliff, Timothy L.; Andersen-Hebbeln Professor; Urology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-MAR-1999; Project End 31-JAN-2003 Summary: (Adapted from the Applicant's Abstract): The bladder, as a mucosal immune organ often exposed to foreign antigens, is linked to the expression of immunity. Examples of bladder-associated immune responsiveness include bacterial infection, response to therapeutic antigens such as BCG (used in treatment of interstitial cystitis and bladder cancer), and although controversial, some have suggested a role for immunity in interstitial cystitis. Considerable data has been published on the histopathology of bladder inflammation. Reports have shown the predominant infiltrating T cell to be CD4+ helper T cells and also have demonstrated the presence of HLA DR expression on transitional epithelial cells. While the expression of immunity in the bladder has important disease-related consequences, the mechanisms by which intravesical antigens initiate immunity and the role of MHC Class II expressing epithelial cells in the expression of immunity have not been established. The objective of the studies outlined herein is to characterize the initiation, expression and regulation of antigen specific CD4+ T cell immunity in the bladder. The working hypothesis is that

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the activation and expression of CD4+ T cell immunity in the bladder is regulated by bladder-associated cytokines and the antigen presenting function of bladder epithelial cells. The hypothesis will be tested through the in vitro characterization of the immunomodulatory potential of bladder epithelial cells and in vivo using the ovalbumin (OVA)-specific CD4+ DO11.10 T cell receptor transgenic mouse model. The studies outlined with DO11.10 T cells, which can be identified with a unique clonotypic antibody, will provide a basis for the critical evaluation of the hypothesis in an in vivo model. Preliminary data show that bladder epithelial cells function as antigen presenting cells for CD4+ T cells, appear to provide sub-optional activation of CD4+ helper T cell responses, and function as target cells for CD4+ T cell-mediated killing through Fas-induced apoptosis. These observations form the basis for experiments aimed at characterizing T cell-induced bladder inflammation, defining regulatory mechanisms of the inflammatory response, and developing approaches for modifying the inflammatory response through re-directing and/or abrogating CD4+ T cell responses. To accomplish these objectives, the following specific aims will be pursued: (1) characterize the effects of antigen presentation by bladder epithelial cells on CD4+ T cell responses in vitro, (2) characterize the effects of bladder epithelial cell antigen presentation on CD4+ T cell activation in vivo using the ovalbumen-specific CD4+ DO11.10 T cell receptor transgenic model, and (3) determine the effects of CD4+ T celldirected chronic bladder inflammation on bladder function and evaluate strategies for modifying the response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT OF ARSENIC ON MORTALITY IN CHILE FROM 1950-2000 Principal Investigator & Institution: Smith, Allan H.; Professor; Environmental Health Sciences; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2003 Summary: (Adapted from applicant's abstract): The purpose of the proposed study is to investigate mortality in Region 11 of Chile from 1950 to 2000. This' region, currently with a population of close to a half million people, experienced a peak exposure to arsenic with a population-weighted average drinking water concentration of 580 micrograms/L, from 1955 to 1970. In contrast, water supplies for the rest of the country mostly contained less than 10 4g/L. Following the installation of arsenic treatment plants, concentrations have gradually been reduced, so that by 1990 the average was less than 50 @ig/l-, the current drinking water standard in much of the world. An investigation of mortality in Region 11 during 1989-1993 indicated that rates for bladder, skin, lung, and kidney cancer were increased compared to the rest of Chile. Bladder cancer mortality was markedly elevated [men, SMR = 6.0, 95 percent confidence interval (CI), 4.8-7.4; women, SMR = 8.2, 95 percent CI, 6.3-10.5] as was lung cancer mortality [men, SMR = 3.8, 95 percent CI, 3.5-4.1; women, SMR = 3.1, 95 percent CI, 2.7-3.7]. It was estimated that arsenic might account for 7 percent of all deaths among those aged 30 years and over. If so, the impact of arsenic on the population mortality in Region 11 of Chile would be greater than that reported anywhere to date from environmental exposure to a carcinogen in a major population. Moreover, the impact may have been even greater in previous years, particularly from arsenic-caused diseases with shorter latencies than cancer. The proposed study will therefore collect and analyze 0 available measurements of arsenic in water, and investigate all causes of mortality from 1950 to 2000, in Region 11. As well as cancer, increased mortality might be expected from noncancer outcomes including cardiovascular, peripheral vascular and cerebrovascular diseases. The impact of arsenic exposure during childhood on pulmonary disease

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mortality in young adults, and on childhood cancer mortality, will also be assessed. This study will provide a unique opportunity to investigate arsenic-caused mortality, including latency patterns, in one of the world's most significant environmental toxic exposures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN-LIKE GROWTH FACTOR-1 STIMULATES CANCER INVASION Principal Investigator & Institution: Dunn, Sandra E.; Anatomy/Physiological Scis Rad; North Carolina State University Raleigh 2230 Stinson Drive Raleigh, Nc 27695 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 09-OCT-2001 Summary: (Adapted from the Candidate's Abstract) The candidate's long-term objectives are to conduct breast cancer research at a medical school. Her primary interest is in the prevention and intervention of metastatic breast cancer. Conducting the research described below will help to identify environmental risk factors that can be modified to prevent the spread of breast cancer in women. Elevated levels of serum insulin-like growth factor-1 (IGF-1) is a risk factor for the development of advanced breast and prostate cancers. Why IGF-1 is elevated is not yet clear, but IGF-1 is known to be an endocrine factor that is regulated both by diet and estrogens. The candidate's laboratory has shown that reducing serum IGF-I through dietary restriction protects against the development of bladder cancer. Antiestrogenic drugs are also known to lower serum IGF-1 in women, therefore, these drugs are being investigated for their potential to prevent breast cancer. The candidate believes that lowering IGF- 1 may also prevent the spread of breast cancer. Their most recent work shows that IGF-1 signaling is necessary for breast cancer invasion and metastasis in an experimental model. To continue their work in this area they will focus on the signal transduction pathway downstream of IGF-1. They will test hypothesis the that IGF-1 stimulates the invasion of breast cancer cells through the phosphotidyl inositol 3-kinase (PI3K) pathway. Initially, the candidate will follow up on preliminary data showing that the inhibiton of P13K blocks IGF-1 stimulated invasion. Next, she will investigate how IGF-1 enhances the metastatic potential of breast cancer cells by determining if IGF-1 increases the expression of extracellular matrix degrading proteins. Finally, Dr. Dunn will inhibit the IGF-1/Pl3K pathway and determine what genes are differentially expressed using microarray. These studies will provide important information on the regulation of breast cancer metastasis by IGF-1 signaling, which may ultimately lead to risk-reduction strategies either through changes in the diet or by antiestrogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERFERON & DEATH RECEPTOR INDUCED APOPTOSIS IN BLADDER Principal Investigator & Institution: Lashinger, Laura M.; Cancer Biology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2002 Summary: (provided by applicant): Long range goals represented by this proposal include obtaining mechanistic knowledge of interferon-based therapies in the context of bladder transitional cell carcinoma treatment ongoing at M.D. Anderson Cancer Center. Bladder cancer is the sixth leading cause of cancer in the United States, excluding skin, and continues to provide a challenge regarding treatment due to its high recurrence rate. The hypothesis is that interferons exhibit antitumoral effects via death receptor

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mechanisms. Based on this, the specific aims for this proposal are as follows: (1) define defects in the interferon signaling pathway contributing to interferon resistance, (2) characterize molecular defects in death receptor pathways contributing to death receptor resistance, and (3) determine death receptor involvement in tumor progression and responses to interferon-based therapy in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERFERON ALPHA PLUS BCG VS BCG FOR TREATMENT OF AGGRESSIVE BLADDER CANCER Principal Investigator & Institution: O'donnell, Michael; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISOTHIOCYANATES IN THE CHEMOPREVENTION OF BLADDER CANCER Principal Investigator & Institution: Zhang, Yuesheng; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This Project focuses on determining the cancerpreventive activity of isothiocyanates (ITCs) in the bladder. The hypothesis to be tested is that selected ITCs can suppress bladder carcinogenesis by disrupting multiple steps in the carcinogenic process: induction of Phase 2 enzymes, induction of apoptosis, and inhibition of cell proliferation. Molecular markers relevant to these biological events, as well as inhibition of tumorigenesis, will be studied. Bladder cancer is an important health problem; effective chemopreventive agents are needed. ITCs are abundant in vegetables and many are known anticarcinogens in non-bladder animal organs. Ingested ITCs are efficiently absorbed and almost exclusively excreted in urine as Nacetylcysteine conjugates (NAC-ITCs), which also are anticarcinogens and can release ITCs, making the bladder epithelium the most exposed tissue to ITCs/NAC-ITCs. The overwhelming majority of bladder cancers originate from the epithelial cells. Four dietary ITCs that displayed potent anti-carcinogenic activity in non-bladder animal organs and their NAC conjugates will be evaluated. Aim 1 is designed to see whether ITCs or NAC-ITCs effectively induce critical Phase 2 detoxification enzymes, including glutathione transferase, quinone reductase-1, and UDPglucuronosyltransferase, whose deficiencies have been linked to increased bladder carcinogenesis. Aim 2 will determine the protective efficacy of ITCs or NAC-ITCs against carcinogen-induced DNA damage in bladder epithelial cells, using total DNA adducts and unscheduled DNA synthesis (UDS) as markers. Imbalance between apoptosis and proliferation also is a risk factor of bladder cancer. Aim 3 will determine whether ITCs or NAC-ITCs can correct the imbalance between apoptosis and proliferation associated with bladder carcinogenesis: Do ITCs or NAC-ITCs induce apoptosis and/or inhibit cell cycle progression in bladder cancer cells? If so, what is the underlying mechanism(s)? Aim 4 will evaluate in rivo the effect of orally administered ITCs on important biomarkers, including the Phase 2 enzymes described in Aim 1, apoptosis (TUNEL), and proliferation (PCNA) in the bladder epithelium of F344 rats. Aim 5 will determine the efficacy of an orally administered ITC in inhibiting N-butyl-N- (4-hydroxybutyl)-nitrosamine-induced bladder tumorigenesis in F344 rats.

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

Project Title: M. D. ANDERSON CANCER SPORE IN GENITOURINARY CANCERS Principal Investigator & Institution: Dinney, Colin P.; Professor; Surgical Oncology & Cell Biol; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: The overall goal of this University of Texas MD Anderson Cancer Center SPORE is to facilitate innovative translational research in the prevention, detection, and treatment of bladder cancer leading to the elimination of this disease as a major health problem. Our Cancer Center contains a unique concentration of talented investigators who are dedicated to clinical, translational, and fundamental bladder cancer research. Our institution has given high priority to the Bladder Cancer Multi- disciplinary Program. The Program has recruited faculty within the institution, strengthened the research infrastructure, and funded several pilot studies. We are now poised to take advantage of the framework developed by this multi-disciplinary group to enable a rapid increase in the understanding of bladder cancer at the molecular and cellular level. Funding of this SPORE will greatly enhance our ability to translate insights from bladder cancer biology to more effective prevention, detection, and treatment of bladder cancer. The SPORE includes 5 projects that deal with 1) early detection and chemoprevention of bladder cancer, 2) epidemiology of bladder cancer 3) death receptors in bladder cancer progression and therapy, 4) biology and therapeutic targeting of the epidermal growth factor receptor in bladder cancer, and 5) improving gene therapy for superficial bladder cancer. This SPORE addresses clinical dilemmas develop effective strategies for chemoprevention, detection, molecular profiling and therapeutics, bioimmunotherapy, chemotherapy, supportive care, and community awareness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MARKERS OF SUSCEPTIBILITY AS PREDICTOR OF BLADDER CANCER Principal Investigator & Institution: Wu, Xifeng; Associate Professor; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: Recurrence is the hallmark of bladder cancer. There is limited information on factors that can affect tumor recurrence. Building upon the epidemiologic and molecular genetic findings from our funded research on bladder cancer (NCI RO1 CA74880). In this translational research, we propose to evaluate epidemiologic profiles and a panel of susceptibility markers on the influence of bladder cancer recurrence in 480 prospectively identified patients with superficial bladder cancer. Fifty percent of these patients are expected to develop recurrence over 4 years of follow up. We will focus on assessing detailed tobacco smoking exposure over time and a panel of genotypic susceptibility markers related to tobacco carcinogen metabolism, DNA repair, disease progression, and nicotine addiction. We hypothesize that patients with recurrence exhibit higher exposure profiles, and may be more likely to exhibit susceptible genotypes than patients who do not develop a recurrence. The following are the specific aims: 1) To compile comprehensive epidemiologic profiles on all patients at registration and on follow-up with specific emphasis on the continued smoking status of patients from the time of diagnosis of their initial primary to development of recurrence. This

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aim will test the hypothesis that continuing exposure to tobacco and specific dietary patterns such as high fat intake and low vegetable and fruit intake may be associated with increased for recurrences. 2). To determine the frequencies of polymorphisms in genes that are related to DNA damage and/or repair, such as myeloperoxidase (MPO), N-acetyltransferase (NAT)1, NAT2, glutathione-S-transferase (GST) M1, GSTT1, GSTP1, XRCC1, XPD, XRCC3, and p53. Our hypothesis is that patients with adverse genotypes are at greater risk for the development of recurrences, because of higher internal dose of tobacco carcinogens through increased activation or decreased detoxification and/or because of sup-optimal DNA repair capacity. 3) To determine the frequencies of polymorphisms in the cancer invasion/progression related genes E-cadherin, cyclin D1 (CCND1), metalloproteinase-1 (MMP-1 and MMP-9), and vascular endothelial growth factor (VEGF). Our hypothesis is that patients with adverse genotypes of these genes are at greater risk for bladder cancer recurrence. 4) To determine the relationship between baseline and follow-up smoking status and potential genetic markers for nicotinedependence (genetic polymorphisms in dopamine receptor genes, DRD2A1 and -B1 and dopamine transporter gene SLC6A3-9) and to correlate these findings with known predictors of smoking cessation and nicotine dependence, such as history of depression and alcohol use. This aim is relevant to recurrence of bladder cancer since nicotine addiction provides the link through which smokers are repeatedly exposed to carcinogenic elements associated with tobacco consumption. There is an important implication to this project in identification of high risk subgroups of bladder cancer patients who can be more intensively screened and treated for recurrence prevention. This project will have interactions with SPORE Administrative, Pathology and Biostatistics Cores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MCAV IN ORGAN-CONFINED BLADDER CA BASED ON P53 STATUS Principal Investigator & Institution: Cote, Richard J.; Associate Professor of Urology and Patho; Pathology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-MAY-1997; Project End 31-MAR-2007 Summary: (provided by applicant): This is a renewal application to our on-going "p53/MVAC" study. Tumor progression in transitional cell carcinoma (TCC) of the urinary bladder is believed to occur through a multistep accumulation of genetic alterations. p53 alterations are involved in the transformation of normal urothelium to carcinoma-in-situ of the bladder and in the progression to invasive disease. We have shown that (1) adjuvant chemotherapy prolongs the recurrence free interval in a group of patients with invasive TCC at high risk for recurrence and that (2) detection of p53 alterations in a bladder tumor is significantly associated with an increased chance of progression in patients with organ-confined TCC managed by radical cystectomy. Our hypothesis is that p53 alterations organ-confined TCC of the bladder significantly increase the risk of recurrence and death, and that adjuvant chemotherapy will improve survival in these high risk patients. To test this we have designed a study that will enroll patients who have already undergone a radical cystectomy with a pathologic stage of P1, P2a/b N0 M0. Patients with TCC demonstrating p53 alterations (p53+) who are willing to be randomized will be assigned either to no further treatment, i.e. observation which is the standard of care for patients with organ-confined disease, or to 3 cycles of MVAC chemotherapy. Those who are p53+ and decline randomization, and those who are p53- (no alteration in p53), will be observed. The specific aims of this prospective

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study are to (I) compare the recurrence free interval and overall survival of p53+ patients who are treated with MVAC to p53+ patients who are observed, (II) compare the recurrence free and overall survival of p53+ patients who are observed to p53patients who are also observed, (III) study the expression of other genes involved in cell cycle regulation that may be involved in the response to chemotherapy, (IV) examine the association of p53 mutational gene status with p53 protein expression, outcome, and response to chemotherapy. This is a new aim to this renewal application. To date over 30 academic institutions in the United States, Canada and Europe participate in this prospective study. The study was activated at the Southwest Oncology Group (SWOG) in 2001 and we are making a substantial effort to attract other Canadian and European institutions to this study. As of May 2002, 281 patients have been registered to the study and 58 p53+ patients have been randomized to MVAC or observation, making this one of the largest adjuvant trials in bladder cancer. The infrastructure to support this study is firmly established including 1) Full compatibility of data management with SWOG. (2) Completion of the interim audit by July 2002. (3) Fourth Annual meeting of the Data Safety Monitoring Committee planned for August 2002. (4) Institution of the patient advocacy program, the first for bladder cancer. (5) The 5th annual investigator's meeting took place May 2002. With the participation of new institutions and with patient accrual and randomization increasing, we expect to complete accrual by 2006 (approximately 33-35 patients randomized per year). This is the first study in bladder cancer in which therapeutic decisions are made based on the status of a molecular alteration. The results of this studio could fundamentally change the management of bladder cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISIMS OF BLADDER CANCER PROGRESSION Principal Investigator & Institution: Lokeshwar, Vinata B.; Urology; University of Miami Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-MAY-2003 Summary: (adapted from the investigator's abstract) Two critical factors that affect the prognosis of bladder cancer patients are high-grade invasive tumors and the high rate of tumor recurrence. Hyaluronidase is an enzyme that degrades hyaluronic acid (HA), a glycosaminoglycan, into small angiogenic fragments. Two hyaluronidases have been identified as potential "molecular markers" of high-grade bladder tumors (BT). The long-term objectives of this proposal are to elucidate functions of these hyaluronidases in BT progression and to develop a simple, non-invasive and accurate test for early detection and post-therapy surveillance of bladder cancer. To test the hypothesis that BT-derived hyaluronidases are structurally distinct from other known hyaluronidases and are expressed in a tumor, tissue, or cell specific manner, BT-derived hyaluronidases will be isolated, purified, cDNA cloned and sequenced (Aim 1). These enzymes will be characterized for substrate specificity and sensitivity to inhibitors and their expression will be examined at protein and mRNA levels in normal tissues, tumor tissues, and tumor cells (Aim 2). To test whether elevated BT-derived hyaluronidase levels confer metastatic phenotype to otherwise indolent BT cells, low-grade BT cells will be transfected with cDNAs of these enzymes and following orthotopic implantation in nude mice metastasis will be examined. In addition, the role of angiogenic HA fragments on functions of BT cells and BT-derived endothelial cells which regulate BT progression will be examined (Aim 3). Urinary HA levels are elevated in BT patients and urinary hyaluronidase levels are elevated in patients with high-grade BT. To test whether a HA-hyaluronidase test can detect bladder tumor recurrence and indicate its

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malignant potential, urinary HA-hyaluronidase levels in 150 BT patients will be measured at scheduled surveillance visits and results will be compared with cystoscopic or urine cytology findings (Aim 4). The proposed study could result in identifying and functionally characterizing a new marker of high-grade BT which could improve diagnosis and treatment of bladder cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METALLOTHIONEIN, ENVIRONMENT INSULT AND BLADDER CANCER Principal Investigator & Institution: Sens, Donald A.; Professor; Urology; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-AUG-2002 Summary: (provided by applicant): Bladder cancer is one of the few malignancies in which occupational and environmental exposures to chemicals have been documented as major risk factors. The metallothioneins (MTs) are a family of low molecular weight proteins that are widely recognized as a major weapon in the cell's armamentarium for protection against and recovery from physical and chemical insult, environmental or otherwise. Thus, it is only logical that MT might have a role in human bladder cancer. In recent studies, the applicant has shown that the third isoform of MT (MT-3) is overexpressed in all human bladder cancers and in most precursor lesions. Similarly, the MT-I and MT-2 proteins have been shown to be overexpressed in some of these bladder cancers and overexpression of the protein correlates to overexpression of the MT-1X gene. The applicant hypothesizes that the early overexpression of MT-3 (and possibly other MT isoforms) sequesters Zn+2 from important regulatory molecules, including p53, through the generation of apoMT and that this in turn renders the early bladder cancer cell as a slow growing, chemotherapeutic resistant, genetically unstable cell destined to progress. The long-term goal of this application is to elucidate the mechanism/s underlying the alterations of MT gene regulation that occur in the development and progression of human bladder cancer. Four specific aims are proposed. The first is to demonstrate that the up-regulation of MT gene expression occurs during bladder cancer progression using a cell culture based model system. The second aim is to show that MT-3 overexpression alters cell growth, drug resistance and genetic stability of bladder urothelial cells consistent with a role in tumor progression and to define the mechanism underlying these alterations. The third specific aim is to correlate MT gene expression to patient outcome by a retrospective analysis of paraffinembedded tissue (PET) from patients with bladder cancer. A major goal being to identify premalignant and established lesions that are likely to progress and follow an aggressive clinical course. The final specific aim is to demonstrate that the presence of MT-3 positive urothelial cells in the urine can predict bladder cancer reoccurrence and adverse workplace exposure. The completion of these studies would provide a strong link between a protein family known to mediate the cell's response to environmental exposure and a cancer strongly associated with exposure to environmental agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICROSATELLITES AS MARKERS FOR BLADDER CANCER Principal Investigator & Institution: Schoenberg, Mark; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001

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Bladder Cancer

Summary: High throughput microsatellite analysis identifies tumor-specific genetic alterations associated with bladder cancer progression. The proposed work seeks to explore several clinical issues related to bladder cancer managed based on the detection of these genetic changes in primary tumors and urine. The specific aims of this project are: (1) to define the sensitivity and specificity of microsatellite marker panels for the detection of recurrent superficial bladder cancers and, (2) to preliminarily explore whether specific patterns for microsatellite alterations (i.e., LOH or instability) correlate with increased risk of disease recurrence or progression in both superficial and invasive cancers. These specific aims will be accomplished through prospective microsatellite analysis of paired tumor and urine specimens obtained from patients with superficial and invasive bladder cancers undergoing therapy with curative intent at the John Hopkins Hospital. The analyses will be performed using molecular methods and technology developed in projects #1 and 2. The larger goal of this project is to lay a practical foundation for future studies of microsatellite analysis for monitoring and for the establishment of risk profiles for patients with different stages of bladder cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BIOMARKERS Principal Investigator & Institution: Wogan, Gerald N.; Professor; Division of Toxicology; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2001; Project Start 25-SEP-1990; Project End 31-MAY-2002 Summary: The overall objectives of this program are to refine and validate molecular biomarkers of human exposures to aromatic and heterocyclic amines, and to utilize the markers to determine the roles of heterocyclic amines on the risk of colon cancer and aromatic amines on the risk of bladder cancer in smokers and nonsmokers in different racial and ethnic groups. In Los Angeles, these will include Latinos, African Americans, Japanese and Whites; defined cohorts will also be studied in Singapore, China and Japan. In Project I, hemoglobin adducts will be used to determine the extent of human exposure to N.hydroxyalkylanilines, as well as the key enzymes regulating their activation. Urinary metabolite excretion will be used to determine metabolic polymorphisms and exposure of different racial and ethnic groups to specific heterocyclic amines, and also determine the relationship between exposure and colon cancer in case- control studies. In project 2, methods for measuring heterocyclic amineDNA adducts in urine and cellular DNA will be developed and validated as markers of biologically effective exposures. The markers will be used to determine relationships between DNA adduct formation and risk of colon cancer in case control studies and to assess exposure in different racial and ethnic groups. Methodology for measuring the major DNA adduct of 4- aminobiphenyl in urine and cellular DNA will be developed and used to determine relationships between DNA adduct formation and risk of bladder cancer in a case-control study. In addition, methodology will be developed for measurement of total DNA adduct levels in cellular DNA in order to assess possible interactions among diverse carcinogen exposures. Project 3 will determine prevalence of exposure to heterocyclic amines and alkylanilines among different racial and ethnic groups, and also determine dietary and other possible environmental correlates of exposure to these compounds within and between racial-ethnic groups. Additionally, preliminary studies will be conducted to investigate relationships between exposure to heterocyclic amines and colorectal cancer, and between arylamine and alkylaniline exposure and bladder cancer. Interrelationships between different biomarkers and each other and to target tissue levels, as well as relationships to enzymatic genotypes/phenotypes within and between racial/ethnic groups will also be

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investigated. Together, the individual projects will provide complementary data for assessing the validity of molecular biomarkers in measuring biologically effective exposures, and testing the hypothesis that exposure to aromatic and heterocyclic amines increases risk for bladder and colon and pancreatic cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR IMAGING OF ADVANCED BLADDER CANCER Principal Investigator & Institution: Frangioni, John V.; Assistant Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: (Verbatim from the Applicant's Abstract): The major hypothesis guiding this research is that modular low-molecular weight ligands, specific for the surface of bladder cancer cells, will be clinically useful reagents. Using peptide phage display screening of live bladder cancer cells, we have discovered two families of peptides, each ten amino acids in iength which bind with high afffinity and specificity to bladder cancer cells, and which exhibit no binding to normai bladder urothelial cells. These ligands offer several potential advantages including rapid biodistribution excellent tissue/tumor penetration, and ease of conjugation to imaging reagents. The long-range goal of this research is to improve bladder cancer staging and treatment by developing novel in vivo molecular imaging reagents and novel therapeutics. The specific aims of this study are designed to expedite future clinical studies of molecular imaging in , advanced bladder cancer. One specific aim is to create, and to optimize, novel magnetic resonance imaging contrast agents by conjugating the bladder cancer-specific peptides to ferromagnetic monocrystalline iron oxide nanocompounds (MlONs). The second specific aim is to create, and to optimize, novel radioscintigraphic imaging reagents by conjugaffng the bladder cancer-specific peptides to radiometal chelators. For each imaging modality, a systematic development scheme including in vitro optimization, in vivo biodistribution and pharrnacokinetics, and in vivo three-dimensional imaging is described. We believe that bladder cancer-specific, low-molecular weight ligands will someday be clinically useful reagents for improved detection and guided therapy of transitional cell carcinoma of the bladder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR CARCINOGENESIS

MECHANISMS

OF

HUMAN

BLADDER

Principal Investigator & Institution: Jones, Peter A.; Professor & Director; Biochem and Molecular Biology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 13-SEP-2002; Project End 31-AUG-2007 Summary: Revised Abstract: The major goals of this Program Project Grant are to utilize two unique and complimentary hospital and population-based bladder cancer databases to further understand the etiology, diagnosis and prognosis of transitional cell carcinoma of the bladder. Project 1 will determine the role of de novo methylation of regulatory genes in the initiation and progression of human bladder cancer and will examine the effects of cigarette smoking and use of non-steroidal anti-inflammatory drugs (NSAIDs) use on the patterns of abnormal methylation. Project 2 will determine the role of COX-2 and DNA Methyltransferase expression in primary tumors and relate the expression levels to exposure levels of cigarette smoking and NSAID use. Project 3 will determine how the altered expression of cell-cycle regulatory genes plays a role in

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Bladder Cancer

the genesis and prognosis of bladder cancer and will examine the expression of proteins encoded by genes studied in Projects 1 and 2, with the long-term goal of developing better techniques for predicting and for establishing better, more rational treatment. The Program Project will cover a wide range of aspects of bladder cancer, extending from cellular and molecular events during genesis of bladder cancer, through epidemiology, to clinically relevant translational issues such as chemoprevention, prediction of risk for recurrence and treatment response. The achievement of these goals will be assisted by three Core Facilities including an Administrative Core, a Biostatistics and Bladder Cancer Database Core and a Pathology Core. The goals of the Program Project Grant will be furthered by the close juxtapositioning of the research labs and the offices of the principal investigators involved in most of the experiments to be performed. The participating investigators have a considerable history of collaboration in the areas of translational research in the field of bladder cancer and these interactions will be formalized and enhanced by this Program Project Grant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: N ACETYLTRANSFERASES--GENOTYPES AND GENOTOXICITY Principal Investigator & Institution: Mcqueen, Charlene A.; Professor; Pharmacology and Toxicology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: (Adapted from the Investigator's Abstract) Arylamine N-acetyltransferases (Nats) catalyze the acetylation of the extracyclic nitrogen of hydrazines and aromatic amines including the tobacco smoke carcinogen 4-aminobiphenyl (4AB). Two genes NAT I and NAT 2 each exhibit polymorphisms that result in variations in enzyme activities. Associations of NAT genes and susceptibility to smoking-related urinary bladder cancer have been reported. However, the involvement of one or both NAT genes, interactions between the two genes and genetic-environmental interactions are not fully understood. The overall goal is to investigate these relationships in geneticallydefined mice. The hypothesis to be tested is that susceptibility to aromatic amine genotoxicity is associated with tissue specific expression of specific combinations of NAT I and NAT 2 genotypes. The specific aims are 1) to identify variants of mouse Nat 1; 2) to create a controllable knockout of Nat I and Nat 2; 3) to over-express Nat I and/or Nat 2 in a particular tissue using tissue specific promoters in transgenic mice; 4) to evaluate Nat 1 and Nat 2 expression in transgenic and knockout mice and 5) to detect 4AB-DNA adducts in mice genetically defined at Nat I and/or Nat 2. The controllable knockout without hepatic Nat genes will be achieved using the Cre-loxP system to knockout the gene then crossing the mice with the "floxed" knockout to albumin promoter Cre transgenic mice. Transgenic animals over-expressing either or both Nat genes will also be developed. An albumin promoter will allow targeting of overexpression to liver. Mice differing in Nat genes will be exposed to 4AB and DNA adducts measured in target and non-target tissue using a monoclonal antibody and immunohistochemistry. These studies will show whether 4AB genotoxicity is modulated by Nat expression. The results will provide insight into genetic regulation of susceptibility to a carcinogen found in tobacco smoke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: N GLUCURONIDATION OF BENZIDINE & ITS METABOLITES ROLE IN BLADDER CANCER Principal Investigator & Institution: Zenser, Terry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130

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Timing: Fiscal Year 2001 Summary: Workers exposed to a high levels of benzidine have a 100-fold increased incidence of bladder cancer. This review evaluates the overall metabolism of benzidine to determine pathways important to initiation of bladder cancer. Upon incubation of benzidine with liver slices from rat, dog, and human, different proportions of this diamine were N-acetylated and N-glucuronidated. With dog, a non-acetylator, Nglucuronidation was the major pathway. In contrast, little glucuronidation was observed in rat with N,N/-diacetylbenzidine the major metabolite. Human liver slices demonstrated both extensive N-acetylation and N-glucuronidation. Differences between rat and human were attributed to rapid deacetylation by human liver with Nacetylbenzidine rather than N,N/-diacetylbenzidine accumulating. N-Acetylbenzidine oxidative metabolism was also observed. The acid lability of glucuronide products of benzidine, N-acetylbenzidine, and oxidation products of N-acetylbenzidine m etabolism was assessed. N-Glucuronides of benzidine, N-acetylbenzidine, and N'-hydroxy-Nacetylbenzidine were acid labile with the latter having a much longer t1/2 than the former two glucuronides. Because bladder epithelium contains relatively high levels of prostaglandin H synthase and not cytochrome P-450, peroxidative metabolism of Nacetylbenzidine was assessed. N'-(3'-Monophospho-deoxyguanosin-8-yl)-Nacetylbenzidine was the only DNA adduct detected. This adduct is also the major adduct detected in bladder cells from workers exposed to benzidine. In urine from these workers, an inverse relationship between urine pH and levels of free (unconjugated) benzidine and N-acetylbenzidine was observed. A similar inverse relationship was observed for urine pH and levels of bladder cell N'-(3'-monophospho-deoxyguanosin-8yl)-N-acetylbenzidine. These results suggest multiple pathways (acetylation, glucuronidation, peroxidation) in multiple organs (liver, blood, kidney, bladder) are important in benzidine-induced bladder cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NONINVASIVE DETECTION OF UROTHELIAL ABNORMALITIES Principal Investigator & Institution: Pan, Yingtian; Assistant Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 31-DEC-2003 Summary: (Adapted from the Applicant's Abstract): This research proposes to apply a novel imaging technology, high fidelity cystoscopic optical coherence tomography (OCT), to image micro-morphology of urinary bladder and to detect urothelial abnormalities (e.g. tumors). Advanced imaging techniques (e.g., fiber-optic Mach Zehnder interferometry, confocal microscopy, polarization detection and electrooptic scanning) will be used, thus allowing imaging diagnosis of bladder lesions in vivo, noinvasively, immediately and at high fidelity. Rat bladder will be imaged ex vivo and compared with histological evaluation to systematically analyze the morphological and physiological changes occurring during the methyl nitrosourea (MNU) induced tumor formation. Porcine bladder will be imaged ex vivo to compare mammalian bladders; normal procine bladder and cat bladder with iterstitial cystitis will be imaged in vivo to test the development of a cystoscopic OCT system. Most bladder cancers (e.g., carcinoma in situ) are treatable (if not curable), if diagnosed prior to metastasis and treated appropriately. Endoscopic visual inspection of surface lesions is presently the clinical standard, and conclusive diagnosis and staging of malignancy relies on surgical biopsy and histological examination. This results in an enormous number of negative biopsies of benign bladder lesions with their attendant risks and complications. Therefore, a noninvasive imaging technique is needed that allows early ultrasound and

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Bladder Cancer

convential endoscopy, are inadequate, either because of poor resolution and limited penetration or technical imperfection. OCT, a new technology, allows noninvasive visualization of vertical cross-sectional micro-morphology (10 mum resolution) at depths of 1-3 mm beneath the bladder surface. Our preliminary results have clearly demonstrated the potential value to provide clinicians with rapid, noninvasive diagnosis of abnormalities. No other technique offers this potential at present. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OLIGONUCLEOTIDE MIMETICS FOR MODULATION OF BCL-XL MRNA Principal Investigator & Institution: Marapaka, Praveen; Annovis, Inc. 34 Mt. Pleasant Dr Aston, Pa 19014 Timing: Fiscal Year 2001; Project Start 23-AUG-2000; Project End 31-JUL-2002 Summary: The overall aim of this research program is to develop an optimal oligonucleotide drug to specifically modulate cancer-associated mRNA in superficial bladder cancer. Bladder cancer represents a significant health problem with 53,000 new cases and 12,000 deaths per year in the US and a high failure rate of available therapies. In Phase I we are talking a broad approach with regard to the choice of oligonucleotide type (antisense, hammerhead ribozyme, external guide sequence, DNA enzyme) and intend to evaluate four different chemical modifications of these oligomers. Each of the combinations will be tested in a well-characterized tissue culture model of superficial bladder cancer using two oligonucleotide delivery reagents. The best oligomer determined from the above experiments will be synthesized in large scale and then tested in mouse orthotopic Implantation xenogralt and endogenous models of superficial bladder cancer. In Phase fl we will evaluate the toxicity profile and continue to study efficacy, bioavailability and delivery of the oligomer with the aim of ultimately entering a human trial. Combination treatments of oligonucleotide with existing drugs will be evaluated PROPOSED COMMERCIAL APPLICATION: The immediate application is the development of a therapeutic for bladder cancer, either alone or as part of a combination drug therapy. The rate of appearance of bladder cancer is 53,000 new cases per year; the revenues for a widely used drug are estimated at $0.5bL. The oligonucleotides discovered in this application could also be used to dissect the role of apoptosis in oncogenesis. The overall technology is further applicable to the general area of functional genomics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ONCOGENE SPECIFICITY IN ORGAN-DEFINED CANCERS Principal Investigator & Institution: Gould, Michael N.; Professor of Oncology; Human Oncology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 08-JUN-1998; Project End 31-MAR-2003 Summary: The goal of this project is to define mechanisms underlying the activation of a single, defined, oncogenic ras family member in cancers of specific organs and tissue. Examples of this specificity include the observations that in human bladder cancer, the activated ras family member is always H-ras, whereas only K-ras activation is found in pancreatic cancer. For reasons of their unique utilities, several rat mammary carcinogenesis models will be used to accomplish the goal of this proposal. For example, rat mammary carcinomas chemically induced by NMU (N-nitrosomethylurea) only have activated H-ras and never have activated K-ras. Based on preliminary data demonstrating that K-vs. H- ras specificity lies in the Ras protein itself, Aim 1 will test

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the hypothesis that subtle differences in the carboxyl end of the Ras proteins (H- or KRas) modify Ras membrane localization, leading to tumor-type specificity. Experimental approaches for this aim include: Ras domain exchanges between H-and K-Ras, Ras-Raf interaction studies, and H- vs. K-Ras immunogold electron microscopic membrane localization studies. In Aim 2, another aspect of ras specificity will be studied using transgenic rats overexpressing wild type H- vs. K-ras. Preliminary data showing that overexpression of wild-type H-ras, but not K-ras, can inhibit NMU-induced mammary carcinoma development will be extended and mechanistically investigated. The differential activation of the H-ras transgene versus the endogenous H-ras gene will also be explored. Aim 3 will follow up preliminary data demonstrating that expression of wild- type H-ras, but not K-ras, driven by a viral MMLV promoter in in situ mammary cells induces mammary carcinomas. This is in contrast to the observation that overexpression of wild-type H-ras does not result in the induction of mammary carcinomas when driven by its own promoter. A hypothesis suggesting that disregulated gene expression is important in wild-type ras-induced carcinogenesis will be investigated. Data generated in this project will provide: insight into the role of ras specificity in the etiology of cancer (approximately 40 percent of human cancers have activated ras), and knowledge for the development of drugs that specifically target single members of the ras family. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: P53 MUTATION ANALYSIS FOR BLADDER CANCER PROGNOSIS Principal Investigator & Institution: Prescott, James L.; Urocor, Inc. Oklahoma City, Ok 73104 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 31-MAY-2003 Summary: The p53 tumor suppressor gene regulates many physiologic pathways that are important in the development of cancer and is the gene most frequently observed to be mutated in metastatic cancers. As a result, p53 mutations in cancer cells indicate that the tumor containing such p53 mutated cells is at high risk for disease progression to a higher clinical stage and/or grade. P53 mutated cancers are also more likely to recur after initial treatment than p53 wild type cancers and respond differently to some therapies. This project consists of a combination of clinical trials and programs of incremental improvement that seek to further develop and validate a robust commercially viable clinical assay to detect p53 gene mutations in bladder cancers cells that are exfoliated into the lumen of the bladder and collected in bladder cytology specimens. The successful completion of this phase II SBIR will change the way bladder cancer patients with stage T1 or greater disease are managed. The improvements in technology delivery and the expanded prospective and retrospective clinical trials will validate both the technology and its clinical utility to assess patient prognosis. These achievements will, in turn, direct patients to their most effective primary and adjuvant therapies. PROPOSED COMMERCIAL APPLICATION: The work proposed in this phase II SBIR grant application will further facilitate the acceptance and adoption of this test by urologists as a tool to be used in managing bladder cancer patients. Thus, the work proposed is also essential for the commercial success of this project at UroCor. The total p53 mutation detection market for bladder cancer prognosis is roughly 60,000 specimens/ year with a market approaching $15 million. Cost savings to the medical community due to more effective treatment of bladder cancer is significantly greater. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Bladder Cancer

Project Title: PATHWAYS OF BLADDER TUMORIGENESIS Principal Investigator & Institution: Pellicer, Angel G.; Professor; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001 Summary: (Taken directly from the application) The long term goal of Project 4 is to understand the molecular basis of bladder tumorigenesis by testing the hypothesis that there are two pathways that can produce a bladder tumor. The first, where p16 is involved, frequently produces superficial papillary tumors with a tendency to recur, but unlikely to progress. The second, which involves p53, starts as a carcinoma in situ and frequently progresses. Towards this goal, we will develop model systems of tumorigenesis in transgenic mice, which contain oncogenetic alterations frequently observed in human transitional cell carcinoma. The need for such tailored system comes from the fact that, although bladder tumors have been experimentally produced by chemical agents, the molecular mechanisms triggering such tumors are frequently unknown, and in the cases where they have been analyzed, they rarely mimic the oncogenic events seen in human transitional cell carcinomas, i.e., changes in epidermal growth factor receptor (EGFR), H-ras, p16 and p53. Until recently, it had been impossible to direct the expression of a gene specifically to the urothelium. However, the recent isolation of such a urothelial specific promoter, from the uroplakin II (UPII) gene, will enable us to generate transgenic mouse lines with specific oncogenic changes in the urothelium. We will therefore use the UPII promoter to drive the urothelial expression of normal and activated EGFR, activated H-ras, and a dominant negative mutant of p53. We will also utilize the cre/loxP system to specifically inactivate p53 and p16 in the mouse urothelium. The effects of these transgenes on urothelial growth and tumor formation will be examined. To maximize the tumor yield, the genes will also be used in specific combinations and, if necessary, together with subcarcinogenic doses of bladder carcinogens. To assess the crucial role of these alterations in the bladder tumors, we will analyze if the appropriate pathways are activated. These model systems of tumorigenesis and the test of the two pathway hypothesis of bladder cancer pathogenesis should lead to a better understanding of the pathogenesis of bladder tumors, and it may also contribute to a more informed therapy of human transitional cell carcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACODYNAMICS OF AGENTS FOR BLADDER CANCER THERAPY Principal Investigator & Institution: Au, Jessie L.; Distinguished University Professor; None; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-JUN-1989; Project End 31-MAY-2003 Summary: This competitive renewal application is to define the pharmacokinetics and pharmacodynamics of the drugs commonly used in intravesical therapy, in order to optimize the treatment regimen. Results of our studies on mitomycin C (MMC) indicate several treatment conditions which need optimization and a low sensitivity of high stage, high grade and rapidly proliferating tumors to MMC. A.l. Pharmacokinetics of intravesical therapy in patients. Our studies of the pharmacokinetics of MMC yielded important information to optimize the treatment protocols. We propose to establish, for doxorubicin and thiotepa, (a) drug concentration-time profiles in blood and urine, (b) extent and rate of systemic absorption of drugs from bladder, and (c) effects of transurethral resection and disease staging on drug absorption. A.2. Drug distribution in

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normal and tumor tissues. We will study the drug distribution in different region; of the bladder and the depth of drug penetration in vivo using bladders removed from dogs and from patients who receive drug instillation at the time of total cystectomy. This will indicate whether effective drug concentrations are achieved at the tumor sites. A.3. Determinants of drug absorption from bladder. Variables including the pH and volume of urine, dwell time, size (molecular weight), acidity/basicity and concentration of a drug can influence the drug absorption from bladder and potentially affect the target site specificity of intravesical therapy in patients. Because patient studies are not always feasible, we propose to study the effect of the selected variables on drug absorption kinetics in animals. Our MMC studies suggest the dog as the most suitable animal model. A.4. Chemosensitivity and pharmacodynamic studies in vitro. An in vitro chemosensitivity assay using patient bladder tumor explants has been established. The proliferative activity of explants is parallel to the tumor pathobiology. We found a 60fold difference in the IC of MMC in explants from different patients, and an inverse relationship between the IC and exposure time. The data also suggest a correlation between tumor sensitivity to MMC and prognostic factors such as DNA ploidy, tumor grade and tumor stage. The pharmacodynamics, correlation of IC with potential prognostic factors, and the effect of pH will be determined. A.5. Evaluate activity of new drugs and combinations for high stage and rapidly proliferating tumors. We found that high stage and rapidly proliferating tumors were less sensitive to MMC than the less malignant tumors. Clinically, MMC is less effective against T2 tumors than Ta and T1 tumors. The high stage and rapidly proliferating tumors are of high risk with respect to recurrence, progression to invasive disease, metastasis, and poor survival. We propose to evaluate the activity of new drugs and combinations for these tumors, and to establish the pharmacodynamics as stated in A.4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOLOGY OF ANTICANCER DRUGS IN ADVANCED AGE Principal Investigator & Institution: Raghavan, Derek; Professor of Medicine and Urology, and c; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-AUG-2003 Summary: Despite the fact that the most rapidly growing segment of the community is the population aged 70 years and older, which is also characterized by the highest overall incidence of cancer, little is known about the detailed pharmacology of cytotoxic agents in this population group. This reflects previous political imperatives, and the conservatism of patients or the medical profession, causing older aged patients to be markedly under-represented in clinical trials. This proposal, from the Women and Special Populations, Genitourinary, Breast and Gastrointestinal Committees of the Southwest Oncology Group, represents the first step in the development of a new paradigm for assessing (a) the feasibility of accrual; (b)the efficacy, toxicity and pharmacology of cytotoxic compounds among patients aged 70 years and older; (c) the feasibility of using standardized self-report measures of comorbidity and functional status in the context of multicenter clinical trials for elderly patients with cancer; (d) at a preliminary level, patterns of expression of key metabolic enzymes in the metabolism of, and resistance to, cytotoxic agents. Fully ambulatory patients in this age group, with metastatic breast cancer, bladder cancer or colorectal malignancy (three of the most common malignancies in this age group) will be treated in a series of standard Phase II trials with docetaxel, gemcitabine-paclitaxel, and uracil-ftorafur [UFT], respectively. The eligibility criteria will be simplified as much as possible to encourage facility of

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recruitment. In this initial study, elderly patients who are medically fit, apart from the presence of cancer, will be selected, to allow pharmacological and clinical assessment of anticancer therapy that is not confounded by life-threatening undercurrent disease. For each tumor type, 60 cases will be treated. In addition to standard Phase II assessment of efficacy and toxicity, patient-completed questionnaires; will be used as a tool for the assessment of comorbidity and will be used to assess whether the elderly are able successfully to complete such questionnaires, and to identify the extent of previously undiagnosed undercurrent medical disorders, depression, and the level of functional status. Pharmacokinetic measurements will be obtained to establish AUC, half 1ives and clearance values in this elderly population. In addition, we will measure gene expression of deoxycytidine kinase and deaminase (assessing the metabolism of gemcitabine), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) (reflecting metabolism and resistance of flucropyrimidines), and mutations of betatubulin (a potential mechanism of resistance to the taxanes) to study the feasibility of assessing age-related genomic regulation of cytotoxic drug metabolism in Phase Il-III clinical trials. A smaller comparison group of patients aged less than 60 years (with the same cancers) will be treated identically to provide pharmacokinetic data and to validate our pharmacokinetic assays against the published literature. This will allow our pharmacokinetic data from the elderly to be set into context. Comparisons between the elderly populations and the limited younger cohorts will not be possible due to the limited case numbers appropriate for the Phase II design of each trial, but the feasibility of data acquisition will be tested and exploration of any obvious correlations between pharmacokinetic characteristics versus efficacy/toxicity will be attempted, but will only be hypothesis-generating in intent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHASE CARCINOFENESIS

III

STUDY

OF

FENRETINIDE

IN

BLADDER

Principal Investigator & Institution: Lippman, Scott M.; Professor and Chair; Cancer Prevention and Control; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-JUL-2004 Summary: (Applicant's Description) Bladder cancer will account for about 5 4 , 5 0 0 new cancer cases and 11,700 deaths in the U.S. in 1997. C h emoprevention to counter the field defect, genetic instability and p r e rnalignant molecular and cellular changes associated with bladder carcinogenesis offers may be effective in reducing the substantial risk of morbidity and mortality from this disease. We propose a phase III clinical trial of fenretinide (4-HPR), to be of intermediate duration (15 months) and size (160 evaluable patients), in preventing superficial bladder tumors (after complete resection) and five correlative laboratory studies. This proposed study may validate between one and five currently promising surrogate endpoint biomarkers (SEBS) for chemoprevention of bladder cancer. Patient eligibility includes superficial (Ta) primary or recurrent (>1 year after primary) bladder tumors not requiring intraves'cal therapy. The five correlative studies are designed to validate the following potential SEBs: apoptosis; retinoid acid receptors; DNA ploidy; numerical abnormalities of chromosomes 4 and 9; and autocrine motility factor receptor. All five markers have been proven to be modulatable in vitro and/or in vivo. A sixth laboratory study will evaluate whether eight other retinamides induce apoptois more effectively than 4-HPR in vitro in bladder cancer cell lines. Hypotheses regarding 4-HPR's effects on these markers will be tested through statistical modeling of marker expression, modulation and clinical

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outcome. Bladder carcinogenesis is an excellent model for chemopreventive study. Eligible patients will have tumors that require no local or systemic treatment postresection; are easily monitored and are associated with a very high rate of second primary tumors (SPTs) post-resection. Multifocal carcinogenesis within the bladder mucosa results in development of primary and second primary bladder tumors. 4 HPR, the most promising chemopreventive retinoid, has an excellent activity:toxicity ratio and strong apoptosis-induction activity in the bladder. The latter can eliminate premalignant clones and so shorten chemoprevention characteristic of other active retinoids. The high incidence of bladder SPTs in these patients provides the opportunity to validate p o t e ntial SEBs against potential cancer-incidence reduction in this intermediate-size and -duration trial. SEB validation is crucial to reduce the size, duration and cost presently required for phase III definitive chemoprevention trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT STUDY--COX2 INHIBITOR IN INVASIVE BLADDER CANCER Principal Investigator & Institution: Knapp, Deborah W.; Veterinary Clinical Sciences; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-MAY-2003 Summary: Invasive urinary bladder cancer kills more than 12,000 people each year in the United States. Most of those deaths are due to invasive transitional cell carcinoma (TCC) that has metastasized and is resistant to chemotherapy. Our long range goal is to develop more effective treatment for invasive TCC. Cyclooxygenase (Cox) inhibitors have induced apoptosis and caused regression of invasive TCC in animal studies. The antitumor activity of Cox inhibitors is thought to be due, at least in part, to inhibition of Cox and the resulting decrease in Cox products (prostaglandins and thromboxanes). The objectives of this application are to establish the effects of a cyclooxygenase-2 (cox-2) inhibitor in: (1) inducing tumor apoptosis and reducing urine bFGF concentration, and (2) controlling the concentration of Cox products in humans with invasive TCC. The central hypothesis is cox-2 inhibitors will block the synthesis of Cox products (thereby limiting concentrations of Cox products in the tumor) and will induce apoptosis in invasive TCC in humans. The central hypothesis is based on strong preliminary data showing antitumor activity of Cox inhibitors and a strong association between the Cox inhibitor-induced tumor regression and doubling of the apoptotic index in invasive TCC in canine studies. Reduction in urine bFGF concentration has also been associated with Cox inhibitor-induced tumor regression in animals, and will be a secondary endpoint in our proposed studies. In addition to being associated with tumor regression with Cox inhibitors, induction of apoptosis and inhibition of bFGF synthesis and release are important effects in control of cancer and response to cancer therapy. A multidisciplinary team has been assembled to perform a pilot study of the cox-2 inhibitor, celecoxib, in humans with muscle invasive TCC. The composition of the team will allow for rapid design and implementation of large-scale clinical trials, should the expected outcomes of the proposed studies occur. The hypothesis will be tested by pursuing two specific aims: (1) determine the activity of a cox- 2 inhibitor in inducing apoptosis in tumor tissue and reducing urine bFGF concentration in humans with invasive TCC, and (2) determine the extent to which a cox-2 inhibitor controls prostaglandin and thromboxane production in invasive TCC in people. The expectation is that the cox-2 inhibitor will control prostaglandin and thromboxane production, will induce tumor apoptosis, and will lower urine bFGF concentration in patients with invasive TCC. The proposed research is significant because it is expected to lead to a more effective approach to treating invasive TCC that will reduce mortality, increase

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Bladder Cancer

quality of life, and reduce overall costs of the medical care of patients with invasive TCC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE STUDIES OF DIET AND CANCER IN MEN AND WONEN Principal Investigator & Institution: Willett, Walter C.; Professor and Chairman; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 23-AUG-1991; Project End 31-MAR-2006 Summary: (provided by Applicant) This proposed Program will use prospectively collected dietary data and frozen plasma and DNA specimens to address a series of hypotheses regarding major cancers in men and women. In addition, these nutritional and genetic exposures will be examined in relation to specific molecular characteristics of tumors. The cancers to be studied are those of the prostate, colon and rectum, bladder, lung, kidney, and ovary. This Program Project supports, and depends on, the continued follow-up of 51,529 men who completed an extensive dietary questionnaire first in 1986 and again in 1990, 1994, and 1998 (the Health Professional?s Follow-up Study, HPFS), and is also closely linked to the Nurses? Health Study (NHS) of 121,700 women. The Program Project has already contributed substantially to information on diet and cancers of the breast, prostate, colon, and bladder. The proposed continuation will extend and refine observations from the first twelve years of follow-up and will also address new hypotheses related to both cancer incidence and survival. Project 1 will examine dietary (lycopene, calcium, and N-3 fatty acid intakes) and other predictors of prostate cancer incidence in relation to risk of PSA relapse among men with apparently successful treatment for localized prostate cancer. In addition, a series of dietary and hormonal factors will be related to specific characteristics of incident cancers, including expression of PTEN and COX-2 and markers of angiogenesis. Project 2 will address hypotheses relating intakes of folic acid, calcium and red meat and plasma levels of IGF1 and its binding proteins to risks of both colorectal cancer and adenomas. Interactions with germline polymorphisms and relationships with specific molecular tumor characteristics will be examined. Project 5 will examine dietary and related risk factors for bladder cancer in both men and women. Exposures will include intakes of cruciferous vegetables and total fluids, and biochemical indicators of selenium and arsenic exposure. Interactions with polymorphisms in carcinogen metabolizing genes and specific association with p53 expression in tumors will also be examined. Project 4 pools data from all eleven major published prospective studies of diet and cancer. Precise and unique information has already been obtained for breast, lung and colon cancers, and the proposed work will extend analyses to cancers of the pancreas and ovary. These highly interrelated studies that integrate dietary factors, established nondietary risk factors, endogenous hormone levels, genetic susceptibility, and molecular characteristics of tumors, will contribute importantly to the understanding and prevention of the major cancers of men and women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROSPECTIVE STUDY OF DIET AND BLADDER CANCER Principal Investigator & Institution: Stampfer, Meir J.; Professor and Chair; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 23-AUG-1991; Project End 31-MAR-2006

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Summary: (provided by Applicant) This project aims to identify dietary, reproductive and genetic factors related to bladder cancer in two large ongoing prospective cohorts of men and women. Risk factors of bladder cancer are largely unknown but this important disease is likely to be largely preventable, given the large regional variations in incidence rates. Compared to some other cancers, bladder has received little attention and support. There are exciting opportunities to improve the understanding and ultimately prevention of this disease. We propose to study bladder cancer in the Nurses? Health Study and the Health Professionals Follow-up Study. By 2004, we project that 562 men and 391 women will be diagnosed with bladder cancer in these two cohorts. We will conduct prospective analyses using both cohorts, and nested casecontrol analyses among members who have provided blood, cheek cells, or toenails. We propose to obtain tumor specimens from participants with bladder cancer to examine specific tumor alterations (specifically p53 overexpression). We propose to examine dietary factors in detail among women who completed the initial dietary questionnaire in 1980; the ?diet? cohort we will have 312 women with bladder cancer. Selenium and arsenic levels will be assessed from toenails of over 500 men and women with bladder cancer and will be compared to 500 controls selected from the same cohorts. We will also examine specific dietary interactions with three polymorphic genes that have been previously related to bladder cancer risk (NAT1, NAT2 and GSTM1). We will use p53 overexpression as an alternative endpoint to determine if specific dietary factors can predict p53 mutations in bladder cancer. Stratified analyses and multiple logistic regression will be used to control for potential confounding by age, smoking, and other relevant nutrients or foods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTATE CANCER MOLECULAR EPIDEMIOLOGY-RETINOID RECEPTOR Principal Investigator & Institution: Mao, Gloria E.; Epidemiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 22-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This proposal is designed to provide the applicant, Dr. Gloria Mao, with the scientific skills and career development necessary for a successful academic career in cancer prevention and control research. Together, with a targeted program of didactic instruction, guided mentorship, collaborative research, and participation in national meetings, this project will prepare the applicant to become a fully independent scientist. A molecular epidemiology study is proposed to characterize the role of the retinoid receptors in prostate carcinogenesis. The retinoic acid receptors, RARs, and the retinoid X receptors, RXRs, mediate the anticarcinogenic effects of retinoic acid. Prostate tissue, pathology records and a life-style/exposures questionnaire have been obtained from 118 prostate cancer cases and 102 bladder cancer cases that may serve as controls in this study. The specific aims of the study are: (1) measure the RARs and RXRs at different levels of expression regulation: mRNA and protein levels and RARbeta promoter methylation in paired prostate tissue containing normal prostate, prostatic intraepithelial neoplasia, and adenocarcinoma; (2) measure the correlations between molecular alterations in the retinoid receptors with clinical and pathological variables including tumor stage, grade, and patient survival; (3) measure the correlations between RARa promoter methylation and RARbeta mRNA and protein levels; (4) evaluate the strength of the associations between molecular alterations in the RARs and RXRs with patient demographics, environmental exposures, dietary factors and serum micronutrient levels. Differential expression of specific retinoid receptors and

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hypermethylation of the RARbeta promoter are hypothesized to exist between normal, PIN and adenocarcinoma. An assessment of whether retinoid receptor molecular alterations are useful biological markers of prostate cancer progression will be made. The strength of the associations between retinoid receptor status with environmental and dietary exposures may be used to identify potential gene-risk factor interactions for prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUANTITATIVE PCR DETECTS MOLECULAR CHANGES IN CANCER Principal Investigator & Institution: Kurnit, David M.; Professor of Pediatrics and Human Geneti; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-JUL-2002 Summary: (Applicant's Description) Using a sensitive fluorescent quantitative-PCR (QPCR) energy-transfer assay, we can determine sequence copy number directly and efficiently. Application of this technology to cancer documents a surprisingly frequent assortment of copy number changes that are not seen in the stable normal genome. In preliminary studies, this technique was compared with standard loss of heterozygosity (LOH) techniques and found to be as accurate and more efficient in determining anomalies of bladder tumors. More recently, we have shown that this technology can be used to diagnose anomalies associated with bladder cancer in the abnormal genomes of tumor cells found in urine sediment and serum. Further, we have found that the absolute amount of DNA found assayed by QPCR in urine sediment is a marker for bladder abnormality. Putting all these techniques together, we propose an effort focused on bladder tumors to determine how QPCR can be used to diagnose and assist the therapy of bladder tumors. Since we have seen these genomic changes in a wide variety of tumors, the technology can ultimately be applied to all cancers. Questions to be addressed are: 1. Can a simplified variant of QPCR be used to screen efficiently for bladder tumors in urine sediment of populations at increased risk? 2. Can QPCR be used to diagnose and stage bladder tumors? 3. Can QPCR be used to monitor the therapy of bladder tumors when the bladder is left by monitoring urine sediment? 4. When the bladder is removed because of extensive disease, can QPCR be used to monitor the therapy of bladder tumors by monitoring serum? 5. Can QPCR be used to monitor the occurrence of metastatic disease by monitoring serum? Answering these questions will determine the roles that are appropriate for QPCR in the diagnosis and treatment of bladder tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RAL IN HUMAN BLADDER CANCER PROGRESSION Principal Investigator & Institution: Theodorescu, Dan; Urology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-SEP-1997; Project End 28-FEB-2008 Summary: (provided by applicant): Background and Significance: 40% of patients presenting with "superficial" (non-muscle-invasive) bladder cancer develop the "invasive" life-threatening form of the disease during follow up. In clinical studies, overexpression of Epidermal Growth Factor Receptor (EGFR), Ha-Ras mutation and loss of tumor suppressor gene PTEN have been associated with this phenotypic tumor transition. However, the exact molecular pathway by which these genes effectively

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trigger or facilitate the invasive process is incompletely understood. Our original R29 hypothesized that EGFR signaling enhances bladder tumor motility in vitro and invasion in vivo and intended to determine the signaling pathways used by EGFR in this process. Since funding of the R29 in 9/97, we have made the following important observations which support the original hypothesis and address the aims of the original application: 1) EGFR and Ras inhibition diminished the motility of invasive bladder cancer cells; 2) EGF stimulates motility in non-invasive cells via PI3K and this requires activity of Rho and Ras effector Rat; 3) In non-invasive cells, baseline RalA activity is low while invasive cells have constitutively higher activation; 4) Invasive cells have low levels of RhoGDI2 expression. Reconstitution of this gene leads to diminished motility and activity of RalA but not RhoA suggesting this gene may be the first RalGDI identified to function as an invasion suppressor; 5) Inhibition of PI3K activity via PTEN reconstitution in invasive cells with inactive PTEN, results in an inhibition of orthotopic invasion in vivo and a decrease in RhoA activity. Since the overall biology of both Ral and RhoGDI2 is poorly understood, but might be critical for regulating tumor invasion in patients with bladder cancer, we propose the Guiding Hypothesis that EGF mediates bladder tumor invasion via Ral activation. We will test this hypothesis with a matrix of technologies ranging from basic biochemistry to clinical oncology to address Ral biology in human bladder cancer. These include: 1) unique paired human bladder cancer cell lines with different invasive abilities; 2) a novel organotypic bladder model allowing in vitro study of tumor invasion; 3) an orthotopic assay evaluating the effects of candidate molecules on in vivo bladder cancer invasion; 4) transgenic and knockout mice with appropriate genetic and phenotypic profiles; 5) a human tissue bank with pathologically and clinically well characterized frozen specimens. Specific Aims: 1) Determine the role and pathobiology of Ral in bladder cancer invasion in organotypic, murine orthotopie and human tumor studies; 2) Determine the regulators of Ral activation (RhoGDI2, etc.) and their effect on intracellular Ral localization and bladder cancer nfigration and invasion; 3) Determine the protein complexes associated with Ral in vitro and in vivo, including those found in human cancer. Conclusion: Completion of these specific aims will provide biologically relevant molecular information on the signaling pathways regulating bladder cancer invasion in vivo and lead to the rational development of diagnostic and prognostic tools predicting the development of invasive disease and therapies to interfere with this process in patients with superficial bladder cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RB4 INTRAVESICAL GENE THERAPY: MECHANISMS OF CELL DEATH Principal Investigator & Institution: Benedict, William F.; Professor; Gas Med Oncology & Digest Dis; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): A modified retinoblastoma gene construct utilizes the second start codon of the RB gene and encodes for a 94 KD protein (pRB94. It is a markedly more potent tumor suppressor and cytotoxic agent than the wild-type RB protein and has been effective against all tumor types tested to date irrespective of tissue type, RB or other gene status, except for that of telomerase. A long-term objective of this project is to understand the cellular and molecular pRB94 interactions that cause such potent effects. Preliminary results suggest that a key mechanism of pRB94 specific induced tumor cell death may involve the production of rapid telomere attrition and chromosomal crisis. These results make the mechanism(s) of RB94 cell kill and tumor

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suppression potentially unique from all other agents or modalities examined to date and has occurred in all telomerase positive tumors or immortalized cells but not in tumor or immortalized cells containing an ALT pathway, i.e. telomerase negative cells. RB94 also has been found not to be cytotoxic or growth inhibitory to normal human cells, including urothelial cells, which are also telomerase negative. One approach will therefore be to determine if interference with the normal telomere complex plays a key role in RB94 produced telomere attrition, with subsequent chromosomal instability and cell death. The role of centrosomes and changes in STK15 kinase activity will also be studied in depth. Techniques will be include the use of microarrays, confocal laser scanning, analysis of chromosomal and telomere status, examination of RB94 specific protein interactions by Western blotting and immunochemical staining as well as immunoprecipitation with sequencing of putative RB94-specific related proteins. Studies will be expanded to examine RB94 cell kill in additional telomerase positive or negative tumor cells and genetically altered, non-tumorigenic immortalized cells. Whether or not these changes are caspase dependent will also be studied. Another specific aim is to optimize intravesical gene therapy and determine the effect of AdRB94 on superficial bladder cancer. An intravesical human bladder cancer model developed by us using GFP expressing cells will be utilized for this purpose. To increase adenovirus-mediated transfer the reagent, Syn3, will be used. Syn3 has been found to markedly increase adenoviralmediated gene transfer without being toxic itself. If these studies are successful, it could have a significant influence in developing a new modality of treatment for recurrent superficial bladder cancer and potentially for other tumor types as well as provide the molecular basis for the unique properties of RB94. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETINOIDS CHEMOPREVENTION

&

RECEPTORS

IN

BLADDER

CANCER

Principal Investigator & Institution: Zou, Changping; Ob, Gyn and Reproductive Scis; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 30-NOV-2003 Summary: (Applicant's Description) Bladder cancer is the 6th most common cancer in the developed world. More than 50,000 new cases of bladder cancer and 11,200 deaths from this cancer occur each year in the United States. Bladder carcinogenesis, like oral premalignancy, is an excellent model for chemopreventive study. Natural and synthetic retinoids have been tested as chemopreventive and chemotherapeutic agents against oral tumors, but the effects of these retinoids on bladder cancers are not well documented. The objective of the proposed study is to explore the feasibility of using natural or synthetic retinoids in the prevention and treatment Of bladder cancer and to investigate the mechanisms of retinoids in this setting. The effect of different retinoids on cell growth, differentiation, apoptosis, and expression of retinoic acid receptors (RARs) in bladder cancer cell lines and normal bladder epithelial cells in short-term cultures will be studied. The hypotheses are: a) retinoids inhibit the growth of bladder cancer cells partially through the induction of apoptosis; b) RARs, especially RARB, play a role in regulating the growth and differentiation of bladder cancer cells; and C) some receptors are down-regulated in certain bladder cancers and can be up-regulated by retinoids in vivo. The hypotheses will be examined by fulfilling the following specific aims: 1) to evaluate the effects of different retinoids on growth and differentiation in normal bladder epithelial cells and bladder cancer cells by examining morphology, cell cycle, and the expression of cytokeratins 4, 7, 8, 13, 18, and 19 using western blotting; 2) to determine the effects of different retinoids on the induction of apoptosis in bladder

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cancer cells by using DNA fragmentation, propidium iodide staining, and terminal deoxynucleotidyl transferase assays and the effects of combinations of RAR-selective and retinoid X receptor (RXR)-selective retinoids on growth inhibition and apoptosis to find possible additive or synergistic actions of these compounds; 3) to examine the expression of retinoid receptors and their induction by different retinoids in normal bladder epithelial cells and bladder cancer cells by using reverse-transcriptase polymerase chain reaction and western blotting to determine the relationship between receptor expression and the chemopreventive effect of different retinoids; and 4) to analyze the expression of retinoid receptors in bladder cancer specimens before and after chemoprevention with 4-(hydroxyphenyl)retinamide (4HPR) by in situ hybridization and polymerase chain reaction. The results of these studies are expected to increase our understanding of the mechanisms of action and potential usefulness of new retinoids in bladder cancer chemoprevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE SUPPRESSION

OF

MISMATCH

REPAIR

IN

SPORADIC

TUMOR

Principal Investigator & Institution: Li, Guo-Min; Associate Professor; Pathology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 14-FEB-2001; Project End 31-JAN-2005 Summary: (Applicant's abstract): The long-term objectives of this project are to understand the molecular mechanism of human mismatch repair and its impact on human cancer. DNA mismatch repair plays a crucial role in maintaining genomic stability by correcting mismatches generated from DNA biosynthetic errors and DNA recombination. Defects in human mismatch repair are the primary cause of both hereditary colorectal cancer and sporadic colorectal cancers that display microsatellite instability. Microsatellite instability, which correlates with mismatch repair deficiency, has also been demonstrated in a substantial fraction of many types of sporadic cancer, including bladder cancers. Recently, sporadic bladder cancers have been shown to display a higher rate of microsatellite instability than other sporadic cancers. The goals of this application are to determine if mismatch repair deficiency is associated with sporadic bladder cancers and to isolate and characterize novel mismatch repair components/genes. Experiments will be developed in the following three specific areas. 1) The mismatch repair proficiency of bladder cell lines with microsatellite instability will be determined using an in vitro biochemical mismatch repair assay. 2) Novel mismatch repair activities will be first characterized by complementation experiments using the known mismatch repair proteins and/or mutant cell lines, and then be purified from HeLa nuclear extracts by virtue of their ability to restore mismatch repair to the novel mutant cell lines. 3) The gene(s) encoding the novel protein(s) will be cloned by the "reverse genetic" approach. Peptide sequences will be obtained from the novel protein(s) and used for designing degenerate primers to amplify DNA fragments of interest, which are in turn used to identify full length cDNAs. This study will not only provide insight into the etiology of sporadic bladder cancers, but also lead to the identification of novel mismatch repair components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOLID TUMOR Principal Investigator & Institution: Bosl, George J.; Chairman; Sloan-Kettering Institute for Cancer Res New York, Ny 10021

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Timing: Fiscal Year 2001; Project Start 01-JAN-1978; Project End 30-JUN-2005 Summary: (Applicant's Description) The Solid Tumor Project supports investigation of new therapy and predictors of outcome for cancers other than leukemia and the Lymphomas. Three specific aims focus on single and combination programs using specific malignancies as model systems on which hypotheses are tested. Specific Aim 1 evaluates new strategies and novel agents. Optimal dose-density achieved through dose escalation or shorter inter treatment intervals, or both, will be tested in patients with germ cell tumors and bladder cancer. Novel drugs, including the geldanamycins (GDM) (which interfere with normal hsp90 function), a new antifol (10-propargyl-10den7~nnlinopterin; PDX), and an epothilone derivative (desoxyepothilone B; dEPL-B) will be tested in single-agent and combination Phase II trials. Over the next five years, small cell and non-small cell lung cancer (NSCLC), bladder cancer, and head and neck cancer (H/N) will be model systems. Specific Aim 2 tests the hypothesis that drugs aimed at known cellular targets or with putative differentiating activity will be effective anticancer therapy. In this aim, vaccines aimed at known peptide, ganglioside, or carbohydrate antigens will be effective immunogenstigenic target. A polyvalent vaccine will be developed and tested prior to clinical trials to test the hypothesis that outcome will improve with treatment of minimal residual disease after surgery, radiation therapy, and/or chemotherapy in patients with breast and prostate cancer. An histone deacetylase inhibitor with putative differentiating capability, pyroximide, will be tested in breast and prostate cancer. In Specific Aim 3, new markers of survival and drug resistance and toxicity will be investigated. Comparative genomic hybridization will be performed on paraffin-embedded tumor tissue to test the hypothesis that highly amplified regions of chromosomal gain will occur more frequently in drug-resistant tumors than drug-sensitive tumors using breast; NSCLC, and H/N cancer as models. Magnetic resonance spectroscopy will test the hypothesis that changes in phospholipid metabolism predicts tumor sensitivity and/or outcome in H/N cancer and in patients with hepatic metastases. Limited sampling strategies will be applied across Phase II trials of PDX, GDM, dEPL-B, and pyroximide to determine pharmacodynamic relationships important to combination and Phase II trials. Most new agents to be studied in this project are the result of new drug development conducted at MSKCC. After Phase II trials, Phase III triais will be conducted if appropriate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUPERFUND TOXIC SUBSTANCES--EXPOSURE AND DISEASE Principal Investigator & Institution: Monson, Richard R.; Professor of Epidemiology; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 01-APR-1992; Project End 31-MAR-2005 Summary: Our theme is the understanding and assessment of risk to human health from exposure to hazardous substances. We approach this theme from the perspective of an interdisciplinary team that integrates exposure assessment, biologic pathogenesis, and epidemiologic studies. Our biomedical studies revolve around three classes of illness: reproductive health, cardio-respiratory health, and cancer. Our non-biomedical studies relate to health of the ecosystem and to factors that affect aquatic organisms. These studies encompass specific exposures to metals and to organo-chlorine compounds. Reproductive health is being evaluated in relation to environmental exposure to lead, mercury, polychlorinated biphenyls (PCBs) and related compounds; cardio-respiratory health is being evaluated in relation to occupational exposure to fuel oil ash, which contains a high level of vanadium and other metals; the occurrence of cancer and its

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precursors are being evaluated in relation to arsenic in drinking water supplies; the health of the ecosystem, specifically of aquatic organisms, is being evaluated in relation to the presence of metals, PCBs, and polyaromatic hydrocarbons (PAHs). Our general goal is to evaluate the relation between chemicals in the environment and their relation to human ill health. Our objectives include the following: - to assess the use of calcium supplements to minimize the adverse effects of lead on the fetus - to assess uncertainties in development effects in children related to multiple environmental exposure to metals and organic compounds - to evaluate the effects of in utero exposure to ambient levels of PCBs on growth and development of the child and on female reproductive health. - to evaluate the cardiac and respiratory effects of fuel-ash oil on the human lung and to determine the mechanism through which vanadium and other metallic components of fuel-ash adversely effect the heart and the lung - to evaluate the nature of the association between arsenic and skin and skin bladder cancers and their precursors and to assess the epigenetic mechanisms through which arsenic may affect human health - to evaluate the effects of these and related chemicals on the aquatic ecosystem so that a comprehensive approach can be developed to assess the health of the ecosystem - to develop an approach for exposure assessment and health evaluation in the community that will enable enlightened interaction between scientists and the community. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNERGISTIC CT BRONCHOSCOPY FOR LUNG CANCER ASSESSMENT Principal Investigator & Institution: Higgins, William E.; Professor; Electrical Engineering; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 28-FEB-2003 Summary: Lung cancer is the most common cause of cancer death in adults. Yet, no real advances have been made in the evaluation of suspected lung-cancer patients since the development of flexible bronchoscopy in the early 1970's and CT scanning in the early 1980's. To improve the care of lung-cancer patients, this project seeks to devise and validate a computer-based system, the 3D Navigator, that ties together threedimensional (3D)high-resolution computed tomographic (HRCT) imaging and bronchoscopy. The project is driven by the following hypothesis: A synergistic combination of 3D HRCT imaging, bronchoscopy, and image processing improves current procedures for HRCT-based lung- cancer assessment. Also, during bronchoscopy, this combination of tooLs permits more accurate assessment and higher biopsy yields. The 3D Navigator consists of a computer-based system that interfaces to a bronchoscope. It is used for initial HRCT assessment and concurrently during bronchoscopy. The system expands upon the new concept of virtual endoscopy: the physician interacts with the system's visual and quantitative tools to explore and evaluate, with impunity, the "virtual anatomy" embodied by a patient's 3D HRCT scan. When used during bronchoscopy, the 3D Navigator-gives the physician augmented vision, potentially increasing the likelihood of successful procedures. The women's Intervention Nutrition Study (WINS) is a prospective, randomized, multi-center clinical trIal testing the hypothesis that dietary fat intake reduction as an adjuvant to standard breast cancer therapy successful procedures. The project'S four specific aims are as follows. Aim 1: Construct the 3D Navigator system, including the maln software and bronchoscope interface. Aim 2: Devise automatic imageprocessing methods for 3D HRCT thoracic analysis; the methods, which assist the physician in CT assessment and bronchoscopy planning, focus on lesion/lymph-node detection, airway analysis,

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quantitation, and computation of "road maps" to suspect lesion sites. Aim 3: For CT-only assessment, validate the 3D Navigator versus standard human assessment. Aim 4: Validate the 3D Navigator when used concurrently with bronchoscopy. For aims 3 and 4, phantom, cadaver, and human studies are done; the impact of CT scanning protocol is also considered. In the long run, we believe that our combination of tools, as embodied in the 3D Navigator, will provide a more effective means for the early detection, staging, diagnosis, and treatment of lung cancer than the traditional approach using CT and bronchoscopy. It also could prove useful for general pulmonary disease assessment and treatment delivery. Finally, our proposed visual and quantitative methodology could have direct applicability to other endoscopic procedures such as mediastinoscopy, colonoscopy (colorectal cancer), and cystoscopy (bladder cancer). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETING GENE THERAPY TO BLADDER CANCER Principal Investigator & Institution: Dougherty, Graeme J.; Radiation Oncology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Bladder cancer is a common malignancy with approximately 55,000 new cases and nearly 12,000 deaths reported in the US annually. Although a high proportion of patients (65-70 percent) present with well or moderately well differentiated superficial transitional cell carcinomas, approximately 60-70 percent of these nevertheless go on to develop recurrent disease after resection of primary lesions. For this reason, surgery is often combined with various adjuvant therapies including intravesical chemotherapy and/or immunotherapy (i.e. BCG). While such treatments do improve control, relapses remain common encouraging consideration of various alternative approaches including gene therapy. The major objective of this proposal is to evaluate a novel gene therapy-based approach to the treatment of bladder cancer in which alternative splicing is used as a means of targeting the expression of the enzyme alkaline phosphatase (ALP) to tumor cells in vivo. Specifically, adenoviral vectors will be constructed in which the expression of ALP is dependent upon the accurate removal from chimeric pre-mRNA transcripts of alternatively spliced intronic sequences. These vectors will be used to confirm the targeting specificity of alternative splicing in vitro following transduction of a panel of bladder tumor cell lines that differ in expression of various alternatively spliced isoforms of the adhesion protein CD44. Adenoviral vectors will also be tested both in vitro and in an ex vivo explant model for their ability to sensitize bladder tumor cells that differ in alternative splicing ability, to killing by the inactive prodrug Etopophos, which is converted to the potent topoisomerase II inhibitor etoposide upon dephosphorylation by ALP. Finally, in order to better identify those patients most likely to benefit for this targeted therapy, studies will be initiated to define the transacting factors and cis-acting sequences that regulate the alternative splicing of CD44 in bladder tumor cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TARGETING PCD FOR CANCER THERAPY Principal Investigator & Institution: Clarke, Michael F.; Professor of Medicine, and Cell and Deve; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-JAN-2004

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Summary: Despite recent advances in the detection and treatment of most cancers, cancer related mortality has not decreased in the United States. In the near future, cancer is predicted to overtake heart disease as the number one cause of death. It is clear that new approaches are needed to treat these diseases. Cancer is the result of disruption of the pathways that regulate cell proliferation. These pathways include mitogenic signals, growth inhibitory signals, and cell survival signals. Preliminary evidence suggests that these latter signals differ between normal cells and cancer cells, as well as between cancers derived from solid tissue cells and hematopoietic cells. We postulate that better understanding these differences will allow the development of novel cancer therapies. The overall goals of this proposal are to understand the perturbations in the programmed cell death (PCD) pathway in cancer cells, and to determine whether the differences between cancer cells and normal cells can be exploited to develop new therapeutic agents. To accomplish these goals, adenovirus vectors will be used to specifically inactivate inhibitory components of the PCD pathway. Viruses that target three different points in the PCD pathway will be analyzed. These vectors, the bcl-x, adenovirus, the mbm-2 adenovirus, and the hrk adenovirus have several qualities that make them ideal agents that can be used to study both the biology and biochemistry of the PCD pathway and used as gene therapy agents. Cancers of Breast, Ovarian, Bladder and Hematopoietic origin will be analyzed. These cancers were chosen to explore differences in PCD pathways in these tumors, and because adenovirus vectors have therapeutic potential in these diseases. The projects in this proposal are integrated to achieve these goals. Project #1, Biochemistry and function of hrk, will examine the role of a new gene, hrk, in PCD in normal and cancer cells. An adenovirus vector that expresses hrk will be made and used by each project to determine the role of this gene in PCD in each respective type of cancer cell. Project #2, Targeting PCD in Breast and Ovarian cancer cells will utilize each of the adenovirus vectors for effects on normal and malignant breast cancer cells. Animal models to test the utility of these vectors are described. Clinical trials using the bcl-x/s adenovirus in high dose chemotherapy and autologous BMT in breast cancer and for treatment of ascites in patients with ovarian cancer are planned. Project #3, targeting PCD in Leukemia, will explore the regulation of PCD in normal and leukemic hematopoietic cells. Strategies to use adenovirus to specifically kill leukemia cells contaminating the bone marrow of cells used for autologous BMT will be tested. Project #4, Targeting PCD in bladder cancer, will determine the role of the bcl-2 family in bladder cancer. Clinical trials using the bcl-x/s adenovirus are envisioned. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETING PCD IN BLADDER CANCER Principal Investigator & Institution: Sanda, Martin G.; Assistant Professor of Urology and Oncol; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001 Summary: Over fifty thousand cases of transitional cell carcinoma (TCC) of the bladder are diagnosed in the United States yearly. Most patients initially present with superficial bladder TCC and those with high grade TCC eventually recur or progress. The preliminary and proposed studies are based on the hypothesis that adenovirus vectormediated gene transfer of apoptosis-inducing genes is a rational alternative for intravesical TCC therapy. WE evaluated basal expression of BCL-X/L (an inhibitor of apoptosis) in human TCC. Immunohistochemistry showed Bcl-X protein overexpression in malignant compared to normal transitional epithelium. Western blot

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determined that this protein was Bcl-X/L and that Bcl-X/S, was not detectable in malignant or normal transitional epithelium. This provided rationale for evaluating the ability of Ad- bcl-x/S (an adenoviral vector carrying the Bclx-S gene) to induce apoptosis in TCC. The receptivity of transitional epithelium for gene transfer by adenoviral vectors in vivo was demonstrated by detecting lacZ expression after intravesical instillation of Ad-lacZ (an adenoviral vector carrying the lacZ reporter gene). Vector dose- dependent apoptosis was specifically induced after infection of TCC by Ad-bcl-X/S in vitro. Analysis of T cell proliferation after administration of Ad-bclX/S showed that the presence of bcl-X/S does not abrogate vector-specific immunity. Based on these preliminary findings, this project will address three specific aims: 1) To determine the effects of Ad-bcl-X/S and Ad-hrk on apoptosis in normal versus cancerous transitional epithelium in vivo. Gene transfer efficiency, apoptosis induction, and tumor progression in vivo and toxicity will be measured after intravesical administration of Ad-bcl-X/S Ad-hrk or AdlacZ in rodent models of TCC. 2) To evaluate resistance mechanism to apoptosis-inducing adenovirus vector efficacy. Effects of Bcl-X/L expression and p53 status on apoptosis induction will be evaluated as possible resistance mechanisms to Ad-bcl-X/S gene therapy. 3) To characterize the immune response to regionally administered , apoptosis- inducing, adenovirus vectors. Effects of presenting cell apoptosis on vector-specific T cell and neutralizing antibody induction and the interaction of tumor-specific and vector-specific immunity will be evaluated. These studies will serve to guide design of clinical trials evaluating the safety and efficacy of apoptosis-inducing adenovirus vectors as intravesical therapy for TCC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF ACTIN POLYMERIZATION IN TUMOR METASTASIS Principal Investigator & Institution: Zhan, Xi; Associate Professor; American National Red Cross Rockville, Md 20855 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant) The long-term goal of this application is to understand the molecular mechanism ot tumor metastasis. Prior works have established that amplification of the chromosome 11q13, which occurs frequently in breast cancer, head and neck squamous carcinomas and bladder cancer, results in overexpression of cortactin or EMS 1, a prominent substrate of protein tyrosine kinase Src with potential to associate with actin filaments. Patients with gene amplification of cortactin tend to have poor prognosis and increased possibility of relapse. However, the mechanism by which cortactin contributes to tumor progression is still unknown. There has been accumulated evidence that cortactin is implicated in the modulation of cell cytoskeletal changes associated with cell motility and cell shape changes. Our recent study further demonstrated that cortactin plays an important role in actin polymerization via interaction with Arp2/3 complex, a key protein machinery to initiate actin polymerization within cells. Furthermore, cortactin modulates the activity of Arp2/3 complex for actin nucleation and actin branching, two important steps in the formation of cell leading edge structures. We also found that overexpression of wild-type cortactin can enhance cell motility in vitro and facilitate tumor metastasis in vivo, whereas overexpression of cortactin mutants either in tyrosine phosphorylation or Arp2/3 binding can impair cell migration and bone metastasis. Based on these observations, we hypothesize that actin polymerization mediated by Arp2/3 complex and cortactin plays an important role in tumor metastasis. To test this hypothesis, we propose to delineate the detailed interactions among Arp2/3 complex and cortactin, explore the regulation of cortactin/Arp2/3 complex by Src, PIP2 and other cellular factors, and to test the

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hypothesis whether or not inhibition of actin polymerization by disruption of these interactions would be effectively able to compromise metastasis in vivo. Thus, the specific aims for this application include: (1) Characterization of the mechanism by which cortactin activates the activity of Arp2/3 complex for actin nucleation and branching. We will characterize the structural basis for the interactions between cortactin and Arp2/3 complex, examine the mechanism by which cortactin enhances actin nucleation and promotes and stabilizes actin branching. (2) Study of the regulation of cortactin/Arp2/3-mediated actin nucleation and branching. We will assess the effect of Src and PIP2 on the actin nucleation and branching mediated by cortactin/Arp2/3 complex in vitro, and search for other cellular factor(s) through which Src, PIP2, Cdc42 and Rac may regulate the function of cortactin/Arp2/3 complex. (3) Analysis of the effects of the mutants derived from Arp2/3 and cortactin on tumor metastasis. We will introduce using retrovirus functional peptides derived from Arp2/3 and cortactin that can disrupt or enhance actin polymerization into MDA-MB-23 1 tumor cells. Next, we will evaluate the motility and metastatic potentials of these cells both in vitro and in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF CAR AND ITS APPLICATION IN BLADDER CANCER Principal Investigator & Institution: Hsieh, Jer-Tsong; Surgery; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): With over 50,000 new cases and 10,000 deaths expected this year in the U.S, bladder cancer is a significant health concern. Variable morphology, natural history, and prognosis demonstrate that transitional cell carcinoma (TCC) of the bladder is not a single disease, but occurs in three distinct forms, each possessing characteristic features (i.e., low grade papillary, noninvasive; carcinoma in situ; high grade, invasive). Recent studies have begun to elucidate the underlying genetic determinants of the morphologic and biologic characteristics of these different presentations of bladder cancer. Molecular and genetic alterations that precede morphologic changes, and which are responsible for tumorigenesis and progression of TCC. Understanding these genetic changes should eventually lead to improved diagnosis and gene therapy for TCC. Identification of a coxsackie and adenovirus receptor (CAR), a high receptor for adenovirus type 5, was recently reported. The heterogeneous expression of CAR is detected in several TCC and prostate cancer cell lines. This expression resulted from the downregulation of CAR gene transcription. By increasing their CAR levels, resistant cells could become highly sensitive to adenoviral infection. Therefore, CAR not only is a surrogate marker to monitor the outcome of gene therapy, but also facilitate the efficiency of gene therapy. The Down-regulation of CAR is often seen in TCC lesions but not in adjacent normal tissue, which suggests that CAR may play a pathophysiologic role in the progression of TCC. Also, CAR is associated with a tight junction protein in differentiated polarized cell. Moreover, increased CAR gene expression can inhibit the in vitro and in vivo growth of tumor cells. On the other hand, decreasing CAR expression (using antisense vector) in several TCC cell lines can facilitate the in vitro and in vivo growth rate. These data indicate that CAR is a tumor inhibitor in TCC cells. To further elucidate the underlying mechanism of CAR in TCC cells, preliminary data indicated that (1) CAR is a typical cell adhesion molecule; (2) CAR is associated with tight junction complex; (3) adhesion activity of CAR parallels its growth inhibitory function; (4) the intracellular domain of CAR is critical for inducing its growth inhibitory signal in TCC cells; (5) CAR is able to inhibit cyclooxygenase 2

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(COX-2) expression. Based on these results, we hypothesize that CAR can inhibit cell growth by reestablishing intercellular interactions of TCC, and the mechanism of CAR action is to inhibit COX-2 expression in TCC. Since the biology of CAR and COX-2 is largely unknown, we plan to (1) establish a reciprocal relationship between CAR and COX-2 from TCC specimens of different grades and stages; (2) unveil downstream pathway(s) elicited by CAR that activates its tumor inhibition and to determine any other ligand(s) capable of activating CAR signaling; (3) determine the biologic significance of the suppression of COX-2 by CAR; (4) increase therapeutic efficacy of TCC gene therapy by enhancing its endogenous CAR expression. The outcome of this study should help us understand the biologic role of CAR in the progression of TCC and develop a new strategy for TCC therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THROMBOSPONDIN-1 IN PROSTATE DEVELOPMENT AND NEOPLASIA Principal Investigator & Institution: Crawford, Susan E.; Associate Professor; Pathology; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Thrombospondin-1 (TSP-1) is a homotrimeric secreted glycoprotein that functions in a wide variety of biologic activities including embryonic development, tissue differentiation, neurite outgrowth, and responses to injury and inflammation. TSP-1 is also a potent inhibitor of angiogenesis, the growth of new blood vessels from the existing vasculature. Decreased TSP-1 expression contributes to the angiogenic environment that supports the growth of glioblastoma, fibrosarcomas and bladder cancer. Data is presented that show TSP-1 expression is down-regulated or lost in benign prostatic hyperplasia (BPH) and prostate cancer and identify TSP-1 as a key functional inhibitor of angiogenesis in the prostate. The normal and diseased prostate is exquisitely sensitive to changes in TSP-1 levels as TSP-1 null mice develop prostatic hyperplasia and TSP-1 expression increased after androgen ablation therapy in human prostate cancer specimens. Thus, we hypothesize that TSP- 1 plays a key role in the regulation of normal prostatic growth and that dysregulated TSP1 expression contributes to disease. To study the functions of TSP-1 in normal prostate growth and discern how dysregulated expression contributes to disease states, we plan to 1) characterize the prostate phenotype in the TSP-1 null mice, establishing a time course of disease development, and determine the underlying mechanism of the hyperplasia (i.e. increased proliferation or angiogenesis, decreased apoptosis or a combination of these), and 2) determine if androgen regulation of TSP-1 expression is critical to modulation of prostatic growth, using in vitro methods and the TSP-1 null mouse model. Results from these experiments should establish the function of TSP-1 in prostatic growth regulation and determine how TSP-1 may be useful as a prognostic indicator or as a treatment for prostatic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TOBACCO AND CANCER RISK--DOSE, METABOLISM AND GENETICS Principal Investigator & Institution: Richie, John P.; Director; Institute for Cancer Prevention 1 Dana Rd Valhalla, Ny 10595 Timing: Fiscal Year 2003; Project Start 08-SEP-1995; Project End 28-FEB-2005

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Summary: (Applicant's Description) Studies from our group and others have demonstrated that the risk for tobacco-related cancers differs by race, gender and type of tobacco product consumed. These important public health differences cannot be fully explained by existing patterns of tobacco consumption. We hypothesize that risk is related to the type of cigarette smoked (e.g., low versus medium yield of carcinogens), the manner in which an individual's smoking habit regulates the dosage that reaches the lungs, metabolic capacity to activate and detoxify smoke-borne carcinogens, and susceptibility to cancer related to genetic factors that may affect metabolism or DNA repair. During the first three years of the study, the program focused on epidemiology, dosage and biomarkers of dose, and metabolic pathways of carcinogen activation and detoxification. In the coming period, the former Project (epidemiology) will be replaced by an epidemiological core facility (Core C) to provide appropriate study subjects for the two continuing projects and one new project. The current Project (Dosimetry of Lung and Bladder Cancer Risk among Cigarette Smokers) is about how smoking behavior affects the "delivered" carcinogen dose, and in turn how dose is related to biomarkers of carcinogen metabolites. Project (Metabolic Epidemiology of TobaccoRelated Cancers in Black and White Americans) is a study of differences between African Americans and Caucasians in metabolic activation and/or detoxification of an array of carcinogens derived from cigarette smoking, such as NNK (a potent lung carcinogen) and 4-aminobiphenyl (a bladder carcinogen). It utilizes metabolic and molecular techniques to study pathways of activation of tobacco-derived nitrosamines related to lung cancer, which is higher in African Americans compared to Caucasians, as well as detoxification of aromatic amines involved in bladder cancer, the rate of which is lower. Project (UDP Glucuronosyltransferases, Detoxification of NNK and Lung Cancer Risk) focuses on a family of detoxification enzymes that may be related to individual risk for developing lung or bladder cancer, and for which genetic polymorphisms exist that might explain variation in cancer risk. A broader understanding of these factors, both individually and comprehensively, will contribute greatly to our understanding of the causes of tobacco-related cancers in a way that can help improve our prevention strategies. The investigators are leaders in their respective fields with a strong history of collaboration. The program is supported by an Administrative Core with an Advisory Board of distinguished scientists and a community representative, by a Biostatistics and Computing Core Facility to provide efficient data management and statistical support, and by an Epidemiology Core Facility to manage accrual of subjects, interviews, acquisition of buccal cells, urine, and blood for biomarker assays, and pathological review. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOXIC METALS IN THE NORTHEAST: FROM BIOLOGICAL TO ENVIRO Principal Investigator & Institution: Hamilton, Joshua W.; Associate Professor; Pharmacology and Toxicology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-MAR-2005 Summary: The overall goal of the Dartmouth SBRP Program Project, Toxic Metals in the Northeast: From Biological to Environmental Implications, is to determine the impact of toxic metals found at Superfund sites, at other waste sites, and in the environment on adverse effects on human health and the environment. Eight of the twenty-two agents on the ATSDR priority list. Over 60% of all Superfund sites contain significant toxic metal contamination, and more than 70% of these contain arsenic, which is the top

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ATSDR agent of concern. The distinct and program-wide focus of this research program is on toxic metals, and particularly on arsenic, which is being examined in all their goals and scientific focus, including chromium, nickel, cadmium, mercury, cobalt and lead. This program consists of five biomedical projects (Projects 1-5), two non-biomedical projects (Projects 6, 7), and three program support cores (Molecular Biology, Trace Metals Analysis and Biostatistics), plus an Administrative core, Training laboratory investigations on the cellular and molecular mechanisms of toxic metal actions in humans and include Project 1 (arsenic-induced vascular disease), Project 2 (arsenic- and chromium- induced cancer), Project 3 (arsenic effects on xenobiotic metabolism) and Project 5 (interactions of toxic metals with cellular proteins). The second includes Project 4 (human epidemiology of arsenic and skin and bladder cancer), Project 6 (sources, fate and third area involves development and implementation of molecular biomarkers of toxic metal exposure and health elucidate the sub-set of genes, mRNAs and proteins whose expression is specifically modified by toxic metal mechanistic laboratory studies and in the ecology and epidemiology projects. The multi- disciplinary nature of this program, combined with its unique program- wide focus on arsenic and other toxic metals, is designed to create and foster an environment for truly inter-disciplinary yet focused research, training and outreach. 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 “bladder 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 bladder cancer in the PubMed Central database: •

Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder. by Vaidyanathan S, Mansour P, Ueno M, Yamazaki K, Wadhwa M, Soni BM, Singh G, Hughes PL, Watson ID, Sett P.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126229

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Relationship between Schistosomiasis and Bladder Cancer. by Mostafa MH, Sheweita SA, O'Connor PJ.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88908

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.

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

A clinical study of PMCJ-9 (Bacillus Calmette-Guerin Connaught strain) treatment of superficial bladder cancer and carcinoma in situ of the bladder. Author(s): Akaza H, Koiso K, Ozono S, Kuroda M, Kameyama S, Okajima E, Kotake T, Kakizoe T, Kawabe K; PMCJ-9 Study Group in Japan. Source: Japanese Journal of Clinical Oncology. 2003 August; 33(8): 382-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523057&dopt=Abstract

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A critical analysis of the use of p53 as a marker for management of bladder cancer. Author(s): Olumi AF. Source: The Urologic Clinics of North America. 2000 February; 27(1): 75-82, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696247&dopt=Abstract

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A multicenter study of the morbidity of radical cystectomy in select elderly patients with bladder cancer. Author(s): Soulie M, Straub M, Game X, Seguin P, De Petriconi R, Plante P, Hautmann RE. Source: The Journal of Urology. 2002 March; 167(3): 1325-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832724&dopt=Abstract

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A randomized trial comparing intravesical instillations of mitoxantrone and doxorubicin in patients with superficial bladder cancer. Author(s): Huang JS, Chen WH, Lin CC, Liaw CC, Wang CH, Lan YJ, Lai CH, Liu JP. Source: Chang Gung Med J. 2003 February; 26(2): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718385&dopt=Abstract

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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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A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire. Author(s): Chahal R, Sundaram SK, Iddenden R, Forman DF, Weston PM, Harrison SC. Source: European Urology. 2003 March; 43(3): 246-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600427&dopt=Abstract

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Accelerated superfractionated radiotherapy with concomitant boost for invasive bladder cancer. Author(s): Yavuz AA, Yavuz MN, Ozgur GK, Colak F, Ozyavuz R, Cimsitoglu E, Ilis E. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 July 1; 56(3): 734-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788179&dopt=Abstract

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Acute mental changes in a 68-year-old man with bladder cancer. Author(s): Griggs H, Cammarata SK. Source: Chest. 1998 August; 114(2): 621-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9726755&dopt=Abstract

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Adherence to surveillance among patients with superficial bladder cancer. Author(s): Schrag D, Hsieh LJ, Rabbani F, Bach PB, Herr H, Begg CB. Source: Journal of the National Cancer Institute. 2003 April 16; 95(8): 588-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697851&dopt=Abstract

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Allelic changes at multiple regions of chromosome 5 are associated with progression of urinary bladder cancer. Author(s): von Knobloch R, Bugert P, Jauch A, Kalble T, Kovacs G. Source: The Journal of Pathology. 2000 February; 190(2): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10657014&dopt=Abstract

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Allelic imbalances in human bladder cancer: genome-wide detection with highdensity single-nucleotide polymorphism arrays. Author(s): Primdahl H, Wikman FP, von der Maase H, Zhou XG, Wolf H, Orntoft TF. Source: Journal of the National Cancer Institute. 2002 February 6; 94(3): 216-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11830611&dopt=Abstract

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Alteration of the PATCHED locus in superficial bladder cancer. Author(s): Aboulkassim TO, LaRue H, Lemieux P, Rousseau F, Fradet Y. Source: Oncogene. 2003 May 15; 22(19): 2967-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771948&dopt=Abstract

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Alternatives to cystectomy in muscle-invasive bladder cancer. Author(s): Goel S. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 1; 21(15): 3003; Author Reply 3003-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885826&dopt=Abstract

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An association between NQO1 genetic polymorphism and risk of bladder cancer. Author(s): Park SJ, Zhao H, Spitz MR, Grossman HB, Wu X. Source: Mutation Research. 2003 April 20; 536(1-2): 131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694753&dopt=Abstract

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An overview of the treatment of superficial bladder cancer. Intravesical chemotherapy. Author(s): Duque JL, Loughlin KR. Source: The Urologic Clinics of North America. 2000 February; 27(1): 125-35, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696251&dopt=Abstract

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Analysis of the Na,K-ATPase alpha- and beta-subunit expression profiles of bladder cancer using tissue microarrays. Author(s): Espineda C, Seligson DB, James Ball W Jr, Rao J, Palotie A, Horvath S, Huang Y, Shi T, Rajasekaran AK. Source: Cancer. 2003 April 15; 97(8): 1859-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673711&dopt=Abstract

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Antineoplastic activity of honey in an experimental bladder cancer implantation model: in vivo and in vitro studies. Author(s): Swellam T, Miyanaga N, Onozawa M, Hattori K, Kawai K, Shimazui T, Akaza H. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 April; 10(4): 213-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657101&dopt=Abstract

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Antitumor effects of piroxicam in spontaneous canine invasive urinary bladder cancer, a relevant model of human invasive bladder cancer. Author(s): Knapp DW, Glickman NW, Mohammed SI, DeNicola DB, Widmer WR, Bonney PL, DeGortari AE. Source: Advances in Experimental Medicine and Biology. 2002; 507: 377-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664613&dopt=Abstract

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Application of Photofrin II as a specific radiosensitising agent in patients with bladder cancer--a report of two cases. Author(s): Schaffer M, Schaffer PM, Vogesser M, Ertl-Wagner B, Rauch J, Oberneder R, Jori G, Hofstetter A, Duhmke E. Source: Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology. 2002 September; 1(9): 686-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665306&dopt=Abstract

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Aromatic amines and human urinary bladder cancer: exposure sources and epidemiology. Author(s): Talaska G. Source: Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews. 2003 May; 21(1): 29-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826031&dopt=Abstract

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Arsenic methylation and bladder cancer risk in Taiwan. Author(s): Chen YC, Su HJ, Guo YL, Hsueh YM, Smith TJ, Ryan LM, Lee MS, Christiani DC. Source: Cancer Causes & Control : Ccc. 2003 May; 14(4): 303-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846360&dopt=Abstract

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bc10: A novel human bladder cancer-associated protein with a conserved genomic structure downregulated in invasive cancer. Author(s): Gromova I, Gromov P, Celis JE. Source: International Journal of Cancer. Journal International Du Cancer. 2002 April 1; 98(4): 539-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920613&dopt=Abstract

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BCG (Bacillus of Calmette Guerin) therapy of high-risk superficial bladder cancer. Author(s): Bassi P. Source: Surgical Oncology. 2002 June; 11(1-2): 77-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031870&dopt=Abstract

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BCG effects on telomerase activity in bladder cancer cell lines. Author(s): Saitoh H, Mori K, Kudoh S, Itoh H, Takahashi N, Suzuki T. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2002 June; 7(3): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109518&dopt=Abstract

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BCG installations for bladder cancer and latent tuberculosis infection. Author(s): Hanson K. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2002 April; 22(2): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11993243&dopt=Abstract

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BCG-induced interleukin-6 upregulation and BCG internalization in well and poorly differentiated human bladder cancer cell lines. Author(s): Bevers RF, de Boer EC, Kurth KH, Schamhart DH. Source: Eur Cytokine Netw. 1998 June; 9(2): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9681394&dopt=Abstract

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Beta-catenin mutations correlate with over expression of C-myc and cyclin D1 Genes in bladder cancer. Author(s): Shiina H, Igawa M, Shigeno K, Terashima M, Deguchi M, Yamanaka M, Ribeiro-Filho L, Kane CJ, Dahiya R. Source: The Journal of Urology. 2002 November; 168(5): 2220-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394763&dopt=Abstract

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Bilateral serous macular detachment in a patient with anaemic retinopathy secondary to gall bladder cancer. Author(s): Kunikata H, Udono T, Nishikawa S, Tamai M. Source: The British Journal of Ophthalmology. 2002 December; 86(12): 1456-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446401&dopt=Abstract

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Bladder cancer among chemical workers exposed to nitrogen products and other substances. Author(s): Marsh GM, Gula MJ, Youk AO, Cassidy LD. Source: American Journal of Industrial Medicine. 2002 October; 42(4): 286-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271476&dopt=Abstract

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Bladder cancer in pregnancy. Author(s): Mitra S, Williamson JG, Bullock KN, Arends M. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 July; 23(4): 440-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881096&dopt=Abstract

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Bladder cancer incidence in the world. Author(s): Yamamoto S. Source: Japanese Journal of Clinical Oncology. 2002 June; 32(6): 224. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123249&dopt=Abstract

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Bladder cancer recurrence by implantation of exfoliated cells: is gamma-linolenic acid an effective tumoricidal agent? Author(s): Solomon LZ, Jennings AM, Foley SJ, Birch BR, Cooper AJ. Source: British Journal of Urology. 1998 July; 82(1): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9698674&dopt=Abstract

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Bladder cancer screening program for a petrochemical cohort with potential exposure to beta-napthylamine. Author(s): Felknor SA, Delclos GL, Lerner SP, Burau KD, Wood SM, Lusk CM, Jalayer AD. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2003 March; 45(3): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661186&dopt=Abstract

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Bladder cancer. Author(s): Borden LS Jr, Clark PE, Hall MC. Source: Current Opinion in Oncology. 2003 May; 15(3): 227-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778017&dopt=Abstract

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Bladder cancer. Author(s): Patton SE, Hall MC, Ozen H. Source: Current Opinion in Oncology. 2002 May; 14(3): 265-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981270&dopt=Abstract

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Bladder cancer: a current update. Author(s): Masood S, Wazait HD, Arya M, Patel HR. Source: Hosp Med. 2003 January; 64(1): 40-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572335&dopt=Abstract

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Bladder cancer: allelic deletions at and around the retinoblastoma tumor suppressor gene in relation to stage and grade. Author(s): Wada T, Louhelainen J, Hemminki K, Adolfsson J, Wijkstrom H, Norming U, Borgstrom E, Hansson J, Sandstedt B, Steineck G. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 February; 6(2): 610-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10690546&dopt=Abstract

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Bladder cancer: epidemiology, diagnosis, and management. Author(s): Pashos CL, Botteman MF, Laskin BL, Redaelli A. Source: Cancer Practice. 2002 November-December; 10(6): 311-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406054&dopt=Abstract

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Bladder cancer--room for improvement. Author(s): Bloomfield DJ. Source: Clin Oncol (R Coll Radiol). 2002 April; 14(2): 139-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12069123&dopt=Abstract

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Bladder-sparing procedure as good as cystectomy for treating invasive bladder cancer. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2002 August 9; 13(15): 7-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553324&dopt=Abstract

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Bropirimine, an orally active anticancer agent for superficial bladder cancer. Author(s): Akaza H, Kotake T, Machida T. Source: European Urology. 1998 August; 34(2): 107-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9693244&dopt=Abstract

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Can p53 staining be used to identify patients with aggressive superficial bladder cancer? Author(s): Masters JR, Vani UD, Grigor KM, Griffiths GO, Crook A, Parmar MK, Knowles MA; MRC Superficial Bladder Cancer Group Mitomycin-C Trial Collaborators. Source: The Journal of Pathology. 2003 May; 200(1): 74-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692844&dopt=Abstract

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Centrosomal abnormality is common in and a potential biomarker for bladder cancer. Author(s): Jiang F, Caraway NP, Sabichi AL, Zhang HZ, Ruitrok A, Grossman HB, Gu J, Lerner SP, Lippman S, Katz RL. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 20; 106(5): 661-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866024&dopt=Abstract

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Centrosome hyperamplification and chromosomal instability in bladder cancer. Author(s): Kawamura K, Moriyama M, Shiba N, Ozaki M, Tanaka T, Nojima T, Fujikawa-Yamamoto K, Ikeda R, Suzuki K. Source: European Urology. 2003 May; 43(5): 505-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705995&dopt=Abstract

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cIAP-2 block apoptotic events in bladder cancer cells. Author(s): Jonsson G, Paulie S, Grandien A. Source: Anticancer Res. 2003 July-August; 23(4): 3311-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926068&dopt=Abstract

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Clinical significance of heat shock protein-70 expression in bladder cancer. Author(s): Syrigos KN, Harrington KJ, Karayiannakis AJ, Sekara E, Chatziyianni E, Syrigou EI, Waxman J. Source: Urology. 2003 March; 61(3): 677-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639682&dopt=Abstract

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Clinical significance of nuclear p53 protein accumulation in bladder cancer. Author(s): Toktas G, Turkeri LN, Unluer E, Caliskan M, Aksoy B, Akdas A. Source: International Urology and Nephrology. 1999; 31(3): 327-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10672952&dopt=Abstract

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Clinical study of G3 superficial bladder cancer without concomitant CIS treated with conservative therapy. Author(s): Saika T, Tsushima T, Nasu Y, Arata R, Kaku H, Kusaka N, Kumon H. Source: Japanese Journal of Clinical Oncology. 2002 November; 32(11): 461-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499418&dopt=Abstract

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Combination of adenovirus-mediated thymidine kinase gene therapy with cytotoxic chemotherapy in bladder cancer in vitro. Author(s): Freund CT, Tong XW, Rowley D, Engehausen D, Frolov A, Kieback DG, Lerner SP. Source: Urologic Oncology. 2003 May-June; 21(3): 197-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810206&dopt=Abstract

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Combined effect of glutathione S-transferase M1 and T1 genotypes on bladder cancer risk. Author(s): Lee SJ, Cho SH, Park SK, Kim SW, Park MS, Choi HY, Choi JY, Lee SY, Im HJ, Kim JY, Yoon KJ, Choi H, Shin SG, Park TW, Rothman N, Hirvonen A, Kang D. Source: Cancer Letters. 2002 March 28; 177(2): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825664&dopt=Abstract

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Comparison of aminolevulinic acid and hexylester aminolevulinate induced protoporphyrin IX distribution in human bladder cancer. Author(s): Marti A, Jichlinski P, Lange N, Ballini JP, Guillou L, Leisinger HJ, Kucera P. Source: The Journal of Urology. 2003 August; 170(2 Pt 1): 428-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853792&dopt=Abstract

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Comparison of human telomerase RNA and telomerase activity in urine for diagnosis of bladder cancer. Author(s): Muller M, Krause H, Heicappell R, Tischendorf J, Shay JW, Miller K. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1998 August; 4(8): 1949-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9717824&dopt=Abstract

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Comparison of molecular and conventional strategies for followup of superficial bladder cancer using decision analysis. Author(s): Nam RK, Redelmeier DA, Spiess PE, Sampson HA, Fradet Y, Jewett MA. Source: The Journal of Urology. 2000 March; 163(3): 752-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10687970&dopt=Abstract

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Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. Author(s): Chen WC, Liaw CC, Chuang CK, Chen MF, Chen CS, Lin PY, Chang PL, Chu SH, Wu CT, Hong JH. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 July 1; 56(3): 726-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788178&dopt=Abstract

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Connexin 26 is abnormally expressed in bladder cancer. Author(s): Gee J, Tanaka M, Grossman HB. Source: The Journal of Urology. 2003 March; 169(3): 1135-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576868&dopt=Abstract

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Contemporary concepts of radical cystectomy and the treatment of bladder cancer. Author(s): Stein JP. Source: The Journal of Urology. 2003 January; 169(1): 116-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478116&dopt=Abstract

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Correlation of preoperative levels of IGF-I and IGFBP-3 with pathologic parameters and clinical outcome in patients with bladder cancer. Author(s): Shariat SF, Kim J, Nguyen C, Wheeler TM, Lerner SP, Slawin KM. Source: Urology. 2003 February; 61(2): 359-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597948&dopt=Abstract

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Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83. Author(s): Brown J, Reading SJ, Jones S, Fitchett CJ, Howl J, Martin A, Longland CL, Michelangeli F, Dubrova YE, Brown CA. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2000 January; 80(1): 37-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653001&dopt=Abstract

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Current understanding of the biology of advanced bladder cancer. Author(s): Al-Sukhun S, Hussain M. Source: Cancer. 2003 April 15; 97(8 Suppl): 2064-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673698&dopt=Abstract

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Current use and questions concerning intravesical bladder cancer group for superficial bladder cancer. Author(s): Dalbagni G, Herr HW. Source: The Urologic Clinics of North America. 2000 February; 27(1): 137-46,. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696252&dopt=Abstract

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Cytofluorimetric evaluation of DNA ploidy in the diagnosis of bladder cancer. Author(s): Armone S, Voce S, dal Pozzo C, Severini G, Montanari F, Monti G, Tavolazzi L. Source: Arch Esp Urol. 1998 June; 51(5): 507-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9675952&dopt=Abstract

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Death receptor 4 and bladder cancer risk. Author(s): Hazra A, Chamberlain RM, Grossman HB, Zhu Y, Spitz MR, Wu X. Source: Cancer Research. 2003 March 15; 63(6): 1157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649168&dopt=Abstract

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Delaying radical cystectomy for muscle invasive bladder cancer results in worse pathological stage. Author(s): Chang SS, Hassan JM, Cookson MS, Wells N, Smith JA Jr. Source: The Journal of Urology. 2003 October; 170(4 Pt 1): 1085-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501697&dopt=Abstract

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Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U.S. population. Author(s): Karagas MR, Tosteson TD, Blum J, Morris JS, Baron JA, Klaue B. Source: Environmental Health Perspectives. 1998 August; 106 Suppl 4: 1047-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9703491&dopt=Abstract

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Detecting homozygous deletions in the CDKN2A(p16(INK4a))/ARF(p14(ARF)) gene in urinary bladder cancer using real-time quantitative PCR. Author(s): Berggren P, Kumar R, Sakano S, Hemminki L, Wada T, Steineck G, Adolfsson J, Larsson P, Norming U, Wijkstrom H, Hemminki K. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 January; 9(1): 235-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538475&dopt=Abstract

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Detection and quantification of soluble intercellular adhesion molecule-1 (sICAM-1) in the serum and urine of patients with bladder cancer. Author(s): Shi BB, Goya N, Okuda H, Ryoji O, Nakazawa H, Toma H. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 1998 July; 5(4): 324-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9712439&dopt=Abstract

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Detection of bladder cancer by multitarget multicolour FISH: comparative analysis on archival cytology and paraffin-embedded tissue. Author(s): Mezzelani A, Dagrada G, Alasio L, Sozzi G, Pilotti S. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2002 October; 13(5): 317-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421448&dopt=Abstract

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Detection of bladder cancer using single-photon emission computed tomography of thallium-201: a preliminary report. Author(s): Yang CC, Shiau YC, Sun SS, Kao CH. Source: Anticancer Res. 2003 May-June; 23(3C): 2977-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926148&dopt=Abstract

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Detection of human telomerase reverse transcriptase mRNA in urine of patients with bladder cancer: evaluation of an emerging tumor marker. Author(s): Melissourgos N, Kastrinakis NG, Davilas I, Foukas P, Farmakis A, Lykourinas M. Source: Urology. 2003 August; 62(2): 362-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893365&dopt=Abstract

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Detection of loss of heterozygosity in the p53 tumor-suppressor gene with PCR in the urine of patients with bladder cancer. Author(s): Friedrich MG, Erbersdobler A, Schwaibold H, Conrad S, Huland E, Huland H. Source: The Journal of Urology. 2000 March; 163(3): 1039-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10688045&dopt=Abstract

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Detection of the presence of catalytic subunit mRNA associated with telomerase gene in exfoliated urothelial cells from patients with bladder cancer. Author(s): Isurugi K, Suzuki Y, Tanji S, Fujioka T. Source: The Journal of Urology. 2002 October; 168(4 Pt 1): 1574-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352460&dopt=Abstract

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Diagnostic value of cytokeratin-18 as a tumor marker in bladder cancer. Author(s): Ramazan Sekeroglu M, Aydin S, Dulger H, Yilmaz Y, Bayrakli H, Noyan T. Source: Clinical Biochemistry. 2002 June; 35(4): 327-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135697&dopt=Abstract

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Dietary soy and increased risk of bladder cancer: the Singapore Chinese Health Study. Author(s): Sun CL, Yuan JM, Arakawa K, Low SH, Lee HP, Yu MC. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 December; 11(12): 1674-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496060&dopt=Abstract

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Differences between local and review urinary cytology in diagnosis of bladder cancer. An interobserver multicenter analysis. Author(s): Raitanen MP, Aine R, Rintala E, Kallio J, Rajala P, Juusela H, Tammela TL; FinnBladder Group. Source: European Urology. 2002 March; 41(3): 284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180229&dopt=Abstract

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Differential expression of hMLH1 and hMSH2 is related to bladder cancer grade, stage and prognosis but not microsatellite instability. Author(s): Catto JW, Xinarianos G, Burton JL, Meuth M, Hamdy FC. Source: International Journal of Cancer. Journal International Du Cancer. 2003 July 1; 105(4): 484-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712438&dopt=Abstract

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Disease specific survival as endpoint of outcome for bladder cancer patients following radical cystectomy. Author(s): Gschwend JE, Dahm P, Fair WR. Source: European Urology. 2002 April; 41(4): 440-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074817&dopt=Abstract

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Distal ureteral stenosis after early adjuvant intravesical mitomycin C application for superficial bladder cancer. Author(s): Oehlschlager S, Loessnitzer A, Froehner M, Hakenberg OW, Manseck A, Wirth MP. Source: Urologia Internationalis. 2003; 70(1): 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566821&dopt=Abstract

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DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk. Author(s): Stern MC, Umbach DM, Lunn RM, Taylor JA. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 September; 11(9): 939-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223443&dopt=Abstract

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Does fluid intake influence the risk for urinary incontinence, urinary tract infection, and bladder cancer? Author(s): Gray M, Krissovich M. Source: Journal of Wound, Ostomy, and Continence Nursing : Official Publication of the Wound, Ostomy and Continence Nurses Society / Wocn. 2003 May; 30(3): 126-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761483&dopt=Abstract

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Does smoking status influence the prognosis of bladder cancer? A systematic review. Author(s): Aveyard P, Adab P, Cheng KK, Wallace DM, Hey K, Murphy MF. Source: Bju International. 2002 August; 90(3): 228-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133057&dopt=Abstract

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Downregulation and growth inhibitory effect of epithelial-type Kruppel-like transcription factor KLF4, but not KLF5, in bladder cancer. Author(s): Ohnishi S, Ohnami S, Laub F, Aoki K, Suzuki K, Kanai Y, Haga K, Asaka M, Ramirez F, Yoshida T. Source: Biochemical and Biophysical Research Communications. 2003 August 22; 308(2): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901861&dopt=Abstract

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Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer. Author(s): Stein JP, Ginsberg DA, Grossfeld GD, Chatterjee SJ, Esrig D, Dickinson MG, Groshen S, Taylor CR, Jones PA, Skinner DG, Cote RJ. Source: Journal of the National Cancer Institute. 1998 July 15; 90(14): 1072-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9672255&dopt=Abstract

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Effect of routine repeat transurethral resection for superficial bladder cancer: a longterm observational study. Author(s): Grimm MO, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, Vogeli TA. Source: The Journal of Urology. 2003 August; 170(2 Pt 1): 433-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853793&dopt=Abstract

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Efficient therapeutic gene delivery after systemic administration of a novel polyethylenimine/DNA vector in an orthotopic bladder cancer model. Author(s): Sweeney P, Karashima T, Ishikura H, Wiehle S, Yamashita M, Benedict WF, Cristiano RJ, Dinney CP. Source: Cancer Research. 2003 July 15; 63(14): 4017-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874000&dopt=Abstract

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Enhancement by cyclosporin A of taxol-induced apoptosis of human urinary bladder cancer cells. Author(s): Nomura T, Yamamoto H, Mimata H, Shitashige M, Shibasaki F, Miyamoto E, Nomura Y. Source: Urological Research. 2002 May; 30(2): 102-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086014&dopt=Abstract

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Enhancement of chemosensitivity in human bladder cancer cells by adenoviralmediated p53 gene transfer. Author(s): Miyake H, Hara I, Gohji K, Yamanaka K, Arakawa S, Kamidono S. Source: Anticancer Res. 1998 July-August; 18(4C): 3087-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713515&dopt=Abstract

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Epidermal growth factor receptor and bladder cancer. Author(s): Colquhoun AJ, Mellon JK. Source: Postgraduate Medical Journal. 2002 October; 78(924): 584-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415079&dopt=Abstract

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Epidermal growth factor receptor targeting of replication competent adenovirus enhances cytotoxicity in bladder cancer. Author(s): van der Poel HG, Molenaar B, van Beusechem VW, Haisma HJ, Rodriguez R, Curiel DT, Gerritsen WR. Source: The Journal of Urology. 2002 July; 168(1): 266-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050554&dopt=Abstract

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ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of invasive bladder cancer. Author(s): Sengelov L; ESMO Guidelines Task Force. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 July; 14(7): 1008-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853338&dopt=Abstract

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Ethical issues in the use of tumor markers in clinical investigation of the management of bladder cancer. Author(s): McCullough LB. Source: Urologic Oncology. 2002 January-February; 7(1): 35-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474539&dopt=Abstract

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Evaluation of cytokeratin-19 & cytokeratin-20 and interleukin-6 in Egyptian bladder cancer patients. Author(s): El-Salahy EM. Source: Clinical Biochemistry. 2002 November; 35(8): 607-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498994&dopt=Abstract

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Evaluation of DD23 as a marker for detection of recurrent transitional cell carcinoma of the bladder in patients with a history of bladder cancer. Author(s): Gilbert SM, Veltri RW, Sawczuk A, Shabsigh A, Knowles DR, Bright S, O'Dowd GJ, Olsson CA, Benson MC, Sawczuk IS. Source: Urology. 2003 March; 61(3): 539-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639642&dopt=Abstract

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Evaluation of the potential of transferrin-adriamycin conjugates in the treatment of bladder cancer. Author(s): Munns J, Yaxley J, Coomer J, Lavin MF, Gardiner RA, Watters D. Source: British Journal of Urology. 1998 August; 82(2): 284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9722768&dopt=Abstract

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Ex vivo chemosensitivity to mitomycin C in bladder cancer and its relationship with P-glycoprotein and apoptotic factors. Author(s): Gontero P, Sargent JM, Hopster DJ, Lewandowic GM, Taylor CG, Elgie AW, Williamson CJ, Sriprasad SI, Muir GH. Source: Anticancer Res. 2002 November-December; 22(6C): 4073-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553035&dopt=Abstract

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Expression and prognostic significance of LIVIN, SURVIVIN and other apoptosisrelated genes in the progression of superficial bladder cancer. Author(s): Gazzaniga P, Gradilone A, Giuliani L, Gandini O, Silvestri I, Nofroni I, Saccani G, Frati L, Agliano AM. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 January; 14(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488298&dopt=Abstract

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Expression of cyclooxygenase-1 and -2 in urinary bladder carcinomas in vivo and in vitro and prostaglandin E2 synthesis in cultured bladder cancer cells. Author(s): Bostrom PJ, Aaltonen V, Soderstrom KO, Uotila P, Laato M. Source: Pathology. 2001 November; 33(4): 469-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827414&dopt=Abstract

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Expression of multidrug resistance proteins P-glycoprotein, multidrug resistance protein 1, breast cancer resistance protein and lung resistance related protein in locally advanced bladder cancer treated with neoadjuvant chemotherapy: biological and clinical implications. Author(s): Diestra JE, Condom E, Del Muro XG, Scheffer GL, Perez J, Zurita AJ, MunozSegui J, Vigues F, Scheper RJ, Capella G, Germa-Lluch JR, Izquierdo MA. Source: The Journal of Urology. 2003 October; 170(4 Pt 1): 1383-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501774&dopt=Abstract

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Expression of p16 and cyclin D1 in bladder cancer and correlation in cancer progression. Author(s): Yang CC, Chu KC, Chen HY, Chen WC. Source: Urologia Internationalis. 2002; 69(3): 190-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372886&dopt=Abstract

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Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human bladder cancer. Author(s): Tanaka T, Yoshiki T, Arai Y, Higuchi K, Kageyama S, Ogawa Y, Isono T, Okada Y. Source: Japanese Journal of Cancer Research : Gann. 1999 December; 90(12): 1344-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665652&dopt=Abstract

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Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the Surveillance, Epidemiology and End Results Program data base. Author(s): Konety BR, Joslyn SA, O'Donnell MA. Source: The Journal of Urology. 2003 March; 169(3): 946-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576819&dopt=Abstract

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Extent of surgery and pathology evaluation has an impact on bladder cancer outcomes after radical cystectomy. Author(s): Herr HW. Source: Urology. 2003 January; 61(1): 105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559278&dopt=Abstract

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Familial bladder cancer in the National Swedish Family Cancer Database. Author(s): Plna K, Hemminki K. Source: The Journal of Urology. 2001 December; 166(6): 2129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696721&dopt=Abstract

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Familial liver and gall bladder cancer: a nationwide epidemiological study from Sweden. Author(s): Hemminki K, Li X. Source: Gut. 2003 April; 52(4): 592-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631675&dopt=Abstract

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Fetal fibronectin: a new screening-marker for bladder cancer? Author(s): Wunderlich H, Reichelt O, Zermann DH, Schubert J, Berndt A, Kosmehl H. Source: Oncol Rep. 2001 May-June; 8(3): 669-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295100&dopt=Abstract

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FEZ1/LZTS1 is down-regulated in high-grade bladder cancer, and its restoration suppresses tumorigenicity in transitional cell carcinoma cells. Author(s): Vecchione A, Ishii H, Baldassarre G, Bassi P, Trapasso F, Alder H, Pagano F, Gomella LG, Croce CM, Baffa R. Source: American Journal of Pathology. 2002 April; 160(4): 1345-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11943719&dopt=Abstract

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Filling the void: urinary markers for bladder cancer risk and diagnosis. Author(s): Gazdar AF, Czerniak B. Source: Journal of the National Cancer Institute. 2001 March 21; 93(6): 413-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11259458&dopt=Abstract

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Fluid consumption and the risk of bladder cancer: results of a multicenter casecontrol study. Author(s): Geoffroy-Perez B, Cordier S. Source: International Journal of Cancer. Journal International Du Cancer. 2001 Sep15; 93(6): 880-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519052&dopt=Abstract

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Fluid intake and bladder cancer. A case control study. Author(s): Radosavljevic V, Jankovic S, Marinkovic J, Djokic M. Source: Neoplasma. 2003; 50(3): 234-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937859&dopt=Abstract

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Fluorescence detection of bladder cancer: a review. Author(s): D'Hallewin MA, Bezdetnaya L, Guillemin F. Source: European Urology. 2002 November; 42(5): 417-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429148&dopt=Abstract

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Fluorescence endoscopy with 5-aminolevulinic acid reduces early recurrence rate in superficial bladder cancer. Author(s): Riedl CR, Daniltchenko D, Koenig F, Simak R, Loening SA, Pflueger H. Source: The Journal of Urology. 2001 April; 165(4): 1121-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257651&dopt=Abstract

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Fluorescence in situ hybridization evaluation of c-erbB-2 gene amplification and chromosomal anomalies in bladder cancer. Author(s): Ohta JI, Miyoshi Y, Uemura H, Fujinami K, Mikata K, Hosaka M, Tokita Y, Kubota Y. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 August; 7(8): 2463-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11489827&dopt=Abstract

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Foods and nutrients in relation to bladder cancer risk: a case-control study in Aichi Prefecture, Central Japan. Author(s): Wakai K, Takashi M, Okamura K, Yuba H, Suzuki K, Murase T, Obata K, Itoh H, Kato T, Kobayashi M, Sakata T, Otani T, Ohshima S, Ohno Y. Source: Nutrition and Cancer. 2000; 38(1): 13-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11341038&dopt=Abstract

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Foods and risk of bladder cancer: a case-control study in Uruguay. Author(s): Balbi JC, Larrinaga MT, De Stefani E, Mendilaharsu M, Ronco AL, Boffetta P, Brennan P. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2001 October; 10(5): 453-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11711760&dopt=Abstract

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Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31. Author(s): Simoneau M, Aboulkassim TO, LaRue H, Rousseau F, Fradet Y. Source: Oncogene. 1999 January 7; 18(1): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9926930&dopt=Abstract

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Fragile sites and bladder cancer. Author(s): Moriarty HT, Webster LR. Source: Cancer Genetics and Cytogenetics. 2003 January 15; 140(2): 89-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645645&dopt=Abstract

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Frequency of positive biopsies after visual disappearance of superficial bladder cancer marker lesions. Author(s): Oosterlinck W, Bono AV, Mack D, Hall R, Sylvester R, de Balincourt C, Brausi M; Members of the EORTC GU Group. Source: European Urology. 2001 November; 40(5): 515-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752858&dopt=Abstract

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Frequent genetic alterations in flat urothelial hyperplasias and concomitant papillary bladder cancer as detected by CGH, LOH, and FISH analyses. Author(s): Obermann EC, Junker K, Stoehr R, Dietmaier W, Zaak D, Schubert J, Hofstaedter F, Knuechel R, Hartmann A. Source: The Journal of Pathology. 2003 January; 199(1): 50-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474226&dopt=Abstract

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Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. Author(s): Chan MW, Chan LW, Tang NL, Lo KW, Tong JH, Chan AW, Cheung HY, Wong WS, Chan PS, Lai FM, To KF. Source: International Journal of Cancer. Journal International Du Cancer. 2003 May 1; 104(5): 611-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594816&dopt=Abstract

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Functional analysis of the mismatch repair system in bladder cancer. Author(s): Thykjaer T, Christensen M, Clark AB, Hansen LR, Kunkel TA, Orntoft TF. Source: British Journal of Cancer. 2001 August 17; 85(4): 568-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506498&dopt=Abstract

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Functional genomic comparison of lineage-related human bladder cancer cell lines with differing tumorigenic and metastatic potentials by spectral karyotyping, comparative genomic hybridization, and a novel method of positional expression profiling. Author(s): Harding MA, Arden KC, Gildea JW, Gildea JJ, Perlman EJ, Viars C, Theodorescu D. Source: Cancer Research. 2002 December 1; 62(23): 6981-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460916&dopt=Abstract

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Functional p53 mutation as a molecular determinant of paclitaxel and gemcitabine susceptibility in human bladder cancer. Author(s): Kielb SJ, Shah NL, Rubin MA, Sanda MG. Source: The Journal of Urology. 2001 August; 166(2): 482-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11458051&dopt=Abstract

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Gall bladder cancer, extrahepatic bile duct cancer and ampullary carcinoma in New Zealand: Demographics, pathology and survival. Author(s): Koea J, Phillips A, Lawes C, Rodgers M, Windsor J, McCall J. Source: Anz Journal of Surgery. 2002 December; 72(12): 857-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485219&dopt=Abstract

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Gall bladder cancer--radical surgery, the key role to improve outcome. Author(s): Bhuta P, Brown MG, Alderdice JM. Source: Ulster Med J. 2002 November; 71(2): 128-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513009&dopt=Abstract

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Gallium nitrate in the treatment of bladder cancer. Author(s): Einhorn L. Source: Seminars in Oncology. 2003 April; 30(2 Suppl 5): 34-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776258&dopt=Abstract

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Ganglioside G(M3) overexpression induces apoptosis and reduces malignant potential in murine bladder cancer. Author(s): Watanabe R, Ohyama C, Aoki H, Takahashi T, Satoh M, Saito S, Hoshi S, Ishii A, Saito M, Arai Y. Source: Cancer Research. 2002 July 1; 62(13): 3850-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097299&dopt=Abstract

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G-CSF production in human bladder cancer and its ability to promote autocrine growth: a review. Author(s): Tachibana M, Murai M. Source: Cytokines, Cellular & Molecular Therapy. 1998 June; 4(2): 113-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9681250&dopt=Abstract

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Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II. Author(s): Neri B, Doni L, Fulignati C, Gemelli MT, Turrini M, Di Cello V, Dominici A, Mottola A, Raugei A, Ponchietti R, Cini G. Source: Anticancer Res. 2002 September-October; 22(5): 2981-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530029&dopt=Abstract

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Gender differences in stage distribution of bladder cancer. Author(s): Mungan NA, Kiemeney LA, van Dijck JA, van der Poel HG, Witjes JA. Source: Urology. 2000 March; 55(3): 368-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699612&dopt=Abstract

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Gender-related differences in clinical and pathological characteristics and therapy of bladder cancer. Author(s): Puente D, Malats N, Cecchini L, Tardon A, Garcia-Closas R, Serra C, Carrato A, Sala M, Boixeda R, Dosemeci M, Real FX, Kogevinas M; EPICURO Study Group Investigators. Source: European Urology. 2003 January; 43(1): 53-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507544&dopt=Abstract

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Gene discovery in bladder cancer progression using cDNA microarrays. Author(s): Sanchez-Carbayo M, Socci ND, Lozano JJ, Li W, Charytonowicz E, Belbin TJ, Prystowsky MB, Ortiz AR, Childs G, Cordon-Cardo C. Source: American Journal of Pathology. 2003 August; 163(2): 505-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875971&dopt=Abstract

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Gene therapy for bladder cancer using E1B-55 kD-deleted adenovirus in combination with adenoviral vector encoding plasminogen kringles 1-5. Author(s): Hsieh JL, Wu CL, Lai MD, Lee CH, Tsai CS, Shiau AL. Source: British Journal of Cancer. 2003 May 6; 88(9): 1492-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778082&dopt=Abstract

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Gene therapy for superficial bladder cancer. Author(s): Rosser CJ, Benedict WF, Dinney CP. Source: Expert Rev Anticancer Ther. 2001 December; 1(4): 531-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113085&dopt=Abstract

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Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer. Author(s): Watters AD, Latif Z, Forsyth A, Dunn I, Underwood MA, Grigor KM, Bartlett JM. Source: British Journal of Cancer. 2002 September 9; 87(6): 654-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237776&dopt=Abstract

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Genetic alterations of p16INK4a and p14ARF genes in human bladder cancer. Author(s): Chang LL, Yeh WT, Yang SY, Wu WJ, Huang CH. Source: The Journal of Urology. 2003 August; 170(2 Pt 1): 595-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853838&dopt=Abstract

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Genetic and phenotypic changes associated with the acquisition of tumorigenicity in human bladder cancer. Author(s): Gildea JJ, Golden WL, Harding MA, Theodorescu D. Source: Genes, Chromosomes & Cancer. 2000 March; 27(3): 252-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679914&dopt=Abstract

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Genetic instability in bladder cancer assessed by the comet assay. Author(s): Schabath MB, Spitz MR, Grossman HB, Zhang K, Dinney CP, Zheng PJ, Wu X. Source: Journal of the National Cancer Institute. 2003 April 2; 95(7): 540-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671022&dopt=Abstract

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Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study. Author(s): Cianciulli AM, Leonardo C, Guadagni F, Marzano R, Iori F, De Nunzio C, Franco G, Merola R, Laurenti C. Source: Human Pathology. 2003 March; 34(3): 214-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673554&dopt=Abstract

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Genome-wide genetic characterization of bladder cancer: a comparison of highdensity single-nucleotide polymorphism arrays and PCR-based microsatellite analysis. Author(s): Hoque MO, Lee CC, Cairns P, Schoenberg M, Sidransky D. Source: Cancer Research. 2003 May 1; 63(9): 2216-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727842&dopt=Abstract

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Growth inhibiting effects of antisense eukaryotic expression vector of proliferating cell nuclear antigen gene on human bladder cancer cells. Author(s): Tong Q, Zeng F, Lin C, Zhao J, Lu G. Source: Chinese Medical Journal. 2003 August; 116(8): 1203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12935412&dopt=Abstract

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GSTT1-null genotype is a protective factor against bladder cancer. Author(s): Kim WJ, Kim H, Kim CH, Lee MS, Oh BR, Lee HM, Katoh T. Source: Urology. 2002 November; 60(5): 913-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429337&dopt=Abstract

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Guidelines on bladder cancer. Author(s): Oosterlinck W, Lobel B, Jakse G, Malmstrom PU, Stockle M, Sternberg C; European Association of Urology (EAU) Working Group on Oncological Urology. Source: European Urology. 2002 February; 41(2): 105-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074395&dopt=Abstract

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Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Author(s): Ohashi Y, Nakai S, Tsukamoto T, Masumori N, Akaza H, Miyanaga N, Kitamura T, Kawabe K, Kotake T, Kuroda M, Naito S, Koga H, Saito Y, Nomata K, Kitagawa M, Aso Y. Source: Urologia Internationalis. 2002; 68(4): 273-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12053032&dopt=Abstract

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HA-HAase urine test. A sensitive and specific method for detecting bladder cancer and evaluating its grade. Author(s): Lokeshwar VB, Block NL. Source: The Urologic Clinics of North America. 2000 February; 27(1): 53-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696245&dopt=Abstract

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Hair dye use and bladder cancer. Author(s): Miller AB, Bartsch H. Source: International Journal of Cancer. Journal International Du Cancer. 2001 December 15; 94(6): 901-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745497&dopt=Abstract

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Hair dyes and bladder cancer: an update. Author(s): La Vecchia C, Tavani A. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2001 June; 10(3): 205-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11432706&dopt=Abstract

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Hammerhead ribozymes as therapeutic agents for bladder cancer. Author(s): Irie A, Kashani-Sabet M, Scanlon KJ, Uchida T, Baba S. Source: Molecular Urology. 2000 Summer; 4(2): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006244&dopt=Abstract

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Health-related quality of life after radical cystectomy for bladder cancer: a comparison of ileal conduit and orthotopic bladder replacement. Author(s): Hara I, Miyake H, Hara S, Gotoh A, Nakamura I, Okada H, Arakawa S, Kamidono S. Source: Bju International. 2002 January; 89(1): 10-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849152&dopt=Abstract

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Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer. Author(s): Roychowdhury DF, Hayden A, Liepa AM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 February 15; 21(4): 673-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586805&dopt=Abstract

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Heat shock protein-90, IL-6 and IL-10 in bladder cancer. Author(s): Cardillo MR, Sale P, Di Silverio F. Source: Anticancer Res. 2000 November-December; 20(6B): 4579-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205307&dopt=Abstract

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Heparanase protein and gene expression in bladder cancer. Author(s): Gohji K, Okamoto M, Kitazawa S, Toyoshima M, Dong J, Katsuoka Y, Nakajima M. Source: The Journal of Urology. 2001 October; 166(4): 1286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11547059&dopt=Abstract

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Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for photodiagnosis of superficial bladder cancer--a multicenter study. Author(s): Jichlinski P, Guillou L, Karlsen SJ, Malmstrom PU, Jocham D, Brennhovd B, Johansson E, Gartner T, Lange N, van den Bergh H, Leisinger HJ. Source: The Journal of Urology. 2003 July; 170(1): 226-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796694&dopt=Abstract

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High frequency loss of heterozygosity in the region of the DBH locus in bladder cancer. Author(s): Yang X, Shen P, Yao K, Mi Z, Liu S, Zhang H, Wang D, Liu C, Liu H. Source: Chinese Medical Journal. 2000 February; 113(2): 117-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775532&dopt=Abstract

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High intake of specific carotenoids and flavonoids does not reduce the risk of bladder cancer. Author(s): Garcia R, Gonzalez CA, Agudo A, Riboli E. Source: Nutrition and Cancer. 1999; 35(2): 212-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10693178&dopt=Abstract

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High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer. Author(s): Simon R, Richter J, Wagner U, Fijan A, Bruderer J, Schmid U, Ackermann D, Maurer R, Alund G, Knonagel H, Rist M, Wilber K, Anabitarte M, Hering F, Hardmeier T, Schonenberger A, Flury R, Jager P, Fehr JL, Schraml P, Moch H, Mihatsch MJ, Gasser T, Sauter G. Source: Cancer Research. 2001 June 1; 61(11): 4514-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389083&dopt=Abstract

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HRAS1 variable number of tandem repeats polymorphism and risk of bladder cancer. Author(s): van Gils CH, Conway K, Li Y, Taylor JA. Source: International Journal of Cancer. Journal International Du Cancer. 2002 August 1; 100(4): 414-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115522&dopt=Abstract

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Human bladder cancer invasion model using rat bladder in vitro and its use to test mechanisms and therapeutic inhibitors of invasion. Author(s): Fujiyama C, Jones A, Fuggle S, Bicknell R, Cranston D, Harris AL. Source: British Journal of Cancer. 2001 February; 84(4): 558-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207054&dopt=Abstract

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Human complement factor H related protein test for monitoring bladder cancer. Author(s): Raitanen MP, Marttila T, Nurmi M, Ala-Opas M, Nieminen P, Aine R, Tammela TL; Finnbladder Group. Source: The Journal of Urology. 2001 February; 165(2): 374-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176376&dopt=Abstract

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Human papilloma virus infection and overexpression of p53 protein in bilharzial bladder cancer. Author(s): Khaled HM, Raafat A, Mokhtar N, Zekri AR, Gaballah H. Source: Tumori. 2001 July-August; 87(4): 256-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693804&dopt=Abstract

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Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer. Author(s): Habuchi T, Takahashi T, Kakinuma H, Wang L, Tsuchiya N, Satoh S, Akao T, Sato K, Ogawa O, Knowles MA, Kato T. Source: Oncogene. 2001 January 25; 20(4): 531-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313984&dopt=Abstract

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Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Author(s): Chan MW, Chan LW, Tang NL, Tong JH, Lo KW, Lee TL, Cheung HY, Wong WS, Chan PS, Lai FM, To KF. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 February; 8(2): 464-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839665&dopt=Abstract

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Hypoxia-induced, perinecrotic expression of endothelial Per-ARNT-Sim domain protein-1/hypoxia-inducible factor-2alpha correlates with tumor progression, vascularization, and focal macrophage infiltration in bladder cancer. Author(s): Onita T, Ji PG, Xuan JW, Sakai H, Kanetake H, Maxwell PH, Fong GH, Gabril MY, Moussa M, Chin JL. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 February; 8(2): 471-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839666&dopt=Abstract

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Identification of two genes differentially expressed upon different spatial configuration of the MGH-U3 human bladder cancer cells. Author(s): Champetier S, Fradet Y, Bachvarov D. Source: Urologic Oncology. 2002 March-April; 7(2): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474523&dopt=Abstract

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IFN gamma-induced up-regulation of PD-ECGF/TP enhances the cytotoxicity of 5fluorouracil and 5'-deoxy-5-fluorouridine in bladder cancer cells. Author(s): Li G, Kawakami S, Kageyama Y, Yan C, Saito K, Kihara K. Source: Anticancer Res. 2002 September-October; 22(5): 2607-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529971&dopt=Abstract

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Immune response following intravesical bacillus Calmette-Guerin instillations in superficial bladder cancer: a review. Author(s): Patard JJ, Saint F, Velotti F, Abbou CC, Chopin DK. Source: Urological Research. 1998; 26(3): 155-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9694595&dopt=Abstract

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Immunoprophylactic intravesical application of bacillus Calmette-Guerin after transurethral resection of superficial bladder cancer. Author(s): Librenjak D, Situm M, Eterovic D, Dogas Z, Gotovac J. Source: Croatian Medical Journal. 2003 April; 44(2): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698510&dopt=Abstract

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Immunotherapy for bladder cancer. Is the black box becoming grayer? Author(s): Grossman HB. Source: The Journal of Urology. 2003 May; 169(5): 1709. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686814&dopt=Abstract

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Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. Author(s): Herr HW, Bochner BH, Dalbagni G, Donat SM, Reuter VE, Bajorin DF. Source: The Journal of Urology. 2002 March; 167(3): 1295-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832716&dopt=Abstract

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Improving and predicting radiosensitivity in muscle invasive bladder cancer. Author(s): Colquhoun AJ, Jones GD, Moneef MA, Bowman KJ, Kockelbergh RC, Symonds RP, Steward WP, Mellon JK. Source: The Journal of Urology. 2003 June; 169(6): 1983-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771703&dopt=Abstract

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In vivo gene therapy of human bladder cancer with PTEN suppresses tumor growth, downregulates phosphorylated Akt, and increases sensitivity to doxorubicin. Author(s): Tanaka M, Grossman HB. Source: Gene Therapy. 2003 September; 10(19): 1636-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923562&dopt=Abstract

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Induction of apoptosis in human bladder cancer cells in vitro and in vivo caused by FTY720 treatment. Author(s): Azuma H, Takahara S, Horie S, Muto S, Otsuki Y, Katsuoka Y. Source: The Journal of Urology. 2003 June; 169(6): 2372-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771800&dopt=Abstract

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Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Author(s): Michaud DS, Pietinen P, Taylor PR, Virtanen M, Virtamo J, Albanes D. Source: British Journal of Cancer. 2002 October 21; 87(9): 960-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434284&dopt=Abstract

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Interleukin-12. Opportunities for the treatment of bladder cancer. Author(s): Clinton SK, Canto E, O'Donnell MA. Source: The Urologic Clinics of North America. 2000 February; 27(1): 147-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696253&dopt=Abstract

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Intravesical Bacillus Calmette-Guerin for treating bladder cancer. Author(s): Boyd LA. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2003 June; 23(3): 189-91, 199; Quiz 192. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861735&dopt=Abstract

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Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer: a formal meta-analysis of comparative studies on recurrence and toxicity. Author(s): Bohle A, Jocham D, Bock PR. Source: The Journal of Urology. 2003 January; 169(1): 90-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478111&dopt=Abstract

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Intravesical bacillus Calmette-Guerin versus mitomycin C for Ta and T1 bladder cancer. Author(s): Shelley MD, Court JB, Kynaston H, Wilt TJ, Coles B, Mason M. Source: Cochrane Database Syst Rev. 2003; (3): Cd003231. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917955&dopt=Abstract

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Intravesical electromotive mitomycin C versus passive transport mitomycin C for high risk superficial bladder cancer: a prospective randomized study. Author(s): Di Stasi SM, Giannantoni A, Stephen RL, Capelli G, Navarra P, Massoud R, Vespasiani G. Source: The Journal of Urology. 2003 September; 170(3): 777-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913696&dopt=Abstract

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Intravesical pH: a potentially important variable affecting efficacy and the further development of anthracycline chemotherapy for superficial bladder cancer. Author(s): Harris NM, Duffy PM, Crook TJ, Anderson WR, Sharpe P, Hayes MC, Cooper AJ, Solomon LZ. Source: Bju International. 2002 December; 90(9): 957-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460364&dopt=Abstract

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Intravesical therapy for bladder cancer. Author(s): Kamat AM, Lamm DL. Source: Urology. 2000 February; 55(2): 161-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10688071&dopt=Abstract

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Is repeated transurethral resection justified in patients with newly diagnosed superficial bladder cancer? Author(s): Schips L, Augustin H, Zigeuner RE, Galle G, Habermann H, Trummer H, Pummer K, Hubmer G. Source: Urology. 2002 February; 59(2): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834389&dopt=Abstract

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Is there a role for bladder preserving strategies in the treatment of muscle-invasive bladder cancer? Author(s): Kuczyk M, Turkeri L, Hammerer P, Ravery V; European Society for Oncological Urology. Source: European Urology. 2003 July; 44(1): 57-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814676&dopt=Abstract

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Isolation and characterization of a novel human bladder cancer cell line: BK10. Author(s): Roberson KM, Yancey DR, Padilla-Nash H, Edwards DW, Nash W, Jacobs S, Padilla GM, Larchian WA, Robertson CN. Source: In Vitro Cellular & Developmental Biology. Animal. 1998 July-August; 34(7): 537-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9719413&dopt=Abstract

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Keyhole limpet hemocyanin immunotherapy of bladder cancer: laboratory and clinical studies. Author(s): Lamm DL, Dehaven JI, Riggs DR. Source: European Urology. 2000; 37 Suppl 3: 41-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10828686&dopt=Abstract

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KIAA1096, a gene on chromosome 1q, is amplified and overexpressed in bladder cancer. Author(s): Huang WC, Taylor S, Nguyen TB, Tomaszewski JE, Libertino JA, Malkowicz SB, McGarvey TW. Source: Dna and Cell Biology. 2002 October; 21(10): 707-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443540&dopt=Abstract

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Lack of evidence for the association of tumor necrosis factor-alpha gene promoter polymorphism with calcium oxalate stone and bladder cancer patients. Author(s): Tsai FJ, Lu HF, Yeh LS, Hsu CD, Chen WC. Source: Urological Research. 2001 December; 29(6): 412-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828995&dopt=Abstract

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Lasermicrodissection--an important prerequisite for the molecular-genetic analysis of bladder cancer. Author(s): Stoehr R, Wild P, Hartmann A. Source: Pathology, Research and Practice. 2003; 199(6): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924435&dopt=Abstract

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Late oncological occurrences following radical cystectomy in patients with bladder cancer. Author(s): Solsona E, Iborra I, Rubio J, Casanova J, Dumont R, Monros JL. Source: European Urology. 2003 May; 43(5): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705992&dopt=Abstract

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Local immune response after intravesical interferon gamma in superficial bladder cancer. Author(s): Stavropoulos NE, Ioachim E, Pavlidis N, Pappa L, Kalomiris P, Agnantis NJ. Source: British Journal of Urology. 1998 June; 81(6): 875-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9666774&dopt=Abstract

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Loss of heterozygosity on chromosome 5p13-12 predicts adverse prognosis in advanced bladder cancer independent of tumor stage and grade. Author(s): Bohm M, Wieland I, Schmidt C, Rubben H, Allhoff EP. Source: The Journal of Urology. 2002 December; 168(6): 2655-8. Erratum In: J Urol. 2003 March; 169(3): 1090. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442004&dopt=Abstract

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Low IL-1alpha expression in bladder cancer tissue and survival. Author(s): Seddighzadeh M, Larsson P, Ulfgren AC, Onelov E, Berggren P, Tribukait B, Torstensson A, Norming U, Wijkstrom H, Linder S, Steineck G. Source: European Urology. 2003 April; 43(4): 362-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667716&dopt=Abstract

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Low plasma cefaclor levels in cystectomized bladder cancer patients with various types of urinary diversion. Author(s): Mattioli F, Tognoni P, Corbu C, Martelli A. Source: European Journal of Clinical Pharmacology. 2003 February; 58(10): 715-6. Epub 2002 December 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610750&dopt=Abstract

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Lung and bladder cancer among Danish urban bus drivers and tramway employees: a nested case-control study. Author(s): Soll-Johanning H, Bach E, Jensen SS. Source: Occupational Medicine (Oxford, England). 2003 February; 53(1): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576562&dopt=Abstract

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Luteolin induces N-acetylation and DNA adduct of 2-aminofluorene accompanying N-acetyltransferase activity and gene expression in human bladder cancer T24 cell line. Author(s): Su CC, Chen GW, Yeh CC, Yang MD, Hung CF, Chung JG. Source: Anticancer Res. 2003 January-February; 23(1A): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680237&dopt=Abstract

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Lymphadenopathy of sinus histiocytosis mimicking metastatic bladder cancer: a case report. Author(s): Asano T, Ohtsuka Y, Takagi K, Aida J, Okada Y, Ito Y. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 June; 8(3): 184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884874&dopt=Abstract

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Lymphocyte subsets in superficial bladder cancer: correlation with biological activity of the tumours. Author(s): Stavropoulos NE, Ioachim E, Hastazeris K, Goussia A, Agnantis NJ. Source: Anticancer Res. 1998 May-June; 18(3B): 2037-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9677463&dopt=Abstract

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Management of bacillus Calmette-Guerin (BCG) refractory superficial bladder cancer: results with intravesical BCG and Interferon combination therapy. Author(s): Punnen SP, Chin JL, Jewett MA. Source: Can J Urol. 2003 April; 10(2): 1790-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773228&dopt=Abstract

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Matrix metalloproteinases (MMPs) in bladder cancer: the induction of MMP9 by epidermal growth factor and its detection in urine. Author(s): Nutt JE, Durkan GC, Mellon JK, Lunec J. Source: Bju International. 2003 January; 91(1): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614260&dopt=Abstract

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Matrix-dependent plasticity of the malignant phenotype of bladder cancer cells. Author(s): Hurst RE, Kyker KD, Bonner RB, Bowditch RD, Hemstreet GP 3rd. Source: Anticancer Res. 2003 July-August; 23(4): 3119-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926044&dopt=Abstract

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Measurements of complement factor H-related protein (BTA-TRAK assay) and nuclear matrix protein (NMP22 assay)--useful diagnostic tools in the diagnosis of urinary bladder cancer? Author(s): Mahnert B, Tauber S, Kriegmair M, Nagel D, Holdenrieder S, Hofmann K, Reiter W, Schmeller N, Stieber P. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 January; 41(1): 104-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636058&dopt=Abstract

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Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer. Author(s): Villanueva CM, Fernandez F, Malats N, Grimalt JO, Kogevinas M. Source: Journal of Epidemiology and Community Health. 2003 March; 57(3): 166-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594192&dopt=Abstract

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Molecular genetic evaluation of fluorescence diagnosis in bladder cancer. Author(s): Junker K, Kania K, Fiedler W, Hartmann A, Schubert J, Werner W. Source: International Journal of Oncology. 2002 March; 20(3): 647-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836583&dopt=Abstract

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Molecular prognostication in bladder cancer--a current perspective. Author(s): Quek ML, Quinn DI, Daneshmand S, Stein JP. Source: European Journal of Cancer (Oxford, England : 1990). 2003 July; 39(11): 1501-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855255&dopt=Abstract

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Molecular targeting and pharmacogenomics in the management of advanced bladder cancer. Author(s): Raghavan D. Source: Cancer. 2003 April 15; 97(8 Suppl): 2083-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673700&dopt=Abstract

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Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology. Author(s): Skacel M, Fahmy M, Brainard JA, Pettay JD, Biscotti CV, Liou LS, Procop GW, Jones JS, Ulchaker J, Zippe CD, Tubbs RR. Source: The Journal of Urology. 2003 June; 169(6): 2101-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771727&dopt=Abstract

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Mutation of cell cycle regulators and their impact on superficial bladder cancer. Author(s): Rabbani F, Cordon-Cardo C. Source: The Urologic Clinics of North America. 2000 February; 27(1): 83-102, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696248&dopt=Abstract

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National and international variation in the registration of bladder cancer. Author(s): Crow P, Ritchie AW. Source: Bju International. 2003 October; 92(6): 563-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511034&dopt=Abstract

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Neoadjuvant chemotherapy for bladder cancer: current status. Author(s): Dreicer R. Source: Expert Opinion on Pharmacotherapy. 2003 June; 4(6): 853-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783582&dopt=Abstract

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Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and metaanalysis. Author(s): Advanced Bladder Cancer Meta-analysis Collaboration. Source: Lancet. 2003 June 7; 361(9373): 1927-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801735&dopt=Abstract

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Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. Author(s): Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Source: The New England Journal of Medicine. 2003 August 28; 349(9): 859-66. Erratum In: N Engl J Med. 2003 November 6; 349(19): 1880. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944571&dopt=Abstract

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Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer -Nordic cystectomy trial 2. Author(s): Sherif A, Rintala E, Mestad O, Nilsson J, Holmberg L, Nilsson S, Malmstrom PU; Nordic Urothelial Cancer Group. Source: Scandinavian Journal of Urology and Nephrology. 2002; 36(6): 419-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623505&dopt=Abstract

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Neural network using combined urine nuclear matrix protein-22, monocyte chemoattractant protein-1 and urinary intercellular adhesion molecule-1 to detect bladder cancer. Author(s): Parekattil SJ, Fisher HA, Kogan BA. Source: The Journal of Urology. 2003 March; 169(3): 917-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576812&dopt=Abstract

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Neural network-based assessment of prognostic markers and outcome prediction in bilharziasis-associated bladder cancer. Author(s): Ji W, Naguib RN, Ghoneim MA. Source: Ieee Transactions on Information Technology in Biomedicine : a Publication of the Ieee Engineering in Medicine and Biology Society. 2003 September; 7(3): 218-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14518736&dopt=Abstract

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Nitrate in public water supplies and risk of bladder cancer. Author(s): Ward MH, Cantor KP, Riley D, Merkle S, Lynch CF. Source: Epidemiology (Cambridge, Mass.). 2003 March; 14(2): 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606884&dopt=Abstract

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Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. Author(s): van Rhijn BW, van Tilborg AA, Lurkin I, Bonaventure J, de Vries A, Thiery JP, van der Kwast TH, Zwarthoff EC, Radvanyi F. Source: European Journal of Human Genetics : Ejhg. 2002 December; 10(12): 819-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461689&dopt=Abstract

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Numeric aberration of chromosome 17 is strongly correlated with p53 overexpression, tumor proliferation and histopathology in human bladder cancer. Author(s): Li B, Kanamaru H, Noriki S, Fukuda M, Okada K. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 1998 July; 5(4): 317-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9712438&dopt=Abstract

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Occupation and bladder cancer: a population-based, case-control study in Iowa. Author(s): Zheng T, Cantor KP, Zhang Y, Lynch CF. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2002 July; 44(7): 685-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134533&dopt=Abstract

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Organ preservation in patients with invasive bladder cancer: initial results of an intensified protocol of transurethral surgery and radiation therapy plus concurrent cisplatin and 5-fluorouracil. Author(s): Rodel C, Grabenbauer GG, Kuhn R, Zorcher T, Papadopoulos T, Dunst J, Schrott KM, Sauer R. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 April 1; 52(5): 1303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955743&dopt=Abstract

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Organ preservation strategies in bladder cancer. Author(s): Hussain SA, James ND. Source: Expert Rev Anticancer Ther. 2002 December; 2(6): 641-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503210&dopt=Abstract

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Organophosphate-based pesticides and genetic damage implicated in bladder cancer. Author(s): Webster LR, McKenzie GH, Moriarty HT. Source: Cancer Genetics and Cytogenetics. 2002 March; 133(2): 112-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11943336&dopt=Abstract

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Orthotopic urinary diversion after cystectomy for bladder cancer: implications for cancer control and patterns of disease recurrence. Author(s): Yossepowitch O, Dalbagni G, Golijanin D, Donat SM, Bochner BH, Herr HW, Fair WR, Russo P. Source: The Journal of Urology. 2003 January; 169(1): 177-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478130&dopt=Abstract

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Outcome of radical cystectomy for bladder cancer according to the disease type at presentation. Author(s): Yiou R, Patard JJ, Benhard H, Abbou CC, Chopin DK. Source: Bju International. 2002 March; 89(4): 374-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872027&dopt=Abstract

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Overview of bladder cancer trials in the Cancer and Leukemia Group B. Author(s): Small EJ, Halabi S, Dalbagni G, Pruthi R, Phillips G, Edelman M, Bajorin D; Cancer and Leukemia Group B. Source: Cancer. 2003 April 15; 97(8 Suppl): 2090-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673701&dopt=Abstract

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Overview of bladder cancer trials in the European Organization for Research and Treatment. Author(s): de Wit R; European Organization for Research and Treatment. Source: Cancer. 2003 April 15; 97(8 Suppl): 2120-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673705&dopt=Abstract

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Overview of bladder cancer trials in the Radiation Therapy Oncology Group. Author(s): Shipley WU, Kaufman DS, Tester WJ, Pilepich MV, Sandler HM; Radiation Therapy Oncology Group. Source: Cancer. 2003 April 15; 97(8 Suppl): 2115-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673704&dopt=Abstract

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Overview of gemcitabine triplets in metastatic bladder cancer. Author(s): de Wit R, Bellmunt J. Source: Critical Reviews in Oncology/Hematology. 2003 February; 45(2): 191-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604129&dopt=Abstract

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p53 and microvessel density in primary resection specimens of superficial bladder cancer. Author(s): Reiher F, Ozer O, Pins M, Jovanovic BD, Eggener S, Campbell SC. Source: The Journal of Urology. 2002 March; 167(3): 1469-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832772&dopt=Abstract

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Patterns of care for the treatment of bladder cancer. Author(s): Snyder C, Harlan L, Knopf K, Potosky A, Kaplan R. Source: The Journal of Urology. 2003 May; 169(5): 1697-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686811&dopt=Abstract

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Perioperative chemotherapy in locally advanced bladder cancer. Author(s): Stadler WM, Lerner SP. Source: Lancet. 2003 June 7; 361(9373): 1922-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801730&dopt=Abstract

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Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2. Author(s): Gago-Dominguez M, Bell DA, Watson MA, Yuan JM, Castelao JE, Hein DW, Chan KK, Coetzee GA, Ross RK, Yu MC. Source: Carcinogenesis. 2003 March; 24(3): 483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663508&dopt=Abstract

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Physiologic changes of the anorectum after pelvic radiotherapy for the treatment of prostate and bladder cancer. Author(s): Kushwaha RS, Hayne D, Vaizey CJ, Wrightham E, Payne H, Boulos PB. Source: Diseases of the Colon and Rectum. 2003 September; 46(9): 1182-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972961&dopt=Abstract

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Polymorphisms in tumour necrosis factor (TNF) are associated with risk of bladder cancer and grade of tumour at presentation. Author(s): Marsh HP, Haldar NA, Bunce M, Marshall SE, le Monier K, Winsey SL, Christodoulos K, Cranston D, Welsh KI, Harris AL. Source: British Journal of Cancer. 2003 September 15; 89(6): 1096-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966432&dopt=Abstract

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Potential value of soluble intercellular adhesion molecule-1 in the serum of patients with bladder cancer. Author(s): Ozer G, Altinel M, Kocak B, Balci M, Altan A, Gonenc F. Source: Urologia Internationalis. 2003; 70(3): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660451&dopt=Abstract

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Preclinical evaluation of a radiosensitizing effect of gemcitabine in p53 mutant and p53 wild type bladder cancer cells. Author(s): Fechner G, Perabo FG, Schmidt DH, Haase L, Ludwig E, Schueller H, Blatter J, Mller SC, Albers P. Source: Urology. 2003 February; 61(2): 468-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597983&dopt=Abstract

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Preoperative plasma levels of interleukin-6 and its soluble receptor predict disease recurrence and survival of patients with bladder cancer. Author(s): Andrews B, Shariat SF, Kim JH, Wheeler TM, Slawin KM, Lerner SP. Source: The Journal of Urology. 2002 March; 167(3): 1475-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832773&dopt=Abstract

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Prognostic factors, pattern of recurrence and survival in a Danish bladder cancer cohort treated with radical cystectomy. Author(s): Knap MM, Lundbeck F, Overgaard J. Source: Acta Oncologica (Stockholm, Sweden). 2003; 42(2): 160-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801135&dopt=Abstract

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Qualitative determination of urinary human complement factor H-related protein (hcfHrp) in patients with bladder cancer, healthy controls, and patients with benign urologic disease. Author(s): Heicappell R, Muller M, Fimmers R, Miller K. Source: Urologia Internationalis. 2000; 65(4): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11112865&dopt=Abstract

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Quality of life after radical cystectomy for bladder cancer in patients with an ileal conduit, cutaneous or urethral kock pouch. Author(s): Hart S, Skinner EC, Meyerowitz BE, Boyd S, Lieskovsky G, Skinner DG. Source: The Journal of Urology. 1999 July; 162(1): 77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10379744&dopt=Abstract

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Quality of life aspects of bladder cancer: a review of the literature. Author(s): Botteman MF, Pashos CL, Hauser RS, Laskin BL, Redaelli A. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2003 September; 12(6): 675-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516177&dopt=Abstract

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Quality-of-life assessment in bladder cancer. Author(s): van der Veen JH, van Andel G, Kurth KH. Source: World Journal of Urology. 1999 August; 17(4): 219-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10460404&dopt=Abstract

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Quantification of 5-aminolevulinic acid induced fluorescence improves the specificity of bladder cancer detection. Author(s): Zaak D, Frimberger D, Stepp H, Wagner S, Baumgartner R, Schneede P, Siebels M, Knuchel R, Kriegmair M, Hofstetter A. Source: The Journal of Urology. 2001 November; 166(5): 1665-8; Discussion 1668-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586198&dopt=Abstract

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Quantitation of bcl-2 protein in bladder cancer tissue by enzyme immunoassay: comparison with Western blot and immunohistochemistry. Author(s): Eissa S, Seada LS. Source: Clinical Chemistry. 1998 July; 44(7): 1423-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9665419&dopt=Abstract

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Quantitative assessment of bladder cancer by nuclear texture analysis using automated high resolution image cytometry. Author(s): Gschwendtner A, Hoffmann-Weltin Y, Mikuz G, Mairinger T. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1999 August; 12(8): 806-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463483&dopt=Abstract

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Quick-staining urinary cytology and bladder wash image analysis with an integrated risk classification: a worthwhile improvement in the follow-up of bladder cancer? Author(s): Wiener HG, Remkes GW, Schatzl G, Susani M, Breitenecker G. Source: Cancer. 1999 October 25; 87(5): 263-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10536351&dopt=Abstract

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Quinolone antibiotics: a potential adjunct to intravesical chemotherapy for bladder cancer. Author(s): Kamat AM, DeHaven JI, Lamm DL. Source: Urology. 1999 July; 54(1): 56-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10414727&dopt=Abstract

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Radical cystectomy for bladder cancer after definitive prostate cancer treatment. Author(s): Schuster TG, Marcovich R, Sheffield J, Montie JE, Lee CT. Source: Urology. 2003 February; 61(2): 342-7; Discussion 347. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597943&dopt=Abstract

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Radical cystectomy for bladder cancer today--a homogeneous series without neoadjuvant therapy. Author(s): Madersbacher S, Hochreiter W, Burkhard F, Thalmann GN, Danuser H, Markwalder R, Studer UE. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 February 15; 21(4): 690-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586807&dopt=Abstract

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Recent aspects in the diagnosis and prognosis of bladder cancer. Author(s): Kontogeorgos G, Aninos D. Source: Tumori. 1998 May-June; 84(3): 301-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9678611&dopt=Abstract

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Relative importance of sources of symptom-induced distress in urinary bladder cancer survivors. Author(s): Henningsohn L, Wijkstrom H, Steven K, Pedersen J, Ahlstrand C, Aus G, Kallestrup EB, Bergmark K, Onelov E, Steineck G. Source: European Urology. 2003 June; 43(6): 651-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767367&dopt=Abstract

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Repeated intravesical instillations of an adenoviral vector in patients with locally advanced bladder cancer: a phase I study of p53 gene therapy. Author(s): Pagliaro LC, Keyhani A, Williams D, Woods D, Liu B, Perrotte P, Slaton JW, Merritt JA, Grossman HB, Dinney CP. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 15; 21(12): 2247-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805322&dopt=Abstract

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Results with radical cystectomy for treating bladder cancer: a 'reference standard' for high-grade, invasive bladder cancer. Author(s): Stein JP, Skinner DG. Source: Bju International. 2003 July; 92(1): 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823375&dopt=Abstract

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Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle-invasive bladder cancer. Author(s): Agerbaek M, Alsner J, Marcussen N, Lundbeck F, von der Maase H. Source: British Journal of Cancer. 2003 July 21; 89(2): 298-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865920&dopt=Abstract

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Role of mitochondria in ciprofloxacin induced apoptosis in bladder cancer cells. Author(s): Aranha O, Zhu L, Alhasan S, Wood DP Jr, Kuo TH, Sarkar FH. Source: The Journal of Urology. 2002 March; 167(3): 1288-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832715&dopt=Abstract

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Role of thymidine phosphorylase in an in vitro model of human bladder cancer invasion. Author(s): Jones A, Fujiyama C, Turner K, Cranston D, Williams K, Stratford I, Bicknell R, Harris AL. Source: The Journal of Urology. 2002 March; 167(3): 1482-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832774&dopt=Abstract

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Routine follow-up cystoscopy in detection of recurrence in patients being monitored for bladder cancer. Author(s): Raitanen MP, Leppilahti M, Tuhkanen K, Forssel T, Nylund P, Tammela T; FinnBladder Group. Source: Ann Chir Gynaecol. 2001; 90(4): 261-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11820414&dopt=Abstract

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Selective reovirus killing of bladder cancer in a co-culture spheroid model. Author(s): Kilani RT, Tamimi Y, Hanel EG, Wong KK, Karmali S, Lee PW, Moore RB. Source: Virus Research. 2003 May; 93(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727337&dopt=Abstract

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Serum vitamins and the subsequent risk of bladder cancer. Author(s): Nomura AM, Lee J, Stemmermann GN, Franke AA. Source: The Journal of Urology. 2003 October; 170(4 Pt 1): 1146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501712&dopt=Abstract

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Significance of protein p53 overexpression in the clinical course of high-risk superficial bladder cancer. Author(s): Gil P, Allepuz C, Blas M, Borque A, del Agua C, Plaza L, Rioja LA. Source: Urologia Internationalis. 2003; 70(3): 172-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660452&dopt=Abstract

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Significance of random bladder biopsies in superficial bladder cancer. Author(s): May F, Treiber U, Hartung R, Schwaibold H. Source: European Urology. 2003 July; 44(1): 47-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814674&dopt=Abstract

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Southwest Oncology Group studies in bladder cancer. Author(s): Crawford ED, Wood DP, Petrylak DP, Scott J, Coltman CA Jr, Raghavan D; Southwest Oncology Group. Source: Cancer. 2003 April 15; 97(8 Suppl): 2099-108. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673702&dopt=Abstract

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Sufficient prophylactic efficacy with minor adverse effects by intravesical instillation of low-dose bacillus Calmette-Guerin for superficial bladder cancer recurrence. Author(s): Irie A, Uchida T, Yamashita H, Matsumoto K, Satoh T, Koh H, Shimura S, Iwamura M, Baba S. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 April; 10(4): 183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657096&dopt=Abstract

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Surgery versus radiotherapy for muscle invasive bladder cancer? Author(s): Shelley MD, Barber J, Wilt TJ, Mason MD. Source: Clin Oncol (R Coll Radiol). 2003 May; 15(3): 167-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801061&dopt=Abstract

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Surgical factors in bladder cancer: more (nodes) + more (pathology) = less (mortality). Author(s): Herr HW. Source: Bju International. 2003 August; 92(3): 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887464&dopt=Abstract

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Surveillance with microsatellite analysis of urine in bladder cancer patients treated by radiotherapy. Author(s): van Rhijn BW, Smit M, van Geenen D, Wijnmaalen A, Kirkels WJ, van der Kwast TH, Kuenen-Boumeester V, Zwarthoff EC. Source: European Urology. 2003 April; 43(4): 369-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667717&dopt=Abstract

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Symptomatic granulomatous prostatitis following bacillus Calmette-Guerin immunotherapy for bladder cancer. Author(s): Noor MA, Biyabani SR, Burney IA, Talatia J. Source: J Pak Med Assoc. 2002 December; 52(12): 578-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627909&dopt=Abstract

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Telomerase activity in diagnosis of bladder cancer. Author(s): Erdem E, Dikmen G, Atsu N, Dogan P, Ozen H. Source: Scandinavian Journal of Urology and Nephrology. 2003; 37(3): 205-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775275&dopt=Abstract

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The predictive value of purified protein derivative results on complications and prognosis in patients with bladder cancer treated with bacillus Calmette-Guerin. Author(s): Bilen CY, Inci K, Erkan I, Ozen H. Source: The Journal of Urology. 2003 May; 169(5): 1702-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686812&dopt=Abstract

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The systemic treatment of advanced and metastatic bladder cancer. Author(s): Hussain SA, James ND. Source: The Lancet Oncology. 2003 August; 4(8): 489-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901963&dopt=Abstract

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Three-dimensional analysis of delineation errors, setup errors, and organ motion during radiotherapy of bladder cancer. Author(s): Meijer GJ, Rasch C, Remeijer P, Lebesque JV. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 April 1; 55(5): 1277-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654438&dopt=Abstract

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Tissue polypeptide antigen (TPA) in comparison with mutations of tumour suppressor gene P53 (TP53) in patients with bladder cancer. Author(s): Ecke TH, Lenk SV, Schlechte HH, Loening SA. Source: Anticancer Res. 2003 March-April; 23(2A): 957-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820330&dopt=Abstract

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Trends in the incidence of bladder cancer in Nova Scotia: a twenty-year perspective. Author(s): McLellan RA, French CG, Bell DG. Source: Can J Urol. 2003 June; 10(3): 1880-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892574&dopt=Abstract

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Tuberculous epididymo-orchitis following intravesical BCG for superficial bladder cancer. Author(s): Bulbul MA, Hijaz A, Beaini M, Araj GF, Tawil A. Source: J Med Liban. 2002 January-April; 50(1-2): 67-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841318&dopt=Abstract

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Tumor markers in the diagnosis of primary bladder cancer. A systematic review. Author(s): Glas AS, Roos D, Deutekom M, Zwinderman AH, Bossuyt PM, Kurth KH. Source: The Journal of Urology. 2003 June; 169(6): 1975-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771702&dopt=Abstract

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Tumor suppressor role for myopodin in bladder cancer: loss of nuclear expression of myopodin is cell-cycle dependent and predicts clinical outcome. Author(s): Sanchez-Carbayo M, Schwarz K, Charytonowicz E, Cordon-Cardo C, Mundel P. Source: Oncogene. 2003 August 14; 22(34): 5298-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917631&dopt=Abstract

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Tumor-associated trypsin inhibitor as a prognostic factor during follow-up of bladder cancer. Author(s): Kelloniemi E, Rintala E, Finne P, Stenman UH; Finnbladder Group. Source: Urology. 2003 August; 62(2): 249-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893328&dopt=Abstract

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Ultraviolet-excited (308 nm) autofluorescence for bladder cancer detection. Author(s): Zaak D, Stepp H, Baumgartner R, Schneede P, Waidelich R, Frimberger D, Hartmann A, Kunchel R, Hofstetter A, Hohla A. Source: Urology. 2002 December; 60(6): 1029-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475664&dopt=Abstract

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Urinary bladder cancer. Author(s): Wai CY, Miller DS. Source: Clinical Obstetrics and Gynecology. 2002 September; 45(3): 844-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370626&dopt=Abstract

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Urinary IL-2 assay for monitoring intravesical bacillus Calmette-Guerin response of superficial bladder cancer during induction course and maintenance therapy. Author(s): Saint F, Kurth N, Maille P, Vordos D, Hoznek A, Soyeux P, Patard JJ, Abbou CC, Chopin DK. Source: International Journal of Cancer. Journal International Du Cancer. 2003 November 10; 107(3): 434-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506744&dopt=Abstract

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Urinary interleukin-8 predicts the response of standard and low dose intravesical bacillus Calmette-Guerin (modified Danish 1331 strain) for superficial bladder cancer. Author(s): Kumar A, Dubey D, Bansal P, Mandhani A, Naik S. Source: The Journal of Urology. 2002 November; 168(5): 2232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394765&dopt=Abstract

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Urinary levels of monocyte chemo-attractant protein-1 correlate with tumour stage and grade in patients with bladder cancer. Author(s): Amann B, Perabo FG, Wirger A, Hugenschmidt H, Schultze-Seemann W. Source: British Journal of Urology. 1998 July; 82(1): 118-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9698673&dopt=Abstract

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Urinary markers in bladder cancer. Author(s): Bailey MJ. Source: Bju International. 2003 June; 91(9): 772-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780829&dopt=Abstract

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Uroplakin gene expression in normal human tissues and locally advanced bladder cancer. Author(s): Olsburgh J, Harnden P, Weeks R, Smith B, Joyce A, Hall G, Poulsom R, Selby P, Southgate J. Source: The Journal of Pathology. 2003 January; 199(1): 41-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474225&dopt=Abstract

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Use of high-throughput DNA microarrays to identify biomarkers for bladder cancer. Author(s): Sanchez-Carbayo M. Source: Clinical Chemistry. 2003 January; 49(1): 23-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507957&dopt=Abstract

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Usefulness of tissue polypeptide antigen in the follow-up of bladder cancer. Author(s): Menendez Lopez V, Galan JA, Fernandez-Suarez A, Lopez-Celada S, Alcover J, Filella X. Source: Urology. 2003 August; 62(2): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893327&dopt=Abstract

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Utility of nuclear matrix protein (NMP22) in the detection of recurrent bladder cancer. Author(s): Grocela JA, McDougal WS. Source: The Urologic Clinics of North America. 2000 February; 27(1): 47-51, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696244&dopt=Abstract

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Vaginal and omental metastasis from superficial bladder cancer. Author(s): Kumar R, Kumar S, Hemal AK. Source: Urologia Internationalis. 2001; 67(1): 117-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11464136&dopt=Abstract

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Value of selective upper tract cytology for recognition of upper tract tumors after treatment of superficial bladder cancer. Author(s): Gogus C, Baltaci S, Sahinli S, Turkolmez K, Beduk Y, Gogus O. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 May; 10(5): 243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694462&dopt=Abstract

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Variation in enzymes of arylamine procarcinogen biotransformation among bladder cancer patients and control subjects. Author(s): Vaziri SA, Hughes NC, Sampson H, Darlington G, Jewett MA, Grant DM. Source: Pharmacogenetics. 2001 February; 11(1): 7-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207033&dopt=Abstract

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Various forms of mutant p53 confer sensitivity to cisplatin and doxorubicin in bladder cancer cells. Author(s): Chang FL, Lai MD. Source: The Journal of Urology. 2001 July; 166(1): 304-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435891&dopt=Abstract

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Vascular endothelial growth factor and its correlation with superficial bladder cancer recurrence rates and stage progression. Author(s): Jones A, Crew J. Source: The Urologic Clinics of North America. 2000 February; 27(1): 191-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696258&dopt=Abstract

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Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. Author(s): Droller MJ. Source: The Journal of Urology. 1998 November; 160(5): 1932. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9783988&dopt=Abstract

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Vascular endothelial growth factor: an important angiogenic mediator in bladder cancer. Author(s): Crew JP. Source: European Urology. 1999 January; 35(1): 2-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9933788&dopt=Abstract

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Visualisation of bladder cancer using (11)C-choline PET: first clinical experience. Author(s): de Jong IJ, Pruim J, Elsinga PH, Jongen MM, Mensink HJ, Vaalburg W. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 October; 29(10): 1283-8. Epub 2002 July 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271408&dopt=Abstract

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Visualizing superficial human bladder cancer cell growth in vivo by green fluorescent protein expression. Author(s): Zhou JH, Rosser CJ, Tanaka M, Yang M, Baranov E, Hoffman RM, Benedict WF. Source: Cancer Gene Therapy. 2002 August; 9(8): 681-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136429&dopt=Abstract

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Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women. Author(s): Jacobs EJ, Henion AK, Briggs PJ, Connell CJ, McCullough ML, Jonas CR, Rodriguez C, Calle EE, Thun MJ. Source: American Journal of Epidemiology. 2002 December 1; 156(11): 1002-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446256&dopt=Abstract

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WAF1/p21 protein expression is an independent prognostic indicator in superficial and invasive bladder cancer. Author(s): Korkolopoulou P, Konstantinidou AE, Thomas-Tsagli E, Christodoulou P, Kapralos P, Davaris P. Source: Applied Immunohistochemistry & Molecular Morphology : Aimm / Official Publication of the Society for Applied Immunohistochemistry. 2000 December; 8(4): 28592. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127920&dopt=Abstract

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Water as a tumoricidal agent in bladder cancer. In vitro studies in parental and resistant cell lines. Author(s): Solomon LZ, Birch BR, Cooper AJ. Source: European Urology. 1998 December; 34(6): 500-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9831792&dopt=Abstract

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What are the immunologically active components of bacille Calmette-Guerin in therapy of superficial bladder cancer? Author(s): Zlotta AR, Van Vooren JP, Denis O, Drowart A, Daffe M, Lefevre P, Schandene L, De Cock M, De Bruyn J, Vandenbussche P, Jurion F, Palfliet K, Simon J, Schulman CC, Content J, Huygen K. Source: International Journal of Cancer. Journal International Du Cancer. 2000 September 15; 87(6): 844-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10956396&dopt=Abstract

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What we could do now: molecular pathology of bladder cancer. Author(s): Knowles MA. Source: Molecular Pathology : Mp. 2001 August; 54(4): 215-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477133&dopt=Abstract

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Where are the 'poster boys' for bladder cancer? Author(s): Soloway MS. Source: Bju International. 2003 June; 91(9): 769-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780826&dopt=Abstract

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White blood cell DNA adducts and fruit and vegetable consumption in bladder cancer. Author(s): Peluso M, Airoldi L, Magagnotti C, Fiorini L, Munnia A, Hautefeuille A, Malaveille C, Vineis P. Source: Carcinogenesis. 2000 February; 21(2): 183-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10657956&dopt=Abstract

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White blood cell DNA adducts, smoking, and NAT2 and GSTM1 genotypes in bladder cancer: a case-control study. Author(s): Peluso M, Airoldi L, Armelle M, Martone T, Coda R, Malaveille C, Giacomelli G, Terrone C, Casetta G, Vineis P. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1998 April; 7(4): 341-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9568791&dopt=Abstract

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WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer. Author(s): Wissmann C, Wild PJ, Kaiser S, Roepcke S, Stoehr R, Woenckhaus M, Kristiansen G, Hsieh JC, Hofstaedter F, Hartmann A, Knuechel R, Rosenthal A, Pilarsky C. Source: The Journal of Pathology. 2003 October; 201(2): 204-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517837&dopt=Abstract

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

Finding Nutrition Studies on Bladder 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 “bladder cancer” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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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 “bladder cancer” (or a synonym): •

A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party. Author(s): Royal South Hants Hospital, Brintons Terrace, Southampton, UK. Source: Mead, G M Russell, M Clark, P Harland, S J Harper, P G Cowan, R Roberts, J T Uscinska, B M Griffiths, G O ParMarch, M K Br-J-Cancer. 1998 October; 78(8): 1067-75 0007-0920

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Angiogenesis in bladder cancer--prognostic marker and target for future therapy. Author(s): Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK. [email protected] Source: Streeter, E H Harris, A L Surg-Oncol. 2002 June; 11(1-2): 85-100 0960-7404

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Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines. Author(s): Department of Urology, Osaka City University Medical School, Osaka, Japan. Source: Ikemoto, S Sugimura, K Yoshida, N Yasumoto, R Wada, S Yamamoto, K Kishimoto, T Urology. 2000 June; 55(6): 951-5 0090-4295

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Are coffee, tea, and total fluid consumption associated with bladder cancer risk? Results from the Netherlands Cohort Study. Author(s): Department of Epidemiology, Maastricht University, The Netherlands. [email protected] Source: Zeegers, M P Dorant, E Goldbohm, R A van den Brandt, P A Cancer-CausesControl. 2001 April; 12(3): 231-8 0957-5243

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Bladder cancer in women. Author(s): University Hospital, Nijmegen, The Netherlands. Source: van der Poel, H G Mungan, N A Witjes, J A Int-Urogynecol-J-Pelvic-FloorDysfunct. 1999; 10(3): 207-12

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Bladder preserving combined modality therapy for invasive bladder cancer. Author(s): Albert Einstein Medical Center, Philadelphia, PA. Source: Held, J Volpe, H Oncol-Nurs-Forum. 1991 Jan-February; 18(1): 49-57 0190-535X

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Combined effect of chemopreventive agent N-(4-hydroxyphenyl) retinamide (4-HPR) and gamma-radiation on bladder cancer cell lines. Author(s): Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Source: Zou, C Wang, L Liebert, M Grossman, H B Lotan, R Wei, Q Int-J-Oncol. 1998 November; 13(5): 1037-41 1019-6439

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Current and future perspectives in advanced bladder cancer: is there a new standard? Author(s): Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. Source: von der Maase, Hans Semin-Oncol. 2002 February; 29(1 Suppl 3): 3-14 0093-7754

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DNA ploidy and S-phase fraction as predictive factors of response and outcome following neoadjuvant methotrexate, vinblastine, epirubicin and cisplatin (M-VEC) chemotherapy for invasive bladder cancer. Author(s): Department of Urology, University of Ankara, School of Medicine, Turkey. Source: Turkolmez, K Baltaci, S Beduk, Y Muftuoglu, Y Z Gogus, O Scand-J-UrolNephrol. 2002 February; 36(1): 46-51 0036-5599

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Effect of lectins on KK-47 bladder cancer cell line. Author(s): Department of Urology, University of Mainz Medical School, F. R. Germany. Source: Bazeed, M A Becht, E Scharfe, T Schmidt, J Jacobi, G H Thuroff, J W Urology. 1988 August; 32(2): 133-5 0090-4295

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Efficacy of antiangiogenic therapy with TNP-470 in superficial and invasive bladder cancer models in mice. Author(s): Department of Surgery, Children's Hospital Boston, Boston, Massachusetts 02115, USA. Source: Beecken, W D Fernandez, A Panigrahy, D Achilles, E G Kisker, O Flynn, E Joussen, A M Folkman, J Shing, Y Urology. 2000 September 1; 56(3): 521-6 1527-9995

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Endogenously formed nitric oxide modulates cell growth in bladder cancer cell lines. Author(s): Department of Urology, Karolinska Hospital, Stockholm, Sweden. Source: Morcos, E Jansson, O T Adolfsson, J Kratz, G Wiklund, N P Urology. 1999 June; 53(6): 1252-7 0090-4295

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Enhancing effect of an inhibitor of nitric oxide synthesis on bacillus CalmetteGuerin-induced macrophage cytotoxicity against murine bladder cancer cell line MBT-2 in vitro. Author(s): Department of Urology, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan. Source: Yamada, H Matsumoto, S Matsumoto, T Yamada, T Yamashita, U Jpn-J-CancerRes. 2000 May; 91(5): 534-42 0910-5050

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Evaluation of chemotherapy in advanced urinary bladder cancer with fast dynamic contrast-enhanced MR imaging. Author(s): Department of Radiology, University Hospital Nijmegen, The Netherlands. Source: Barentsz, J O Berger Hartog, O Witjes, J A Hulsbergen van der Kaa, C Oosterhof, G O VanderLaak, J A Kondacki, H Ruijs, S H Radiology. 1998 June; 207(3): 791-7 00338419

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Evaluation of systemic chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin for advanced bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin. Author(s): Dept. of Urology, Center for Adult Diseases, Osaka, Japan. Source: Kotake, T Akaza, H Isaka, S Kagawa, S Koiso, K Machida, T Maru, A Matsumura, Y Miyagawa, I Niijima, T et al. Cancer-Chemother-Pharmacol. 1992; 30 SupplS85-9 0344-5704

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Evaluation of the influence of systemic neoadjuvant chemotherapy on the survival of patients treated for invasive bladder cancer. Author(s): Urology Department, District Hospital, Legnica, Poland. Source: Kolaczyk, W Dembowski, J Lorenz, J Dudek, K BJU-Int. 2002 April; 89(6): 616-9 1464-4096

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Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human transitional bladder cancer and its role in inducing cell death. Author(s): Division of Nephrology, Veterans Administration Medical Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Source: Guan, Y F Zhang, Y H Breyer, R M Davis, L Breyer, M D Neoplasia. 1999 October; 1(4): 330-9 1522-8002

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Foods and risk of bladder cancer: a case-control study in Uruguay. Author(s): Seccion de Epidemiologia, Instituto Nacional de Oncologia, Montevideo, Uruguay.

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Source: Balbi, J C Larrinaga, M T De Stefani, E Mendilaharsu, M Ronco, A L Boffetta, P Brennan, P Eur-J-Cancer-Prevolume 2001 October; 10(5): 453-8 0959-8278 •

Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. Author(s): Aarhus University Hospital, Denmark. [email protected] Source: von der Maase, H Hansen, S W Roberts, J T Dogliotti, L Oliver, T Moore, M J Bodrogi, I Albers, P Knuth, A Lippert, C M Kerbrat, P Sanchez Rovira, P Wersall, P Cleall, S P Roychowdhury, D F Tomlin, I Visseren Grul, C M Conte, P F J-Clin-Oncol. 2000 September; 18(17): 3068-77 0732-183X

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Human bladder cancer: epidemiological, pathological and mechanistic aspects. Author(s): Istituto di Richerche Farmacologiche Mario Negri, Universita degli Studi de Milano, Milan, Italy. Source: La Vecchia, C Airoldi, L IARC-Sci-Publ. 1999; (147): 139-57 0300-5038

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Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Author(s): Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, People's Republic of China. Source: Chan, Michael W Y Chan, Lun W Tang, Nelson L S Tong, Joanna H M Lo, Kwok W Lee, Tin L Cheung, Ho Y Wong, Wai S Chan, Peter S F Lai, Fernand M M To, Ka F Clin-Cancer-Res. 2002 February; 8(2): 464-70 1078-0432

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In vitro evaluation of flavopiridol, a novel cell cycle inhibitor, in bladder cancer. Author(s): Section of Urology, University of Chicago, IL 60637, USA. Source: Chien, M Astumian, M Liebowitz, D Rinker Schaeffer, C Stadler, W M CancerChemother-Pharmacol. 1999; 44(1): 81-7 0344-5704

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Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Author(s): Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA. [email protected] Source: Michaud, D S Pietinen, P Taylor, P R Virtanen, M Virtamo, J Albanes, D Br-JCancer. 2002 October 21; 87(9): 960-5 0007-0920

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Intra-arterial administration of methotrexate, adriamycin, and cisplatin as neoadjuvant chemotherapy for bladder cancer. Author(s): Department of Urology, Gifu University School of Medicine, Japan. Source: Kuriyama, M Takahashi, Y Nagatani, Y Shinoda, I Yamamoto, N Nagai, T Ueno, K Takeuchi, T Maeda, S Isogai, K et al. Cancer-Chemother-Pharmacol. 1992; 30 SupplS14 0344-5704

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Localized bladder cancer. Author(s): Department of Urology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 110, Houston, TX 77030, USA. Source: Izawa, J I Grossman, H B Curr-Treat-Options-Oncol. 2000 December; 1(5): 423-32 1527-2729

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MVAC chemotherapy-induced apoptosis and p53 alterations in the rat model of bladder cancer. Author(s): Department of Urology, Kagawa Medical University Miki-cho, Kagawa, Japan. Source: Zhang, X Jin, L Takenaka, I Urology. 1998 November; 52(5): 925-31 0090-4295

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Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome. Author(s): Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [email protected] Source: Herr, H W Bajorin, D F Scher, H I J-Clin-Oncol. 1998 April; 16(4): 1298-301 0732183X

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New chemotherapy combinations for advanced bladder cancer. Author(s): Medical Oncology Service, General University Vall d'Hebron Hospital, Barcelona, Spain. [email protected] Source: Bellmunt, J Albiol, S Curr-Opin-Urol. 2001 September; 11(5): 517-22 0963-0643

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New chemotherapy regimens for advanced bladder cancer. Author(s): Department of Medicine, University of Chicago, IL 60637, USA. Source: Fagbemi, S O Stadler, W M Semin-Urol-Oncol. 1998 February; 16(1): 23-9 10810943

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Organophosphate-based pesticides and genetic damage implicated in bladder cancer. Author(s): School of Biomedical Sciences, Faculty of Health Studies, Charles Sturt University, Wagga Wagga, Australia. Source: Webster, Lucy R McKenzie, Geoff H Moriarty, Helen T Cancer-GenetCytogenet. 2002 March; 133(2): 112-7 0165-4608

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Phase 1/2 study of synchronous methotrexate, cisplatin, vincristine (MOPq10) chemotherapy and radiation for patients with locally advanced bladder cancer. Author(s): Department of Medical Oncology, School of Medicine and Dentistry, St. Bartholomew's and Royal London Hospitals, Queen Mary and Westfield College, Smithfield, London, UK. [email protected] Source: Goonewardene, T I Bozcuk, H Oliver, R T Barua, J Nargund, V Philip, T Mair, G Gibbs, S Urol-Int. 2001; 67(4): 293-7 0042-1138

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Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. Author(s): Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA. Source: Shipley, W U Winter, K A Kaufman, D S Lee, W R Heney, N M Tester, W R Donnelly, B J Venner, P M Perez, C A Murray, K J Doggett, R S True, L D J-Clin-Oncol. 1998 November; 16(11): 3576-83 0732-183X

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Plenary debate of randomized phase III trial of neoadjuvant MVAC plus cystectomy versus cystectomy alone in patients with locally advanced bladder cancer. Author(s): Genitourinary and Head and Neck Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Source: Bajorin, D F J-Clin-Oncol. 2001 September 15; 19(18 Suppl): 17S-20S 0732-183X

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Potential lifestyle and dietary supplement options for the prevention and postdiagnosis of bladder cancer. Author(s): Department of Urology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0330, USA. [email protected] Source: Moyad, Mark A Urol-Clin-North-Am. 2002 February; 29(1): 31-48, viii 0094-0143

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Preliminary results of simultaneous radiochemotherapy with paclitaxel for urinary bladder cancer. Author(s): Department of Radiotherapy, Martin-Luther-University Halle-Wittenberg, Germany. [email protected] Source: Dunst, J Weigel, C Heynemann, H Becker, A Strahlenther-Onkol. 1999 October; 175 Suppl 37-10 0179-7158

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Progress in the management of metastatic bladder cancer. Author(s): Division of Medical Oncology at the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, 90089-9173, USA. Source: Parimoo, D Raghavan, D Cancer-Control. 2000 Jul-August; 7(4): 347-56 10732748

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Rethinking the secondary prevention of superficial bladder cancer: is there a role for retinoids? Author(s): Academic Unit of Radiotherapy and Oncology, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, UK. [email protected] Source: Nutting, C Huddart, R A BJU-Int. 2000 June; 85(9): 1023-6 1464-4096

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Retinoids in the chemoprevention of bladder cancer. Author(s): Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston 77030-4095, USA. Source: Sabichi, A L Lerner, S P Grossman, H B Lippman, S M Curr-Opin-Oncol. 1998 September; 10(5): 479-84 1040-8746

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Retinoids in the prevention of bladder cancer. Author(s): Institute of Cancer Research and Royal Marsden NHS Trust, Fulham Road, London SW3 6JJ, UK. [email protected] Source: Nutting, C M Huddart, R A Expert-Rev-Anticancer-Ther. 2001 December; 1(4): 541-5 1473-7140

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Reversal of P-Glycoprotein-mediated Paclitaxel Resistance by New Synthetic Isoprenoids in Human Bladder Cancer Cell Line. Author(s): Department of Urology, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan. [email protected] Source: Enokida, H Gotanda, T Oku, S Imazono, Y Kubo, H Hanada, T Suzuki, S Inomata, K Kishiye, T Tahara, Y Nishiyama, K Nakagawa, M Jpn-J-Cancer-Res. 2002 September; 93(9): 1037-46 0910-5050

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Secondary leukaemia after treating advanced bladder cancer with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy and radiotherapy. Author(s): Institut Gustave Roussy, Villejuif, France. Source: Theodore, C Bayle, C Bernheim, A Wibault, P BJU-Int. 2002 September; 90(4): 470-1 1464-4096

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Second-line chemotherapy in advanced bladder cancer. Author(s): Institute of Urology, University of Palermo, Italy. Source: Pavone Macaluso, M Sternberg, C Urol-Int. 2000; 64(2): 61-9 0042-1138

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Tea consumption: fluid intake and bladder cancer risk in Southern Taiwan. Author(s): Department of Urology, Tian-Sheng Memorial Hospital, Pingtung, Taiwan. Source: Lu, C M Lan, S J Lee, Y H Huang, J K Huang, C H Hsieh, C C Urology. 1999 November; 54(5): 823-8 0090-4295

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The NAT2* slow acetylator genotype is associated with bladder cancer in Taiwanese, but not in the Black Foot Disease endemic area population. Author(s): College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.

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Source: Su, H J Guo, Y L Lai, M D Huang, J D Cheng, Y Christiani, D C Pharmacogenetics. 1998 April; 8(2): 187-90 0960-314X •

The natural history of a T1 bladder cancer: life-long tumour diathesis. Author(s): Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA. Source: Herr, H W BJU-Int. 1999 December; 84(9): 1102-3 1464-4096

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The potential application of Allium sativum (garlic) for the treatment of bladder cancer. Author(s): Department of Urology, Robert C. Byrd Health Science Center, West Virginia University, Morgantown, USA. [email protected] Source: Lamm, D L Riggs, D R Urol-Clin-North-Am. 2000 February; 27(1): 157-62, xi 0094-0143

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The present and future of combination chemotherapy in bladder cancer. Author(s): Department of Medicine, CRLC Val d'Aurelle, Cedex, France. Source: Culine, Stephane Semin-Oncol. 2002 June; 29(3 Suppl 9): 32-9 0093-7754

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The role of adjuvant chemotherapy for locally advanced bladder cancer. Author(s): Department of Urology, University Saarland, 66421 Homburg/Saar, Germany. [email protected] Source: Lehmann, J Retz, M Stockle, M World-J-Urol. 2001 April; 19(2): 133-40 0724-4983

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The role of combined method in organ-sparing treatment of muscle-invasive bladder cancer recurrences. Author(s): Central Hospital No 122, Central Roentgenoradiological Institute of Scientific Research, St.-Petersburg, Russia. [email protected] Source: Startsev, V Y Arch-Ital-Urol-Androl. 2002 June; 74(2): 54-6 1124-3562

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TP53 accumulation predicts improved survival in patients resistant to systemic cisplatin-based chemotherapy for muscle-invasive bladder cancer. Author(s): Department of Urology, Royal Hallamshire Hospital, The Central Sheffield University Hospitals, Sheffield, United Kingdom. [email protected] Source: Qureshi, K N Griffiths, T R Robinson, M C Marsh, C Roberts, J T Hall, R R Lunec, J Neal, D E Clin-Cancer-Res. 1999 November; 5(11): 3500-7 1078-0432

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Ukrain therapy of stage T1N0M0 bladder cancer patients. Author(s): Oncology Department of Grodno Medical School, Belarus. Source: Uglianitsa, K N Nechiporenko, N A Nefyodov, L I Brzosko, W J Drugs-ExpClin-Res. 1998; 24(5-6): 227-30 0378-6501

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Use of methotrexate, vinblastine, adriamycin, and cisplatin in combination with radiation and hyperthermia as neo-adjuvant therapy for bladder cancer. Author(s): Department of Urology, Yokohama City University, Japan. Source: Noguchi, S Kubota, Y Miura, T Shuin, T Hosaka, M Cancer-ChemotherPharmacol. 1992; 30 SupplS63-5 0344-5704

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/

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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

The following is a specific Web list relating to bladder 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: •

Vitamins Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com

Nutrition

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Food and Diet Coffee Source: Healthnotes, Inc.; www.healthnotes.com

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

A phase II study of 5-fluorouracil and high dose folinic acid in cisplatin-refractory metastatic bladder cancer. Author(s): Huan SD, Aitken SE, Stewart DJ. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1995 October; 6(8): 836-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8589024&dopt=Abstract

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A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party. Author(s): Mead GM, Russell M, Clark P, Harland SJ, Harper PG, Cowan R, Roberts JT, Uscinska BM, Griffiths GO, Parmar MK.

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A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. Author(s): Freiha F, Reese J, Torti FM. Source: The Journal of Urology. 1996 February; 155(2): 495-9; Discussion 499-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8558644&dopt=Abstract

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Accelerated cisplatin-based chemotherapy for advanced bladder cancer. Author(s): Boshoff C, Oliver RT, Gallagher CJ, Ong J. Source: European Journal of Cancer (Oxford, England : 1990). 1995 September; 31A(10): 1633-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7488414&dopt=Abstract

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Adenovirus-mediated delivery of p16 to p16-deficient human bladder cancer cells confers chemoresistance to cisplatin and paclitaxel. Author(s): Grim J, D'Amico A, Frizelle S, Zhou J, Kratzke RA, Curiel DT. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1997 December; 3(12 Pt 1): 2415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9815642&dopt=Abstract

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Adenovirus-mediated gene therapy for bladder cancer: efficient gene delivery to normal and malignant human urothelial cells in vitro and ex vivo. Author(s): Chester JD, Kennedy W, Hall GD, Selby PJ, Knowles MA. Source: Gene Therapy. 2003 January; 10(2): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571646&dopt=Abstract

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Adjuvant and neoadjuvant chemotherapy for invasive bladder cancer. Author(s): Natale RB. Source: Current Oncology Reports. 2000 September; 2(5): 386-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122869&dopt=Abstract

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Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study and further clinical experience. Author(s): Stockle M, Meyenburg W, Wellek S, Voges GE, Rossmann M, Gertenbach U, Thuroff JW, Huber C, Hohenfellner R. Source: The Journal of Urology. 1995 January; 153(1): 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7966789&dopt=Abstract

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Advanced bladder cancer: the need to identify new agents in the post-M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) world. Author(s): Roth BJ, Bajorin DF. Source: The Journal of Urology. 1995 March; 153(3 Pt 2): 894-900. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7853569&dopt=Abstract

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Advances in chemotherapy of invasive bladder cancer. Author(s): Akaza H. Source: Current Opinion in Urology. 2000 September; 10(5): 453-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005451&dopt=Abstract

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Anti-neoplastic activity of paclitaxel on experimental superficial bladder cancer: in vivo and in vitro studies. Author(s): Nativ O, Aronson M, Medalia O, Moldavsky T, Sabo E, Ringel I, Kravtsov V. Source: International Journal of Cancer. Journal International Du Cancer. 1997 January 27; 70(3): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9033631&dopt=Abstract

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Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines. Author(s): Ikemoto S, Sugimura K, Yoshida N, Yasumoto R, Wada S, Yamamoto K, Kishimoto T. Source: Urology. 2000 June; 55(6): 951-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10840124&dopt=Abstract

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Biochemical mechanism of cross-resistance to paclitaxel in a mitomycin c-resistant human bladder cancer cell line. Author(s): Bleicher RJ, Xia H, Zaren HA, Singh SV. Source: Cancer Letters. 2000 March 31; 150(2): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704734&dopt=Abstract

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Bladder cancer chemotherapy trial generates more questions than it answers. Author(s): Newman L. Source: Journal of the National Cancer Institute. 2001 July 4; 93(13): 973-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438559&dopt=Abstract

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Bladder cancer mortality associated with arsenic in drinking water in Argentina. Author(s): Hopenhayn-Rich C, Biggs ML, Fuchs A, Bergoglio R, Tello EE, Nicolli H, Smith AH. Source: Epidemiology (Cambridge, Mass.). 1996 March; 7(2): 117-24. Erratum In: Epidemiology 1997 May; 8(3): 334. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8834549&dopt=Abstract

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Bladder cancer recurrence: Part II. What do I tell my patients about lifestyle changes and dietary supplements? Author(s): Moyad MA. Source: Current Opinion in Urology. 2003 September; 13(5): 379-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917513&dopt=Abstract

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Bladder preservation by combined modality therapy for invasive bladder cancer. Author(s): Kachnic LA, Kaufman DS, Heney NM, Althausen AF, Griffin PP, Zietman AL, Shipley WU. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1997 March; 15(3): 1022-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9060542&dopt=Abstract

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Camptothecin analogues/cisplatin: an effective treatment of advanced bladder cancer in a preclinical in vivo model system. Author(s): Keane TE, El-Galley RE, Sun C, Petros JA, Dillahey D, Gomaa A, Graham SD Jr, McGuire WP 3rd. Source: The Journal of Urology. 1998 July; 160(1): 252-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9628659&dopt=Abstract

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Chemoprevention of bladder cancer. Author(s): Kamat AM, Lamm DL. Source: The Urologic Clinics of North America. 2002 February; 29(1): 157-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109342&dopt=Abstract

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Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Author(s): Knapp DW, Glickman NW, Widmer WR, DeNicola DB, Adams LG, Kuczek T, Bonney PL, DeGortari AE, Han C, Glickman LT. Source: Cancer Chemotherapy and Pharmacology. 2000; 46(3): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11021739&dopt=Abstract

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Cisplatin-based neoadjuvant chemotherapy for invasive bladder cancer. Author(s): Kadena H, Igawa M, Shigeta M, Nakamoto T, Usui T. Source: Hiroshima J Med Sci. 1995 December; 44(4): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8857236&dopt=Abstract

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Clinical application of an in vitro chemosensitivity test, the Histoculture Drug Response Assay, to urological cancers: wide distribution of inhibition rates in bladder cancer and renal cell cancer. Author(s): Hirano Y, Ushiyama T, Suzuki K, Fujita K.

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Source: Urological Research. 1999 December; 27(6): 483-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10651138&dopt=Abstract •

Combination chemotherapy with intra-arterial cisplatin and doxorubicin plus intravenous methotrexate and vincristine for locally advanced bladder cancer. Kyushu University Urological and Radiological Oncology Group. Author(s): Naito S, Kuroiwa T, Ueda T, Hasuo K, Masuda K, Kumazawa J. Source: The Journal of Urology. 1995 November; 154(5): 1704-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7563327&dopt=Abstract

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Combination transurethral resection, systemic chemotherapy, and pelvic radiotherapy for invasive (T2-T4) bladder cancer unsuitable for cystectomy: a phase I/II Southwestern Oncology Group study. Author(s): Einstein AB Jr, Wolf M, Halliday KR, Miller GJ, Hafermann M, Lowe BA, Meyers FJ, Leimert JT, Crawford ED. Source: Urology. 1996 May; 47(5): 652-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8650861&dopt=Abstract

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Comparative study of sequential combinations of paclitaxel and methotrexate on a human bladder cancer cell line. Author(s): Cos J, Bellmunt J, Soler C, Ribas A, Lluis JM, Murio JE, Margarit C. Source: Cancer Investigation. 2000; 18(5): 429-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10834027&dopt=Abstract

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Comparison between a cisplatin-containing regimen and a carboplatin-containing regimen for recurrent or metastatic bladder cancer patients. A randomized phase II study. Author(s): Petrioli R, Frediani B, Manganelli A, Barbanti G, De Capua B, De Lauretis A, Salvestrini F, Mondillo S, Francini G. Source: Cancer. 1996 January 15; 77(2): 344-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8625244&dopt=Abstract

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Conservative management of advanced bladder cancer. Author(s): Lekili M, Ayder AR, Minareci S, Nergis S, Durgun MN. Source: International Urology and Nephrology. 1995; 27(6): 747-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8725041&dopt=Abstract

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Conservative management of stage T2 or T3a bladder cancer with deep transurethral resection followed by four cycles of chemotherapy. Author(s): Uygur MC, Yaman I, Altug U, Erol D. Source: British Journal of Urology. 1996 August; 78(2): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8813913&dopt=Abstract

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Cross-resistance and combined cytotoxic effects of paclitaxel and cisplatin in bladder cancer cells. Author(s): Pu YS, Chen J, Huang CY, Guan JY, Lu SH, Hour TC. Source: The Journal of Urology. 2001 June; 165(6 Pt 1): 2082-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11371932&dopt=Abstract

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Current and future perspectives in advanced bladder cancer: is there a new standard? Author(s): von der Maase H. Source: Seminars in Oncology. 2002 February; 29(1 Suppl 3): 3-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894002&dopt=Abstract

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Current trends in bladder cancer treatment. Author(s): Lamm DL, Allaway M. Source: Ann Chir Gynaecol. 2000; 89(3): 234-41. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11079794&dopt=Abstract

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Dietary soy and increased risk of bladder cancer: the Singapore Chinese Health Study. Author(s): Sun CL, Yuan JM, Arakawa K, Low SH, Lee HP, Yu MC. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 December; 11(12): 1674-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496060&dopt=Abstract

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DNA ploidy and P-glycoprotein expression as predictive factors of response to neoadjuvant chemotherapy for invasive bladder cancer. Author(s): Sandlow J, Cohen MB, Robinson RA, Dreicer R, Williams RD. Source: Urology. 1994 June; 43(6): 787-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7910989&dopt=Abstract

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DNA ploidy and S-phase fraction as predictive factors of response and outcome following neoadjuvant methotrexate, vinblastine, epirubicin and cisplatin (M-VEC) chemotherapy for invasive bladder cancer. Author(s): Turkolmez K, Baltaci S, Beduk Y, Muftuoglu YZ, Gogus O. Source: Scandinavian Journal of Urology and Nephrology. 2002 February; 36(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002357&dopt=Abstract

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Early response of tumour to radiotherapy should be assessed by both uptake and retention of single photon tracers: in vitro analysis with 201Tl-chloride, 99Tcmsestamibi and 99Tcm-tetrofosmin in human bladder cancer cells and human leukocytes. Author(s): Kinuya S, Yokoyama K, Watanabe N, Hiramatsu T, Tega H, Konishi S, Shuke N, Aburano T, Takayama T, Michigishi T, Tonami N.

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Source: Nuclear Medicine Communications. 1999 June; 20(6): 581-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10451872&dopt=Abstract •

Early results of the value of p53 in predicting survival in a homogeneous cohort of patients with invasive bladder cancer treated with a neoadjuvant carboplatin-based regimen (M-CAVI). Author(s): Ribas A, Bellmunt J, Albanell J, De Torres I, Bermejo B, De Torres JA, Morote J, Gallardo E, Vera R, Carulla J, Sole-Calvo LA. Source: Tumori. 1996 November-December; 82(6): 554-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9061063&dopt=Abstract

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Effects of the cyclooxygenase inhibitor, piroxicam, in combination with chemotherapy on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer. Author(s): Mohammed SI, Craig BA, Mutsaers AJ, Glickman NW, Snyder PW, deGortari AE, Schlittler DL, Coffman KT, Bonney PL, Knapp DW. Source: Molecular Cancer Therapeutics. 2003 February; 2(2): 183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589035&dopt=Abstract

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Effects of the cyclooxygenase inhibitor, piroxicam, on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer. Author(s): Mohammed SI, Bennett PF, Craig BA, Glickman NW, Mutsaers AJ, Snyder PW, Widmer WR, DeGortari AE, Bonney PL, Knapp DW. Source: Cancer Research. 2002 January 15; 62(2): 356-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809678&dopt=Abstract

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Electromotive diffusion (EMD) and photodynamic therapy with deltaaminolaevulinic acid (delta-ALA) for superficial bladder cancer. Author(s): Stenzl A, Eder I, Kostron H, Klocker H, Bartsch G. Source: Journal of Photochemistry and Photobiology. B, Biology. 1996 November; 36(2): 233-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9002267&dopt=Abstract

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Enhanced immunocompetence by garlic: role in bladder cancer and other malignancies. Author(s): Lamm DL, Riggs DR. Source: The Journal of Nutrition. 2001 March; 131(3S): 1067S-70S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238818&dopt=Abstract

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Enhancement by cyclosporin A of taxol-induced apoptosis of human urinary bladder cancer cells. Author(s): Nomura T, Yamamoto H, Mimata H, Shitashige M, Shibasaki F, Miyamoto E, Nomura Y.

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Source: Urological Research. 2002 May; 30(2): 102-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086014&dopt=Abstract •

Estimation of risk of developing bladder cancer among workers exposed to coal tar pitch volatiles in the primary aluminum industry. Author(s): Tremblay C, Armstrong B, Theriault G, Brodeur J. Source: American Journal of Industrial Medicine. 1995 March; 27(3): 335-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7747740&dopt=Abstract

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Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. Author(s): Goebell PJ, Otto T, Suhr J, Rubben H. Source: The Journal of Urology. 2002 July; 168(1): 72-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050495&dopt=Abstract

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Evaluation of chemotherapy in advanced urinary bladder cancer with fast dynamic contrast-enhanced MR imaging. Author(s): Barentsz JO, Berger-Hartog O, Witjes JA, Hulsbergen-van der Kaa C, Oosterhof GO, VanderLaak JA, Kondacki H, Ruijs SH. Source: Radiology. 1998 June; 207(3): 791-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9609906&dopt=Abstract

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Evaluation of the influence of systemic neoadjuvant chemotherapy on the survival of patients treated for invasive bladder cancer. Author(s): Kolaczyk W, Dembowski J, Lorenz J, Dudek K. Source: Bju International. 2002 April; 89(6): 616-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942977&dopt=Abstract

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First-line chemotherapy with cisplatin, methotrexate and vinblastine in metastatic bladder cancer. Author(s): Pajk B, Cufer T, Cervek J, Zakotnik B. Source: Tumori. 1996 September-October; 82(5): 453-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9063522&dopt=Abstract

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Five-year results of neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy plus radical cystectomy in locally advanced bladder cancer. Author(s): Scattoni V, Da Pozzo L, Nava L, Broglia L, Galli L, Torelli T, Campo B, Maffezzini M, Rigatti P. Source: European Urology. 1995; 28(2): 102-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8529731&dopt=Abstract

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Functional p53 mutation as a molecular determinant of paclitaxel and gemcitabine susceptibility in human bladder cancer. Author(s): Kielb SJ, Shah NL, Rubin MA, Sanda MG. Source: The Journal of Urology. 2001 August; 166(2): 482-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11458051&dopt=Abstract

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Gemcitabine and cisplatin for advanced, metastatic bladder cancer. Author(s): Cohen MH, Rothmann M. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 February 15; 19(4): 1229-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11181690&dopt=Abstract

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Gemcitabine and cisplatin in locally advanced and/or metastatic bladder cancer. Author(s): von der Maase H. Source: European Journal of Cancer (Oxford, England : 1990). 2000 July; 36 Suppl 2: 13-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908843&dopt=Abstract

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Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. Author(s): von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 September; 18(17): 3068-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001674&dopt=Abstract

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Gemcitabine in advanced bladder cancer. Author(s): von der Maase H. Source: Seminars in Oncology. 2001 April; 28(2 Suppl 7): 11-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11372046&dopt=Abstract

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High incidence of brain metastases in patients treated with an M-VAC regimen for advanced bladder cancer. Author(s): Dhote R, Beuzeboc P, Thiounn N, Flam T, Zerbib M, Christoforov B, Debre B. Source: European Urology. 1998; 33(4): 392-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9612683&dopt=Abstract

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High intake of specific carotenoids and flavonoids does not reduce the risk of bladder cancer. Author(s): Garcia R, Gonzalez CA, Agudo A, Riboli E.

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Ifosfamide in the treatment of bladder cancer. Author(s): Roth BJ. Source: Seminars in Oncology. 1996 June; 23(3 Suppl 6): 50-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8677450&dopt=Abstract

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Impact of surgical resection of bladder cancer metastases refractory to systemic therapy on performance score: a phase II trial. Author(s): Otto T, Krege S, Suhr J, Rubben H. Source: Urology. 2001 January; 57(1): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164143&dopt=Abstract

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In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. Author(s): Syrigos KN, Rowlinson-Busza G, Epenetos AA. Source: International Journal of Cancer. Journal International Du Cancer. 1998 December 9; 78(6): 712-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9833764&dopt=Abstract

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Increased expression of DNA topoisomerase I gene and collateral sensitivity to camptothecin in human cisplatin-resistant bladder cancer cells. Author(s): Kotoh S, Naito S, Yokomizo A, Kumazawa J, Asakuno K, Kohno K, Kuwano M. Source: Cancer Research. 1994 June 15; 54(12): 3248-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8205547&dopt=Abstract

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Inhibition of human bladder cancer cell motility by genistein is dependent on epidermal growth factor receptor but not p21ras gene expression. Author(s): Theodorescu D, Laderoute KR, Calaoagan JM, Guilding KM. Source: International Journal of Cancer. Journal International Du Cancer. 1998 December 9; 78(6): 775-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9833772&dopt=Abstract

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Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC. Author(s): Millikan R, Dinney C, Swanson D, Sweeney P, Ro JY, Smith TL, Williams D, Logothetis C.

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Intensified M-VEC chemotherapy with G-CSF support as outpatient treatment for advanced bladder cancer. Author(s): Pronzato P, Bertelli G, Bruna F, Tani F, Vaira F, Vanoli M, Vigani A. Source: Anticancer Res. 1997 May-June; 17(3C): 2325-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9216710&dopt=Abstract

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Intra-arterial chemotherapy for muscle-invasive urinary bladder cancer. Author(s): Takahashi N, Nishimura S, Kawaguchi T. Source: Hinyokika Kiyo. 1996 April; 42(4): 263-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8693957&dopt=Abstract

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Invasive bladder cancer: a single-institution experience with bladder-sparing approach. Author(s): Zapatero A, Martin de Vidales C, Marin A, Cerezo L, Arellano R, Rabadan M, Perez-Torrubia A. Source: International Journal of Cancer. Journal International Du Cancer. 2000 October 20; 90(5): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11091353&dopt=Abstract

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Invasive bladder cancer: our experience with bladder sparing approach. Author(s): Cervek J, Cufer T, Zakotnik B, Kragelj B, Borstnar S, Matos T, Zumer-Pregelj M. Source: International Journal of Radiation Oncology, Biology, Physics. 1998 May 1; 41(2): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9607341&dopt=Abstract

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Involvement of mitochondrial pathway in Taxol-induced apoptosis of human T24 bladder cancer cells. Author(s): Yuan SY, Hsu SL, Tsai KJ, Yang CR. Source: Urological Research. 2002 October; 30(5): 282-8. Epub 2002 September 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389115&dopt=Abstract

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Localized bladder cancer. Author(s): Izawa JI, Grossman HB. Source: Curr Treat Options Oncol. 2000 December; 1(5): 423-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057150&dopt=Abstract

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Mechanism of increased sensitivity to etoposide in a mitomycin C-resistant human bladder cancer cell line. Author(s): Xia H, Bleicher RJ, Gupta V, Zaren HA, Singh SV. Source: International Journal of Cancer. Journal International Du Cancer. 1997 March 4; 70(5): 606-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9052763&dopt=Abstract

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Methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy and cystectomy for unresectable bladder cancer. Author(s): Donat SM, Herr HW, Bajorin DF, Fair WR, Sogani PC, Russo P, Sheinfeld J, Scher I. Source: The Journal of Urology. 1996 August; 156(2 Pt 1): 368-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8683681&dopt=Abstract

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MVAC chemotherapy-induced apoptosis and p53 alterations in the rat model of bladder cancer. Author(s): Zhang X, Jin L, Takenaka I. Source: Urology. 1998 November; 52(5): 925-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9801132&dopt=Abstract

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Neoadjuvant chemotherapy (MVAC) in locally invasive bladder cancer. Author(s): Sagaster P, Flamm J, Flamm M, Mayer A, Donner G, Oberleitner S, Havelec L, Lepsinger L, Ludwig H. Source: European Journal of Cancer (Oxford, England : 1990). 1996 July; 32A(8): 1320-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8869093&dopt=Abstract

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Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome. Author(s): Herr HW, Bajorin DF, Scher HI. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 April; 16(4): 1298-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9552029&dopt=Abstract

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Neoadjuvant chemotherapy and partial cystectomy for invasive bladder cancer. Author(s): Herr HW, Scher HI. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1994 May; 12(5): 975-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8164050&dopt=Abstract

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Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5 year follow-up. Author(s): Scher HI.

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Source: The Journal of Urology. 1995 February; 153(2): 545-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7815640&dopt=Abstract •

Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up. Author(s): Schultz PK, Herr HW, Zhang ZF, Bajorin DF, Seidman A, Sarkis A, Fair WR, Scherr D, Bosl GJ, Scher HI. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1994 July; 12(7): 1394-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8021730&dopt=Abstract

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Neoadjuvant chemotherapy is not (yet) standard treatment for muscle-invasive bladder cancer. Author(s): Sternberg CN, Parmar MK. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 September 15; 19(18 Suppl): 21S-26S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560967&dopt=Abstract

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Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. Author(s): Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Source: The New England Journal of Medicine. 2003 August 28; 349(9): 859-66. Erratum In: N Engl J Med. 2003 November 6; 349(19): 1880. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944571&dopt=Abstract

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Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscleinvasive bladder cancer: a randomised controlled trial. Author(s): Droller MJ. Source: The Journal of Urology. 2000 May; 163(5): 1602-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798921&dopt=Abstract

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Neoadjuvant CMV chemotherapy plus radical cystectomy in locally advanced bladder cancer: the impact of pathologic response on long-term results. Author(s): Scattoni V, Bolognesi A, Cozzarini C, Francesca F, Grasso M, Galli L, Torelli T, Campo B, Villa E, Rigatti P. Source: Tumori. 1996 September-October; 82(5): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9063525&dopt=Abstract

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Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. Author(s): Tester W, Caplan R, Heaney J, Venner P, Whittington R, Byhardt R, True L, Shipley W.

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Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1996 January; 14(1): 119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8558186&dopt=Abstract •

Neoadjuvant treatment for invasive bladder cancer: is it worthwhile? Author(s): Hall RR. Source: Acta Urol Belg. 1996 May; 64(2): 39-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8701809&dopt=Abstract

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New approaches to treatment of metastatic bladder cancer. Author(s): Edelman MJ. Source: Current Oncology Reports. 2000 September; 2(5): 379-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122868&dopt=Abstract

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New chemotherapy combinations for advanced bladder cancer. Author(s): Bellmunt J, Albiol S. Source: Current Opinion in Urology. 2001 September; 11(5): 517-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11493774&dopt=Abstract

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New chemotherapy regimens for advanced bladder cancer. Author(s): Fagbemi SO, Stadler WM. Source: Semin Urol Oncol. 1998 February; 16(1): 23-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9508079&dopt=Abstract

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Non-P-glycoprotein-mediated atypical multidrug resistance in a human bladder cancer cell line. Author(s): Naito S, Hasegawa S, Yokomizo A, Koga H, Kotoh S, Kuwano M, Kumazawa J. Source: Japanese Journal of Cancer Research : Gann. 1995 November; 86(11): 1112-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8567404&dopt=Abstract

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Oral piritrexim in advanced bladder cancer: an effective drug after progression on MVAC chemotherapy? Author(s): Feun LG, Savaraj N, Benedetto P, Waldman S, Collier M, Clendennin NJ. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 1994 October; 17(5): 448-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8092120&dopt=Abstract

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Overexpression of Bcl-2 regulates sodium butyrate- and/or docetaxel-induced apoptosis in human bladder cancer cells both in vitro and in vivo. Author(s): Miyake H, Hara S, Arakawa S, Kamidono S, Hara I.

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Source: International Journal of Cancer. Journal International Du Cancer. 2001 July 1; 93(1): 26-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391617&dopt=Abstract •

Overexpression of HER-2/neu enhances the sensitivity of human bladder cancer cells to urinary isoflavones. Author(s): Su S, Lai M, Yeh T, Chow N. Source: European Journal of Cancer (Oxford, England : 1990). 2001 July; 37(11): 1413-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435074&dopt=Abstract

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Paclitaxel and carboplatin in bladder cancer: recent developments. Author(s): Vaughn DJ. Source: European Journal of Cancer (Oxford, England : 1990). 2000 July; 36 Suppl 2: 7-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908842&dopt=Abstract

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Palliative chemotherapy in advanced bladder cancer. Author(s): Roth BJ. Source: Seminars in Oncology. 1995 April; 22(2 Suppl 3): 10-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7537896&dopt=Abstract

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Perioperative chemotherapy for invasive bladder cancer--what should we tell our patients? Author(s): Raghavan D. Source: The Journal of Urology. 1996 April; 155(4): 1246-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8632541&dopt=Abstract

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Phase 1/2 study of synchronous methotrexate, cisplatin, vincristine (MOPq10) chemotherapy and radiation for patients with locally advanced bladder cancer. Author(s): Goonewardene TI, Bozcuk H, Oliver RT, Barua J, Nargund V, Philip T, Mair G, Gibbs S. Source: Urologia Internationalis. 2001; 67(4): 293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741131&dopt=Abstract

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Phase II study of a new combined primary chemotherapy regimen, intravenous methotrexate and vincristine and intraarterial adriamycin and cisplatin, for locally advanced urinary bladder cancer: preliminary results. Author(s): Kuroiwa T, Naito S, Hasuo K, Kishikawa T, Masuda K, Kumazawa J. Source: Cancer Chemotherapy and Pharmacology. 1995; 35(5): 357-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7850915&dopt=Abstract

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Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and

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chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. Author(s): Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 November; 16(11): 3576-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9817278&dopt=Abstract •

Phenotypic characterization of bladder cancer. Author(s): Fradet Y. Source: European Urology. 1998; 33 Suppl 4: 5-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9615196&dopt=Abstract

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Photodynamic therapy for refractory superficial bladder cancer: long-term clinical outcomes of single treatment using intravesical diffusion medium. Author(s): Manyak MJ, Ogan K. Source: Journal of Endourology / Endourological Society. 2003 October; 17(8): 633-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622483&dopt=Abstract

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Plasma glutathione S-transferase pi 1-1 AND alpha 1-1 levels in patients with bladder cancer. Author(s): Berendsen CL, Mulder TP, Peters WH. Source: The Journal of Urology. 2000 December; 164(6): 2126-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061940&dopt=Abstract

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Plenary debate of randomized phase III trial of neoadjuvant MVAC plus cystectomy versus cystectomy alone in patients with locally advanced bladder cancer. Author(s): Bajorin DF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 September 15; 19(18 Suppl): 17S-20S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560966&dopt=Abstract

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Potential lifestyle and dietary supplement options for the prevention and postdiagnosis of bladder cancer. Author(s): Moyad MA. Source: The Urologic Clinics of North America. 2002 February; 29(1): 31-48, Viii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109354&dopt=Abstract

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Preliminary experience with paclitaxel in advanced bladder cancer. Author(s): Roth BJ. Source: Seminars in Oncology. 1995 June; 22(3 Suppl 6): 1-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7541150&dopt=Abstract

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Preliminary results of simultaneous radiochemotherapy with paclitaxel for urinary bladder cancer. Author(s): Dunst J, Weigel C, Heynemann H, Becker A. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 1999 October; 175 Suppl 3: 7-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554638&dopt=Abstract

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Primary cisplatin, methotrexate and vinblastine aiming at bladder preservation in invasive bladder cancer: multivariate analysis on prognostic factors. Author(s): Angulo JC, Sanchez-Chapado M, Lopez JI, Flores N. Source: The Journal of Urology. 1996 June; 155(6): 1897-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8618282&dopt=Abstract

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Prognostic factors in bladder cancer after primary M-VAC. Author(s): Paz-Ares L, Paul J, Kaye S. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1995 January; 13(1): 300-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7799035&dopt=Abstract

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Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC. Author(s): Scher HI. Source: The Journal of Urology. 1995 November; 154(5): 1969. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7563393&dopt=Abstract

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Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC. Author(s): Sarkis AS, Bajorin DF, Reuter VE, Herr HW, Netto G, Zhang ZF, Schultz PK, Cordon-Cardo C, Scher HI. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1995 June; 13(6): 1384-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7751883&dopt=Abstract

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Progress in the management of metastatic bladder cancer. Author(s): Parimoo D, Raghavan D. Source: Cancer Control : Journal of the Moffitt Cancer Center. 2000 July-August; 7(4): 347-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895129&dopt=Abstract

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Prospective study of dietary supplements, macronutrients, micronutrients, and risk of bladder cancer in US men. Author(s): Michaud DS, Spiegelman D, Clinton SK, Rimm EB, Willett WC, Giovannucci E.

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Source: American Journal of Epidemiology. 2000 December 15; 152(12): 1145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130620&dopt=Abstract •

Radiofrequency capacitive hyperthermia combined with irradiation or chemotherapy for patients with invasive bladder cancers. Author(s): Uchibayashi T, Yamamoto H, Kunimi K, Koshida K, Nakajima K. Source: International Urology and Nephrology. 1995; 27(6): 735-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8725039&dopt=Abstract

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Recent advances in bladder cancer chemotherapy. Author(s): Vaughn DJ, Malkowicz SB. Source: Cancer Investigation. 2001; 19(1): 77-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11291559&dopt=Abstract

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Recent developments in chemotherapy for bladder cancer. Author(s): Vaughn DJ, Malkowicz SB. Source: Oncology (Huntingt). 2001 June; 15(6): 763-71, 775; Discussion 775-6, 779-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430208&dopt=Abstract

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Reversal of P-glycoprotein-mediated paclitaxel resistance by new synthetic isoprenoids in human bladder cancer cell line. Author(s): Enokida H, Gotanda T, Oku S, Imazono Y, Kubo H, Hanada T, Suzuki S, Inomata K, Kishiye T, Tahara Y, Nishiyama K, Nakagawa M. Source: Japanese Journal of Cancer Research : Gann. 2002 September; 93(9): 1037-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359058&dopt=Abstract

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Secondary leukaemia after treating advanced bladder cancer with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy and radiotherapy. Author(s): Theodore C, Bayle C, Bernheim A, Wibault P. Source: Bju International. 2002 September; 90(4): 470-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175412&dopt=Abstract

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Second-line chemotherapy in advanced bladder cancer. Author(s): Pavone-Macaluso M, Sternberg C. Source: Urologia Internationalis. 2000; 64(2): 61-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10810266&dopt=Abstract

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St John's wort helps to fight bladder cancer. Author(s): Orellane C.

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Source: The Lancet Oncology. 2001 July; 2(7): 399. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11905732&dopt=Abstract •

Tea consumption: fluid intake and bladder cancer risk in Southern Taiwan. Author(s): Lu CM, Lan SJ, Lee YH, Huang JK, Huang CH, Hsieh CC. Source: Urology. 1999 November; 54(5): 823-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10565741&dopt=Abstract

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The effect of cystectomy, and perioperative methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy on the risk and pattern of relapse in patients with muscle invasive bladder cancer. Author(s): Ennis RD, Petrylak DP, Singh P, Bagiella E, O'Toole KM, Benson MC, Olsson CA. Source: The Journal of Urology. 2000 May; 163(5): 1413-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10751847&dopt=Abstract

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The efficacy of neoadjuvant chemotherapy in invasive bladder cancer. Author(s): Cam K, Yildirim A, Ozveri H, Turkeri L, Akdas A. Source: International Urology and Nephrology. 2002; 33(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090338&dopt=Abstract

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The natural history of a T1 bladder cancer: life-long tumour diathesis. Author(s): Herr HW. Source: Bju International. 1999 December; 84(9): 1102-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10571647&dopt=Abstract

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The potential application of Allium sativum (garlic) for the treatment of bladder cancer. Author(s): Lamm DL, Riggs DR. Source: The Urologic Clinics of North America. 2000 February; 27(1): 157-62, Xi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696254&dopt=Abstract

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The present and future of combination chemotherapy in bladder cancer. Author(s): Culine S. Source: Seminars in Oncology. 2002 June; 29(3 Suppl 9): 32-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094336&dopt=Abstract

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The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy. Author(s): Inoue K, Slaton JW, Karashima T, Yoshikawa C, Shuin T, Sweeney P, Millikan R, Dinney CP.

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Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 December; 6(12): 4866-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156246&dopt=Abstract •

The role of adjuvant chemotherapy for locally advanced bladder cancer. Author(s): Lehmann J, Retz M, Stockle M. Source: World Journal of Urology. 2001 April; 19(2): 133-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11374316&dopt=Abstract

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The role of combined method in organ-sparing treatment of muscle-invasive bladder cancer recurrences. Author(s): Startsev VY. Source: Arch Ital Urol Androl. 2002 June; 74(2): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161935&dopt=Abstract

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The role of paclitaxel in chemosensitive urological malignancies: current strategies in bladder cancer and testicular germ-cell tumors. Author(s): Bokemeyer C, Hartmann JT, Kuczyk MA, Truss MC, Beyer J, Jonas U, Kanz L. Source: World Journal of Urology. 1996; 14(6): 354-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8986035&dopt=Abstract

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The role of paclitaxel in the therapy of bladder cancer. Author(s): Roth BJ. Source: Seminars in Oncology. 1995 October; 22(5 Suppl 12): 33-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7481859&dopt=Abstract

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The systemic treatment of advanced and metastatic bladder cancer. Author(s): Hussain SA, James ND. Source: The Lancet Oncology. 2003 August; 4(8): 489-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901963&dopt=Abstract

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Therapeutic effect of CDDP and VP-16 against human bladder cancers. Author(s): Gotoh A, Mizuno Y, Okada H, Arakawa S, Kitazawa S, Maeda S, Kamidono S. Source: In Vivo. 1995 May-June; 9(3): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8562894&dopt=Abstract

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TP53 accumulation predicts improved survival in patients resistant to systemic cisplatin-based chemotherapy for muscle-invasive bladder cancer. Author(s): Qureshi KN, Griffiths TR, Robinson MC, Marsh C, Roberts JT, Hall RR, Lunec J, Neal DE.

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Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 November; 5(11): 3500-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589764&dopt=Abstract •

Visualisation of bladder cancer using (11)C-choline PET: first clinical experience. Author(s): de Jong IJ, Pruim J, Elsinga PH, Jongen MM, Mensink HJ, Vaalburg W. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 October; 29(10): 1283-8. Epub 2002 July 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271408&dopt=Abstract

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Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women. Author(s): Jacobs EJ, Henion AK, Briggs PJ, Connell CJ, McCullough ML, Jonas CR, Rodriguez C, Calle EE, Thun MJ. Source: American Journal of Epidemiology. 2002 December 1; 156(11): 1002-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446256&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/

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The following is a specific Web list relating to bladder 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 Cancer Prevention (reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Beta-carotene Source: Prima Communications, Inc.www.personalhealthzone.com Cysteine Source: Integrative Medicine Communications; www.drkoop.com

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

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

Dissertations on Bladder 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 bladder 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: •

A Morphological and Molecular Study of Bladder Cancer in a Rat Model Induced by N-butyl-n-(4-hydroxybutyl) Nitrosamine and Human Bladder Cancer: with Special Focus on the Changes in Mitochondria and Mitochondrial Dna by Chen, Guang Fu; Phd from Chinese University of Hong Kong (people's Republic of China), 2002, 221 pages http://wwwlib.umi.com/dissertations/fullcit/3066623

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Allelotyping and Promoter Hypermethylation of Urinary Bladder Cancer by Chan, Wing Yan Michael; Phd from Chinese University of Hong Kong (people's Republic of China), 2003, 215 pages http://wwwlib.umi.com/dissertations/fullcit/3077684

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Experimental Diagnostics and Therapeutics of Invasive Bladder Cancer by Sherif, Amir; Phd from Uppsala Universitet (sweden), 2003 http://wwwlib.umi.com/dissertations/fullcit/f148705

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Function of Dbccr1, Deleted in Bladder Cancer Chromosome Region 1 by Wright, Leslie Kate O.; Phd from The University of Rochester, 2003, 249 pages http://wwwlib.umi.com/dissertations/fullcit/3078418

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Warfarin Therapy and Risk of Bladder Cancer by Blumentals, William Andrew; Phd from University of South Florida, 2002, 72 pages http://wwwlib.umi.com/dissertations/fullcit/3052632

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 BLADDER CANCER Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning bladder cancer.

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

BCG With or Without Mitomycin in Treating Patients With Bladder Cancer Condition(s): stage 0 bladder cancer; recurrent bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Genito-Urinary Tract Cancer Cooperative Group; Associazone Urologi Ospedalieri; National Cancer Research Institute (NCRI); German Association of Urologic Oncology; Finnbladder; South European Uroncological Group Purpose - Excerpt: RATIONALE: Biological therapies such as BCG use different ways to stimulate the immune system and stop tumor cells from growing. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with biological therapy may kill more tumor cells. It is not yet known if BCG is more effective with or without mitomycin. PURPOSE: Randomized phase II trial to compare the effectiveness of BCG plus mitomycin with that of BCG alone in treating patients who have bladder cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023842

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These are listed at www.ClinicalTrials.gov.

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Bladder Cancer Case Control Study of Arsenic in Water Condition(s): Bladder Cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: This study is examining the relationship between ingested arsenic and bladder cancer in two areas of California where a large percentage of the population was exposed to drinking water containing arsenic at low to moderate levels. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011518

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BMS-247550 in Treating Patients With Advanced Urinary Tract Cancer Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative 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 BMS-247550 in treating patients who have progressive or metastatic urinary tract cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021099

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Bortezomib in Treating Patients With Advanced or Metastatic Transitional Cell Cancer of the Bladder, Renal Pelvis, or Ureter Condition(s): recurrent bladder cancer; stage IV bladder cancer; metastatic transitional cell cancer of the renal pelvis and ureter; recurrent transitional cell cancer of the renal pelvis and ureter; regional transitional cell cancer of the renal pelvis and ureter; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): Princess Margaret Hospital; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have advanced or metastatic transitional cell cancer of the bladder, renal pelvis, or ureter. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066352

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Bortezomib in Treating Patients With Advanced Transitional Cell Carcinoma of the Urothelium Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have advanced transitional cell carcinoma of the urothelium. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072150

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Celecoxib in Treating Patients With Bladder Cancer Condition(s): recurrent bladder cancer Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of celecoxib may be an effective way to prevent the recurrence of bladder cancer. PURPOSE: Randomized phase IIb/III trial to study the effectiveness of celecoxib in preventing disease recurrence in patients who have bladder cancer. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006124

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Chemotherapy With or Without Surgery in Treating Patients With Bladder Cancer Condition(s): stage 0 bladder cancer; stage I bladder cancer; recurrent bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Genito-Urinary Tract Cancer Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Infusing chemotherapy drugs directly into the bladder may kill more cancer cells. It is not yet known if surgery followed by chemotherapy is more effective than chemotherapy alone in treating bladder cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy alone with that of transurethral resection followed by chemotherapy in treating patients who have bladder cancer. Phase(s): Phase III Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042887 •

Cisplatin and Gemcitabine Compared With Observation in Treating Patients Who Have Undergone Surgery for Bladder Cancer Condition(s): stage II bladder cancer; stage III bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): Italian National Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if combination chemotherapy is effective in preventing relapse in patients who have undergone radical cystectomy for bladder cancer. PURPOSE: Phase III trial to compare the effectiveness of cisplatin combined with gemcitabine with that of observation in treating patients with bladder cancer who have undergone surgery to remove the bladder. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054626

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Cisplatin Plus Gemcitabine With or Without Paclitaxel in Treating Patients With Stage IV Urinary Tract Cancer Condition(s): stage IV bladder cancer; transitional cell carcinoma of the bladder; urethral cancer associated with invasive bladder cancer; metastatic transitional cell cancer of the renal pelvis and ureter; regional transitional cell cancer of the renal pelvis and ureter Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Genito-Urinary Tract Cancer Cooperative Group; National Cancer Institute (NCI); Groupe D'Etude des Tumeurs Uro-Genitales; National Cancer Research Institute (NCRI); Central European Cooperative Oncology Group; National Cancer Institute of Canada; Southwest Oncology Group; German Association of Urologic Oncology; Spanish Oncology Genito-Urinary Group; 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. It is not yet known which combination chemotherapy regimen is more effective for urinary tract cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin plus gemcitabine with or without paclitaxel in treating patients who have stage IV urinary tract cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022191

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Combination Chemotherapy and Radiation Therapy With or Without Surgery In Treating Patients With Stage II or Stage III Bladder Cancer Condition(s): stage II bladder cancer; stage III bladder cancer Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy 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. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of combination chemotherapy plus radiation therapy with or without surgery is more effective in treating bladder cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of two combination chemotherapy regimens and radiation therapy with or without radical cystectomy in treating patients who have stage II or stage III bladder cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055601

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Combination Chemotherapy Followed by Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Urothelium Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest 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. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy consisting of gemcitabine, paclitaxel, and carboplatin followed by cisplatin and radiation therapy in treating patients who have locally advanced or recurrent cancer of the urothelium. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055835

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Combination Chemotherapy Followed By Observation or Surgery in Treating Patients With Stage II or Stage III Cancer of the Urothelium Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest 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. Combining more than one

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drug may kill more tumor cells and decrease the need for surgery. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by observation or surgery to remove the bladder (cystectomy) in treating patients who have stage II or stage III cancer of the urothelium. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045630 •

Combination Chemotherapy Following Surgery in Treating Patients With Urinary Tract Cancer Condition(s): stage III bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder; localized transitional cell cancer of the renal pelvis and ureter; regional transitional cell cancer of the renal pelvis and ureter Study Status: This study is currently recruiting patients. Sponsor(s): Tulane 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 more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy following surgery in treating patients who have urinary tract cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028860

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Combination Chemotherapy in Patients With Advanced Urinary Tract Cancer Condition(s): Bladder Cancer; Urethral Cancer 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 tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells. PURPOSE: Phase II trial to study the effects of combination chemotherapy with cisplatin, ifosfamide, and paclitaxel in treating patients with metastatic urinary tract cancer that cannot be treated with surgery. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002684

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Combination Chemotherapy in Treating Patients With Advanced Bladder or Kidney Cancer Condition(s): stage III bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder; metastatic transitional cell cancer of the renal pelvis and ureter; localized transitional cell cancer of the renal pelvis and ureter; regional transitional cell cancer of the renal pelvis and ureter 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 use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy consisting of gemcitabine, doxorubicin, paclitaxel, and carboplatin in treating patients with advanced bladder or kidney cancer and impaired kidney function. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003342

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Combination Chemotherapy in Treating Patients With Bladder Cancer Condition(s): stage I bladder cancer; stage II bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI); National Cancer Institute of Canada 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. It is not yet known whether combination chemotherapy is more effective than observation alone in treating bladder cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with that of observation alone in treating patients who have bladder cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005047

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Combination Chemotherapy in Treating Patients With Transitional Cell Cancer of the Urothelium Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Genito-Urinary Tract Cancer 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

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drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is most effective for transitional cell cancer of the urothelium. PURPOSE: Randomized phase II/III trial to compare different combination chemotherapy regimens in treating patients who have transitional cell cancer of the urothelium. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014274 •

Comparison of Immediate and Delayed Chemotherapy After Surgery in Treating Patients With Stage III or Stage IV Bladder Cancer Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Genito-Urinary Tract Cancer Cooperative Group; Groupe D'Etude des Tumeurs Uro-Genitales; Southwest Oncology Group; Nordic Urothelial Cancer Group; National Cancer Institute of Canada; National Cancer Research Institute (NCRI); American College of Surgeons 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 and giving them after surgery may kill more tumor cells. It is not yet known if combination chemotherapy is more effective when given immediately after surgery to remove the bladder or when the cancer returns. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy given immediately after surgery or chemotherapy given when the cancer returns in treating patients who have stage III or stage IV bladder cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028756

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Cystoscopy and Hexyl 5-Aminolevulinate in Detecting Carcinoma In Situ in Patients With Bladder Cancer Condition(s): Bladder Cancer; recurrent bladder cancer; stage 0 bladder cancer Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Diagnostic procedures such as cystoscopy may improve the ability to detect cancer and to determine the extent of disease. PURPOSE: Diagnostic trial to compare the effectiveness of cystoscopy using hexyl 5aminolevulinate and two light sources in detecting carcinoma in situ in patients who have bladder cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00052637 •

Fenretinide to Prevent Cancer Recurrence in Treating Patients With Bladder Cancer Condition(s): stage 0 bladder cancer; stage I bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. It is not yet known if fenretinide is effective in preventing the recurrence of bladder cancer. PURPOSE: Randomized phase III trial to study the effectiveness of fenretinide in treating patients who are at risk for recurrent bladder cancer following surgery to remove the tumor. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004154

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Gefitinib Plus Combination Chemotherapy in Treating Patients With Locally Advanced or Metastatic Bladder Cancer Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; 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. Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Combining chemotherapy with gefitinib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy with gefitinib in treating patients who have metastatic transitional cell cancer of the urothelium. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041106

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Gemcitabine and Paclitaxel in Treating Patients With Advanced or Recurrent Cancer of the Urinary Tract Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest 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. Giving more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of

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combining gemcitabine and paclitaxel in treating patients who have advanced or recurrent cancer of the urinary tract. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022633 •

Gemcitabine, Cisplatin, and Amifostine Following Surgery in Treating Patients With Locally Advanced Bladder Cancer Condition(s): stage II bladder cancer; stage III bladder cancer; stage IV bladder cancer; Drug Toxicity Study Status: This study is currently recruiting patients. Sponsor(s): University of Chicago Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine, cisplatin, and amifostine following surgery in treating patients who have locally advanced bladder cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006105

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Irinotecan in Treating Patients With Recurrent or Refractory Advanced Transitional Cell Cancer of the Urothelium Previously Treated With Chemotherapy Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as irinotecan 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 patients who have recurrent or refractory advanced transitional cell cancer of the urothelium. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066612

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Pemetrexed Disodium in Treating Patients With Locally Advanced or Metastatic Recurrent Cancer of the Urothelium Condition(s): recurrent bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder; metastatic transitional cell cancer of the renal pelvis and ureter; regional transitional cell cancer of the renal pelvis and ureter; recurrent transitional cell cancer of the renal pelvis and ureter Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of pemetrexed disodium in treating patients who have locally advanced or metastatic recurrent cancer of the urothelium. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039260

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PV701 Followed By Surgery to Remove the Bladder in Treating Patients With Bladder Cancer Condition(s): recurrent bladder cancer; stage I bladder cancer; stage II bladder cancer; stage III bladder cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of Chicago Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Infusing PV701 directly into the bladder may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase I trial to study the effectiveness of PV701 followed by surgery to remove the bladder in treating patients who have bladder cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049153

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Radiation Therapy With or Without Carbogen and Niacinamide in Treating Patients With Bladder Cancer Condition(s): stage I bladder cancer; stage II bladder cancer; stage III bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): Mount Vernon Hospital Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as carbogen and niacinamide may make tumor cells more sensitive to radiation therapy. It is not yet known whether radiation therapy is more effective with or without carbogen and niacinamide in treating patients who have bladder cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of

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radiation therapy with or without carbogen and niacinamide in treating patients who have locally advanced bladder cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033436 •

Radiation Therapy With or Without Chemotherapy in Treating Patients With Stage II or Stage III Bladder Cancer Condition(s): stage II bladder cancer; stage III bladder cancer; transitional cell carcinoma of the bladder; squamous cell carcinoma of the bladder; adenocarcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): Cancer Research Campaign Clinical Trials Centre Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy such as fluorouracil and mitomycin use different ways to stop tumor cells from dividing so they stop growing or die. Fluorouracil and mitomycin may make the tumor cells more sensitive to radiation therapy. It is not yet known if radiation therapy is more effective with or without chemotherapy in treating bladder cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy to all or part of the bladder with or without chemotherapy in treating patients who have stage II or stage III bladder cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00024349

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Suramin in Treating Patients With Recurrent Bladder Cancer Condition(s): stage 0 bladder cancer; stage I bladder cancer; recurrent bladder cancer Study Status: This study is currently recruiting patients. Sponsor(s): Cancer Research Campaign Clinical Trials Centre Purpose - Excerpt: RATIONALE: Suramin may stop the growth of bladder cancer by stopping blood flow to the tumor. PURPOSE: Phase I trial to study the effectiveness of suramin in treating patients who have recurrent bladder cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006476

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Surgery and BCG in Treating Patients With Bladder Cancer Condition(s): stage 0 bladder cancer; stage I bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Genito-Urinary Tract Cancer Cooperative Group

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Purpose - Excerpt: RATIONALE: Biological therapies such as BCG use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Randomized phase III trial to compare the effectiveness of BCG at different dosages and lengths of time following surgery in treating patients with bladder cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002990 •

Tipifarnib in Treating Patients With Recurrent Bladder Cancer Condition(s): recurrent bladder cancer; stage 0 bladder cancer; stage I bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is currently recruiting patients. Sponsor(s): Princess Margaret Hospital; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of tipifarnib in treating patients who have recurrent bladder cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047216

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Trastuzumab and Combination Chemotherapy in Treating Patients With Locally Recurrent or Metastatic Urinary Tract Cancer Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of Michigan Comprehensive 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. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with combination chemotherapy in treating patients who have locally recurrent or metastatic urinary tract cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005831

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Vaccine Therapy in Treating Patients With Transitional Cell Cancer of the Bladder Condition(s): transitional cell carcinoma of the bladder; stage I bladder cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Biological therapies, such as BCG and sargramostim, use different ways to stimulate the immune system and stop tumor cells from growing. Combining vaccine therapy with biological therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining vaccine therapy with BCG and sargramostim in treating patients who have undergone cystectomy for transitional cell cancer of the bladder. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070070

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Chemotherapy in Treating Patients With Early-Stage Bladder Cancer Condition(s): transitional cell carcinoma of the bladder; stage I bladder cancer; stage 0 bladder cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group 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 chemotherapy in treating patients with early-stage bladder cancer that has not responded to BCG therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003129

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Cisplatin, Paclitaxel, and Gemcitabine in Treating Patients With Progressive Unresectable Regional or Metastatic Bladder Cancer Condition(s): stage III bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is no longer recruiting patients. Sponsor(s): GERCOR 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 combining cisplatin, paclitaxel, and gemcitabine in treating patients who have progressive unresectable regional or metastatic bladder cancer. Phase(s): Phase II Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006118 •

Combination Chemotherapy in Treating Patients With Advanced Cancer of the Urothelium and Decreased Kidney Function Condition(s): Bladder Cancer; Cancer of the Renal Pelvis and Ureter; Gastrointestinal Cancer; Urethral Cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Eastern Cooperative 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. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have advanced cancer of the urothelium with decreased kidney function. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005644

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Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Bladder Cancer Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter Study Status: This study is no longer recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients with metastatic or locally advanced bladder cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003105

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Combination Chemotherapy in Treating Patients With Stage IV Locally Advanced or Metastatic Bladder Cancer Condition(s): transitional cell carcinoma of the bladder; stage IV bladder cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Chicago Cancer Research Center 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

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combination chemotherapy in treating patients who have stage IV locally advanced or metastatic bladder cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005086 •

Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II or Stage III Bladder Cancer Condition(s): stage III bladder cancer; stage II bladder cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Radiation Therapy Oncology Group Purpose - Excerpt: RATIONALE: Radiation therapy uses x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy and surgery may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy plus combination chemotherapy in treating patients who have stage II or stage III bladder cancer that can be removed by surgery. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003930

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Radiation Therapy, Chemotherapy, or Observation in Treating Patients With Bladder Cancer Condition(s): stage I bladder cancer; transitional cell carcinoma of the bladder Study Status: This study is no longer recruiting patients. Sponsor(s): Medical Research Council Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not known whether receiving either radiation therapy, chemotherapy, or observation is more effective for cancer of the bladder. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy, chemotherapy, or observation following tumor surgery in treating patients who have bladder cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002490

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SCH 66336 Plus Gemcitabine in Treating Patients With Advanced Cancer of the Urinary Tract Condition(s): recurrent bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder; recurrent urethral cancer; anterior urethral cancer; posterior urethral cancer; urethral cancer associated with invasive bladder cancer; metastatic transitional cell cancer of the renal pelvis and ureter; recurrent transitional cell cancer of the renal pelvis and ureter Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC New Drug Development Group; EORTC Genito-Urinary Tract Cancer Cooperative Group; EORTC Pharmacology and Molecular Mechanisms Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining SCH 66336 and gemcitabine may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of SCH 66336 plus gemcitabine in treating patients who have advanced cancer of the urinary tract. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006351

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ZD 1839 in Treating Patients With Advanced Cancer of the Urinary Tract Condition(s): recurrent urethral cancer; transitional cell carcinoma of the bladder; recurrent bladder cancer; stage IV bladder cancer; urethral cancer associated with invasive bladder cancer; recurrent transitional cell cancer of the renal pelvis and ureter; metastatic transitional cell cancer of the renal pelvis and ureter Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Southwest Oncology Group Purpose - Excerpt: RATIONALE: Biological therapies such as ZD 1839 may interfere with the growth of the tumor cells and slow the growth of cancer of the urinary tract. PURPOSE: Phase II trial to study the effectiveness of ZD 1839 in treating patients who have advanced cancer of the urinary tract. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014144

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A Phase I Trial Using Suramin to Treat Superficial Transitional Cell Carcinoma of the Bladder Condition(s): Bladder Neoplasms; Carcinoma, Transitional Cell Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Patients with superficial transitional cell carcinoma of the bladder will be treated with intravesical suramin in a phase I dose escalating study. The toxicity of suramin administered in this fashion will be evaluated.

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Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001381 •

AD 32 Alone or With BCG Following Surgery in Treating Patients With Newly Diagnosed or Recurrent Superficial Bladder Cancer Condition(s): stage I bladder cancer; stage 0 bladder cancer; recurrent bladder cancer Study Status: This study is completed. Sponsor(s): Anthra Pharmaceuticals Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies such as BCG use different ways to stimulate the immune system and stop cancer cells from growing. It is not yet known whether AD 32 alone is more effective than AD 32 plus BCG following surgery for superficial bladder cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of AD 32 alone or with BCG following surgery in treating patients who have newly diagnosed or recurrent superficial bladder cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003759

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Gene Therapy in Treating Patients With Advanced Bladder Cancer Condition(s): stage III bladder cancer; stage II bladder cancer; transitional cell carcinoma of the bladder; stage I bladder cancer; recurrent bladder cancer; stage IV bladder cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); M.D. Anderson Cancer Center Purpose - Excerpt: RATIONALE: Inserting the p53 gene into a person's bladder cancer cells may improve the body's ability to fight cancer. PURPOSE: Phase I trial to study the effectiveness of gene therapy in treating patients with advanced bladder cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003167

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Keyhole Limpet Hemocyanin Compared With Doxorubicin in Treating Patients With Bladder Cancer Condition(s): stage 0 bladder cancer; recurrent bladder cancer Study Status: This study is suspended. Sponsor(s): Intracel Purpose - Excerpt: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet

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known whether keyhole limpet hemocyanin is more effective than doxorubicin for bladder cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of keyhole limpet hemocyanin with that of doxorubicin in treating patients who have bladder cancer that has not responded to BCG or in those patients who cannot tolerate BCG. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006034 •

LMB-9 Immunotoxin in Treating Patients With Advanced Colon, Breast, Non-small Cell Lung, Bladder, Pancreatic, or Ovarian Cancer Condition(s): Lung Cancer; ovarian epithelial cancer; Pancreatic Cancer; ovarian sarcoma; Colon Cancer; Bladder Cancer; Breast Cancer Study Status: This study is completed. Sponsor(s): University of Maryland Greenebaum Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: The LMB-9 immunotoxin can locate tumor cells and kill them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of LMB-9 immunotoxin in treating patients who have advanced colon, breast, non-small cell lung, bladder, pancreatic, or ovarian cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005858

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Neoadjuvant Intravesical Vaccine Therapy in Treating Patients With Muscle-Invasive Bladder Carcinoma Condition(s): Bladder Cancer Study Status: This study is not yet open for patient recruitment. Sponsor(s): Cancer Institute of New Jersey; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Placing a vaccine directly into the bladder may cause a stronger immune response and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of neoadjuvant intravesical vaccine therapy in treating patients who are undergoing surgery for muscle-invasive bladder carcinoma (cancer). Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072137

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Pemetrexed Disodium and Gemcitabine in Treating Patients With Advanced Cancer of the Urothelium Condition(s): Bladder Cancer; transitional cell cancer of the renal pelvis and ureter; Urethral Cancer Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining pemetrexed disodium with gemcitabine may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining pemetrexed disodium with gemcitabine in treating patients who have advanced cancer of the urothelium. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053209

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

Patents on Bladder Cancer By performing a patent search focusing on bladder 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 bladder cancer: •

Antibodies to bladder cancer nuclear matrix proteins and their use Inventor(s): Getzenberg; Robert H. (Pittsburgh, PA) Assignee(s): University of Pittsburgh (Pittsburgh, PA) Patent Number: 6,280,956 Date filed: August 28, 1998 Abstract: Nuclear matrix proteins (NMP) which are characterized by a defined expression in bladder tissue are provided, which can be used to generate antibodies that differentiate between normal and cancerous bladder tissue. These NMPs are useful markers in diagnosing and monitoring the stage of malignancy of a bladder cell and treating bladder cell proliferative disorders associated with the NMP. Also provided are substantially purified polypeptides and nucleotide sequences encoding the NMPs of the invention. Excerpt(s): The present invention relates generally to bladder nuclear matrix proteins, called "NMPs" here, and more specifically to novel nuclear matrix proteins of the bladder which are associated with cell-proliferative disorders. The early diagnosis of bladder cancer is central to the effective treatment of the disease. Currently, there are no methods available to easily and specifically identify the presence of bladder cancer cells. The prevailing technique for diagnosis of bladder cancer is to identify bladder cancer cells by morphological examination of the cells by a pathologist. A cellular hallmark of the transformed phenotype is abnormal nuclear shape, the presence of multiple nucleoli and altered patterns of chromatin organization. Nuclear structural alterations are so prevalent in cancer cells that they are commonly used as a pathological marker of transformation for many types of cancer. Nuclear shape is determined in part by the nuclear matrix, the dynamic skeleton of the nucleus. The nuclear matrix is the structural component of the nucleus that determines nuclear morphology, organizes the DNA in a three-dimensional fashion that is tissue specific, and has a central role in the regulation of a number of nuclear processes including the regulation of gene expression. The nuclear matrix has been demonstrated to play a central role in the regulation of important cellular processes such as DNA replication and transcription. Getzenberg, J. Cell Biochem. 55: 22-31 (1994). The nuclear matrix is the framework or scaffolding of the nucleus and consists of the peripheral laminas and pore complexes, an internal ribonucleic protein network, and residual nucleoli. Berezney et al., Biochem. Biophys. Res. Comm. 60: 1410-17 (1974). The nuclear matrix consists of approximately 10% of the nuclear proteins and is virtually devoid of lipids, DNA and histones. Fey et al., Critical Reviews in Eukaryotic Gene Expression 1: 127-44 (1991). Web site: http://www.delphion.com/details?pn=US06280956__

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Apoptosis inducing adamantyl derivatives and their usage as anti-cancer agents Inventor(s): Lu; Xian-Ping (San Diego, CA), Pfahl; Magnus (Solana Beach, CA), Rideout; Darryl (San Diego, CA), Zhang; Hongyue (La Jolla, CA) Assignee(s): Galderma Research & Development, S.N.C. (Valbonne, FR) Patent Number: 6,127,415 Date filed: April 14, 1999 Abstract: The present invention relates to specific adamantyl or adamantyl group derivative containing retinoid compounds induce apoptosis of cancer cells. These adamantyl retinoid derivatives are useful for the treatment of many cancers and solid tumors, especially androgen-independent prostate cancer, skin cancer, pancreatic carcinomas, colon cancer, melanoma, ovarian cancer, liver cancer, small cell lung carcinoma, non-small cell lung carcinoma, cervical carcinoma, brain cancer, bladder cancer, breast cancer, neuroblastoma/glioblastoma, and leukemia. Also, the invention relates to novel adamantyl or adamantyl group derivative compounds which are useful as active agents for the treatment or prevention of keratinization disorders and other dermatological conditions, and other diseases. Excerpt(s): This application is a 371 of PCT/US97/11564 Jul. 8, 1999. The invention relates to the discovery that specific adamantyl or adamantyl group derivative containing retinoid related compounds induce apoptosis of cancer cells and therefore may be used for the treatment of cancer, including advanced cancers. Also, the present invention relates to novel adamantyl or adamantyl group derivative containing retinoid related compounds and their use for the treatment and/or prevention of cancer, keratinization disorders, dermatological conditions and other therapies. Solid tumors are the leading cause of death attributable to cancers worldwide. Conventional methods of treating cancer include surgical treatments, the administration of chemotherapeutic agents, and recently immune based treatments which typically involve the administration of an antibody or antibody fragment which may be conjugated to a therapeutic moiety such as a radio-nuclide. However, to date, such treatments have been of limited success. Web site: http://www.delphion.com/details?pn=US06127415__

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Biomarkers and targets for diagnosis, prognosis and management of prostate, breast and bladder cancer Inventor(s): An; Gang (Oklahoma City, OK), O'Hara; S. Mark (Oklahoma City, OK), Ralph; David (Edmund, OK), Veltri; Robert (Oklahoma City, OK) Assignee(s): UroCor, Inc. (Oklahoma City, OK) Patent Number: 6,218,529 Date filed: June 12, 1998 Abstract: Disclosed are diagnostic techniques for the detection of human prostate, bladder and breast cancer. Genetic probes and methods useful in monitoring the progression and diagnosis of prostate, bladder and breast cancer are described. The invention relates particularly to probes and methods for evaluating the presence of RNA species that are differentially expressed in prostate, bladder and breast cancer compared to normal human prostate, benign prostatic hyperplasia, or normal bladder or breast tissue.

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Excerpt(s): The present invention relates generally to nucleic acid sequences useful as probes for the diagnosis of cancer and methods relating thereto. More particularly, the present invention concerns probes and methods useful in diagnosing, identifying and monitoring the progression of prostate cancer, benign prostatic hyperplasia, bladder cancer or breast cancer through measurements of gene products. Genetic detection of human disease states is a rapidly developing field (Taparowsky et al., 1982; Slamon et al., 1989; Sidransky et al., 1992; Miki et al., 1994; Dong et al., 1995; Morahan et al., 1996; Lifton, 1996; Barinaga, 1996). However, some problems exist with this approach. A number of known genetic lesions merely predispose to development of specific disease states. Individuals carrying the genetic lesion may not develop the disease state, while other individuals may develop the disease state without possessing a particular genetic lesion. In human cancers, genetic defects may potentially occur in a large number of known tumor suppresser genes and proto-oncogenes. The genetic detection of cancer has a long history. One of the earliest genetic lesions shown to predispose to cancer was transforming point mutations in the ras oncogenes (Taparowsky et al., 1982). Transforming ras point mutations may be detected in the stool of individuals with benign and malignant colorectal tumors (Sidransky et al, 1992). However, only 50% of such tumors contained a ras mutation (Sidransky et al., 1992). Similar results have been obtained with amplification of HER-2/neu in breast and ovarian cancer (Slamon et al., 1989), deletion and mutation of p53 in bladder cancer (Sidransky et al., 1991), deletion of DCC in colorectal cancer (Fearon et al., 1990) and mutation of BRCA1 in breast and ovarian cancer (Miki et al., 1994). Web site: http://www.delphion.com/details?pn=US06218529__ •

Bladder cancer detection Inventor(s): DeFazio; Sally R. (Watertown, MA), Gozzo; James J. (Westwood, MA), Monaco; Anthony P. (Newton, MA) Assignee(s): New England Deaconess Hospital (Boston, MA) Patent Number: 4,447,545 Date filed: June 15, 1982 Abstract: Disclosed is a technique for screening populations to detect potential bladder cancer patients. The screening test is based on a discovered correlation between the respective ratios of C-reactive protein to total protein in urine and serum and the incidence of bladder cancer. Excerpt(s): This invention relates to a method of detecting the presence of bladder cancer in humans. More particularly, it relates to the discovery that if the ratio of Creactive protein ("CRP") to total protein in urine is higher than the ratio of CRP to total protein in serum, this is indicative of bladder cancer and to a method for making this determination. Bladder cancer ranks eleventh in cancer deaths in the United States. In general, the five year survival rate for people with low grade tumors is greater than 60 percent, while the five year survival rate for people with high grade and often metatastic tumors is less than 15 percent. Currently, the diagnosis and management of bladder cancer patients involves utilization of methods such as cystoscopy, urinary cytology, and the quantitation of normal and abnormal plasma related components in urine. Repeated cystoscopy involves patient discomfort, is costly, and may expose patients to certain surgical risks. Normal serum and plasma related components appear to have limited usefullness in the early diagnosis of bladder cancer as many of these same components are also present in increased concentrations in urine from patients with

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non-neoplastic disease. The discovery of a substance in the urine of patients afflicted with bladder cancer which was associated with the cancer and indicative of its presence could provide a basis for a diagnostic test for the presence of bladder cancer. The development of a reliable and sensitive assay capable of detecting the presence of such a substance in urine would have many advantages over current methods of detecting bladder neoplasms. Since such a test would be non-invasive, it could be routinely employed to test urine from groups of high risk individuals such as those with occupational exposures to certain bladder carcinogens and other high risk groups. To verify the initial diagnosis of potential bladder cancer, further tests could be conducted. Web site: http://www.delphion.com/details?pn=US04447545__ •

Cell analysis method using quantitative fluorescence image analysis Inventor(s): Bonner; Rebecca B. (Oklahoma City, OK), Hemstreet, III; George P. (Oklahoma City, OK), Hurst; Robert E. (Oklahoma City, OK), Rao; Jian Yu (Edmond, OK) Assignee(s): The Board of Regents of the University of Oklahoma (Norman, OK) Patent Number: 5,733,721 Date filed: December 20, 1992 Abstract: A system for evaluating one or more biochemical markers for evaluating individual cancer risk, cancer diagnosis and for monitoring therapeutic effectiveness and cancer recurrence, particularly of bladder cancer. The system uses automated quantitative fluorescence image analysis of a cell sample collected from a body organ. Cells are treated with a fixative solution which inhibits crystal formation. Cell images are selected and stored as grey level images for further analysis. Cell images may be corrected for autofluorescence using a novel autofluorescence correction method. A neural net computer may be used to distinguish true-positive images from false-positive images to improve accuracy of cancer risk assessment. Cells having images positive for a marker amy be compared to threshold quantities related to predetermined cancer risk. Excerpt(s): This invention relates to methods for screening cell samples for cytological factors using quantitative fluorescence image analysis, and more particularly, but not by way of limitation, to a method for screening cell samples for cytological factors indicative of cancer or for an increased risk for cancer using quantitative fluorescence image analysis. An estimated 47,000 cases of bladder cancer were diagnosed in 1991. Approximately 10,000 people were estimated to have died from bladder cancer in 1991. Most of the deaths occurred in people who were not diagnosed early while the cancer was curable. The 5-year survival for noninvasive disease is about 88%, but only 50% for invasive disease, even without nodal involvement. The 5-year survival with metastasis to the lymph nodes is only about 18%. This means that such patients will almost certainly die from bladder cancer or metastases. Bladder cancer develops by two routes-papillary and flat lesions. Approximately 15% of tumors progress from relatively noninvasive nonmetastatic lesions that are not life threatening to dangerous invasive, metastatic lesions. Papillary lesions progress from benign papillomas that protrude from the bladder surface, to noninvasive malignancies growing into the bladder lumen, and finally to invasive, metastatic malignancies capable of causing death. At the lower grades of this progression, cells are cytologically "atypical," and appear similar to those seen in other conditions not related to cancer, notably inflammation, obstruction, or stones. In the higher grades, such cells are cytologically "suspicious" or "positive" and have a quite characteristic appearance. Flat lesions progress through several stages of

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dysplasia (a premalignant lesion), culminating in carcinoma in situ (CIS), a noninvasive lesion in which the cells appear highly aberrant and are generally classified as "suspicious," even though the lesion is not cancer per se. However, approximately onethird of such lesions progress to high-grade invasive cancer that is rapidly life threatening. The key to controlling bladder cancer is to detect lesions before they become invasive, and failing that, to detect invasive lesions as early as possible. Web site: http://www.delphion.com/details?pn=US05733721__ •

Characterization of oncogenes and assays based thereon Inventor(s): Bradley; Scott M. (McLean, VA), Tabin; Clifford J. (Cambridge, MA), Weinberg; Robert A. (Brookline, MA) Assignee(s): Massachusetts Institute of Technology (Cambridge, MA) Patent Number: 4,535,058 Date filed: October 1, 1982 Abstract: Experiments designed to define the differences between an oncogene isolated from human bladder cancer cells and its corresponding proto-oncogene are described herein. By a series of in vitro recombinations, the difference was initially isolated to a 350 kb segment of DNA; sequencing defined the difference as a change in the Gly.sup.12 codon causing the p21 protein of the oncogene to contain valine at a location where the p21 protein of the proto-oncogene contained glycine. Assays for detecting carcinogenesis based on such differences are also described. In one type of assay, a restriction enzyme specific for either the altered or non-altered DNA segment of the genes are employed to detect carcinogenesis. In another type of assay, seralogical reagents, such as antibody specific for either p21 protein expressed from the protooncogene or oncogene, or a common site therein, are described. Excerpt(s): This invention is in the field of molecular biology and more specifically relates to defining differences between mutant alleles and their corresponding wild type alleles, particularly oncogenes and proto-oncogenes, and to assays which take advantage of such differences. Previous work relating to chemical carcinogenesis has demonstrated that carcinogenic potency of a compound often correlates with its mutagenic power. See McCann, J., Choi, E., Yamasaki, E. and Ames, B. N. Proc. Natl. Acad. Sci. USA 72: 5135-5139 (1975); McCann, J. and Ames, B. N. Proc. Natl. Acad. Sci. USA 73: 950-954 (1976); Bridges, B. A. Nature 261: 195-200 (1976); and, Bouck, N. and diMayorca, G. Nature 264: 722-727 (1976). This suggests that DNA is the ultimate target of carcinogenic activation. Because of this, researchers have attempted to identify and study DNA segments in tumor cells, often referred to as "oncogenes," whose alteration is critically important for oncogenic conversion. One recent approach to isolation of an oncogene involved the transfer of tumor cell DNA from the EJ bladder carcinoma cell line into non-transformed NIH3T3 mouse fibroblasts. It was discovered that the phenotype of cellular transformation could be passed from cell to cell in this manner. Tumor DNA was able to induce foci of transformed cells in the recipient NIH monolayer culture while DNA from normal, untransformed donor cells failed to produce foci. See Shih, C., Shilo, B., Goldfarb, M. P., Dannenberg, A. and Weinberg, R. A. Proc. Natl. Acad. Sci. USA 76: 5714-5718 (1979); Cooper, G. M., Okenquist, S. and Silverman, L. Nature 284: 418-421 (1980); Shih, C., Padhy, L. C., Murray, M. J. and Weinberg, R. A. Nature 290: 261-264 (1981); Krontiris, T. G. and Copper, G. M. Proc. Natl. Acad. Sci. USA 78: 1181-1184 (1981); and, Perucho, M. et al. Cell 27: 467-476 (1981).

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These results demonstrated oncogenic factors present in the EJ tumor cell line DNA which were apparently absent from the DNA of normal cells. Web site: http://www.delphion.com/details?pn=US04535058__ •

Composition and method for the treatment of bladder cancer Inventor(s): Filion; Mario C. (Montreal, CA), Phillips; Nigel C. (Pointe Claire, CA) Assignee(s): Bioniche Life Sciences Inc. (Belleville, CA) Patent Number: 6,329,347 Date filed: August 5, 1998 Abstract: The present invention relates to a composition and method useful for treating cancer in the urinary bladder. The present invention particularly relates to a composition comprising a Mycobacterium phlei deoxyribonucleic acid (M-DNA)Mycobacterium phlei cell wall complex (MCC), wherein the M-DNA is preserved and complexed on the Mycobacterium phlei cell wall, and a pharmaceutically acceptable carrier. The MCC composition inhibits proliferation of and induces apoptosis in cancer cells in the urinary bladder and stimulates the responsive cells of the immune system to produce cytokines and reactive oxygen species. Methods of making MCC and methods of using MCC also are disclosed. Excerpt(s): The present invention relates to a composition and method useful for treating cancer in the urinary bladder of an animal, including a human, comprising a mycobacterial deoxyribonucleic acid (B-DNA)-mycobacterial cell wall complex (BCC), wherein the B-DNA is preserved and complexed on the bacterial cell wall, such that the BCC is effective for treating bladder cancer. More particularly, the present invention relates to a Mycobacterium phlei DNA (M-DNA)-Mycobacterium phlei cell wall complex (MCC), wherein the M-DNA is preserved and complexed on the M. phlei cell wall, such that the MCC is effective in inhibiting proliferation of and inducing apoptosis in bladder cancer cells, and in stimulating responsive cells of the immune system to produce bioactive molecules. Methods of making MCC and methods of using MCC also are disclosed. Cancer is an aberrant net accumulation of atypical cells, which can result from an excess of proliferation, an insufficiency of apoptosis, or a combination of the two. Apoptosis is a genetically programmed, non-inflammatory, energy-dependent form of cell death in tissue, including adult tissue (Steller H. Science 267:1445-1449, 1995), and is associated with nuclear DNA-fragmentation, release of nuclear matrix proteins (NuMA), and loss of cell substrate contact. Apoptosis can be initiated by ligands which bind to cell surface receptors including, but not limited to, Fas (CD95) (French et al. Journal of Cell Biology 133:355-364, 1996) and tumor necrosis factor receptor 1 (TNFR1). FasL binding to Fas and TNF binding to TNFR1 initiate intracellular signaling resulting in the activation of cysteine aspartyl proteases (caspases), which initiate the lethal proteolytic cascade of apoptosis execution (Muzio et al. Cell 85:817827, 1996). Mutations in Fas or in TNFR1 can cause a failure of apoptosis. Web site: http://www.delphion.com/details?pn=US06329347__

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Controlled-pH formulation for intravesicular instillation of TGF.alpha.PE.sub.40 ab Inventor(s): Marquis-Omer; Dorothy (Lansdale, PA), Middaugh; C. Russell (Quakertown, PA), Sanyal; Gautam (Harleysville, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,612,313 Date filed: June 27, 1996 Abstract: A buffered intravesicular pharmaceutical dosage system for delivery of TGF.alpha.PE.sub.40 ab to a human bladder for bladder cancer chemotherapy, in which a buffer system of 100 mM phosphate at an initial pH of 7.8 maintains a pH range in the bladder of 6.5 to 7.8 that is sufficient to maximize interaction of TGF.alpha.PE.sub.40 ab with the EGF receptor expressed on the surface of bladder cancer cells and to prevent aggregation of the TGF.alpha.PE.sub.40 ab while in the bladder. Excerpt(s): Pseudomonas aeruginosa produces the bacterial exotoxin Pseudomonas exotoxin A. The exotoxin consists of four structural domains, namely Ia, II, Ib and III. When domain Ia is cleaved off the exotoxin, the resulting protein is known as PE.sub.40. Transforming growth factor alpha (TGF.alpha.) is a protein that can be genetically fused to the amino terminus of PE.sub.40 to produce the chimeric protein TGF.alpha.PE.sub.40. When cysteine residues in domain II of PE.sub.40 are deleted or substituted by non-cysteinyl amino acids, the resulting protein is PE.sub.40 ab, which when genetically fused to TGF.alpha. produces TGF.alpha.PE.sub.40 ab. The present invention is an intravesicular preparation of TGF.alpha.PE.sub.40 ab containing a buffer system comprising a phosphate or modified phosphate system present in an amount sufficient to maintain a pH that is optimal for binding of TGF.alpha.PE.sub.40 ab to its receptor site. The optimum buffering range during residence of the TGF.alpha.PE.sub.40 ab in the bladder is 6.5-7.8. An additional criterion is that a pH of no less than 6.5 be maintained as inflow of urine causes a dilution of up to threefold the initial volume in the bladder over a two hour dwell time. Furthermore, a preferred buffer must retain bioactivity of TGF.alpha.PE.sub.40 ab for at least six hours prior to instillation into the bladder, as a significant amount of time may pass in a clinical setting in between preparation of the solution and actual instillation of the solution into the bladder. Preferred buffer systems include 100 mM, 250 mM and 400 mM sodium phosphate at an initial pH of any one value of 7.5, 7.8 or 8.2 and 50 mM phosphate with 150 mM glycinamide at an initial pH of 8.2. Web site: http://www.delphion.com/details?pn=US05612313__

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Detection of bladder cancer Inventor(s): Wang; Mary Ge (Rockville, MD) Assignee(s): Oncor, Inc. (Gaithersburg, MD) Patent Number: 6,573,042 Date filed: October 15, 1996 Abstract: Cells collected from bladder washings or urine may be analyzed by in situ hybridization. Such analysis includes detection of bladder cancer or carcinoma-in-situ. Excerpt(s): The present invention relates to methods for the early detection of bladder cancer. In particular, bladder cancer is detected early by use of in situ hybridization of cells obtained from urine or bladder washings. The publications and other materials

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used herein to illuminate the background of the invention and in particular cases to provide additional details respecting its practice are incorporated by reference and for convenience are numerically referenced in the following text and respectively grouped in the appended bibliography. Cancer of the bladder is the fifth most common cancer in the United States with an annual incidence of about 18 cases per 100,000 or over 50,000 new cases per year, leading to more than 10,000 deaths annually. The incidence (80% of the cases) is highest in the 50-79 year age group; the disease prevalence peaks in the seventh decade of life with a strong male predominance. Bladder cancer accounts for 7% of all new cases of cancer among men and 3% among women, as well as 2% of cancer deaths among men and 1% among women. Occupational exposure may account for 2125% of bladder cancer in white males in the United States. Web site: http://www.delphion.com/details?pn=US06573042__ •

Distal urinary replacement prosthesis Inventor(s): Salkind; Henry (3415 Fifth Ave., Youngstown, OH 44505) Assignee(s): none reported Patent Number: 4,228,550 Date filed: June 29, 1979 Abstract: An implant prosthesis for surgically by-passing the distal portion of the natural urethral tract for the removal of biological liquids, especially urine, consists of one or more artificial ureters disposed in a conical sheath connected with flexible tubing joining a tank forming a bladder replacement which in turn is connected by flexible tubing to the urethra when retained or extends to provide a controlled valved vent at the surface of a patient's body in which the prosthesis is surgically implanted, as for example following the removal of bladder cancer and its associated damaged distal urinary system. Excerpt(s): This invention relates to the field of surgical implants and is particularly directed toward the implant of a distal urinary replacement prosthesis in a human patient. The distal urinary replacement prosthesis disclosed herein is believed to be totally new as an acceptacle solution involving replacement in such entities as extrophy of the bladder and trauma and other circumstances which make the urethra and/or bladder non-functioning. Urethral shunt tube implants have been proposed for veterinary use as seen in U.S. Pat. No. 3,881,199 wherein a tubular implant replaces a portion of the natural urethral tract. Web site: http://www.delphion.com/details?pn=US04228550__

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Human uroplakin II gene and methods for detecting and classifying bladder cancer via human uroplakin genes Inventor(s): Sun; Tung-Tien (Scarsdale, NY), Wu; Xue-Ru (New York, NY) Assignee(s): New York University (New York, NY) Patent Number: 6,277,968 Date filed: November 13, 1997

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Abstract: The human gene for uroplakin II is identified and sequenced. Using this gene, oligonucleotide primers were constructed which were then used to identify bladder cancer cells in blood and tissue. Excerpt(s): Histological differentiation markers are useful in the diagnosis of carcinoma metastases where the location of the primary tumor is uncertain or unknown. Unfortunately, markers specific for a single epithelium or organ are currently available for a only few types of carcinoma, e.g., prostate-specific antigen for prostate carcinomas and thyroglobulin for thyroid carcinomas. Less specific markers of transitional cell carcinomas have been identified and associated with malignant transformation, tumor progression and the prognosis. Many of these markers are epithelial membrane antigen (EMA) or oncogene/tumor suppressor gene products. For example, Summerhayes et al. (1985. JNCI 75:1025-1038) have described a series of monoclonal antibodies (group III), directed against the urothelium which produce luminal-membrane staining of normal superficial (umbrella) cells of the urothelium. Other markers are expressed in superficial bladder tumors but disappear in invasive and metastatic transitional cell carcinomas. All of these markers are antibodies most of which stain non-urinary epithelia and carcinomas too. Certain antigens such as involucrin, E48 antigen and SCC antigen are markers shared by both transitional and stratified squamous epithelia (of skin, esophagus, cervix, etc. ) and their carcinomas. However, no differentiation or lineage marker specific for transitional cell carcinomas and their metastases has been identified to date. Normal urothelium contains tissue-specific differentiation products that have been well characterized morphologically and biochemically. It has been found that large numbers of urothelial plaques are present in the superficial plasma membrane of urothelial superficial or umbrella cells. These plaques are characterized by a highly unusual membrane structure, i.e., the asymmetric unit membrane (AUM), whose luminal leaflet is twice as thick as its cytoplasmic leaflet. The thickening of the luminal leaflet is due to the presence of particles exhibiting a semi-crystalline organization. The molecular constituents principally comprise four transmembrane proteins: uroplakin (UP) Ia (27 kDa); UP Ib (28 kDa); UP II (15 kDa) and UP III (47 kDa). These UPs, particularly UP Ia, Ib, and II, are characterized by their markedly asymmetric mass distribution, with the extracellular domain being considerably larger than the intracellular one. This accounts for the clearly visible ultrastructural thickening of the luminal leaflet of the unit membrane. UP III is believed to play a role in the formation of the urothelial glycocalyx and may interact, via its cytoplasmic portion, with the cytoskeleton. Web site: http://www.delphion.com/details?pn=US06277968__ •

Method for determining bladder tumors by assaying for MAGE-1,2,3 or 4 Inventor(s): Boon-Falleur; Thierry (Brussels, BE), Brasseur; Francis (Brussels, BE), Patard; Jean-Jacques (Brussels, BE) Assignee(s): Ludwig Institute For Cancer Research (New York, NY) Patent Number: 5,512,444 Date filed: November 30, 1994 Abstract: A method for screening for bladder cancer by identifying expression of one or more of MAGE-1, MAGE-2, MAGE-3 and MAGE-4 is the disclosed invention. Expression can be determined by a number of methods, including nucleotide amplification assays.

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Excerpt(s): This invention relates to cancer diagnosis. More particularly, it relates to the "tumor rejection antigen precursors" referred to as MAGE-1, MAGE-2, MAGE-3 and MAGE-4, which have been identified as "markers" for bladder cancers. The study of the recognition or lack of recognition of cancer cells by a host organism has proceeded in many different directions. Understanding of the field presumes some understanding of both basic immunology and oncology. Early research on mouse tumors revealed that these displayed molecules which led to rejection of tumor cells when transplanted into syngeneic animals. These molecules are "recognized" by T-cells in the recipient animal, and provoke a cytolytic T-cell response with lysis of the transplanted cells. This evidence was first obtained with tumors induced in vitro by chemical carcinogens, such as methylcholanthrene. The antigens expressed by the tumors and which elicited the Tcell response were found to be different for each tumor. See Prehn, et al., J. Natl. Canc. Inst. 18: 769-778 (1957); Klein et al., Cancer Res. 20: 1561-1572 (1960); Gross, Cancer Res. 3: 326-333 (1943), Basombrio, Cancer Res. 30: 2458-2462 (1970) for general teachings on inducing tumors with chemical carcinogens and differences in cell surface antigens. This class of antigens has come to be known as "tumor specific transplantation antigens" or "TSTAs". Following the observation of the presentation of such antigens when induced by chemical carcinogens, similar results were obtained when tumors were induced in vitro via ultraviolet radiation. See Kripke, J. Natl. Canc. Inst. 53: 333-1336 (1974). Web site: http://www.delphion.com/details?pn=US05512444__ •

Method for diagnosing cancer using specific PSCA antibodies Inventor(s): Reiter; Robert E. (Los Angeles, CA), Witte; Owen N. (Sherman Oaks, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,261,791 Date filed: May 25, 1999 Abstract: The invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, bladder cancer and bone metastasis of prostate cancer. Antibodies specific to PSCA are used for diagnosis of these cancers. Excerpt(s): Throughout this application, various publications are referenced within parentheses. The disclosures of these publications are hereby incorporated by reference herein in their entireties. Prostate cancer is currently the most common type of cancer in American men and the second leading cause of cancer related death in this population. In its advanced stages, prostate cancer metastasizes preferentially to bone, where it forms ostebclastic lesions. After initial treatment with androgen ablation therapy, most metastatic prostate cancers become hormone-refractory and lethal. Current diagnostic and therapeutic modalities are limited by a lack of specificity and an inability to predict which patients are at risk of developing metastatic disease. Most prostate cancers initially occur in the peripheral zone of the prostate gland, away from the urethra. Tumors within this zone may not produce any symptoms and, as a result, most men with early-stage prostate cancer will not present clinical symptoms of the disease until significant progression has occurred. Tumor progression into the transition zone of the prostate may lead to urethral obstruction, thus producing the first symptoms of the disease. However, these clinical symptoms are indistinguishable from the common nonmalignant condition of benign prostatic hyperplasia (BPH). Web site: http://www.delphion.com/details?pn=US06261791__

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Method for localization and therapy of occult bladder cancer Inventor(s): Eruzzi; Silvio (Mantova, IT), Lugnani; Franco (Trieste, IT), Rossi; Cino (Rome, IT), Stephen; Robert L. (Salt Lake City, UT) Assignee(s): Physion S.r.l. (Mirandola, IT) Patent Number: 5,301,688 Date filed: August 7, 1992 Abstract: Intravesical electromotive administration of specified dye substances for localisation and treatment of occult bladder cancers, is disclosed. Innocuous dye substances will provide differential staining of cancerous and normal urothelium; and anticancer dye substances will demonstrate differential staining and also initiate therapy of cancerous lesions. The addition of vasodilating agents will accentuate the differential staining and further promote therapy of the cancerous sites. Excerpt(s): The present invention relates to the diagnosis of cancer. In particular, this invention describes electromotive administration of dye substances into the bladder wall, with and without vasodilatation, for the localisation, or localisation and treatment, of occult cancerous sites in persons with diagnosed cancer of the bladder. Origins: Cancer of the bladder is usually multifocal in nature with malignant changes in normal tissues appearing in multiple sites. This situation has given rise to two schools of thought: 1) bladder cancer is multiclonal in origin or; 2) it is monoclonal in nature with facilitated spread laterally through bladder tissues and/or dispersion of viable cancer cells throughout the bladder cavity to seed at other sites. The -merits of these two hypotheses are still unresolved but, whichever is correct, the important aspect related to this invention is the frequent occurrence of multiple tumors at different sites within the bladder wall. Treatment of Bladder Cancer: Following diagnosis of bladder cancer, there are three mainstays of therapy. Web site: http://www.delphion.com/details?pn=US05301688__

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Method for selectively inducing biomarker expression in urologic tumor tissue for diagnosis and treatment thereof Inventor(s): Marley; Garry M. (Oklahoma City, OK), Veltri; Robert W. (Oklahoma City, OK) Assignee(s): UroCor, Inc. (Oklahoma City, OK) Patent Number: 5,856,112 Date filed: June 16, 1994 Abstract: A method for selectively inducing expression of biomarkers for urologic cancers, including prostate and bladder cancer, is disclosed. Tumor cells are cultured using a low shear rotational three-dimensional technique under conditions effective to induce said selective expression. The method is useful for diagnostic and therapeutic applications. Excerpt(s): This invention relates to the field of tissue-culturing of mammalian cells for purposes of diagnosing and treating neoplastic disease. Tissue culturing of mammalian cells has become a preferred technique for scientists to study various aspects of cancer, including its etiology and its treatment. A convenient form of tissue culturing is known as two-dimensional monolayer cell culturing. In this technique, cells admixed with appropriate life-sustaining media are placed in a specially-treated plastic petri dish or

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flask. The cells adhere to the bottom surface of the container, assuming a characteristic flattened pattern during spreading, and replicate on that surface as a single layer, called a monolayer. The media remains on top of the flat layer of cells and is changed periodically to provide the growing cells with essential nutrients. The container wall surface area determines the number of cells that can be effectively cultured. When it is desired to split the cultures, an enzyme such as trypsin is utilized to destroy the anchorage of the cells to the dish so that subcultures can be made. While the cells are in culture, various agents can be applied to the media in the plates and the effect on the cells observed. For example, suspected carcinogens can be added to individual cultures of non-cancerous cells to ascertain if the carcinogen causes the cells to exhibit the growth pattern characteristic of cancerous cells. Tissue culture offers an effective screening tool that increases the number of agents that can be rapidly screened as compared to using animals for the same purpose. With regard to potential treatment of cancerous disease, tissue culture may be used to determine if experimental drugs or antibodies would be effective in destroying cancerous cells. Tissue culture can also be used to attempt to determine whether particular antibodies might bind to cancer cells in order to provide for targeting of particular cells with drugs conjugated to such antibodies. Even though two-dimensional monolayer tissue culture has provided great benefits to scientists and clinicians, it suffers from a lingering disadvantage as well. Tumors do not grow twodimensionally in the body, and therefore, monolayer cultures of tumor cells cannot reflect their true in vivo three-dimensional growth architecture. In addition, monolayer cultures reflect a homogeneous cell population in which every cell is exactly like every other cell in culture. This is not the case for solid tumors, which are vascularized within the host and most often exhibit a heterogenous cell population believed to result from cell differentiation induced by differences in biochemical environment such as hormones, growth factors, oxygen tension, and catabolic waste products between blood vessels and the tumor core. The solid tumor has a population of dynamic cells, meaning that they may be constantly changing in response to their environment. Cells may exhibit different morphological, biochemical and histological properties. Web site: http://www.delphion.com/details?pn=US05856112__ •

Method of determining metastatic potential of bladder tumor cells Inventor(s): Nabi; Ivan R. (Montreal, CA), Otto; Thomas (Essen, DE), Raz; Avraham (West Bloomfield, MI), Watanabe; Hideomi (Maebashi, JP) Assignee(s): Michigan Cancer Foundation (Detroit, MI) Patent Number: 5,382,521 Date filed: July 14, 1992 Abstract: Methods and compositions useful in the screening of human bladder cancer cells and malignant tumors are provided. Certain human autocrine motility factor receptors or proteins (gp78-hAMFR) have been identified which are useful in the screening of human bladder cancer cells and malignant tumors. Methods and assay kits for the screening of human bladder cancer, human cancer cells, and tumors, are provided wherein antibodies or other probes are used which recognize gp78-hAMFR expression. These methods and assays readily distinguish between non-malignant and malignant cancer cells and tumors and can be used to gauge metastatic potential. Excerpt(s): The present invention relates generally to methods and compositions useful in the analysis of human cancer cells and malignant tumors. More specifically, the present invention provides techniques for determining the presence and level of

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expression of autocrine motility factor receptors on human cells. In one aspect, the level of expression of human autocrine motility factor receptors in cancerous bladder tissue cells is determined to predict metastatic potential. In this manner, the invention provides a means by which treatment may be more accurately administered. This invention also relates to assay kits for cancer analysis. The method and assays of the present invention readily distinguish between non-malignant and malignant cancer cells and tumors and can be used to gauge metastatic potential. A considerable amount of research effort has been directed towards the development of techniques to detect cancer cells or to distinguish between non-malignant and malignant cancer cells or tumors. For those patients with cancerous cells or tumors, it is important to determine which patients have the greatest risk for tumor progression or metastasis. For these patients, aggressive therapy, including surgery and chemotherapy, may be selectively employed. For patients demonstrating a lower risk of progression and metastasis, less aggressive therapy may be employed, particulary since progression or metastasis can now be readily monitored as provided in the present invention. Thus, one of the major problems of cancer treatment and research is the development of reliable and predictive methods of cancer detection. Recently, various methods for analyzing tumor specimens or exfoliated cells have been developed to detect genetic alterations, tumor suppressor genes, oncogenes, tumor cell products, and angiogenic factors. It is known that cancer progression in stage or grade is associated with increasing chromosomal anomalies that can be assessed by measuring tumor cell DNA content, by cytogenetic studies, or by measuring the function of activation in oncogenes and inactivation of tumor suppressor genes. Web site: http://www.delphion.com/details?pn=US05382521__ •

Method of diagnosing bladder cancer Inventor(s): Goldberg; Itzhak D. (Engelwood, NJ), Rosen; Eliot M. (Port Washington, NY), Weiss; Gary H. (Port Washington, NY) Assignee(s): Long Island Jewish Medical Center (New Hyde Park, NY) Patent Number: 5,656,443 Date filed: July 29, 1994 Abstract: This invention relates to a method of diagnosing and screening for transitional cell carcinoma of the bladder. Urine from an individual suspected of having transitional cell carcinoma of the bladder is analyzed for the presence of an increased level of scatter factor, an increased level of scatter factor indicating that said individual has bladder cancer. This invention further relates to a method of monitoring bladder cancer activity by measuring the level of scatter factor in urine, and to a method of determining the prognosis of an individual having bladder cancer by measuring the level of scatter factor in tumor extract from the individual. Excerpt(s): This invention relates to a method of diagnosing bladder cancer. Specifically, this invention is directed to a method of diagnosing and screening for transitional cell carcinoma of the bladder, to a method for monitoring the course of bladder cancer and to a method of determining the prognosis of an individual having transitional cell carcinoma of the bladder. Carcinoma is a malignant epithelial neoplasm which invades surrounding tissue and metastasizes to distant regions of the body. Transitional cell carcinoma is a malignant, usually papillary tumor derived from transitional stratified epithelium, which occurs most frequently in the bladder. Most tumors in the collecting system of the human body are transitional cell carcinomas. In order to diagnose

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transitional cell carcinoma in the bladder, it is necessary to do a biopsy. A biopsy is the removal of a small sample of living tissue from an organ, such as the bladder, for microscopic examination to confirm or establish a diagnosis, estimate prognosis, or follow the course of a disease. Biopsies are invasive procedures, and are therefore not desirable as it is necessary for a person undergoing biopsy to undergo anesthesia. In addition, as with any invasive procedure, an individual undergoing biopsy runs the risk of infection. Further, the entire bladder cannot be biopisied to determine whether bladder cancer is present. Biopsy procedures often require individuals to be admitted into hospitals. Alternatively, urinary cytology analysis can be performed to diagnose transitional cell carcinoma of the bladder. However, urinary cytology analysis is a time-consuming procedure, which is not always accurate. Therefore, a need exists to develop a method of diagnosing and screening for carcinoma, including transitional cell carcinoma of the bladder, as well as for monitoring cancer activity and determining the prognosis of an individual having bladder cancer. Web site: http://www.delphion.com/details?pn=US05656443__ •

Method of preparing and using isoflavones for the treatment of cancer Inventor(s): Empie; Mark (Forsyth, IL), Gugger; Eric (Latham, IL) Assignee(s): Archer Daniels Midland Company (Decatur, IL) Patent Number: 6,395,279 Date filed: July 13, 2000 Abstract: A composition is prepared by extracting phytochemicals from plant matter and is administered to provide treatment for cancer and especially for breast, prostate, skin, colon, urinary and bladder cancer. This composition is enriched preferably with two or more fractions of phytochemicals refined from plant matter, namely: isoflavones, lignans, saponins, sapogenins, catechins and phenolic acids. The isoflavones are selected from a group including malonyl, acetyl, glucoside, and aglycone. Soy is the preferred source of these chemicals; however, other plants may also be used, such as wheat, psyllium, rice, oats, red clover, kudzu, alfalfa, flax, and cocoa. The composition is a dietary supplement for treatment of various cancers and other syndromes and disorders. In particular, the dietary supplement is in a concentrated, easy to use or consume form, such as creams, pills, tablets, capsules, pellets, dry powder, health bars, food ingredients and supplements, tablets, soft gels, and the like. Excerpt(s): This invention relates to compositions extracted from vegetable matter and more particularly to phytochemicals, including saponogenins and saponins, lignans, phenolic acids, catechins and isoflavones, and especially those extracted from a family of plants including soy, flax, tea, and cocoa and methods of using these compositions as nutritional supplements or food additives. As used herein, the term "isoflavone" includes malonyl, acetyl, glucoside, and aglycone forms of the isoflavones. Currently, there is almost an epidemic of cancer, at least some of which is thought to be either caused or exacerbated by foods having a hormonal supplement derived from an animal origin. This thought is especially true for breast and prostate cancer. Other forms of cancers which are of special concern are skin cancer, colon cancer, urinary cancer, bladder and the like. Web site: http://www.delphion.com/details?pn=US06395279__

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Method of treating bladder cancer cells Inventor(s): Ahern; Janet (Horsham, PA), Heimbrook; David C. (Ringoes, NJ), Oliff; Allen I. (Gwynedd Valley, PA), Stirdivant; Steven M. (Warrington, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,690,928 Date filed: April 11, 1994 Abstract: Methods and compositions for treating bladder cancer using TGF-alpha or EGF fused to PE.sub.40 or cysteine modified derivatives are taught. Also, a method of producing TGF-alpha-PE.sub.40 derivatives of enhanced potency is described. Excerpt(s): Traditional cancer chemotherapy relies on the ability of drugs to kill minor cells in cancer patients. Unfortunately, these same drugs frequently kill normal cells as well as the tumor cells. The extent to which a cancer drag kills tumor cells rather than normal cells is an indication of the compound's degree of selectivity for tumor cells. One method of increasing the tumor cell selectivity of cancer drugs is to deliver drugs preferentially to the tumor cells while avoiding normal cell populations. Another term for the selective delivery of chemotherapeutic agents to specific cell populations is "targeting". Drug targeting to tumor cells can be accomplished in several ways. One method relies on the presence of specific receptor molecules found on the surface of tumor cells. Other molecules, referred to as "targeting agents", can recognize and bind to these cell surface receptors. These "targeting agents" include, e.g., antibodies, growth factors, or hormones. "Targeting agents" which recognize and bind to specific cell surface receptors are said to target the cells which possess those receptors. For example, bladder tumor cells possess a protein on their surfaces called the epidermal growth factor receptor. Transforming growth factor-alpha (TGF-alpha) recognizes and binds to the EGF receptor on bladder tumor cells. TGF-alpha is therefore, a "targeting agent" for these tumor cells. Pseudomonas exotoxin A intoxicates mammalian cells by first binding to the cell's surface, then entering the cell cytoplasm and inactivating elongation factor 2 which is a cellular protein required for protein synthesis. Pseudomonas exotoxin A has been used to construct anticancer hybrid molecules using monoclonal antibodies and protein hormones. However, one problem with these hybrid molecules is that they exhibit toxicity towards normal cells. At least part of the toxicity associated with hybrid molecules containing pseudomonas exotoxin A is due to the ability of pseudomonas exotoxin A by itself to bind to and enter many types of mammalian cells. Therefore, hybrid molecules formed between pseudomonas exotoxin A and specific "targeting agents" can bind to many normal cells in addition to the cells recognized by the "targeting agent". One method of dealing with this problem is to modify pseudomonas exotoxin A so that it is no longer capable of binding to normal cells. This can be accomplished by removing that portion of the pseudomonas exotoxin A molecule which is responsible for its cellular binding activity. A truncated form of the pseudomonas exotoxin A molecule has been prepared which retains the ability to inactivate elongation factor 2 but no longer is capable of binding to mammalian cells. This modified pseudomonas exotoxin A molecule is called pseudomonas exotoxin-40 or PE.sub.40 (Hwang, et al., Cell 48:129-136 1987). 1. U.S. Pat. No. 4,545,985 teaches that pseudomonas exotoxin A can be chemically conjugated to an antibody or to epidermal growth factor. While this patent further teaches that these conjugates can be used to kill human tumor cells, these chemically linked toxins have been shown to have undesirable, nonspecific levels of activity. Web site: http://www.delphion.com/details?pn=US05690928__

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Method of treating bladder cancer with a keyhole limpet hemocyanin composition with enhanced anti-tumor activity Inventor(s): Ebert; Ray F. (Derwood, MD), Swerdlow; Richard D. (Silver Spring, MD) Assignee(s): Akzo, N.V. (Arnhem, NL) Patent Number: 5,407,912 Date filed: April 19, 1993 Abstract: The present invention is directed to a stabilized keyhole limpet hemocyanin (KLH) composition in which (i) its intact non-degraded subunit is approximately 400,000 in molecular weight based on SDS-PAGE analysis; and (ii) are contained at least about 50% didecameric or higher KLH multimers, based on sedimentation-equilibrium and/or sedimentation-velocity ultracentrifugation analyses. The KLH composition is stabilized at 4.degree. C. by dissolving and storing it in an isotonic buffer preferably containing calcium and magnesium. It is critical that the KLH not have been frozen or lyophilized during its preparation or storage. The KLH composition demonstrates enhanced immunogenic activity, particularly enhanced anti-tumor activity, which is reduced if the KLH is frozen or lyophilized. The KLH composition of the present invention exhibits enhanced anti-tumor activity in a murine bladder tumor model and thereby represents a new and useful anti-tumor immunotherapeutic agent. Excerpt(s): The present invention relates to a keyhole limpet hemocyanin (KLH) composition that has enhanced immunogenic properties, particularly enhanced antitumor activity. Specifically, the present invention relates to an immunogenic agent comprised of KLH formulated to contain >50% didecameric or higher KLH multimers that range in molecular weight from approximately 8-10 million. The immunogenic agent is useful as a cancer therapeutic agent and as an adjuvant or carrier protein. The publications and other materials used to illuminate the background of the invention or provide additional details respecting the practice are incorporated herein by reference numerals in parentheses, and for convenience are respectively grouped in the appended List of References. For decades it has been known that hemocyanins are among the most potent of immunogens. Keyhole limpet hemocyanin (KLH; from the primitive gastropod mollusc, Megathura crenulata) has been among the most widely used and thoroughly studied of these (1-4). Thus, a single subcutaneous injection of KLH, without adjuvant, will elicit a strong antibody response in virtually 100% of animals, including humans. Web site: http://www.delphion.com/details?pn=US05407912__

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Method of treating bladder cancer with wild type vaccinia virus Inventor(s): Lattime; Edmund C. (Princeton, NJ), Mastrangelo; Michael J. (Jenkintown, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 6,177,076 Date filed: December 7, 1998 Abstract: Methods of treating bladder cancer in a patient by administration of wildtype vaccinia virus are provided. Excerpt(s): The standard care for patients with superficial bladder cancer is transurethral resection of the bladder tumor followed by six weeks of intravesical

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administration of the mycobacterium Bacillus Calmette-Guerin (BCG). This approach not only increases the surgical cure rate but also prolongs the time to recurrence in patients not cured by the surgery. It is believed that the superficial cystitis caused by BCG treatment results in tumor cell death as a bystander effect. However, relapses following this treatment are proving to be more common. Eventually, a significant population of superficial bladder cancer patients will have recurrence of BCG-resistant disease. Currently, there is no good treatment for this group of patients. Accordingly, a more effective treatment is needed for bladder cancer, particularly for superficial cancer and BCG-refractory superficial bladder cancer. An object of the present invention is to provide a method of treating patients having bladder cancer which comprises intravesically administering wild type vaccinia virus to the bladder of the patients. It is a further object of the invention to provide a method of treating patients having superficial bladder cancer, and BCG-refractory superficial bladder cancer in particular, comprising intravesically administering wild type vaccinia virus to the bladder of the patients. Web site: http://www.delphion.com/details?pn=US06177076__ •

Methods for detection and evaluation of bladder cancer Inventor(s): Lokeshwar; Vinata B. (12615 SW. 112 Ct., Miami, FL 33176), Pham; Henry T. (6550 Mapleridge, Suite 122, Houston, TX 77081) Assignee(s): none reported Patent Number: 6,350,571 Date filed: March 10, 1999 Abstract: The present invention relates to novel methods for detecting and evaluating bladder cancer. The methods of the present invention are based on the discovery that normalized amounts of hyaluronic acid (HA) and hyaluronidase (HAase) are diagnostic markers for the detection of bladder cancer, evaluation of its grade, monitoring of the efficacy of its treatment, and tumor recurrence. Excerpt(s): This invention relates to novel methods for detecting and evaluating bladder cancer, utilizing hyaluronic acid (HA) and hyaluronidase (HAase). Bladder carcinoma is the most common cancer of the urinary tract, accounting for 51,000 new cases and 11,000 deaths each year in the United States. Transitional cell carcinomas (TCCs) account for.apprxeq.90% of the bladder tumors. These tumors are heterogeneous in their ability to progress. For example, some TCCs behave in a benign fashion (low-grade, G1 tumors) whereas others are intermediate (G2 tumors) to highly aggressive (G3 tumors and carcinoma in situ (CIS)). The high-grade tumors generally metastasize quickly; indeed, at the time of clinical presentation (e.g., hematuria, irritative voiding symptoms etc.), invasive disease already exists for many patients with high-grade bladder tumors. The two most important prognostic factors for TCCs are grade and stage (which indicates the depth of invasion) (American Joint Committee on Cancer: Staging of cancer at genito-urinary sites. In: Manual for Staging Cancer, 3.sup.rd edition, pp. 194-195, J. B. Lippincott Co., Philadelphia, 1988). Low-grade (G1) tumors are mostly confined to the mucosa (stage Ta) and have a <2% chance of progression (Heney, Natural history of superficial bladder cancer. Urol. Clin. North Am., 19: 429-435, 1992; Heney and Flanagan, Superficial bladder cancer progression and recurrence. J. Urol., 130: 10831086, 1983). Intermediate-grade (G2) tumors range from being non-invasive (Ta) to invasive (stages T1-T4). The G2, Ta tumors have.about.11% chance of progression (Heney, Natural history of superficial bladder cancer. Urol. Clin. North Am., 19: 429-

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435, 1992). With the exception of carcinoma in situ (CIS), most high-grade tumors are initially detected at least at stage T1 (invading lamina propria) and are thus invasive. Muscle invasion (stage T2) by the tumor is ominous, as 50% of these patients develop distant metastasis within two years of diagnosis despite radical surgery, and 60% of them die within 5 years, however treated (Heney and Flanagan, Superficial bladder cancer progression and recurrence. J. Urol., 130: 1083-1086, 1983; Friedell et al., Summary of workshop on carcinoma-in-situ of the bladder. J. Urol., 136: 1047-1048, 1986; Soloway, Invasive bladder cancer: Selection of primary treatment. Semin. Oncol., 17: 551-554, 1990). Due to the malignant nature of high-grade TCCs, their early detection prior to muscle invasion, is crucial for a favorable prognosis. Web site: http://www.delphion.com/details?pn=US06350571__ •

Non-invasive diagnostic method for interstitial cystitis and bladder cancer Inventor(s): Haak-Frendscho; Mary (Madison, WI), Niles; Andrew L. (Madison, WI), Okragly; Angela J. (Madison, WI), Saban; Ricardo (Madison, WI) Assignee(s): Promega Corporation (Madison, WI) Patent Number: 6,008,003 Date filed: October 28, 1997 Abstract: Disclosed is a method of diagnosing or monitoring interstitial cystitis or bladder cancer in a mammal. The method comprises analyzing urine of the mammal for the concentration of a urine-soluble protein selected from the group consisting of neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor, tryptase, and combinations thereof. Excerpt(s): The invention is drawn to a non-invasive method for diagnosing or monitoring interstitial cystitis and bladder cancer in mammals, including humans. Complete bibliographic citations to the references cited below can be found in the "Bibliography," immediately preceding the claims. Each of the references cited below is incorporated herein by reference in its entirety. Interstitial cystitis (IC) is a chronic inflammatory bladder condition characterized by urinary frequency and urgency, burning, and suprapubic pain. IC occurs predominately in women, many who suffer for years before a correct diagnosis is made. Sant, 1993. The etiology and pathogenesis of IC are unknown. Autoimmune and immune mechanisms have been implicated based on findings of immunoglobulin and complement deposits in affected bladders and of alterations in bladder mucin. Lynes et al., 1987. Defects in the protective mucosal layer of the bladder have also been suggested as a cause of IC. See, for instance, Parsons and Mulholland, 1987; Gillespie, 1993; and Parsons, 1993. A defect in the bladder surface glycosaminoglycan layer may allow toxic substances in the urine to enter the bladder wall and establish an inflammatory response. Matilla, 1983. However, defective bladder lining is not a uniform finding in IC patients. Nickel et al., 1993. Other proposed causes of interstitial cystitis include viral and bacterial infection, vascular or lymphatic obstruction, abnormal vasomotor control, genetic or endocrinologic deficiencies, and neurogenic or allergic causes. Messing, 1991. Web site: http://www.delphion.com/details?pn=US06008003__

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Optically active anthracyclinones Inventor(s): Arcamone; Federico (Nerviano, IT), Bernardi; Luigi (Milan, IT), Di Marco; Aurelia (Milan, IT), Patelli; Bianca (Milan, IT) Assignee(s): Societa' Farmaceutici Italia, S.p.A. (Milan, IT) Patent Number: 4,077,988 Date filed: January 16, 1976 Abstract: Disclosed are optically active anthracyclinones and their daunosaminyl derivatives, which are useful for the treatment of malignant diseases, particularly sarcomas, breast cancer, bronchogenic carcinoma, malignant lymphomas, neuroblastomas, acute leukemia and bladder cancer. Excerpt(s): This application is related to and incorporates by reference the entire contents of applications, Ser. No. 560,105 (now U.S. Pat. No. 4,039,663), 568,437 (now abandoned) and 579,901 (now U.S. Pat. No. 4,046,878), filed respectively on Mar. 19, 1975; Apr. 16, 1975; and May 22, 1975, all of which are owned by the assignee hereof. The invention relates to certain novel optically active anthracyclinones of the daunomycin group, daunosaminyl derivatives of said compounds and methods for the preparation thereof. While the optically active anthracyclinones of the invention are novel, the corresponding racemates of certain of them have been described in the literature; see C. M. Wong et al, Canad.J.Chem., 49, 2712 (1971) and Canad.J.Chem., 51, 466 (1973). Web site: http://www.delphion.com/details?pn=US04077988__

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Transgenic mouse models for human bladder cancer Inventor(s): Sun; Tung-Tien (Scarsdale, NY), Wu; Xue-Ru (Woodside, NY) Assignee(s): New York University (New York, NY) Patent Number: 6,323,390 Date filed: May 22, 1998 Abstract: A transgenic mouse, containing an oncogene or a tumor suppressor gene operably linked to a urothelium-specific promoter in its germ cells and somatic cells serves as an animal model system for human bladder cancer. Excerpt(s): The present invention relates to transgenic animal models for human bladder cancer and their use as in vivo models for testing potential carcinogens, preventative measures, as well as therapeutic modalities for intervention in the progression of human bladder cancer. Bladder cancer is the fifth most common cancer affecting predominantly the aging male population and the twelfth leading cause of cancer deaths. Despite aggressive therapy, bladder cancer still continues to be one of the leading causes of cancer deaths in the United States. The American Cancer Society estimated that in 1997 there were 54,500 new cases diagnosed and 11,700 deaths resulting from this disease in the United States. A major cornerstone in bladder cancer research is the recognition of two distinct forms of bladder cancer (Koss, 1985 and 1992). About 80% of transitional cell carcinomas (TCCs) are superficial, well-differentiated, papillary tumors. This type of TCC is often multifocal and recurrent but rarely progresses to muscle invasion. Another type accounts for 20% of all TCCs and is either present as a carcinoma in situ (CIS) or as poorly differentiated, invasive tumors. It is believed that the majority of invasive TCCs are not derived from the superficial type but

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directly from CIS and related urothelial abnormalities (Koss, 1992). Interestingly, recent genetic studies suggest that these two forms of bladder cancer may have distinct underlying genetic causes. Cordon-Cardo et al. (1994) proposed that the inactivation of p16 may be responsible for the formation of superficial TCCs, while the inactivation of p53 underlies the invasive form of TCCs. Web site: http://www.delphion.com/details?pn=US06323390__ •

Unique protein marker for bladder cancer Inventor(s): Babaian; Richard J. (Houston, TX), Zhau; Haiyen E. (Houston, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX) Patent Number: 5,221,612 Date filed: March 3, 1989 Abstract: The present invention involves a method for detecting bladder cancer in a subject. The method preferably comprises first collecting a urine sample from the subject. The presence of a proteinaceous substance having a molecular weight of about 180 kDa according to its relative electrophoretic migration rate through detergentcontaining polyacrylamide gel is then measured. This substance reversibly binds concanavalin A and is complexed with gamma globulin while in the urine. The gamma globulin complex binds to Staphlococcal protein A. Said proteinaceous substance, when present in detectable amount, is an indicator of bladder cancer.The method of the present invention for diagnosing bladder cancer in a subject may also be described as comprising detection in a urine sample from said subject of a proteinaceous substance having a molecular weight of about 180 kDa and being unreactive with antibodies specifically binding to carcinoembryonic antigen or epidermal growth factor receptor. When an antibody is used for the present method of diagnosis, an initial step for preparing an antibody specifically binding a urinary 180 kDa antigen present in urine of bladder cancer victims is carried out. This antibody of course may be prepared by others and merely obtained by commercial purchase. In any case said antibody may be used to detect the bladder cancer-specific 180 kDa antigen of the present invention in patient urine. This antibody is most preferably monoclonal or may be polyclonal. Excerpt(s): The present invention involves the diagnosis of bladder cancer comprising detection of a particular and unique proteinaceous urine component. Bladder cancer consists of a heterogenous group of tumors with varied capacities for invasion and metastasis. This disease accounts for 2 percent of all malignancies and is the 5th most prevalent cancer among adults in the United States.sup.1 In the effort to identify biochemical markers that may have diagnostic and prognostic value, various noninvasive tests have been developed, including tests to identify tumor-associated markers in the urine, serum, and bladder cancer tissue specimens. Among the various tumor-associated markers studied, urinary immunoglobulins have been found to increase in persons who have bladder cancer.sup.2-7 and appear to have some diagnostic and prognostic value.sup.8-10 There are no data, however, to indicate that these antibodies are specifically directed toward bladder carcinoma antigens. Web site: http://www.delphion.com/details?pn=US05221612__

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Urethral catheter and catheterization process Inventor(s): Hanna, Jr.; Michael G. (Frederick, MD), Morales; Alvaro (Kingston, CA) Assignee(s): Akzo N.V. (Arnhem, NL) Patent Number: 5,120,316 Date filed: September 28, 1990 Abstract: A device for delivering medication into a human body, comprising a catheter having proximate and distal ends, and first and second lumina extending substantially the entire length of the catheter. A first opening in the catheter near its distal end drains fluid from a body when the catheter is inserted therein. There is a second opening in the catheter between the first opening and the distal end of the catheter. The second opening is fluidly connected with the second lumen. A diaphragm is located adjacent to the second opening for blocking off the second opening from the second lumen, and the diaphragm is burstable by a predetermined pressure for unblocking the second opening for fluidly connecting it with the second lumen. Thus, medications can be safely administered without the possibility of premature contact of the medication with the body. The catheter is particularly well suited to the administration of toxic substances such as BCG vaccine into the bladder of bladder cancer patients. Excerpt(s): This invention relates to a urethral catheter, and to a method of delivering medication such as infectious vaccines, for example, bacillus Calmette-Guerin (BCG) vaccine, into the bladder for treating bladder cancer. Urethral catheters are known for insertion through the urethra into the bladder for administering medication or radiopaque dyes into the bladder. Drawbacks of known urethral catheters include catheter traumatization of the urethral canal by the insertion and presence of the catheter in the urethra. In addition, inflammation and infection of the urethra can result from fluids passing from the catheter and into contact with the irritated urethra. Previous attempts to prevent urethral infection include the indwelling urinary catheter disclosed in U.S. Pat. No. 4,579,554, in which deep grooves are provided along the length of the catheter for washing and cleansing the outside of the catheter so that the mucosa of the penile urethral canal is irrigated to reduce infection. Furthermore, a balloon is attached to the distal end of the catheter for being inflated when the catheter is in place in the bladder. The balloon both anchors the catheter and seats snugly against the wall of the bladder to resist escape of infected fluids into the sterilely treated urethra. This catheter is apparently designed chiefly for draining the bladder over a period of time, and has no mechanism for ensuring that a medication is not prematurely administered. Web site: http://www.delphion.com/details?pn=US05120316__

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Use of heterocyclic compounds for iontophoretic treatment Inventor(s): Thiel; Karl H. (Mandrystrasse 10, D-7100 Heilbronn, DE) Assignee(s): none reported Patent Number: 5,002,956 Date filed: March 22, 1989 Abstract: What is disclosed is the use of dissociable heterocycle compounds from the group including aminoacridine, aminocholine and aminopyridine as well as their derivatives substituted on the basic structure, which are present in tautomeric diimine

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form, for the selective iontophoretic treatment or for production of a pharmaceutical for iontophoretic treatment and relapse prophylaxis of bladder cancer as well as for iontophoretic treatment of malignant skin and mucus membrane tumors.It is further disclosed and proven that the antineoplastic effect observed with use of the above compositions in animal experiments and in clinical treatment is selective and healthy tissue is not damaged.The common denominator for the characteristic and proven antineoplastic selective effect of the three classes of materials is the tautomeric diimine form.As a pre- and/or post-treatment medium with the treatment of bladder cancer, preferably a lubricant, anesthetic and prophylactic medium is used, which includes(a) a nonionic, water miscible lubricant with an electric conductivity lower than 2 mS/cm and a viscosity (at 25.degree. C.) in the range of 50 to 2000 mPa.s, and(b) a local, nonionic mucus membrane anesthetic which does not penetrate into the bloodstream,in which the mixture of (a) and (b) has a pH level between approximately 5 and 7.5, preferably between 6.5 and 6.8. Excerpt(s): The invention relates to the use of certain heterocyclic compounds for iontophoretic treatment or for the production of pharmaceuticals for iontophoretic treatment of malignant tumors as well as a lubricant or parting compound, anesthetic and prophylactic for introduction and use during this treatment. It is already known that certain heterocyclic compounds, i.e. acridine, quinoline and pyridine derivatives with a nitrogen atom in a heterocyclic ring and at least one amino group remaining separate from the ring structure, which with the nitrogen atom in the ring structure can develop a tautomeric diimine structure, represent mitotic poisons (cf. Lettre H.: Uber Mitosegifte, Ergebnisse der Physiologie, /On Mitotic Poisons, Physiology Publications/, 46, 379-452 (1950)). Some of these heterocyclic compounds with two or more condensed aromatic ring structures have the capacity to and may become incorporated in the double helix of the deoxyribonucleic acid (DNA) of bacteria or tissue cells in such a manner that both the replication and the biochemical transcription can no longer elapse in an orderly manner. These molecules are designated as intercalaries (cf. D. Schmael, Arzneimittelforschung/Pharmaceutical Digest/, 21st supplement, 3d edition (1981), p. 424). The biological interaction of these heterocyclic compounds, especially the acridine compounds, probably is based on an intercalation with the DNA by placement or implantation between the base pair layers, which is conditioned by the flat structure of these heterocyclic compounds. Guanine-cytosine-base pairs are thus preferred, and the formation of a complex with DNA and a repair enzyme probably occurs. The activity of the polymer is reduced, and the DNA cannot be uncased. Furthermore the DNA helix is broken down into single and double strands with consecutive DNA-protein bonds. Web site: http://www.delphion.com/details?pn=US05002956__

Patent Applications on Bladder 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 bladder cancer:

10

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

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Antiproliferative factor Inventor(s): Hise, Michael K.; (Columbia, MD), Keay, Susan K.; (Ellicott City, MD), Kleinberg, Michael; (Baltimore, MD), Warren, John W.; (Baltimore, MD) Correspondence: David L. Marks; University OF Maryland; Baltimore Office OF Research & DEV.; 515 West Lombard Street, Suite 500; Baltimore; MD; 21201-1602; US Patent Application Number: 20020016443 Date filed: April 21, 2001 Abstract: The invention relates to a novel antiproliferative factor (APF) present in urine of patients with interstitial cystitis (IC). APF is useful as a marker for disease activity and its antagonists are useful as therapeutic medicaments for IC and other conditions associated with elevated APF. APF and its agonists are useful in the treatment of diseases associated with cell proliferation, such as bladder cancer. Excerpt(s): This application is a CIP of U.S. patent application Ser. No. 09/307,686 filed on May 10, 1999, now abandoned. U.S. Pat. No. 09/307,686 is a Divisional of U.S. Pat. No. 5,962,645 issued on Oct. 5, 1999 and filed on Oct. 3, 1997 as U.S. patent application Ser. No. 08/944,202 which claims priority to U.S. patent application Ser. No. 60/027,646 filed on Oct. 4, 1996 (now abandoned). This application claims priority to U.S. patent application Ser. No. 09/307,686, U.S. Pat. No. 5,962,645, and U.S. patent application Ser. No. 60/027,646. This application also claims priority to and is related to U.S. patent application 60/218,272 filed on Jul. 13, 2000 and to U.S. patent application Ser. No. 60/232,911 filed on Sep. 15, 2000. The invention relates to a novel antiproliferation factor found in subjects with interstitial cystitis; to methods for isolating the antiproliferation factor; to methods for using the antiproliferation factor in the treatment of conditions characterized by cellular proliferation; and to methods for diagnosing and treating interstitial cystitis. Art relating to the background of the invention is reviewed in the ensuing sections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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BPC-1: a secreted brain-specific protein expressed and secreted by prostate and bladder cancer cells Inventor(s): Afar, Daniel E.; (Pacific Palisades, CA), Hubert, Rene S.; (Los Angeles, CA), Jakobovits, Aya; (Beverly Hills, CA), Leong, Kahan; (Playa Del Rey, CA), Raitano, Arthur B.; (Los Angeles, CA), Saffran, Douglas C.; (Los Angeles, CA) Correspondence: Attention OF Karen S. Canady; Gates & Cooper Llp; Howard Hughes Center; 6701 Center Drive West, Suite 1050; Los Angeles; CA; 90045; US Patent Application Number: 20020161212 Date filed: June 21, 2001 Abstract: Described is a novel gene and its encoded secreted tumor antigen, termed BPC-1, and to diagnostic and therapeutic methods and compositions useful in the management of various cancers which express BPC-1, particularly including prostate cancer and bladder cancer. In human normal tissues, BPC-1 is only expressed in certain tissues of the brain. However, BPC-1 is expressed at high levels in prostate cancer cells and is also expressed in bladder cancer cells. The structure of BPC-1 includes a signal sequence and a CUB domain. BPC-1 protein is secreted. Preliminary experimental evidence suggests that BPC-1 is directly involved in oncogenesis or maintenance of the

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transformed phenotype of cancer cells expressing BPC-1. BPC-1 also appears to bind specifically to a cellular protein expressed in prostate cancer cells and other cells. Excerpt(s): The invention described herein relates to a novel gene and its encoded secreted tumor antigen, termed BPC-1, and to diagnostic and therapeutic methods and compositions useful in the management of various cancers which express BPC-1, particularly including prostate cancer and bladder cancer. Cancer is the second leading cause of human death next to coronary disease. Worldwide, millions of people die from cancer every year. In the United States alone, cancer causes the death of well over a halfmillion people each year, with some 1.4 million new cases diagnosed per year. While deaths from heart disease have been declining significantly, those resulting from cancer generally are on the rise. In the early part of the next century, cancer is predicted to become the leading cause of death. Worldwide, several cancers stand out as the leading killers. In particular, carcinomas of the lung, prostate, breast, colon, pancreas, and ovary represent the primary causes of cancer death. These and virtually all other carcinomas share a common lethal feature. With very few exceptions, metastatic disease from a carcinoma is fatal. Moreover, even for those cancer patients who initially survive their primary cancers, common experience has shown that their lives are dramatically altered. Many cancer patients experience strong anxieties driven by the awareness of the potential for recurrence or treatment failure. Many cancer patients experience physical debilitations following treatment. Many cancer patients experience a recurrence. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Curcumin and curcuminoid inhibition of angiogenesis Inventor(s): Arbiser, Jack L.; (Atlanta, GA) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20010025034 Date filed: January 18, 2001 Abstract: Methods for treating diseases or disorders of the skin which are characterized by angiogenesis have been developed using curcumin and curcumin analogs. Based on the results obtained with curcumin, it has been determined that other angiogenesis inhibitors can also be used to treat these skin disorders. It has further been discovered that curcumin acts to inhibit angiogenesis in part by inhibition of basic fibroblast growth factor (bFGF), and thereby provides a means for treating other disorders characterized by elevated levels of bFGF, such as bladder cancer, using curcumin and other analogues which also inhibit bFGF. Representative skin disorders to be treated include the malignant diseases angiosarcoma, hemangioendothelioma, basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Karposi's sarcoma, and the nonmalignant diseases or conditions including psoriasis, lymphangiogenesis, hemangioma of childhood, Sturge-Weber syndrome, verruca vulgaris, neurofibromatosis, tuberous sclerosis, pyogenic granulomas, recessive dystrophic epidermolysis bullosa, venous ulcers, acne, rosacea, eczema, molluscum contagious, seborrheic keratosis, and actinic keratosis. Excerpt(s): The invention is generally in the field of methods of inhibiting angiogenesis, and more specifically is drawn to methods and compositions for inhibiting angiogenesis. Current treatments of cancer and related diseases have limited effectiveness and numerous serious unintended effects. Based primarily on chemical,

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radiation and surgical therapy, these treatments have progressed only incrementally during more than thirty years of intensive research to discover the origins and devise improved therapies of neoplastic diseases. Current research strategies emphasize the search for effective therapeutic modes with less risk, including the use of natural products and biological agents. This change in emphasis has been stimulated by the fact that many of the consequences, to patients and their offspring, of conventional cancer treatment, including new cancers, mutations and congenital defects, result from their actions on genetic material and mechanisms. Hong et al., J. Natl. Cancer Inst. Monogr. 17:49-53 (1995). Efforts continue to discover the origins of cancer at the genetic level, and correspondingly new treatments, but such interventions also may have serious unanticipated effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Human urothelial cell specific uroplakin transcriptional regulatory sequences, vectors comprising uroplakin-specific transcriptional regulatory sequences, and methods of use thereof Inventor(s): Henderson, Daniel R.; (Palo Alto, CA), Yu, De-Chao; (Foster City, CA), Zhang, Hong; (Cupertino, CA) Correspondence: Debra J. Glaister; Morrison & Foerster Llp; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20020120117 Date filed: March 21, 2001 Abstract: The invention provides new urothelial cell specific transcriptional regulatory sequences derived from human uroplakin II (hUPII), as well as polynucleotide constructs such as adenoviral vectors and methods of using hUPII-derived TREs. Additionally, the invention provides adenoviral vectors comprising a gene, preferably an adenovirus gene, under transcriptional control of a urothelial cell-specific transcriptional regulatory element (TRE). These vectors display urothelial cell-specific cytotoxicity, which is especially useful in the context of bladder cancer, in which destruction of these cells is desirable. The invention further provides compositions and host cells comprising the vectors, as well as method of using the adenoviral vectors. Excerpt(s): The invention provides new human DNA sequences which confer urothelialcell specific expression on heterologous genes. Additionally, the invention relates to cell transduction using adenoviral vectors, and more particularly to adenoviral vectors which replicate preferentially in urothelial cells. Approximately 51,200 new cases of bladder cancer are diagnosed each year in the United States. Of these, approximately 38,000 cases are in men and 13,200 in women. Of the 51,200 new cases, approximately 80 percent will be classified at diagnosis as superficial, i.e., the cell have not invaded the muscularis propria. Of these, approximately 10 to 15 percent will eventually progress to invasive disease. The estimated number of deaths from bladder cancer in the United States in 1994 was 7,000 in men and 3,600 in women. In the United States, transitional cell carcinoma (TCC) accounts for 90 to 95 percent of all tumors of the bladder. Squamous cell carcinoma (SCC) represents 5 to 10 percent, and adenocarcinoma approximately 1 to 2 percent. Squamous cell and adenomatous elements are often found in association with transitional cell tumors, especially with high grade tumors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Medical compositions for intravesical treatment of bladder cancer Inventor(s): Beijnen, Jos H.; (Amsterdam, NL), Nuijen, Bastiaan; (Amsterdam, NL), Pfadenhauer, Ernie; (Irvine, CA) Correspondence: Oppenheimer Wolff & Donnelly Llp; Suite 700; 840 Newport Center Drive; Newport Beach; CA; 92660; US Patent Application Number: 20030133954 Date filed: November 1, 2002 Abstract: Anti-cancer coating compositions comprising 3-hydroxymethyl-5-aziridinyl-1-1-methyl-2-[1H-indole-4,7-dione]propenol (E09) are disclosed. More specifically, the coating compositions comprise EO9 and a formulation vehicle. The formulation vehicle improves the solubility and stability of EO9. Additionally, the coating compositions can include coating agents that provide better adhesion of the coating composition to the bladder wall during intravesical delivery of the coating composition. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/344,446, filed Nov. 1, 2001, and whose entire contents are hereby incorporated by reference. Bladder cancer accounts for approximately 2% of all malignant cancers and is the fifth and tenth most common cancer in men and women, respectively. The American Cancer Society estimated that 54,500 new cases and 11,700 deaths would have occurred in 1997. Superficial bladder cancers (pTa, pT1 and CIS) account for 70-80% of cancers at first presentation. Management of superficial bladder cancer may be achieved by endoscopic surgical resection often followed by a course of adjuvant intravesical chemotherapy or immunotherapy with the aim of both eradicating remaining tumor cells and preventing tumor recurrence (Herr H W (1987) Intravesical therapy-a critical review. Urol Clin N Am 14:399-404). Both anti-neoplastics (Mitomycin C [MMC], epirubicin and thioTEPA) and immunotherapy (BCG) administered intravesically are effective at reducing tumor recurrence rates although it is unclear whether disease progression to muscle invasive tumors is prevented (Newling D (1990) Intravesical therapy in the management of superficial transitional cell carcinoma of the bladder: the experience of the EORTC GU group, Br J Cancer 61:497-499; Oosterlink et al. (1993) A prospective European Organization for Research and Treatment of Cancer Genitourinary Group randomized trial comparing transurethral resection followed by a single instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder. J Urol 149:749-752). This observation in conjunction with the fact that mortality from bladder cancer is still high underscores the need to develop more effective therapeutic agents (Oosterlink et al. 1993). One such therapeutic agent is MMC which belongs to a class of compounds known as bioreductive drugs (Workman 1994). MMC represents one of the antineoplastic agents used to treat superficial bladder cancers (Maffezzini et al, 1996, Tolley et al, 1996). MMC is activated to a cytotoxic species by cellular reductases although the role of specific reductase enzymes involved in bioreductive activation remains poorly defined and controversial (Cummings et al, 1998a). This is particularly true for the enzyme NQO1 (NAD(P)H:Quinone oxidoreductase, EC 1.6.99.2) which is a cytosolic flavoprotein which catalyses the two electron reduction of various quinone based compounds using either NADH or NADPH as electron donors (Schlager and Powis, 1988, Siegel et al, 1990). The structurally related compound E09 (5-aziridinyl-3-hydroxymethyl-1 methyl-2-[1Hindole-4,7-dione]prop-(3-en-a-ol), is however a much better substrate for NQO1 than MMC (Walton et al, 1991) and a good correlation exists between NQO1 activity and chemosensitivity in vitro under aerobic conditions (Robertson et al, 1994, Fitzsimmons et al, 1996, Smitkamp-Wilms et al, 1994). Under hypoxic conditions however, EO9's

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properties are markedly different with little or no potentiation of EO9 toxicity observed in NQO1 rich cells (Plumb and Workman, 1994). In NQO1 deficient cell lines however, large hypoxic cytotoxicity ratios have been reported (Workman, 1994). Therefore, EO9 has the potential to exploit the aerobic fraction of NQO1 rich tumors or the hypoxic fraction of NQO1 deficient tumors (Workman, 1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus for delivery of genes, enzymes and biological agents to tissue cells Inventor(s): Desai, Ashvin H.; (San Jose, CA) Correspondence: Pillsbury Winthrop Llp; 2550 Hanover Street; Palo Alto; CA; 94304; US Patent Application Number: 20030073908 Date filed: October 4, 2002 Abstract: A method and apparatus for delivery of genes, enzymes and biological agents to tissue cells, including a method and apparatus wherein treatment fluids, including genes, enzymes and biological agents, are injected into a target area of a body providing selective attachment to the specific target cells without affecting normal tissue cells. The method is used to treat prostate cancer, breast cancer, uterine cancer, bladder cancer, stomach, lung, colon, and brain cancer, etc. A hollow core needle is inserted into a body, the needle being visually guided by a selected imaging technique. A first embodiment utilizes an endoscopic instrument, wherein a probe is inserted into the body, guided by the endoscope to the vicinity of the target area. The hollow core needle is guided to the vicinity by a channel through the probe. A needle adjustment apparatus is used to extend or retract the needle and adjust needle tip orientation toward a target area. The endoscope provides a view to an operator for adjustment of the apparatus to extend the tip of the needle into and through tissue, interstitially, to a target area for deposit of the specific treatment fluid. A non-invasive imaging technique is used either alone, or in addition to the endoscope, to give an operator a view of the needle for guiding the needle tip to the precise target area. Typical non-invasive techniques include CT scan, MRI, ultrasound, etc. Excerpt(s): This application is a Continuation-in-Part of copending U.S. patent application Ser. No. 09/105,896 filed Jun. 26, 1998. The present invention relates generally to methods and apparatus for injecting treatment fluid into a body, and more particularly to a method for interstitially injecting treatment fluid including genes, enzymes, biological agents, etc., using a needle, guided to a target tissue of any body organ through use of minimally invasive endoscopic instruments or non-invasive imaging techniques. A variety of treatment fluids are currently known to be of benefit in treating illness in particular body parts. For example, there are a number of tumor suppressor genes, viral vectors, markers, vaccines, enzymes, proteins and biological agents that can be used for gene therapy and cancer treatment. The current method of delivery of these substances is to inject them into the blood stream through use of a conventional needle and syringe. The result is that the substance is carried by the blood to every part of the body. In many cases, it would be advantageous to be able to treat only a particular organ, or part of an organ. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for the in vitro diagnosis of a predisposition to bladder cancer or of the occurrence of bladder cancer and a kit for performing said diagnostic method Inventor(s): Gaub, Marie-Pierre; (Strasbourg, FR), Jacqmin, Didier; (Lingolsheim, FR), Lang, Herve; (Strasbourg, FR), Oudet, Pierre; (Strasbourg, FR), Schneider, Anne; (Strasbourg, FR) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20030113758 Date filed: August 14, 2002 Abstract: A new in vitro method for diagnosing the predisposition of a human individual to bladder cancer or for diagnosing the occurrence of a bladder cancer in a human individual, makes use of a comparison between the allelic ratios of a serial of microsatellite markers associated with this disease, respectively in the urine DNA and in the blood cell DNA of said human individual. Excerpt(s): The present invention relates to a new in vitro method for diagnosing the predisposition of a human individual to bladder cancer or for diagnosing the occurrence of a bladder cancer in a human individual, wherein said method makes use of a comparison between the allelic ratios of a serial of microsatellite markers associated with this disease, respectively in the urine DNA and in the blood cell DNA of said human individual. It is also directed to diagnostic kits which are useful for carrying out the method above. Throughout this Application, various publications are cited. The disclosures of these publications referenced in this Application are hereby incorporated by reference into the present disclosure to more fully describe the state of the art to which this invention pertains. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and compositions for delivery of pharmaceutical agents Inventor(s): Esuvaranathan, Kesavan; (Singapore, SG), Lawrencia, Carmel; (Singapore, SG), Mahendran, Ratha; (Singapore, SG) Correspondence: Gladys H. Monroy; Morrison & Foerster Llp; 755 Page Mill Road; Palo Alto; CA; 94304; US Patent Application Number: 20020146830 Date filed: March 1, 2002 Abstract: Methods and compositions for delivering pharmaceutical agents into cells, in particular urothelial cells of the bladder, are provided. In the methods and compositions of the invention, a solubilized cholesterol composition is used to facilitate delivery of pharmaceutical agents. Preferably, the cholesterol is solubilized by a cyclodextrin (e.g., methyl-.beta.-cyclodextrin) and the pharmaceutical agent comprises a polynucleotide and either a cationic lipid, a cationic polymer or a dendrimer. Improved methods for transfecting polynucleotides into cells thus are also provided, using cationic lipids, cationic polymers or dendrimers and solubilized cholesterol, wherein the transfection efficiency is enhanced compared to use of cationic lipids, cationic polymers or dendrimers alone. Preferred methods of the invention involve transfecting polynucleotides into urothelial cells, preferably for therapeutic treatment of bladder

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cancer using, for example, a polynucleotide(s) encoding an interleukin(s), an interferon(s), a colony stimulating factor(s) and/or a tumor suppressor(s). Excerpt(s): This application claims priority to Australian Provisional Application No. PQ2593/99, the entire contents of which are hereby incorporated by reference. The present invention generally relates to the delivery of pharmaceutical agents into cells, particularly the delivery of polynucleotides into cells by non-viral methods, either in vitro or in vivo. The present invention further relates to delivery of pharmaceutical agents for the treatment of cancer, in particular the treatment of bladder cancer. Despite many recent advances in gene therapy methods, effective therapeutic delivery of genes into various cell types, in particular in vivo delivery, has not been achieved simply because methods are not available to cause delivery of therapeutically effective amounts of such genes into the particular cells of a patient in need of treatment. Efficient delivery of therapeutically sufficient amounts of genes, as well as other therapeutic molecules, often has proved difficult, if not impossible, since, for example, the cell membrane presents a selectively-permeable barrier. Additionally, even when genes, or other biologically active molecules, successfully enter targeted cells, they may be degraded, inappropriately transported or, in the case of genes, may fail to be transcribed properly. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for detecting and classifying bladder cancer via human uroplakin genes Inventor(s): Sun, Tung-Tien; (Scarsdale, NY), Wu, Xue-Ru; (New York, NY) Correspondence: Browdy And Neimark, P.L.L.C.; Patent And Trademark Causes; Suite 300; 624 Ninth Street, N.W.; Washington; DC; 20001-5303; US Patent Application Number: 20020009745 Date filed: June 1, 2001 Abstract: The human gene for uroplakin II is identified and sequenced. Using this gene, oligonucleotide primers were constructed which were then used to identify bladder cancer cells in blood and tissue. Excerpt(s): Histological differentiation markers are useful in the diagnosis of carcinoma metastases where the location of the primary tumor is uncertain or unknown. Unfortunately, markers specific for a single epithelium or organ are currently available for a only few types of carcinoma, e.g., prostate-specific antigen for prostate carcinomas and thyroglobulin for thyroid carcinomas. Less specific markers of transitional cell carcinomas have been identified and associated with malignant transformation, tumor progression and the prognosis. Many of these markers are epithelial membrane antigen (EMA) or oncogene/tumor suppressor gene products. For example, Summerhayes et al. (1985. JNCI 75:1025-1038) have described a series of monoclonal antibodies (group III), directed against the urothelium which produce luminal-membrane staining of normal superficial (umbrella) cells of the urothelium. Other markers are expressed in superficial bladder tumors but disappear in invasive and metastatic transitional cell carcinomas. All of these markers are antibodies most of which stain non-urinary epithelia and carcinomas too. Certain antigens such as involucrin, E48 antigen and SCC antigen are markers shared by both transitional and stratified squamous epithelia (of skin, esophagus, cervix, etc.) and their carcinomas. However, no differentiation or lineage marker specific for transitional cell carcinomas and their metastases has been identified to date. Normal urothelium contains tissue-specific differentiation products that have been well characterized morphologically and biochemically. It has been found that large

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numbers of urothelial plaques are present in the superficial plasma membrane of urothelial superficial or umbrella cells. These plaques are characterized by a highly unusual membrane structure, i.e., the asymmetric unit membrane (AUM), whose luminal leaflet is twice as thick as its cytoplasmic leaflet. The thickening of the luminal leaflet is due to the presence of particles exhibiting a semi-crystalline organization. The molecular constituents principally comprise four transmembrane proteins: uroplakin (UP) Ia (27 kDa); UP Ib (28 kDa); UP II (15 kDa) and UP III (47 kDa). These UPs, particularly UP Ia, Ib, and II, are characterized by their markedly asymmetric mass distribution, with the extracellular domain being considerably larger than the intracellular one. This accounts for the clearly visible ultrastructural thickening of the luminal leaflet of the unit membrane. UP III is believed to play a role in the formation of the urothelial glycocalyx and may interact, via its cytoplasmic portion, with the cytoskeleton. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treating bladder disorders Inventor(s): Hedley, Mary Lynne; (Lexington, MA) Correspondence: Janis K. Fraser, PH.D.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020193332 Date filed: February 12, 2002 Abstract: Methods of treating bladder disorders, including bladder cancer and inflammatory bladder diseases such as interstitial cystitis are disclosed. The methods include identifying a mammal that has or is at risk for having a bladder disorder and administering isolated nucleic acid sequences to the mammal. Nucleic acids used in the methods of the invention contain unmethylated CpG sequences, which are thought to modulate the immune response. Also included are methods that use nucleic acids encoding alpha-MSH. The nucleic acid sequences may be administered individually or together or can be included in the same nucleic acid. Excerpt(s): This application claims priority from U.S. Provisional Application No. 60/268,175, filed Feb. 12, 2001, the entire content of which is incorporated herein by reference. The invention relates to methods of treating bladder disorders. Specifically, the methods can be used to treat disorders such as bladder cancer and inflammatory bladder diseases such as interstitial cystitis. Bladder disorders, including bladder cancer and bladder inflammatory disorders, are on the rise. Bladder cancer is the most common urologic malignancy and was predicted to affect approximately 54,000 people in 1998 (de Vere White & Stapp (1998) Oncology (Huntingt) 12:1717-26). Current treatments include local resection, use of intravesical agents and radical cystectomy (Whittlestone & Persad (2000) Hosp Med 5:336-40). Bladder cancer is the fourth most commonly diagnosed malignancy in men and the eighth most common in women and represents a wide spectrum of disease, ranging from superficial, well-differentiated disease to highly malignant tumors (Metts et al. (2000) J. Matl. Med. Assoc. 92: 285-94). Primary radical surgery remains the standard of care for invasive bladder cancer (Kim & Steinberg (2000) J. Urol. 164(3 Pt 1): 627-32). Transurethral resection (TUR) of the superficial transitional cell carcinoma (TCC) of the bladder is known to be insufficient in controlling the disease because of the unacceptable rates of recurrence, progression and ultimate cystectomy. Adjuvant intravesical chemo-and/or immunotherapy is

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administered in an effort to enhance the efficacy of surgery alone (Melekos & Moutzouris (2000) Curr Pharm Des 3:345-59). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods to determine prognosis after therapy for bladder cancer Inventor(s): Lerner, Seth P.; (Houston, TX), Shariat, Shahrokh; (Dallas, TX), Slawin, Kevin M.; (Houston, TX) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030032074 Date filed: May 24, 2002 Abstract: A method to diagnose, stage and predict prognosis of bladder cancer patients is provided, e.g., using TGF-.beta.1, IL-6, IL-6sR, uPA, uPAR and IGFBP-3. These markers, and potentially others, in combination with standard clinical and pathologic features, may be used to create a nomogram that would be useful for managing bladder cancer patients. Excerpt(s): This application claims the benefit of the filing date of U.S. application Serial No. 60/295,512, filed Jun. 1, 2001 under 35 U.S.C.sctn.119(e). Carcinoma of the urinary bladder is a significant cause of morbidity and mortality in the United States, accounting for an estimated 54,300 new cases and 12,400 resultant deaths in 2001 (Greenlee et al., 2001). At initial presentation, approximately 70% to 80% of the bladder cancers are confined to the epithelium or subepithelial connective tissue, whereas the remainder of patients present with muscle invasive cancer. Most of these patients respond well to local resection and adjuvant intravesical therapy. Unfortunately, 50% to 80% of these patients will experience recurrence within the first two years. Up to one-half of patients with invasive disease have either measurable metastatic disease or have disease destined to recur due to occult metastases. While patients with low-grade papillary disease (Ta, T1) rarely progress to muscle invasive transitional cell carcinoma (TCC), as many as 30% of patients with Tis or high-grade papillary disease are refractory to treatment with intravesical immunotherapy and/or chemotherapy and progress to more advance disease (Thrasher and Crawford, 1993). Radical cystectomy provides effective local control of refractory Ta, T1 and Tis bladder cancer and muscle invasive TCC (Stein et al., 2001). However, despite this, approximately 14%-33% of patients with nodenegative muscle invasive disease will die of their disease within five years of surgery, presumably due to dissemination of microscopic metastatic disease prior to cystectomy (Lerner and Skinner, 1999). Patients who have pathologically confirmed metastases to regional lymph nodes have an even higher risk of progression and death than those who do not (Lerner et al., 1993). Ultimately at least 50% of the patients undergoing cystectomy for muscle invasive disease will eventually develop clinical metastases and most of these patients will die of their disease (Raghavan et al., 1990; von der Maase et al., 2000). Conventional staging modalities such as transurethral bladder tumor resection (Lerner et al., 1993; Frazier et al, 1993; Pagano et al., 1991), computed tomography (Buszello et al., 1994; Nurmi et al. 1988, Voges et al., 1989), and magnetic resonance imaging (Persad et al., 1993) have a limited role in tumor staging and predicting lymph node involvement in patients with bladder cancer because of their poor performance in detecting early, small-volume metastases. Early detection of patients harboring occult micrometasteses, who have a high probability of developing disease progression and

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shortened survival, could potentially be spared either the morbidity of an unsuccessful local treatment or selected for a combined modality program. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nucleic Acids, Proteins, and antibodies Inventor(s): Barash, Steven C.; (Rockville, MD), Rosen, Craig A.; (Laytonsvile, MD), Ruben, Steven M.; (Olney, MD) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20030199008 Date filed: February 22, 2002 Abstract: The present invention relates to novel bladder related polynucleotides and the polypeptides encoded by these polynucleotides herein collectively known as "bladder antigens," and the use of such bladder antigens for detecting disorders of the bladder system, particularly the presence of bladder cancer and bladder cancer metastases. More specifically, isolated bladder associated nucleic acid molecules are provided encoding novel bladder associated polypeptides. Novel bladder polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human bladder associated polynucleotides and/or polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to the bladder, including bladder cancer, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and/or compositions for inhibiting the production and function of the polypeptides of the present invention. Excerpt(s): The Sequence Listing may be viewed on an IBM-PC machine running the MS-Windows operating system. The present invention relates to novel bladder related polynucleotides, the polypeptides encoded by these polynucleotides herein collectively referred to as "bladder antigens," and antibodies that immunospecifically bind these polypeptides, and the use of such bladder polynucleotides, antigens, and antibodies for detecting, treating, preventing and/or prognosing disorders of the bladder system, including, but not limited to, the presence of bladder cancer and bladder cancer metastases. More specifically, isolated bladder nucleic acid molecules are provided encoding novel bladder polypeptides. Novel bladder polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human bladder polynucleotides, polypeptides, and/or antibodies. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to the bladder, including bladder cancer, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The invention further relates to methods and/or compositions for inhibiting or promoting the production and/or function of the polypeptides of the invention. The urinary system is a subgroup of organs, consisting of the kidneys, ureters, bladder, and uretha, specialized in removing waste materials and water from the blood. This waste is generated from the normal breakdown of food and other energy sources and is translated into urine as it passes through the kidneys. Once waste, in the form of urine,

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is released from the kidneys, it travels down two thin tubes called ureters to the bladder. The bladder is a hollow, balloon-shaped organ responsible for storing urine until the nerves in the bladder cause the need for urination. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Polymer controlled delivery of a therapeutic agent Inventor(s): Haller, Michael F.; (Baltimore, MD), Leong, Kam; (Ellicott City, MD), Levisage, Catherine S.; (Baltimore, MD), Malavaud, Bernard A.; (Toulouse, FR) Correspondence: Dike, Bronstein, Roberts & Cushman; Intellectual Property Practice Group; Edwards & Angell, Llp; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20030008015 Date filed: October 11, 2001 Abstract: Featured are highly useful pharmaceutical compositions that include a microparticle having a polymeric support material preferably adapted to disperse therapeutic agent. In a particular invention embodiment, the support material comprises at least 50% w/w of a homopolymer as described herein. Also featured are methods of making the compositions as well as using same to treat diseases such as bladder cancer. Excerpt(s): This application claims the benefit of U.S. Provisional Applications Serial Nos. 60/239,498 and 60/239,385 both filed Oct. 11, 2000, the teachings of which are incorporated herein by reference. The present invention generally relates to polymers, delivery vehicles, and methods of use thereof. In one aspect, the invention features polymeric microparticle delivery vehicles for controlled administration of a therapeutic or prophylactic compound. The invention has a wide spectrum of important applications including providing for localized administration of a pharmaceutical composition such as an anti-cancer agent. There is recognition that many therapeutic agents can be administered with a delivery vehicle or vector to facilitate uptake. In many cases, poor solubility of the therapeutic agent in an aqueous medium such as water, blood, or saline, and the like can limit drug delivery and efficacy. For example, compounds with low water solubility are frequently formulated with a solubilizing agent. Many prior delivery vehicles have undesirable side effects including exhibiting high toxicity or acting as a sensitizing agent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Prediction of cancer by detection of ATM mutations Inventor(s): Gilad, Shlomit; (Gedera, IL), Yahalom, Joachim; (New York, NY) Correspondence: John P. White; Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030162195 Date filed: September 20, 2002 Abstract: There is provided a method of testing a subject to determine if the subject has a predisposition for developing a cancer, a cancer of epithelial origin such as lung cancer, colon cancer, prostate cancer, ovarian cancer, bladder cancer, and cancer of the pancreas, and also a lymphoproliferative malignancy such as Hodgkin's disease and non-Hodgkin's lymphoma. This method includes the steps of detecting a mutation in

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the open reading frame of the ATM gene (SEQ.ID.NO:1) in a cDNA sample or a genomic DNA sample from the subject, which mutation is selected from the group consisting of the mutations set forth in Table 3 and Table 4; or, detecting a mutation in the mRNA corresponding to the open reading frame of the ATM gene (SEQ.ID.NO:1) in a mRNA sample from the subject, which mutation is selected from the group consisting of RNA complementary to the mutations set forth in Table 3 and Table 4, wherein the presence of such a mutation indicates that the subject has a predisposition for developing cancer. Also provided is an isolated cDNA molecule having a nucleotide sequence which differs from the sequence set forth in SEQ.ID.NO:1 by a mutation selected from the group consisting of mutations 378 T.fwdarw.A, 3383 A.fwdarw.G, 1636 C.fwdarw.G, 2614 C.fwdarw.T, 6437 G.fwdarw.C, 2932 T.fwdarw.C, 2289 T.fwdarw.A, 6096 A.fwdarw.T, 6176 C.fwdarw.T, 6919 C.fwdarw.T, 2442 C.fwdarw.A, 3925 G.fwdarw.A, 6067 G.fwdarw.A, 2119 T.fwdarw.C, 1810 C.fwdarw.T, and 4388 T.fwdarw.G. An oligonucleotide probe which is capable of detecting a mutation in the open reading frame of the ATM gene is also provided. Additionally, kits for detection and prediction of cancer are provided. Excerpt(s): This invention is a continuation-in-part and claims the benefit of U.S. Provisional Application No. 60/323,766, filed Sep. 20, 2001, the contents of which are hereby incorporated by reference into this application. The present invention generally relates to the relationship of ATM germine point mutations to cancer, in particular cancers of epithelial origin such as lung cancer, colon cancer, prostate cancer, ovarian cancer, bladder cancer, and cancer of the pancreas. The present invention also relates to the relationship of an ATM germline point mutation to a lymphoproliferative malignancy such as Hodgkin's disease and non-Hodgkin's lymphoma. More specifically, the present invention relates to the use of this relationship in prediction and detection of cancers prior to large tumor growth. Ataxia Telangiectasia (A-T) is a pleiotrophic inherited disease characterized by neurodegeneration, cancer, immunodeficiencies, radiation sensitivity, and genetic instability. The gene, a mutation in which is responsible for A-T, is called ATM, and it was discovered by Shiloh et al. in 1995 (Savitsky, K et al., 1995). The ATM gene extends over 150 kb of genomic DNA (Uziel, T et al., 1996) and is transcribed into a large transcript of about 13 kb, representing 66 exons (Uziel, T et al., 1996; Savitsky, K et al., 1995; Savitsky, K et al., 1997). The open reading frame of this transcript predicts a 370 kDa protein composed of 3,056 amino acids. The ATM product is homologous to several cell cycle checkpoint proteins from other organisms and is thought to play a crucial role in a signal transduction network that modulates cell cycle checkpoints, genetic recombination, apoptosis and other cellular responses to DNA damage (Meyn, MS, 1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapeutic compositions and methods useful in modulating protein tyrosine phosphatases Inventor(s): Yi, Taolin; (Solon, OH) Correspondence: Benesch, Friedlander, Coplan & Aronoff Llp; Attn: IP Department Docket Clerk; 2300 BP Tower; 200 Public Square; Cleveland; OH; 44114; US Patent Application Number: 20030072738 Date filed: September 9, 2002 Abstract: In one embodiment, a therapeutic composition containing a pentavalent antimonial is provided. The pentavalent antimonial can be sodium stibogluconate,

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levamisole, ketoconazole, and pentamidine and biological equivalents of said compounds. Additionally, pentavalent antimonials that can be used in accordance with the present invention may be any such compounds which are anti-leishmaniasis agents. The therapeutic composition of this embodiment contains an effective amount of pentavalent antimonial that can be used in treating infectious diseases. The types of diseases that can be treated with the present invention include, but are not limited to, the following: diseases associated with PTPase activity, immune deficiency, cancer, infections (such as viral infections), hepatitis B, and hepatitis C. The types of cancers that the present embodiment can be used to treat include those such as lymphoma, multiple myeloma, leukemia, melanoma, prostate cancer, breast cancer, renal cancer, bladder cancer. The therapeutic composition enhances cytokine activity. The therapeutic composition may include a cytokine, such as interferon.alpha., interferon.beta., interferon.gamma., or granulocyte/macrophage colony stimulating factor. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/317,993 filed Sep. 7, 2001. Intercellular protein tyrosine phosphorylation is regulated by extracellular stimuli, such as cytokines, to control cell growth, differentiation and functional activities. This signaling mechanism depends on the interplay of protein tyrosine kinases, which initiate signaling cascades through phosphorylating tyrosine residues in protein substrates, and by protein tyrosine phosphatases that terminate signaling via substrate dephosphorylation. Chemical compounds that modulate the activity of protein tyrosine kinases or phosphatases can induce cellular changes through affecting the balance of intracellular protein tyrosine phosphorylation and redirecting signaling. Such compounds can be of value as experimental tools and, importantly, as potent therapeutic reagents. So far, few specific inhibitors of protein tyrosine phosphatases have been reported despite extensive efforts in the last decade to identify them. Although a number of chemicals that broadly inhibit protein tyrosine phosphatases are known, including sodium orthovanadate and iodoacetic acid, their usefulness as therapeutic agents is severely limited due to their general toxicity in vivo. Recently, it has been reported that Suramin, a polysulfonated naphthylurea compound, can act in vitro as a competitive and reversible inhibitor of several protein tyrosine phosphatases. Such an inhibitory activity of Suramin against protein tyrosine phosphatases is consistent with its activity in augmenting tyrosine phosphorylation of cellular proteins and may explain its antitumor activity and its therapeutic effect in treating trypanosomiasis and onchocerciasis. 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 bladder 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 “bladder 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 bladder cancer. You can also use this procedure to view pending patent applications concerning bladder 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 BLADDER CANCER Overview This chapter provides bibliographic book references relating to bladder cancer. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bladder 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: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “bladder cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on bladder cancer: •

Overcoming Bladder Disorders: Compassionate, Authoritative Medical and Self-Help Solutions for Incontinence, Cystitis, Interstitial Cystitis, Prostate Problems, and Bladder Cancer Source: New York, NY: HarperPerennial. 1991. 338 p. Contact: Available from HarperCollins Publishers. Box 588, Dunmore, PA 18512. (800) 242-7737 or (800) 331-3861. Fax (800) 822-4090. PRICE: $12.50 plus $2.75 shipping and handling (as of 1996). ISBN: 0060920831. Summary: This guidebook provides current information on the diagnosis, treatment, and prevention of bladder disorders. Ten chapters cover taking control of bladder problems; the anatomy and physiology of the healthy bladder; incontinence; cystitis and urethritis; painful bladder syndrome, including interstitial cystitis and urethral syndrome; prostate problems; bladder cancer; strategies for enhancing sexuality; and

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coping strategies for everyday survival. The book also includes an index of diagnostic tests; a drug glossary; a glossary of urological terms; a reference list; and a subject index. Each chapter includes a brief list of resources for readers who wish to explore a particular topic in more depth. 18 figures. 115 references.

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 “bladder cancer” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “bladder cancer” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “bladder cancer” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

21st Century Complete Medical Guide to Bladder Cancer - Authoritative Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment Options by PM Medical Health News; ISBN: 1592480004; http://www.amazon.com/exec/obidos/ASIN/1592480004/icongroupinterna

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A Comprehensive guide to the therapeutic use of methotrexate in bladder cancer; ISBN: 0919839010; http://www.amazon.com/exec/obidos/ASIN/0919839010/icongroupinterna

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Advances in the Treatment of Superficial Bladder Cancer: Optimizing Bcg Immunotherapy: Proceedings of a Symposium Held at the 23rd World Congress O by D.L. Lamm (Editor), International Society Of Urology (1995); ISBN: 3805561377; http://www.amazon.com/exec/obidos/ASIN/3805561377/icongroupinterna

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Bcg - A New Standard for Superficial Bladder Cancer: Journal: European Urology, Suppl. 2, 1992 by D. L. Lamm (Editor) (1992); ISBN: 3805556209; http://www.amazon.com/exec/obidos/ASIN/3805556209/icongroupinterna

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BCG in superficial bladder cancer : proceedings of an EORTC Genitourinary Group sponsored meeting held at Erenstein Castle Kerkrade, the Netherlands, on September 7-8, 1988, organized by the Department of Urology, University of Nijmegen, the Netherlands; ISBN: 0845151606; http://www.amazon.com/exec/obidos/ASIN/0845151606/icongroupinterna

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Bcg: The Optimal Approach in Superficial Bladder Cancer (European Urology) by A. Bohle (Editor) (1999); ISBN: 3805570198; http://www.amazon.com/exec/obidos/ASIN/3805570198/icongroupinterna

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Biology and Clinical Management of Bladder Cancer by E.H. Cooper, R.E. Williams (Editor); ISBN: 0801610982; http://www.amazon.com/exec/obidos/ASIN/0801610982/icongroupinterna

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Bladder Cancer by Ernst J. Zingg; ISBN: 0387132392; http://www.amazon.com/exec/obidos/ASIN/0387132392/icongroupinterna

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Bladder Cancer by Javadpour Nasser (Editor); ISBN: 0683043560; http://www.amazon.com/exec/obidos/ASIN/0683043560/icongroupinterna

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Bladder Cancer (Butterworth International Medical Reviews. Urology, Vol 1) by Philip H. Smith (Editor), et al (1984); ISBN: 0407023585; http://www.amazon.com/exec/obidos/ASIN/0407023585/icongroupinterna

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Bladder Cancer (Cancer Surveys, Vol 31) by R. T. D. Oliver (Editor), M. J. Coptcoat (Editor) (1998); ISBN: 0879695293; http://www.amazon.com/exec/obidos/ASIN/0879695293/icongroupinterna

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Bladder cancer : a series of workshops on the biology of human cancer, report no. 13; ISBN: 9290180609; http://www.amazon.com/exec/obidos/ASIN/9290180609/icongroupinterna

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Bladder Cancer, Part B: Radiation, Local and Systemic Chemotherapy, and New Treatment Modalities (Progress in Clinical and Biological Research, Vol 1 by Rene Kuss, et al; ISBN: 0471833908; http://www.amazon.com/exec/obidos/ASIN/0471833908/icongroupinterna

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Bladder Cancer: Ava Monograph (Aua Monographs, V. 1) by American Urological Association Seminar on Bladder Cancer, William W. Bonney (1982); ISBN: 0683009192; http://www.amazon.com/exec/obidos/ASIN/0683009192/icongroupinterna

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Bladder Cancer: Biology, Diagnosis, and Management by Konstantinos N. Syrigos (Editor), Donald G. Skinner (Editor) (1999); ISBN: 0192630385; http://www.amazon.com/exec/obidos/ASIN/0192630385/icongroupinterna

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Bladder Cancer: Biology, Diagnosis, Management by Konstantinos Syrigos; ISBN: 0471981621; http://www.amazon.com/exec/obidos/ASIN/0471981621/icongroupinterna

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Bladder Cancer: Cancer of the Bilharzial Bladder by Ismail Elsebai (Editor) (1983); ISBN: 0849357349; http://www.amazon.com/exec/obidos/ASIN/0849357349/icongroupinterna

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Bladder Cancer: Current Diagnosis and Treatment by Michael J., Md. Droller (Editor); ISBN: 0896038181; http://www.amazon.com/exec/obidos/ASIN/0896038181/icongroupinterna

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Bladder Cancer: General Review by Ismail T. Elsebai (Editor) (1983); ISBN: 0849357330; http://www.amazon.com/exec/obidos/ASIN/0849357330/icongroupinterna

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Clinical Bladder Cancer by L. Denis; ISBN: 030640835X; http://www.amazon.com/exec/obidos/ASIN/030640835X/icongroupinterna

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Clinical Management of Bladder Cancer by Roger D. Soloway (1991); ISBN: 0815180667; http://www.amazon.com/exec/obidos/ASIN/0815180667/icongroupinterna

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Clinical Management of Bladder Cancer by Reginald Hall (Editor), Reginald R. Hall; ISBN: 0340740922; http://www.amazon.com/exec/obidos/ASIN/0340740922/icongroupinterna

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Developments in Bladder Cancer by L. Denis (1986); ISBN: 0845150715; http://www.amazon.com/exec/obidos/ASIN/0845150715/icongroupinterna

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Developments in Bladder Cancer: Proceedings of the First International Consensus Development Conference on Guidelines for Clinical Research in Bladd by Louis

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Denis, et al; ISBN: 0471625086; http://www.amazon.com/exec/obidos/ASIN/0471625086/icongroupinterna •

Eortc Genitourinary Group Monograph, No. 6: Bcg in Superficial Bladder Cancer by Frans M. Debruyne (Editor), et al; ISBN: 0471516015; http://www.amazon.com/exec/obidos/ASIN/0471516015/icongroupinterna

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Evaluation of chemotherapy in bladder cancer; ISBN: 0443046441; http://www.amazon.com/exec/obidos/ASIN/0443046441/icongroupinterna

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Hypericin As a Phototherapeutic Tool in Bladder Cancer: An in Vitro & in Vivo Evaluation (Acta Biomedica Lovaniensia, 267) by Rugemalira Kamuhabwa (2002); ISBN: 9058672522; http://www.amazon.com/exec/obidos/ASIN/9058672522/icongroupinterna

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Invasive Bladder Cancer by Isis Press, et al; ISBN: 1901865126; http://www.amazon.com/exec/obidos/ASIN/1901865126/icongroupinterna

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Neoadjuvant Chemotherapy in Invasive Bladder Cancer (Progress in Clinical and Biological Research V353) by Ted A W Splinter (Editor), et al; ISBN: 0471568171; http://www.amazon.com/exec/obidos/ASIN/0471568171/icongroupinterna

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Superficial Bladder Cancer by Francesco Pagano; ISBN: 1899066535; http://www.amazon.com/exec/obidos/ASIN/1899066535/icongroupinterna

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The Biology and clinical management of bladder cancer; ISBN: 063209480X; http://www.amazon.com/exec/obidos/ASIN/063209480X/icongroupinterna

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The Guide to Living With Bladder Cancer by Mark P. Schoenberg, Johns Hopkins Genitourinary Oncology Gro (Contributor); ISBN: 0801864062; http://www.amazon.com/exec/obidos/ASIN/0801864062/icongroupinterna

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The Management of Bladder Cancer by Derek Raghavan (Editor); ISBN: 0713145285; http://www.amazon.com/exec/obidos/ASIN/0713145285/icongroupinterna

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The Official Patient's Sourcebook on Bladder Cancer: A Revised and Updated Directory for the Internet Age by Icon Health Publications, Inc. Staff Icon Group International (Compiler) (2002); ISBN: 0597833435; http://www.amazon.com/exec/obidos/ASIN/0597833435/icongroupinterna

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The Pathology of Bladder Cancer by George T. and Cohen, Samuel M. Bryan (Editor) (1983); ISBN: 0849362261; http://www.amazon.com/exec/obidos/ASIN/0849362261/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 “bladder 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 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

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Bladder cancer: principles of combination therapy Author: Hendry, W. F.; Year: 1981; London; Boston: Butterworth, 1981; ISBN: 0407001875 http://www.amazon.com/exec/obidos/ASIN/0407001875/icongroupinterna

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Bladder cancer, a symposium. Program chairman: William B. Deichmann. Editor: Kenneth F. Lampe. Spanish language editors: Rafael A. Penalver [and] Aida Soto. Symposium summary: Jack L. Radomski. Author: Lampe, Kenneth F.; Year: 1967; Birmingham, Aesculapius Pub. Co. [c1967]

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Detection of bladder cancer: associated with schistosomiasis Author: El-Bolkainy, Mohamed N.; Year: 1981; Cairo, Egypt: National; ISBN: 0977721644

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Management of bladder cancer Author: Whitmore, Willet F.,; Year: 1979; Chicago: Year Book Medical Publishers, 1979; ISBN: 081519918X http://www.amazon.com/exec/obidos/ASIN/081519918X/icongroupinterna

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New trends in diagnosis and treatment of bladder cancer: proceedings on the 4th International Symposium on Advances in Urologic Oncology, San Remo (Italy, March 18-20, 1993 Author: Giuliani, Luciano.; Year: 1994; München: Sympomed, 1994; ISBN: 3927759074

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Overcoming bladder disorders: compassionate, authoritative medical and self-help solutions for incontinence, cystitis, interstitial cystitis, prostate problems, and bladder cancer Author: Chalker, Rebecca.; Year: 1990; New York: Harper; Row, c1990; ISBN: 0060162775 http://www.amazon.com/exec/obidos/ASIN/0060162775/icongroupinterna

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Request for assisstance in preventing bladder cancer from exposure to o-toluidine and aniline: NIOSH alert.; Year: 1990; Cincinnati, Ohio: U.S. Dept. of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health; Washington, D.C.: For sale by Super. of Docs, G.P.O., [1990]

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Selected abstracts on treatment of bladder cancer Author: Johnson, Douglas E.,; Year: 1985; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National

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The biochemistry of bladder cancer. Author: Boyland, Eric,; Year: 1963; Springfield, Ill., Thomas [c1963]

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The guide to living with bladder cancer Author: Schoenberg, Mark P.; Year: 1984; Baltimore: Johns Hopkins University Press, c2000; ISBN: 0801865190 http://www.amazon.com/exec/obidos/ASIN/0801865190/icongroupinterna

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The Pathology of bladder cancer Author: Bryan, George T. (George Terrell),; Year: 1983; Boca Raton, Fla.: CRC Press, c1983; ISBN: 0849362253 http://www.amazon.com/exec/obidos/ASIN/0849362253/icongroupinterna

Chapters on Bladder Cancer In order to find chapters that specifically relate to bladder cancer, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and bladder cancer using the “Detailed Search” option. Go to the following 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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hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “bladder cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on bladder cancer: •

Hyperthermia in Urology Source: in Gautherie, M., ed. Interstitial, Endocavitary, and Perfusional Hyperthermia: Methods and Clinical Trials. New York: Springer-Verlag. 1990. p. 43-58. Contact: Available from Springer-Verlag. 44 Hartz Way, Secaucus, NJ 07094. (800) 7774643 or (201) 348-4033. PRICE: $101. ISBN: 0387509836. Summary: At present, hyperthermia in urology is mainly used in the treatment of bladder and prostatic cancer. Additionally, local hyperthermia is used in the treatment of benign prostatic hyperplasia (BPH) and chronic abacterial prostatitis. This chapter, from a book about the methods and clinical trials of interstitial, endocavitary, and perfusional hyperthermia, discusses hyperthermia in urology. Hyperthermia of the urinary bladder is discussed in five sections: the development of the use of hyperthermia of the bladder; animal experiments in hyperthermia of the bladder; hyperthermia as monotherapy in bladder cancer; hyperthermia as part of an integrated combined treatment in bladder cancer; and the results of combined hyperthermia and locoregional chemoembolization. Hyperthermia of the prostate is discussed in three sections: cancer of the prostate; benign hyperplasia of the prostate; and chronic prostatitis and prostatodynia. The author concludes that hyperthermia as monotherapy has no sufficient tumor-damaging effect; however, the inclusion of hyperthermia in an integrated tumor treatment regimen shows promise. 4 tables. 16 figures. 42 references.

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Geriatric Urology Source: in Landau, L.; Kogan, B.A. 20 Common Problems in Urology. New York, NY: McGraw-Hill, Inc. 2001. p. 133-144. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $45.00;plus shipping and handling. ISBN: 0070634130. Summary: Geriatric urology is a specialized area of adult urology that concentrates on the evaluation and management of urologic (urinary tract) problems in older patients. In particular, it is focused on the care of frail, elderly individuals with multiple comorbidities (other diseases and problems that may have an impact on each other). This chapter on geriatric urology is from a text on common problems in urology (written for the primary care provider). Although elderly individuals are seen for a wide spectrum of urologic complaints, the two most common disorders seen in this age group are urinary incontinence (UI, the involuntary loss of urine) and urinary tract infections (UTIs). Other common disorders in this age group include urologic malignancies (particularly prostate and bladder cancer), stone disease, benign prostatic hyperplasia (BPH, overgrowth of the prostate), and erectile dysfunction (formerly called impotence). This chapter focuses on the evaluation and treatment of elderly patients who present with UI and UTIs, as these conditions are commonly seen in geriatric patients, and their management may differ from that of younger patients with similar clinical problems. Specific types of UI covered include transient, stress, urge, mixed, overflow, and functional incontinence. 2 tables. 23 references.

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Interstitial Cystitis: Painful Bladder Syndromes Source: in Blaivas, J.G. Conquering Bladder and Prostate Problems: The Authoritative Guide for Men and Women. New York, NY: Plenum Publishing Corporation. 1998. p. 129-146. Contact: Available from Kluwer Academic-Plenum Publishing Corporation. 233 Spring Street, New York, NY 10013-1578. (800) 221-9369 or (212) 620-8035. Fax (212) 647-1898. Website: www.plenum.com. PRICE: $26.95. ISBN: 0306458640. Summary: Interstitial cystitis is a painful urinary disease that is characterized by marked frequency of urination and pain in the lower abdomen or vaginal area. This chapter on interstitial cystitis (IC) is from a book for people who have urinary bladder and prostate problems: people who urinate too often, who plan their daily activities around the availability of a bathroom, men with prostate problems, women with incontinence, and people with bladder pain. The book is written in a clear, nontechnical, humorous style that makes the material more accessible to the lay reader. IC is an uncommon condition that afflicts about 250,000 to 500,000 Americans, over 90 percent of whom are women. The cause is unknown. The most important aspect of the evaluation for IC is to have a proper checkup to be sure that the symptoms are not caused by a simple problem like a urinary tract infection, and to exclude more serious conditions such as bladder cancer. Treatment is empirical, and there are many different therapeutic regimens, but treatment can be successful in the majority of patients. The author discusses the role of behavior modification, oral medications, intravesical instillations of medications, and hydrodistension of the bladder as treatment options. A detailed case study is presented to show the use of behavior modification to treat IC. 1 figure.

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Pelvic Lymphadenectomy Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 269-274. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: The pelvic lymph nodes are the initial site from which prostatic, bladder, and proximal urethral malignancies spread. Tumors of the penis, scrotum, and distal urethra spread primarily to the inguinal lymph nodes but can involve the pelvic lymph nodes. Most urologists perform pelvic lymph node dissections (lymphadenectomy) in patients with prostate or bladder cancer. This chapter on pelvic lymphadenectomy is from an exhaustive textbook on urologic surgery. Pelvic lymph node dissection may be performed as a staging procedure before definitive radiation therapy, as a separate procedure for prostate cancer (i.e., before a radical perineal prostatectomy), or concomitant with a radical retropubic prostatectomy. The authors describe the procedures used, including those for prostate and bladder cancers, and then review the potential complications and anticipated results. Although pelvic lymph node dissection is usually a relatively short procedure with little morbidity, it has a potential for significant complications both intraoperative and postoperative. Ureteral injuries are uncommon and require repair when encountered. Prolonged lymph drainage and lymphocele formation may occur in 3 to 12 percent of patients. Any patient with prolonged or excessive lymph drainage must be evaluated for a urinary leak. 3 figures. 1 table. 10 references.

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Your Kidneys and Urinary Tract Source: in Larson, D.E., ed. Mayo Clinic Family Health Book. 2nd ed. New York, NY: William Morrow and Company, Inc. 1996. p. 825-858. Contact: Available from Mayo Clinic. 200 First Street, S.W., Rochester, MN 55905. (800) 291-1128 or (507) 284-2511. Fax (507) 284-0161. Website: www.mayo.edu. PRICE: $39.95 plus shipping and handling. ISBN: 0688144780. Summary: This chapter on the kidneys and urinary tract is from a family health book published by the Mayo Clinic. The chapter first reviews the anatomy and physiology of the urinary tract and kidneys, and briefly describes the use of urinalysis to screen for kidney function. Urinalysis is the first step in determining the presence of kidney or related disease and in separating major problems from minor ones. The chapter then covers congenital kidney disorders, including anatomic abnormalities, medullary sponge kidney, and vesicoureteral reflux; inherited kidney disorders, including polycystic kidney disease, cystinuria, renal tubule defects, Alport's syndrome, congenital nephrotic syndrome, and sickle cell disease; injury and inflammation of the kidneys and urinary tract, including injury of the kidney and ureters, traumatic injury of the bladder and urethra, toxic injury of the kidney, acute interstitial nephritis, acute glomerulonephritis, chronic glomerulonephritis, and nephrotic syndrome; urinary tract infections (UTIs), including acute pyelonephritis (kidney infection), cystitis (bladder infection), interstitial cystitis, and urethritis; stones, cysts, and tumors, including kidney and bladder cancer; blood vessel problems, including acute arterial occlusion, renal artery stenosis, malignant hypertension, and renal vein thrombosis; and acute and chronic kidney failure, including end stage renal disease. In each section, this consumer oriented reference book explains symptoms, diagnostic tests, treatment choices, and patient care considerations. 8 figures.

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Urology Source: in Tierney, L.M.; McPhee, S.J.; Papadakis, M.A., eds. Current Medical Diagnosis and Treatment 1999. 38th ed. Stamford, CT: Appleton and Lange. 1999. p. 894-931. Contact: Available from McGraw-Hill Companies. 1221 Avenue of the Americas, New York, NY 10020. (800) 352-3566 or (212) 512-4100. Fax (212) 512-4105. Website: www.mcgraw-hill.com. PRICE: $47.50 plus shipping and handling. ISBN: 0838515509. Summary: This chapter on urology is from a general medical textbook designed as a single source reference for practitioners in both hospital and ambulatory settings. The textbook offers extensive coverage of all primary care topics, including gynecology, obstetrics, dermatology, ophthalmology, otolaryngology, psychiatry, neurology, and urology. The chapter begins with a review of urologic evaluation. The first section covers diagnostic issues: the patient history, including systemic manifestations, pain, hematuria (blood in the urine), irritative voiding symptoms, obstructive voiding symptoms, and incontinence; physical examination; and urinalysis, including collection of specimens, dipstick urinalysis, and microscopic urinalysis. The chapter then addresses the evaluation of hematuria, and discusses genitourinary tract infections, including acute cystitis, acute pyelonephritis, acute bacterial prostatitis, chronic bacterial prostatitis, nonbacterial prostatitis, prostatodynia, and acute epididymitis. The reminder of the chapter covers urinary stone disease, urinary incontinence, male erectile dysfunction (impotence) and sexual dysfunction, male infertility, benign prostatic hyperplasia (BPH), malignant genitourinary tract disorders, bladder cancer, cancers of the ureter and renal pelvis, and primary and secondary tumors of the kidney. For each condition, the authors discuss the essentials of diagnosis, general considerations

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(including etiology), clinical findings, treatment course, and prognosis. Each section offers relevant references, and some sections conclude with a brief list of relevant World Wide Web sites. 1 figure. 13 tables. 49 references. •

Radical Cystectomy in Women Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 195-203. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: Total cystectomy is the most effective means of pelvic control of potentially lethal transitional cell carcinoma (TCC) of the bladder. This chapter on radical cystectomy in women is from an exhaustive textbook on urologic surgery. Bladder cancer is more common in men, and thus, cystectomy is more commonly performed in men than women. However, in many ways the cystectomy is more difficult in women. Urologists have fewer opportunities for familiarity with major pelvic surgery in women than in men. In addition, the uterus is commonly removed with the bladder, and a hysterectomy is a procedure that urologists do not routinely perform. If the urethra is removed entirely, its reconstruction and reconstruction of the vagina can be done in several ways. And orthotopic diversion in women is done routinely now, but preparation of the urethra for maximum preservation of a normal voiding pattern is different from that done in a male. The author details the surgical techniques used, including perioperative care, operative technique, and postoperative care. Complications from the cystectomy include bleeding and subsequent coagulation abnormalities and rectal injury. The author stresses that the postoperative care after cystectomy requires a diligence over and above that seen with other urologic procedures. Some complications are not preventable, but recognition early in their evolution may drastically minimize the negative consequences, and a high index of suspicion is essential. 10 figures. 1 table. 10 references.

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

Video Recordings An excellent source of multimedia information on bladder cancer is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “bladder cancer” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “bladder cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on bladder cancer: •

Laparoscopic Radical Cystectomy with Urinary Diversion-Completely Intracorporeal Technique in the Male and Female Source: Houston, TX: American Urological Association (AUA) Office of Education. 2000. (videocassette). Contact: Available from AUA Office of Education. 2425 West Loop South, Suite 333, Houston, Texas 77027. (800) 282-7077. Fax: (713) 622-2898. PRICE: $20.00. Item number HV2248. Summary: This videotape program demonstrates the step by step technique of laparoscopic radical cystectomy (removal of the urinary bladder, done with a laparoscope, an illuminated tube that permits transcutaneous, or through the skin, surgery). The program first reviews the patient preparation and trocar placement (how and where on the abdomen the laparoscopes are placed), then details the operative technique used. Each step of the surgery is shown in 3 dimensional graphics; then the actual surgery is depicted in a male patient and in a female patient. Graphics are

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interspersed and overlaid to help visualize the steps of each procedure. Also shown is the creation of an ileal stoma (an opening in the abdominal wall used for urine removal). The program concludes by offering statistics and information about complications in a series of 11 patients, a brief discussion of the advantages of laparoscopic cystectomy, and postoperative photographs of the patients' abdomens (showing only tiny scars where the trocars had been placed). The program concludes that laparoscopic cystectomy is a viable option for selected patients with muscle invasive bladder cancer.

Bibliography: Multimedia on Bladder 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 bladder 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 bladder cancer: •

Approaches to the treatment of recurrent and incurable prostate and bladder cancer [sound recording] Source: American College of Surgeons; Year: 1978; Format: Sound recording; [Chicago]: The College, [1978]

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Bladder cancer [slide] Source: [presented by the Ohio Medical Education Network]; Year: 1988; Format: Slide; [Columbus, Ohio]: The Network, [1988]

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Bladder cancer update [sound recording] Source: George R. Prout. [et al.]; Year: 1977; Format: Sound recording; New York: Roerig: [for sale by Robert A. Becker Co., Audiovisual Division], c1977

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Cancer and men [videorecording]: prostate and bladder cancer Source: [presented by] Films for the Humanities & Sciences; a presentation of KCBD-TV & Medstar Communications, Inc; Year: 1995; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1995

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Treatment options for superficial bladder cancer [videorecording]: what to do when BCG fails Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1995; Format: Videorecording; Marshfield, WI: The Clinic, [1995]

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

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

Drinking a lot doesn't stop bladder cancer return Source: Reuters Health eLine Date: November 07, 2003

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Vitamins don't curb bladder cancer risk Source: Reuters Health eLine Date: October 10, 2003

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Supercharged chemo blasts bladder cancer Source: Reuters Health eLine Date: September 04, 2003

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Spectrum reports promising early clinical data for bladder cancer drug Source: Reuters Industry Breifing Date: June 11, 2003

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FDA approves Matritech bladder cancer test for general screening Source: Reuters Industry Breifing Date: April 28, 2003

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Bladder cancer test approved for general screening Source: Reuters Health eLine Date: April 28, 2003

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Matritech gets conditional approval for office-based bladder cancer screen Source: Reuters Industry Breifing Date: March 03, 2003

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Adoptive immunotherapy shows promise as treatment for bladder cancer Source: Reuters Industry Breifing Date: January 24, 2003

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Vitamin E use tied to reduced risk of bladder cancer mortality Source: Reuters Industry Breifing Date: December 13, 2002

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MDI, DiagnoCure aim to commercialize automated bladder cancer test Source: Reuters Industry Breifing Date: December 12, 2002

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Vitamin E, bladder cancer risk studied Source: Reuters Health eLine Date: December 09, 2002

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Arsenic in water tied to bladder cancer mutations Source: Reuters Health eLine Date: November 20, 2002

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HER2 expression has prognostic importance in advanced bladder cancer Source: Reuters Industry Breifing Date: October 02, 2002

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PhotoCure says bladder cancer diagnostic shows benefit in phase III Source: Reuters Industry Breifing Date: September 03, 2002

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Gemcitabine helpful in BCG-refractory bladder cancer Source: Reuters Industry Breifing Date: August 13, 2002

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FDA clears Matritech bladder cancer test Source: Reuters Industry Breifing Date: August 01, 2002

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Urine test may catch bladder cancer early Source: Reuters Health eLine Date: July 17, 2002

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Matritech files for US approval of in-office NMP-based bladder cancer test Source: Reuters Industry Breifing Date: April 29, 2002

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FDA clears strengthened label for Abbott Laboratories' bladder cancer test Source: Reuters Industry Breifing Date: March 07, 2002

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Bladder cancer risk at least partly genetic: study Source: Reuters Health eLine Date: January 21, 2002

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Protein linked to prognosis in bladder cancer Source: Reuters Health eLine Date: December 24, 2001

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Good response to BCG in bladder cancer patients linked to Th1 profile Source: Reuters Industry Breifing Date: December 24, 2001

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BCG more effective than epirubicin in treatment of bladder cancer Source: Reuters Industry Breifing Date: August 20, 2001

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Vysis wins FDA clearance for DNA-based bladder cancer test Source: Reuters Industry Breifing Date: August 02, 2001

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Bladder cancer: early chemotherapy boosts survival Source: Reuters Health eLine Date: May 15, 2001

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US Summit to market Matritech's POC bladder cancer test in Southeast Asia Source: Reuters Industry Breifing Date: May 14, 2001

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Nitrates may up bladder cancer risk in women Source: Reuters Health eLine Date: April 24, 2001

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BioChem Pharma recalls one lot of bladder cancer treatment Pacis Source: Reuters Industry Breifing Date: April 17, 2001

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Women smokers more vulnerable to bladder cancer Source: Reuters Health eLine Date: April 03, 2001

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Urine test spots early signs of bladder cancer Source: Reuters Health eLine Date: March 21, 2001

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Hair dyes may raise bladder cancer risk: study Source: Reuters Health eLine Date: January 26, 2001

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Use of some hair dyes may increase bladder cancer risk in women Source: Reuters Industry Breifing Date: January 25, 2001

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Intravesical vitamin D a prospect for bladder cancer treatment Source: Reuters Industry Breifing Date: January 19, 2001

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Timm Medical to distribute Matritech's point-of-care bladder cancer test in US Source: Reuters Industry Breifing Date: January 18, 2001

•

Cheap, quick urine test may detect bladder cancer Source: Reuters Health eLine Date: January 16, 2001

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Coffee may cut bladder cancer risk in smokers Source: Reuters Health eLine Date: December 13, 2000

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Tumor genes may be key to bladder cancer detection Source: Reuters Health eLine Date: December 06, 2000

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Vysis files for FDA approval of DNA probe for bladder cancer Source: Reuters Industry Breifing Date: November 30, 2000

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Urine test helps detect bladder cancers early Source: Reuters Health eLine Date: November 20, 2000

•

Possible bladder cancer drug targets found Source: Reuters Health eLine Date: November 09, 2000

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Gemcitabine and cisplatin safer than MVAC for advanced bladder cancer Source: Reuters Industry Breifing Date: August 30, 2000

•

Smoking triples risk of bladder cancer Source: Reuters Health eLine Date: August 03, 2000

•

Gene may be key to bladder cancer screening test Source: Reuters Health eLine Date: May 18, 2000

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Urine test may help diagnose bladder cancer Source: Reuters Health eLine Date: December 30, 1999

•

Smoking may hasten spread of bladder cancer Source: Reuters Health eLine Date: November 30, 1999

•

Tea drinking may increase risk of bladder cancer Source: Reuters Health eLine Date: November 24, 1999

Periodicals and News

•

High fluid intake reduces bladder cancer risk Source: Reuters Health eLine Date: May 05, 1999

•

Urine test detects bladder cancer Source: Reuters Health eLine Date: April 27, 1999

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Cabbage, broccoli lower bladder cancer risk Source: Reuters Health eLine Date: April 12, 1999

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FDA approves at-home bladder cancer test Source: Reuters Health eLine Date: December 29, 1998

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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 “bladder 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. 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 “bladder cancer” (or synonyms). If you know the name of a company that is relevant to bladder cancer, you can go to any stock trading Web site (such as http://www.etrade.com/)

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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 “bladder cancer” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “bladder cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on bladder cancer: •

ILSI North America Saccharin Technical Committee Completes Research Source: ILSI News. p.5. January-March 2000. Contact: International Life Sciences Institute. 1126 16th St., NW, Suite 110, Washington, DC 20036-4810. (202) 659-0074. [email protected]. www.ilsi.org. Summary: The International Life Sciences Institute North American Saccharin Technical Committee was formed in 1983 to examine the scientific issues related to the safety of saccharin and to conduct research on these issues. The committee sponsored research into the link between sodium saccharin and the bladder tumors that occur in male rats. These and other investigations have now shown that these tumors are unique to rats and that sodium saccharin does not increase the risk of bladder cancer for humans. A large body of experimental evidence has also supported the conclusion that sodium saccharin is not related to bladder cancer in humans.

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

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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 bladder 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 non-profit 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 bladder 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 bladder cancer: Bacillus Calmette-Guйrin (Bcg) Live for Cancer •

Mucosal-Local - U.S. Brands: Pacis; TheraCys http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202079.html

Cisplatin •

Systemic - U.S. Brands: Platinol; Platinol-AQ http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202143.html

Cyclophosphamide •

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

Docetaxel •

Systemic - U.S. Brands: Taxotere http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202920.html

Etoposide •

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

Gallium Nitrate •

Systemic - U.S. Brands: Ganite http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202254.html

Gemcitabine •

Systemic - U.S. Brands: Gemzar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203038.html

Interferons, Alpha •

Systemic - U.S. Brands: Alferon N; Intron A; Roferon-A http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202299.html

Mitomycin •

Systemic - U.S. Brands: Mutamycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202376.html

Mitoxantrone •

Systemic - U.S. Brands: Novantrone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202378.html

Thiotepa •

Systemic - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202378.html

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Valrubicin •

Mucosal-Local - U.S. Brands: Valstar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203706.html

Vinblastine •

Systemic - U.S. Brands: Velban http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202593.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. 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

•

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

•

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

•

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

•

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

•

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

•

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

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

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

•

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

•

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

•

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

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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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

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

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

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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/

•

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

•

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

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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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “bladder cancer” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “bladder cancer” (or synonyms) into the “For these words:” box. The following is a sample result: •

Report on the Management of Non-Muscle-Invasive Bladder Cancer (Stages Ta, T1 and Tis) Source: Baltimore, MD: American Urological Association. 1999. 60 p. Contact: Available from American Urological Association. 1120 North Charles Street, Baltimore, MD 21201. (410) 727-1100. Fax (410) 223-4370. E-mail: [email protected]. Website: www.auanet.org. PRICE: $35.00 for members; $50.00 for nonmembers; plus shipping and handling. Summary: The American Urological Association (AUA) convened the Bladder Clinical Guidelines Panel to analyze the literature regarding available methods of treating nonmuscle invasive bladder cancer, and to make policy recommendations based primarily on treatment outcomes data; this report is the result of the panel's work. The panel searched the MEDLINE database for articles related to nonmuscle invasive bladder cancer published from January 1998 to the present. Outcomes data were extracted from articles accepted for panel review and meta analyzed to produce comparative probability estimates for alternative treatments. At any age, most bladder cancers, when initially diagnosed, have not invaded the detrusor muscle; these noninvasive types (stages Ta, T1, and Tis) are the focus of this study. All of the intravesical agents (thiotepa, bacillus Calmette Guerin, mitomycin C, and doxorubicin), when used as adjuvant therapy after transurethral resection, resulted in a lower probability of recurrence compared to resection alone. However, there is no evidence that intravesical therapy with these agents affects long term progression. The panel concludes that, for patients with no prior intravesical therapy, adjuvant intravesical chemotherapy or immunotherapy is a treatment option for endoscopic removal of low grade Ta bladder cancers. Intravesical instillation of bacillus Calmette Guerin or mitomycin C is recommended for cancer in situ, and after endoscopic removal of T1 and high grade Ta tumors. The report concludes with three appendices: data presentation, the data extraction form, and data analysis; a subject index is also provided. 6 tables. 114 references.

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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 “bladder 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 28670 210 894 6 0 29780

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

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are 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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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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 Bladder Cancer In the following section, we will discuss databases and references which relate to the Genome Project and bladder 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. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “bladder 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 bladder cancer: 21

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

Physician Resources

•

Bladder Cancer Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?109800

•

Breast and Bladder Cancer Overexpressed Gene 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606048

•

Deleted in Bladder Cancer Chromosome Region Candidate 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602865

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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 baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner

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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

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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “bladder cancer” (or synonyms) into the search box and click “Go.”

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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 “bladder 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 bladder 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 bladder 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 bladder 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 “bladder cancer”:

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Guides on bladder cancer Bladder Cancer http://www.nlm.nih.gov/medlineplus/bladdercancer.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html

•

Other guides Bladder Diseases http://www.nlm.nih.gov/medlineplus/bladderdiseases.html Cancer Alternative Therapy http://www.nlm.nih.gov/medlineplus/canceralternativetherapy.html Kidney Cancer http://www.nlm.nih.gov/medlineplus/kidneycancer.html Prostate Cancer http://www.nlm.nih.gov/medlineplus/prostatecancer.html

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

General/Overviews Bladder Cancer Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00177 What Is Bladder Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_bladder_cancer_ 44.asp?sitearea=cri

•

Diagnosis/Symptoms Can Bladder Cancer Be Found Early? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_can_bladder_cancer_be_f ound_early_44.asp?sitearea=cri Cystoscopy http://www.nlm.nih.gov/medlineplus/tutorials/cystoscopyloader.html Cystoscopy and Ureteroscopy Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/cystoscopy/index.htm Hematuria (Blood in the Urine) Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/hematuria/index.htm How Is Bladder Cancer Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_bladder_cancer_ diagnosed_44.asp?sitearea=cri

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How Is Bladder Cancer Staged? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_bladder_cancer_ staged_44.asp?sitearea=cri •

Treatment Biological Therapies: Using the Immune System to Treat Cancer Source: National Cancer Institute http://cis.nci.nih.gov/fact/7_2.htm Bladder Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/bladder/patient/ Transitional Cell Cancer of the Renal Pelvis and Ureter (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/transitionalcell/patient/ Urethral Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/urethral/patient/

•

Specific Conditions/Aspects Do We Know What Causes Bladder Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_do_we_know_what_caus es_bladder_cancer_44.asp?sitearea=cri What Should You Ask Your Doctor About Bladder Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_5x_what_should_you_ask_y our_doctor_about_bladder_cancer_44.asp?sitearea=cri

•

From the National Institutes of Health What You Need to Know about Bladder Cancer Source: National Cancer Institute http://www.cancer.gov/cancerinfo/wyntk/bladder

•

Latest New Drinking a Lot Doesn't Stop Bladder Cancer Return Source: 11/07/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14568 .html

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Organizations American Cancer Society http://www.cancer.org/ American Foundation for Urologic Disease http://www.afud.org/

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National Cancer Institute http://www.cancer.gov/ UrologyHealth.org Source: American Urological Association http://urologyhealth.org/ •

Pictures/Diagrams Atlas of the Body: The Urinary System Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZFQ0XCGJC &sub_cat=316 Bladder Cancer - Anatomical Drawings Source: American Urological Association http://www.urologyhealth.org/adult/index.cfm?cat=03&topic=37&drawings=yes

•

Prevention/Screening Bladder Cancer (PDQ): Screening Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/screening/bladder/patient/ Bladder Cancer Questionnaire Source: Harvard Center for Cancer Prevention http://www.yourcancerrisk.harvard.edu/hccpquiz.pl?func=start&quiz=bladder Can Bladder Cancer Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_can_bladder_cancer_be_ prevented_44.asp?sitearea=cri What Are the Risk Factors for Bladder Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_what_are_the_risk_factor s_for_bladder_cancer_44.asp?sitearea=cri

•

Research Bladder Cancer Recurrence Held at Bay With Improved Drug Delivery Source: American Cancer Society http://www.cancer.org/docroot/nws/content/update/nws_1_1xu_improved_dru g_therapy_holds_bladder_cancer_at_bay_.asp Bladder Cancer Survival Inches up with Chemotherapy Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Bladder_Cancer_Surv ival_Inches_Up_With_Chemotherapy.asp Bladder Cancer: Removal of the Bladder May Not Be Necessary Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Bladder_Cancer_Rem oval_Of_The_Bladder_May_Not_Be_Necessary.asp

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Chemotherapy Can Save the Bladder of Some Bladder Cancer Patients Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_2_1x_Chemotherapy_Can_ Save_The_Bladder_Of_Some_Bladder_Cancer_Patients.asp Follow-Up Care Lacking For Many Bladder Cancer Patients Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_FollowUp_Care_Lacking_For_Many_Bladder_Cancer_Patients.asp Genetic Connection In Link Between Permanent Hair Dye Use And Bladder Cancer Risk Source: National Institute of Environmental Health Sciences http://www.niehs.nih.gov/centers/2002News/news9.htm Researchers Confirm Smoking Increases Risk of Bladder Cancer Source: American Cancer Society http://www.cancer.org/docroot/nws/content/nws_1_1x_smoking_increases_risk _of_bladder_cancer.asp Spiral CT Scan Finds Bladder Cancer in Those at High Risk: “Virtual Cystoscopy” Still Not Ready for Wide Use Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Spiral_CT_Scan_Find s_Bladder_Cancer_in_Those_at_High_Risk.asp Treatment to Prevent Bladder Cancer Return Is Improving Source: American Cancer Society http://www.cancer.org/docroot/nws/content/nws_1_1x_treatment_to_prevent_bl adder_cancer_return_is_improving.asp What's New in Bladder Cancer Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new_in_bladder_c ancer_research_and_treatment_44.asp?sitearea=cri •

Statistics Snapshot of Bladder Cancer Source: National Cancer Institute http://prg.nci.nih.gov/snapshots/Bladder-Snapshot.pdf Urinary Bladder: U.S. Racial/Ethnic Cancer Patterns Source: National Cancer Institute http://www.cancer.gov/statistics/cancertype/urinary-racial-ethnic What Are the Key Statistics for Bladder Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_the_key_statist ics_for_bladder_cancer_44.asp?sitearea=cri

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

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unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on bladder cancer. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Answers to Your Questions About Bladder Cancer Source: Baltimore, MD: American Foundation for Urologic Disease. 1999. 16 p. Contact: Available from American Foundation for Urologic Disease (AFUD). 1128 North Charles Street, Baltimore, MD 21201. (800) 242-2383. Website: www.afud.org. PRICE: $13.00 for pack of 50; plus shipping and handling. Summary: Most bladder cancers can be treated without major surgery. However, early detection is vital; it allows the prompt treatment that gives patients the best chance for a favorable outlook. This brochure, written for people recently diagnosed with bladder cancer, explains how the bladder works, the tests that are used after bladder cancer has been diagnosed (to determine the stage of the cancer), and treatment options. The brochure begins with a six item pretest to determine the reader's knowledge of the bladder and bladder cancer. The lining inside the bladder is composed of a layer of cells that protect the tissues beneath them from urine. A growth, or tumor, means that cells of the bladder lining are producing new cells that are not normal. However, abnormal masses of cells may not always be cancerous. Diagnostic tests to determine the presence and classification of the cancer can include biopsy, intravenous pyelogram, cystoscopy, and urinary cytology. The treatment for bladder cancer depends on how deeply the tumor has grown into the bladder. Removal of a bladder tumor is sometimes called a transurethral resection. In most cases, bladder tumors are superficial and need no additional treatment. Often, bladder tumors recur, especially within the first year or two after discovery of the first tumor. In patients with invasive bladder cancer, the surgery may include removal of the entire bladder (cystectomy); chemotherapy may also be indicated. The brochure includes preventive steps to keep the bladder healthy. The brochure concludes with a list of information resources, a glossary of terms used in the text, and the answers to the pretest. 5 figures. 1 table.

•

Understanding Bladder Cancer Source: San Bruno, CA: StayWell Company. 1999. 15 p. Contact: Available from Staywell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. PRICE: $1.35 per copy; plus shipping and handling. Order number 1783. Summary: This educational booklet helps patients understand the treatment options for bladder cancer. The author stresses that bladder cancer found in its early stages has an excellent chance to be cured; there are also many types of treatment for bladder cancer at most stages. The booklet is designed to help patients understand the treatment

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options to make better choices for their own care and treatment. Topics include the anatomy and physiology of the bladder, the diagnosis of bladder cancer, staging and grading bladder cancer, transurethral resection, intravesical therapy, chemotherapy, radiation therapy, cystectomy (bladder removal), the patients' role on their own health care team, and the emotional aspects of bladder cancer and its treatment. The booklet describes three types of bladder cancer that may form: papillary tumors, sessile tumors, and carcinoma in situ. Treatment options include transurethral resection (TUR), intravesical therapy, chemotherapy, radiation, and cystectomy. For each treatment option, the booklet reviews the short term side effects, the risks, and possible complications. The booklet also reviews the different types of urostomies that may be used for people who undergo a cystectomy (bladder removal). The booklet concludes with a brief list of resource organizations and their toll free telephone numbers. The booklet is illustrated with full color line drawings. 29 references. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “bladder cancer” (or synonyms). The following was recently posted: •

Management of non-muscle-invasive bladder cancer Source: American Urological Association, Inc. - Medical Specialty Society; 1999; 66 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2143&nbr=1369&a mp;string=bladder+AND+cancer

•

Use of adjuvant chemotherapy following cystectomy in patients with deep muscleinvasive transitional cell carcinoma of the bladder Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2001 October 9 (revised online 2002 Oct); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3607&nbr=2833&a mp;string=bladder+AND+cancer 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: •

Bladder Cancer (PDQ®): Treatment Information for Patients Summary: Based on information in the PDQ summary for health professionals on bladder cancer, this patient resource presents facts about current treatment of bladder cancer by cancer stage. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6191

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Bladder Cancer Home Page Summary: This web site links patients, health care professionals, and the general public to a range of topics related to bladder cancer, including diagnosis, screening, treatment, disease management, coping Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6192

•

What You Need To Know About™ Bladder Cancer Summary: Patient information about bladder cancer, including detection/screening, staging, treatment options, treatment side effects and research. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6190 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 bladder 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 bladder cancer. By consulting all of associations

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listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with bladder 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 bladder 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. 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 “bladder 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 “bladder 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 “bladder 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 “bladder cancer” (or a synonym) into the search box, and click “Submit Query.”

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249

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.

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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

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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

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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

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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/

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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.

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•

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

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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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

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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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

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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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/

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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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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

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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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

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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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 bladder cancer: •

Basic Guidelines for Bladder Cancer Bladder cancer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000486.htm Cancer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001289.htm Carcinoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001289.htm Tumor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001310.htm

•

Signs & Symptoms for Bladder Cancer Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm

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Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Blood in the urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Bone pain or tenderness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003180.htm Dysuria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003145.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Flank pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003113.htm Hematuria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Lethargy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Painful urination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003145.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Urinary frequency Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm Urinary urgency Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm

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Vesicles Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •

Diagnostics and Tests for Bladder Cancer Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Bladder biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003902.htm Bone scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003833.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Complete blood count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Cystoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003903.htm Intravenous pyelogram - IVP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003782.htm IVP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003782.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm Urinalysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003579.htm Urine cytology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003905.htm

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Surgery and Procedures for Bladder Cancer ORIF Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002966.htm

•

Background Topics for Bladder Cancer Anterior Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002232.htm Blood clots Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Cigarette smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm Foley catheter Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003981.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Invasive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002384.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.htm Mucosa Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002264.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm Radiotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm Renal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002289.htm Smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm

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Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm Systemic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002294.htm Vagina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002342.htm

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

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BLADDER CANCER DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinic keratosis: A precancerous condition of thick, scaly patches of skin. Also called solar or senile keratosis. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU]

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Adduct: Complex formed when a carcinogen combines with DNA or a protein. [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] 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]

Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [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 intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU]

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Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alfalfa: A deep-rooted European leguminous plant (Medicago sativa) widely grown for hay and forage. [NIH] 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]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allium: A genus of liliaceous herbs containing onions (Allium cepa), garlic (Allium sativum), and others; many produce pungent, often bacteriostatic and physiologically active compounds and are used as food, condiment, and medicament, the latter in traditional medicine. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a

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single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] 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] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdalin: A cyanogenic glycoside found in the seeds of Rosaceae. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but

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shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] 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] Angiogenesis Factor: Substance causing proliferation of new blood vessels. It is found in tissues with high metabolic requirements, such as the retina, and in certain cancers. The factor is also released by hypoxic macrophages at the edges or outer surfaces of wounds and initiates revascularization in wound healing. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] 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]

Anomalies: Birth defects; abnormalities. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific

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tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidote: A remedy for counteracting a poison. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimitotic: Inhibiting or preventing mitosis. [EU] Antimony: A metallic element that has the atomic symbol Sb, atomic number 51, and atomic weight 121.75. It is used as a metal alloy and as medicinal and poisonous salts. It is toxic and an irritant to the skin and the mucous membranes. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH]

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Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arsenicals: Inorganic or organic compounds that contain arsenic. [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] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU]

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Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] 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 variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autocrine Motility Factor: A member of the class of cytokines secreted by tumor cells. It elicits increases in cell motility and phosphoinositide metabolism in the secreting or producing cell via a pertussis toxin-sensitive G-protein signal transduction pathway. The factor has also been used as a marker for bladder cancer. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [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] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH]

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Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. [NIH] Beta-Glucosidase: An enzyme that catalyzes the hydrolysis of terminal non-reducing residues in beta-D-glucosides with release of beta-glucose. EC 3.2.1.21. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the

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digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Bladder Neoplasms: Cancer or tumors of the bladder. [NIH] Blasts: Immature blood cells. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH]

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Blood Glucose: Glucose in blood. [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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain metastases: Cancer that has spread from the original (primary) tumor to the brain. [NIH]

Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchoscope: A thin, lighted tube used to examine the inside of the trachea and bronchi, the air passages that lead into the lungs. [NIH] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buccal mucosa: The inner lining of the cheeks and lips. [NIH]

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Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Cadaver: A dead body, usually a human body. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [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] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbogen: An inhalant of oxygen and carbon dioxide that increases the sensitivity of tumor cells to the effects of radiation therapy. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the

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epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH]

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Cefaclor: Semisynthetic, broad-spectrum antibiotic derivative of cephalexin. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of cephaloridine or cephalothin, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU]

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Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Checkup: A general physical examination. [NIH] Chemoembolization: A procedure in which the blood supply to the tumor is blocked surgically or mechanically, and anticancer drugs are administered directly into the tumor. This permits a higher concentration of drug to be in contact with the tumor for a longer period of time. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemosensitivity assay: A laboratory test to analyze the responsiveness of a tumor to a specific drug. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorine Compounds: Inorganic compounds that contain chlorine as an integral part of the molecule. [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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] 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

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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 leukemia: A slowly progressing cancer of the blood-forming tissues. [NIH] Chronic prostatitis: Inflammation of the prostate gland, developing slowly and lasting a long time. [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 transplantation to replace the work of the kidneys. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [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] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [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 Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] 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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH]

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Coal Tar: A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) (Merck Index, 11th ed). [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [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] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combined Modality Therapy: The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, radioimmunotherapy,

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chemoradiotherapy, cryochemotherapy, and salvage therapy are seen most frequently, but their combinations with each other and surgery are also used. [NIH] Comet Assay: A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the 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] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [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

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biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] 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] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of

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disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cruciferous vegetables: A family of vegetables that includes kale, collard greens, broccoli, cauliflower, cabbage, brussels sprouts, and turnip. These vegetables contain substances that may protect against cancer. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cutaneous: Having to do with the skin. [NIH] 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]

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Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]

Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cystectomy: Used for excision of the urinary bladder. [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]

Cystinuria: An inherited abnormality of renal tubular transport of dibasic amino acids leading to massive urinary excretion of cystine, lysine, arginine, and ornithine. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices.

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The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

De novo: In cancer, the first occurrence of cancer in the body. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] 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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deoxycytidine: A drug that protects healthy tissues from the toxic effects of anticancer drugs. [NIH] Deoxycytidine Kinase: An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (Herpesvirus hominis). EC 2.7.1.74. [NIH]

Deoxycytidine Monophosphate: Deoxycytidine (dihydrogen phosphate). A deoxycytosine nucleotide containing one phosphate group esterified to the deoxyribose moiety in the 2'-,3'or 5- positions. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]

Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until

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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] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [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] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diethylcarbamazine: An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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] Dissection: Cutting up of an organism for study. [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

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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] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [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]

Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] 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 of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH]

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Duodenum: The first part of the small intestine. [NIH] Dwell time: In peritoneal dialysis, the amount of time a bag of dialysate remains in the patient's abdominal cavity during an exchange. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ecosystem: A dynamic complex of plant, animal and micro-organism communities and their non-living environment interacting as a functional unit. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric Conductivity: The ability of a substrate to allow the passage of electrons. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endemic: Present or usually prevalent in a population or geographical area at all times; said

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of a disease or agent. Called also endemial. [EU] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]

for

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other health-

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related event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epirubicin: An anthracycline antibiotic which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, pancreatic cancer, gastric cancer, small-cell lung cancer and acute leukemia. It is equal in activity to doxorubicin but exhibits less acute toxicities and less cardiotoxicity. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] 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]

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Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evaluable patients: Patients whose response to a treatment can be measured because enough information has been collected. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon,

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hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members. [NIH]

Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fenretinide: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] 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] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ,

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usually as a consequence of inflammation or other injury. [NIH] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Food Additives: Substances which are of little or no nutritive value, but are used in the processing or storage of foods or animal feed, especially in the developed countries; includes antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents (both plain and local), vehicles, excipients and other similarly used substances. Many of the same substances are pharmaceutic aids when added to pharmaceuticals rather than to foods. [NIH]

Food Coloring Agents: Natural or synthetic dyes used as coloring agents in processed foods. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] 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] Gallium nitrate: A drug that lowers blood calcium. Used as treatment for hypercalcemia (too much calcium in the blood) and for cancer that has spread to the bone (bone metastases). [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] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized

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connective tissue located outside the central nervous system. [NIH] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] 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 Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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

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arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ cell tumors: Tumors that begin in the cells that give rise to sperm or eggs. They can occur virtually anywhere in the body and can be either benign or malignant. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] 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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9.

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[NIH]

Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic radicals as well as epoxides and arene oxides to glutathione. Addition takes place at the sulfur atom. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite. EC 2.5.1.18. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonorrhoea: Infection due to Neisseria gonorrhoeae transmitted sexually in most cases, but also by contact with infected exudates in neonatal children at birth, or by infants in households with infected inhabitants. It is marked in males by urethritis with pain and purulent discharge, but is commonly asymptomatic in females, although it may extend to produce suppurative salpingitis, oophoritis, tubo-ovarian abscess, and peritonitis. Bacteraemia occurs in both sexes, resulting in cutaneous lesions, arthritis, and rarely meningitis or endocarditis. Formerly called blennorrhagia and blennorrhoea. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU]

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Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulomas: Small lumps in tissues caused by inflammation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Hair Color: Color of hair or fur. [NIH] Hair Dyes: Dyes used as cosmetics to change hair color either permanently or temporarily. [NIH]

Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Hairy cell leukemia: A type of chronic leukemia in which the abnormal white blood cells appear to be covered with tiny hairs when viewed under a microscope. [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] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Hazardous Substances: Substances which, upon release into the atmosphere, water, or soil, or which, in direct contact with the skin, eyes, or mucous membranes, or as additives to food, cause health risks to humans or animals through absorption, inhalation, or ingestion. The concept includes safe handling, transportation, and storage of these substances. [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] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid.

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The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [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] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin

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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] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hyaluronidase: An enzyme that splits hyaluronic acid and thus lowers the viscosity of the acid and facilitates the spreading of fluids through tissues either advantageously or disadvantageously. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to

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an increase in the number of cells. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] 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] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Image Cytometry: A technique encompassing morphometry, densitometry, neural networks, and expert systems that has numerous clinical and research applications and is particularly useful in anatomic pathology for the study of malignant lesions. The most common current application of image cytometry is for DNA analysis, followed by quantitation of immunohistochemical staining. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompetence: The ability of lymphoid cells to mount a humoral or cellular immune response when challenged by antigen. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [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]

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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] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] 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] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local

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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]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] 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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Instillation: . [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] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family

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contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Interferometry: Measurement of distances or movements by means of the phenomena caused by the interference of two rays of light (optical interferometry) or of sound (acoustic interferometry). [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-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] 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] Intravenous: IV. Into a vein. [NIH] Intravenous pyelogram: IVP. A series of x-rays of the kidneys, ureters, and bladder. The xrays are taken after a dye is injected into a blood vessel. The dye is concentrated in the urine, which outlines the kidneys, ureters, and bladder on the x-rays. [NIH] Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU]

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Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodoacetic Acid: Iodoacetic acid and its salts and derivatives. Iodoacetic acid reacts with cysteine (-SH) groups to form a carboxymethylated protein and is used as an enzyme inhibitor in biochemical research. [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] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isoprenoids: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [NIH] Isothiocyanates: Organic compounds with the general formula R-NCS. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [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] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH]

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Keratosis: Any horny growth such as a wart or callus. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Keyhole: A carrier molecule. [NIH] Keyhole limpet hemocyanin: KLH. One of a group of drugs called immune modulators, given as a vaccine to help the body respond to cancer. [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] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Kringles: Triple-looped protein domains linked by disulfide bonds. These common structural domains, so-named for their resemblance to Danish pastries known as kringlers, play a role in binding membranes, proteins, and phospholipids as well as in regulating proteolysis. Kringles are also present in coagulation-related and fibrinolytic proteins and other plasma proteinases. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laparoscopes: Endoscopes for examining the interior of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH]

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Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] 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] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [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] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH]

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Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locoregional: The characteristic of a disease-producing organism to transfer itself, but typically to the same region of the body (a leg, the lungs, .) [EU] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lycopene: A red pigment found in tomatoes and some fruits. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. Also called lymph node dissection. [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] Lymphocele: Cystic mass containing lymph from diseased lymphatic channels or following surgical trauma or other injury. [NIH]

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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] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macronutrients: Nutrients in the diet that are the key sources of energy, namely protein, fat, and carbohydrates. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] 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] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] 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 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] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mediastinoscopy: Endoscopic examination, therapy or surgery of the anterior superior mediastinum of the thorax. [NIH] Mediastinum: The area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the esophagus, the bronchi, and lymph nodes. [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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Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medicament: A medicinal substance or agent. [EU] 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] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] 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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy. It may cause blood dyscrasias. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [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

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the body. [NIH] Methylcholanthrene: A carcinogen that is often used in experimental cancer studies. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microscopy, Polarization: Microscopy using polarized light in which phenomena due to the preferential orientation of optical properties with respect to the vibration plane of the polarized light are made visible and correlated parameters are made measurable. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Miscible: Susceptible of being mixed. [EU] Mistletoe lectin: A substance that comes from the mistletoe plant, and that is being studied as a treatment for cancer. A lectin is a complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [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]

Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH]

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Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monocyte Chemoattractant Protein-1: A chemokine that is a chemoattractant for human monocytes and may also cause cellular activation of specific functions related to host defense. It is produced by leukocytes of both monocyte and lymphocyte lineage and by fibroblasts during tissue injury. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones

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proteinuria, and anemia. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [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] Neoadjuvant Therapy: Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment. [NIH]

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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] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] 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] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [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,

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and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH] Node-negative: Cancer that has not spread to the lymph nodes. [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] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily

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present in the nucleus. [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] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleoli: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats,

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waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Onchocerciasis: Infection with nematodes of the genus Onchocerca. Characteristics include the presence of firm subcutaneous nodules filled with adult worms, pruritus, and ocular lesions. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Orchitis: Inflammation of a testis. The disease is marked by pain, swelling, and a feeling of weight. It may occur idiopathically, or it may be associated with conditions such as mumps, gonorrhoea, filarial disease, syphilis, or tuberculosis. [EU] Orderly: A male hospital attendant. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Preservation: The process by which organs are kept viable outside of the organism from which they were removed (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH]

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Ovarian epithelial cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] 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] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Painful bladder syndrome: Another name for interstitial cystitis. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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]

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Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papillary tumor: A tumor shaped like a small mushroom, with its stem attached to the epithelial layer (inner lining) of an organ. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [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] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Passive transport: The transport that occurs through the membrane at non-specific sites. [NIH]

Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [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]

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Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perineal: Pertaining to the perineum. [EU] Perineal prostatectomy: Surgery to remove the prostate through an incision made between the scrotum and the anus. [NIH] Perineum: The area between the anus and the sex organs. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Perioperative Care: Interventions to provide care prior to, during, and immediately after surgery. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU]

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Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutic Aids: Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include solvents, diluting agents, and suspending agents, and emulsifying agents. Also, antioxidants; preservatives, pharmaceutical; dyes (coloring agents); flavoring agents; vehicles; excipients; ointment bases. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [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] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylating: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light.

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These drugs kill cancer cells. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piritrexim: An anticancer drug. [NIH] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [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, 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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert

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plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [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]

Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polychlorinated Biphenyls: Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] 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

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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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyvalent: Having more than one valence. [EU] 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] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU]

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Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Pregnancy Maintenance: Physiological mechanisms that sustain the state of pregnancy. [NIH]

Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [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] Progeny: The offspring produced in any generation. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]

Prophylaxis: An attempt to prevent disease. [NIH] Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH]

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Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [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 gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [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] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of

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secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. [NIH] Prostatitis: Inflammation of the prostate. [EU] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [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 Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein p53: Nuclear phosphoprotein encoded by the p53 gene whose normal function is to control cell proliferation. A mutant or absent p53 protein has been found in leukemia, osteosarcoma, lung cancer, and colorectal cancer. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-

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oncogenes have names of the form c-onc. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] 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]

Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] 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]

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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 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] Radical cystectomy: Surgery to remove the bladder as well as nearby tissues and organs. [NIH]

Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] 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] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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] Ras gene: A gene that has been found to cause cancer when it is altered (mutated). Agents that block its activity may stop the growth of cancer. A ras peptide is a protein fragment produced by the ras gene. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by

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inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] 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] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] 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] Recurrent cancer: Cancer that has returned, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with

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risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal cell cancer: Cancer that develops in the lining of the renal tubules, which filter the blood and produce urine. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal vein thrombosis: Blood clots in the vessel that carries blood away from the kidney. This can occur in people with the nephrotic syndrome. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] 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] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative,

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noninflammatory condition of the retina). [EU] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [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] 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] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Saccharin: Flavoring agent and non-nutritive sweetener. [NIH] Saline: A solution of salt and water. [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] Sapogenins: The aglucon moiety of a saponin molecule. It may be triterpenoid or steroid, usually spirostan, in nature. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is

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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] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [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] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [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] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] 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] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH]

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Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sessile: Attached directly by the base, denoting a tumor without penduncle or stalk; in zoology, attached so that it is not possible to move about. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Single-agent: The use of a single drug or other therapy. [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] Smallpox: A generalized virus infection with a vesicular rash. [NIH]

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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, 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] 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] Somatic cells: All the body cells except the reproductive (germ) cells. [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] Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., wounds, gunshot; whiplash injuries; etc.). [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells

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resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

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] 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] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stoma: A surgically created opening from an area inside the body to the outside. [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] Stool: The waste matter discharged in a bowel movement; feces. [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] 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]

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Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [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] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [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] Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. [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] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]

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Synthetic retinoid: A substance related to vitamin A that is produced in a laboratory. [NIH] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Taxanes: Anticancer drugs that inhibit cancer cell growth by stopping cell division. Also called antimitotic or antimicrotubule agents or mitotic inhibitors. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] 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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH]

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Thermal: Pertaining to or characterized by heat. [EU] Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] 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] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [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] Thymidine Phosphorylase: The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC 2.4.2.4. [NIH] Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [NIH] Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue

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culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tissue Polypeptide Antigen: Serological tumor marker composed of a molecular complex of cytokeratins 8, 18, and 19. It is used in the diagnosis and staging of bronchogenic carcinoma. [NIH] 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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] 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] Toxicologic: Pertaining to toxicology. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcutaneous: Transdermal. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group

Dictionary 337

or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [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] Transurethral: Performed through the urethra. [EU] 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] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Tretinoin: An important regulator of gene expression, particularly during growth and development and in neoplasms. Retinoic acid derived from maternal vitamin A is essential for normal gene expression during embryonic development and either a deficiency or an excess can be teratogenic. It is also a topical dermatologic agent which is used in the treatment of psoriasis, acne vulgaris, and several other skin diseases. It has also been approved for use in promyelocytic leukemia. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the

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appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] 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] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urethral Obstruction: Obstruction anywhere along the urethra. [NIH] Urethritis: Inflammation of the urethra. [EU] Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Uridine Diphosphate Glucuronic Acid: A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. [NIH]

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Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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]

Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Urothelium: The epithelial lining of the urinary tract. [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] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For

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dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] 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] Venous: Of or pertaining to the veins. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verruca: A circumscribed, cutaneous excrescence having a papilliferous surface; a small, circumscribed, epidermal tumor. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicoureteral: An abnormal condition in which urine backs up into the ureters, and occasionally into the kidneys, raising the risk of infection. [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] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [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]

Dictionary 341

Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wounds, Gunshot: Disruption of structural continuity of the body as a result of the discharge of firearms. [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] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

343

INDEX A Abdomen, 209, 213, 261, 271, 287, 294, 300, 302, 304, 314, 316, 331, 332, 335, 340 Abdominal, 214, 255, 261, 283, 285, 314, 316, 327, 328 Aberrant, 8, 172, 173, 261 Ablation, 62, 177, 261 Acceptor, 261, 282, 303, 314, 335, 337 Acetylcholine, 261, 275, 288, 311 Acetylcysteine, 35, 261 Acetyltransferases, 42, 99, 261 Acne, 191, 261, 337 Acne Vulgaris, 261, 337 Acoustic, 261, 300 Actin, 9, 14, 60, 261 Actinic keratosis, 191, 261 Acute leukemia, 186, 261, 287 Adaptability, 261, 274 Adaptation, 261, 308, 319 Adduct, 22, 23, 40, 43, 94, 262 Adenocarcinoma, 25, 30, 51, 156, 192, 262, 311, 322 Adenosine, 262, 268, 272, 317 Adenovirus, 54, 59, 61, 72, 78, 85, 122, 192, 262 Adjustment, 194, 261, 262 Adjuvant, 4, 37, 45, 57, 58, 76, 117, 122, 130, 140, 183, 193, 197, 198, 232, 245, 262, 291 Adjuvant Therapy, 117, 232, 262 Adrenal Glands, 262, 327 Adrenergic, 262, 284, 287, 333 Adverse Effect, 57, 63, 104, 262, 330 Aerobic, 193, 262, 307, 309, 314, 324 Aerobic Metabolism, 262, 314 Aerobic Respiration, 262, 314 Affinity, 262, 304, 321, 331 Age Groups, 5, 262 Aged, 80 and Over, 262 Agonist, 262, 284, 311 Airway, 26, 57, 263 Albumin, 23, 42, 263, 313, 318 Alertness, 263, 272 Alfalfa, 181, 263 Algorithms, 263, 270 Alkaline, 58, 263, 264, 272, 278, 314, 334 Alkaline Phosphatase, 58, 263 Alkaloid, 263, 272, 277, 311

Alkylating Agents, 263, 338 Alleles, 25, 172, 263, 303, 304 Allergic Rhinitis, 263, 272 Allium, 117, 139, 263 Allylamine, 263, 264 Alpha Particles, 263, 325 Alternative medicine, 219, 263 Alternative Splicing, 58, 263, 323 Aluminum, 128, 264 Amifostine, 154, 264 Amine, 23, 40, 42, 264 Amino Acid Sequence, 264, 265, 288, 291 Amino Acids, 41, 174, 201, 264, 277, 281, 291, 316, 320, 323, 328, 329, 333, 337 Aminolevulinic Acid, 72, 81, 101, 264 Ammonia, 264 Amplification, 27, 60, 170, 176, 264 Ampulla, 264, 286 Amygdalin, 130, 264 Anabolic, 264, 283, 288 Anaesthesia, 264, 298 Anal, 11, 18, 21, 264, 287, 309 Analgesic, 264, 297, 302, 333 Analog, 264, 290, 321 Analogous, 264, 336 Anaphylatoxins, 264, 278 Anaplasia, 265, 323 Anatomical, 114, 242, 265, 298, 304, 329 Anemia, 236, 256, 265, 272, 277, 290, 309 Anesthesia, 181, 263, 265 Angiogenesis, 9, 10, 12, 15, 20, 29, 50, 62, 112, 127, 139, 191, 265, 286, 305 Angiogenesis Factor, 20, 139, 265 Angiogenesis inhibitor, 15, 191, 265, 286 Angiosarcoma, 191, 265 Animal model, 6, 9, 17, 47, 59, 186, 265, 338 Anions, 263, 265, 301 Annealing, 265, 320 Anomalies, 52, 81, 180, 265, 334 Antagonism, 265, 272 Anthracycline, 91, 265, 282, 287 Antiangiogenic, 113, 265 Antibacterial, 265, 331 Antibiotic, 265, 271, 274, 282, 284, 287, 307, 316, 331 Antibodies, 4, 168, 176, 177, 179, 182, 187, 196, 199, 265, 296, 297, 305, 308, 318, 325

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Antibody therapy, 157, 265 Anticarcinogenic, 51, 266 Anticoagulant, 266, 323 Anticonvulsant, 266, 306 Antidote, 266, 303 Antifungal, 266, 302 Antigen-Antibody Complex, 266, 278 Anti-infective, 266, 290 Anti-Infective Agents, 266, 290 Anti-inflammatory, 41, 266, 274, 292, 297, 298, 302, 315, 318, 333 Anti-Inflammatory Agents, 266, 274 Antimetabolite, 266, 290 Antimicrobial, 266, 274, 276 Antimitotic, 266, 334 Antimony, 5, 266 Antineoplastic Agents, 193, 263, 266, 340 Antioxidant, 266, 267, 314 Antiproliferative, 190, 266 Antipruritic, 266, 277 Antipyretic, 266, 302 Antiviral, 261, 266, 288, 290, 300 Anuria, 266, 302 Anus, 264, 267, 271, 316, 326 Aorta, 267, 327 Applicability, 58, 267 Approximate, 18, 21, 267 Aqueous, 200, 267, 269, 281, 304 Arachidonate 12-Lipoxygenase, 267, 304 Arachidonate 15-Lipoxygenase, 267, 304 Arachidonate Lipoxygenases, 267, 304 Arachidonic Acid, 22, 267, 303, 322 Arginine, 264, 267, 281, 311, 313, 337 Aromatic, 23, 40, 42, 63, 68, 189, 267, 293, 317 Arsenicals, 6, 267 Arterial, 114, 125, 131, 210, 263, 267, 296, 323, 334 Arteries, 267, 271, 280, 307, 309, 335 Arterioles, 267, 271, 272, 309 Ascites, 59, 267 Ascorbic Acid, 22, 267, 296, 314 Assay, 7, 16, 45, 52, 53, 55, 95, 106, 124, 171, 172, 179, 180, 267, 278, 297 Astringents, 268, 306 Astrocytoma, 268, 292 Ataxia, 201, 235, 268, 334 ATP, 268, 284, 291, 317, 323, 335, 336 Atrophy, 235, 268 Attenuated, 268, 283 Atypical, 95, 134, 171, 173, 268 Autacoids, 268, 298

Autocrine Motility Factor, 9, 48, 179, 180, 268 Autologous, 59, 268 Autonomic, 261, 264, 268, 311 B Bacillus, 65, 68, 90, 91, 94, 104, 105, 106, 113, 184, 188, 224, 232, 268 Bacteriophage, 268, 336 Bacteriostatic, 263, 268 Bacterium, 268, 279 Bacteriuria, 268, 339 Basal cell carcinoma, 29, 191, 268 Basal cells, 268, 269 Basal Ganglia, 268, 269, 292 Basal Ganglia Diseases, 268, 269 Base, 11, 12, 18, 26, 27, 80, 189, 268, 269, 281, 282, 288, 291, 301, 302, 319, 330, 334 Basement Membrane, 7, 269, 273, 288, 302 Basophils, 269, 294, 303 Benign, 43, 62, 100, 169, 170, 171, 177, 184, 208, 210, 269, 292, 294, 310, 315, 322, 325 Benign prostatic hyperplasia, 62, 169, 170, 177, 208, 210, 269 Benzene, 8, 269, 301 Benzo(a)pyrene, 15, 269 Beta-Glucosidase, 130, 269 Beta-Thromboglobulin, 269, 300 Bilateral, 19, 69, 269 Bile, 83, 269, 270, 286, 290, 292, 304, 332 Bile Acids, 269, 332 Bile Acids and Salts, 269 Bilirubin, 263, 270, 292 Bioavailability, 44, 270 Biological Markers, 52, 270 Biological response modifier, 270, 300 Biological therapy, 10, 145, 158, 270, 294 Biological Transport, 270, 283 Biopsy, 8, 9, 26, 43, 57, 181, 244, 257, 270 Biosynthesis, 267, 270, 329, 338 Biotechnology, 64, 65, 206, 219, 231, 234, 235, 236, 270 Biotransformation, 108, 270 Bladder Neoplasms, 161, 171, 270 Blasts, 216, 270 Blood Coagulation, 270, 272, 335 Blood Glucose, 271, 295, 299 Blood pressure, 271, 296, 308, 331 Blot, 7, 59, 101, 271 Body Fluids, 270, 271, 284, 331, 338 Bone Marrow, 59, 261, 269, 271, 297, 304, 308, 321, 331, 332, 335 Bone metastases, 271, 290

Index 345

Boron, 271, 280 Bowel, 264, 271, 283, 300, 332 Bowel Movement, 271, 283, 332 Brachytherapy, 271, 300, 301, 325, 341 Bradykinin, 271, 311, 318 Brain metastases, 129, 271 Branch, 25, 114, 253, 271, 281, 304, 315, 324, 327, 331, 334 Breakdown, 199, 271, 283, 291 Broad-spectrum, 271, 274 Bronchi, 25, 271, 287, 305, 336 Bronchoscope, 57, 271 Bronchoscopy, 57, 271 Buccal, 26, 63, 271 Buccal mucosa, 26, 271 Budesonide, 15, 272 C Cadaver, 58, 272 Cadmium, 64, 272 Cadmium Poisoning, 272 Caffeine, 25, 272 Calcium, 50, 57, 93, 183, 272, 278, 290, 296, 303, 305, 315, 330, 334 Calcium Oxalate, 93, 272 Calculi, 272 Callus, 272, 302 Camptothecin, 124, 130, 272, 301 Capillary, 32, 271, 272, 340 Capsules, 181, 272, 291 Carbogen, 155, 272 Carbohydrate, 56, 272, 293, 312, 320 Carbon Dioxide, 272, 327 Carboplatin, 125, 127, 135, 149, 151, 272 Carcinoembryonic Antigen, 187, 272 Carcinogen, 13, 23, 28, 33, 35, 36, 40, 42, 50, 63, 179, 262, 269, 273, 307, 309, 335 Carcinogenesis, 7, 8, 13, 14, 18, 19, 21, 28, 35, 44, 48, 51, 54, 68, 99, 110, 172, 273, 275 Carcinogenic, 6, 8, 29, 35, 37, 172, 263, 269, 273, 277, 299, 311, 313, 321, 332, 338 Carcinoma in Situ, 43, 46, 61, 65, 152, 172, 184, 186, 245, 273 Cardiac, 57, 263, 272, 273, 280, 287, 309, 332 Cardiotoxicity, 273, 287 Cardiovascular, 33, 273, 303 Carotene, 142, 273 Carotenoids, 12, 88, 91, 114, 129, 273 Case report, 94, 273, 276 Case series, 273, 276 Case-Control Studies, 5, 273, 287

Caspase, 54, 273 Catecholamine, 273, 284 Catheterization, 188, 273, 301 Catheters, 188, 273, 298, 300 Caudal, 273, 320 Causal, 6, 8, 10, 29, 273, 287, 328 Cause of Death, 59, 169, 191, 273 Cefaclor, 93, 274 Celecoxib, 13, 49, 147, 274 Cell Adhesion, 9, 61, 274, 300 Cell Cycle, 10, 12, 13, 30, 35, 38, 54, 96, 114, 201, 274, 276, 281, 288, 321, 323 Cell Death, 53, 59, 113, 173, 184, 267, 274, 288, 309 Cell Differentiation, 179, 274, 330 Cell Division, 235, 268, 274, 281, 288, 294, 300, 307, 318, 329, 334 Cell membrane, 196, 270, 274, 282, 301, 317 Cell motility, 60, 130, 268, 274 Cell proliferation, 15, 35, 59, 60, 190, 274, 323, 330 Cell Respiration, 262, 274, 307, 314, 327 Cell Survival, 10, 59, 274, 294 Cellobiose, 274 Cellulose, 22, 274, 318 Central Nervous System, 261, 269, 272, 274, 291, 292, 294, 303, 316 Cephalexin, 274 Cerebellar, 268, 274, 326 Cerebral, 268, 269, 274, 275, 287, 292 Cerebral hemispheres, 269, 274, 275, 292 Cerebrospinal, 274, 275, 330 Cerebrospinal fluid, 275, 330 Cerebrovascular, 33, 269, 275, 334 Cerebrum, 274, 275, 338 Cervical, 169, 275 Cervix, 176, 196, 275, 327 Checkup, 209, 275 Chemoembolization, 208, 275 Chemoprevention, 14, 36, 42, 48, 55, 116, 124, 147, 153, 275 Chemopreventive, 12, 13, 14, 35, 49, 54, 112, 275, 289 Chemosensitivity assay, 47, 275 Chemotactic Factors, 275, 278 Chlorine, 56, 275 Chlorine Compounds, 56, 275 Cholesterol, 195, 269, 275, 328, 332 Choline, 108, 141, 275 Cholinergic, 275, 311 Chromatin, 168, 267, 275, 286, 311

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Bladder Cancer

Chromium, 64, 275 Chromosomal, 6, 8, 30, 53, 56, 71, 81, 180, 264, 275, 276, 318, 328, 334 Chromosome, 8, 60, 66, 82, 92, 93, 97, 144, 235, 276, 279, 291, 294, 303, 304, 329, 334 Chronic, 6, 9, 30, 33, 185, 208, 210, 235, 258, 261, 276, 283, 286, 294, 299, 302, 303, 319, 324, 332, 339, 341 Chronic Disease, 30, 276, 303 Chronic leukemia, 276, 294 Chronic prostatitis, 208, 276 Chronic renal, 276, 319 Ciprofloxacin, 103, 276 CIS, 29, 58, 72, 172, 184, 186, 193, 241, 276 Citrus, 267, 276 Clear cell carcinoma, 276, 283 Clinical Medicine, 276, 320 Clinical study, 65, 72, 276 Clonic, 276, 306 Cloning, 270, 276 Coagulation, 211, 270, 276, 295, 302, 318 Coal, 128, 269, 276, 277 Coal Tar, 128, 277 Cobalt, 64, 277 Codon, 53, 76, 172, 277, 291 Coenzyme, 261, 267, 277, 311 Cofactor, 277, 311, 323, 335 Cohort Studies, 277, 287 Colchicine, 277, 338 Collagen, 15, 269, 277, 289, 291, 305, 319, 321 Collapse, 271, 277 Colloidal, 263, 277, 285 Colonoscopy, 58, 277 Colorectal, 19, 26, 31, 40, 47, 50, 55, 58, 170, 277, 323 Colorectal Cancer, 19, 40, 50, 55, 58, 170, 277, 323 Combination chemotherapy, 22, 117, 125, 139, 148, 149, 150, 151, 152, 157, 159, 160, 277 Combination Therapy, 94, 207, 277 Combined Modality Therapy, 112, 124, 277 Comet Assay, 85, 278 Comorbidity, 47, 278 Compassionate, 203, 207, 278 Complement, 7, 88, 95, 100, 185, 264, 278, 299, 318 Complementary and alternative medicine, 121, 142, 278 Complementary medicine, 121, 278

Complementation, 55, 278 Computational Biology, 231, 234, 278 Computed tomography, 75, 198, 279 Computerized axial tomography, 279 Computerized tomography, 279 Conception, 279, 289, 332 Concomitant, 15, 29, 66, 72, 82, 209, 279 Confounding, 5, 51, 279 Conjugated, 130, 169, 179, 182, 269, 279, 281, 311, 312, 328 Conjugation, 41, 270, 279 Connective Tissue, 9, 198, 267, 271, 277, 279, 289, 291, 304, 306, 328 Connective Tissue Cells, 279 Consumption, 5, 12, 25, 37, 63, 81, 95, 110, 112, 116, 139, 279, 283, 327 Contamination, 5, 63, 279 Contraindications, ii, 279 Contralateral, 279, 289, 326 Conventional therapy, 29, 279, 280 Conventional treatment, 280 Coordination, 20, 280 Cornea, 280, 293, 332 Coronary, 12, 191, 280, 307, 309 Coronary Disease, 191, 280 Coronary Thrombosis, 280, 307, 309 Coronary Vessels, 280 Corpus, 280, 316 Cortex, 268, 280, 326 Cortisol, 263, 280 Cowpox, 280, 339 Cowpox Virus, 280, 339 Criterion, 174, 280 Crossing-over, 280, 326 Cross-Sectional Studies, 280, 287 Cruciferous vegetables, 50, 280 Curative, 40, 280, 334 Curcumin, 191, 280 Cutaneous, 19, 100, 280, 293, 303, 339, 340 Cyclic, 272, 280, 294, 311, 322 Cyclin, 12, 37, 69, 80, 281 Cyclin-Dependent Kinases, 12, 281 Cyclophosphamide, 224, 281, 297 Cysteine, 142, 173, 174, 182, 261, 281, 301, 333 Cystine, 281 Cystinuria, 210, 281 Cystitis, 32, 43, 184, 185, 190, 197, 203, 207, 209, 210, 281, 314 Cystoscopy, 7, 58, 87, 103, 152, 170, 240, 243, 244, 257, 281 Cytochrome, 43, 99, 281

Index 347

Cytogenetics, 18, 82, 98, 281 Cytokine, 22, 69, 202, 281, 300, 329 Cytoplasm, 182, 267, 269, 274, 281, 286, 294, 328 Cytosine, 189, 281, 282 Cytoskeleton, 176, 197, 281, 299, 307 Cytotoxic, 47, 53, 72, 126, 193, 281, 325, 330 Cytotoxic chemotherapy, 72, 281 Cytotoxicity, 78, 89, 113, 130, 192, 194, 263, 276, 281 D Data Collection, 18, 281 Databases, Bibliographic, 231, 282 Daunorubicin, 282, 284 De novo, 41, 282 Defense Mechanisms, 282, 300 Degenerative, 282, 295, 313, 327 Deletion, 170, 267, 282, 304 Denaturation, 282, 320 Density, 31, 56, 66, 86, 99, 282, 313, 321 Deoxycytidine, 48, 282 Deoxycytidine Kinase, 48, 282 Deoxycytidine Monophosphate, 282 Deoxyguanosine, 22, 282 Deoxyribonucleic, 173, 189, 282 Deoxyribonucleic acid, 173, 189, 282 Deoxyribonucleotides, 282 Depolarization, 282, 330 Dermatitis, 282, 285 Dermatology, 16, 210, 282 DES, 24, 148, 152, 264, 282 Detoxification, 35, 37, 63, 283, 292 Developed Countries, 283, 290 Diabetes Mellitus, 283, 295, 316 Diagnostic procedure, 152, 167, 219, 283 Dialysate, 283, 285 Diaphragm, 188, 283 Diastolic, 283, 296 Diathesis, 117, 139, 283 Diethylcarbamazine, 283, 333 Diffusion, 127, 136, 270, 283, 299 Digestion, 269, 270, 271, 283, 300, 304, 332 Digestive system, 165, 283, 308 Digestive tract, 283, 330, 332 Dihydrotestosterone, 283, 326 Dilatation, 283, 321, 340 Dilution, 174, 283 Diploid, 278, 283, 318, 319 Direct, iii, 7, 12, 17, 30, 32, 45, 46, 58, 223, 276, 283, 284, 294, 326 Disease Progression, 36, 45, 193, 198, 283

Dissection, 209, 283, 304 Dissociation, 262, 283, 301 Distal, 76, 175, 188, 209, 284, 324 Diuresis, 272, 284 DNA Topoisomerase, 284, 291 Docetaxel, 47, 134, 224, 284 Dopamine, 37, 284, 317 Dorsal, 284, 320 Dose-dependent, 13, 284 Drive, ii, vi, 27, 32, 34, 46, 111, 115, 284 Drug Interactions, 225, 284 Drug Resistance, 15, 39, 56, 284 Drug Tolerance, 284 Duct, 83, 264, 273, 284, 288, 328 Duodenum, 269, 285, 286, 332 Dwell time, 47, 174, 285 Dyes, 11, 87, 188, 218, 269, 285, 290, 294, 317 Dysmenorrhea, 285, 318 Dysplasia, 172, 236, 285 Dystrophic, 191, 285, 287 Dystrophy, 235, 285 E Ecosystem, 56, 285 Eczema, 191, 285 Edema, 285, 309, 310 Effector, 53, 261, 278, 285, 310 Efficacy, 7, 10, 11, 13, 14, 15, 29, 35, 44, 47, 60, 62, 91, 104, 113, 139, 184, 198, 200, 285, 337 Elastin, 277, 285, 289 Elective, 103, 285 Electric Conductivity, 189, 285 Electrocoagulation, 276, 285 Electrolyte, 285, 302, 331 Electrons, 266, 269, 285, 301, 314, 325 Electrophoresis, 32, 278, 285 Embryo, 274, 285, 298 Empirical, 209, 285 Encapsulated, 285, 304 Endemic, 8, 9, 116, 285, 331 Endocrinology, 286, 294 Endometrial, 31, 286 Endometrium, 286 Endoscope, 194, 286 Endoscopic, 43, 58, 193, 194, 232, 271, 277, 281, 286, 305 Endoscopy, 44, 57, 81, 286 Endostatin, 15, 286 Endothelial cell, 15, 38, 73, 80, 286, 289, 300, 335 Endothelium, 286, 311, 319

348

Bladder Cancer

Endothelium-derived, 286, 311 Endotoxin, 286, 338 End-stage renal, 276, 286, 319 Enterohepatic, 286, 333 Enterohepatic Circulation, 286, 333 Enteropeptidase, 286, 337 Environmental Exposure, 10, 18, 24, 30, 33, 39, 51, 56, 270, 286, 313 Environmental Health, 5, 6, 33, 56, 74, 113, 146, 230, 232, 243, 286 Environmental Pollutants, 286, 319 Enzymatic, 22, 40, 272, 273, 278, 281, 286, 289, 320 Eosinophils, 286, 294, 303 Epidemic, 181, 286, 331 Epidemiologic Studies, 19, 20, 56, 270, 287 Epidemiological, 9, 13, 23, 27, 29, 63, 80, 114, 287 Epidermal, 16, 29, 36, 46, 52, 78, 94, 130, 182, 187, 287, 301, 306, 340 Epidermal Growth Factor, 16, 36, 46, 52, 94, 130, 182, 187, 287 Epidermis, 268, 269, 287, 301 Epidermoid carcinoma, 287, 332 Epidermolysis Bullosa, 191, 287 Epigastric, 287, 314 Epinephrine, 262, 284, 287, 311, 338 Epirubicin, 112, 126, 193, 217, 287 Epithelial Cells, 32, 35, 54, 287, 295, 302, 322 Epithelium, 35, 43, 59, 176, 180, 196, 198, 269, 286, 287, 322 Erectile, 208, 210, 287, 316 Erection, 287 Erythrocytes, 265, 271, 287, 326 Escalation, 56, 287 Esophagus, 19, 176, 196, 283, 287, 305, 317, 326, 332 Essential Tremor, 235, 288 Estrogens, 34, 288 Ethidium, 288, 321 Ethnic Groups, 19, 40, 288 Etoposide, 58, 132, 224, 288 Eukaryotic Cells, 288, 298, 312, 313 Evaluable patients, 48, 288 Excipients, 288, 290, 317 Excrete, 266, 288, 302, 327 Exocrine, 288, 314 Exogenous, 20, 270, 285, 288, 292, 323 Exon, 26, 264, 288 Exotoxin, 174, 182, 288 Expert Systems, 288, 297

Extensor, 288, 324 External-beam radiation, 288, 301, 325, 341 Extracellular, 34, 176, 197, 202, 279, 288, 289, 299, 305, 331, 334 Extracellular Matrix, 34, 279, 288, 289, 299, 305 Extracellular Matrix Proteins, 288, 305 Extracellular Space, 288, 289 Extraction, 232, 289 Extrapyramidal, 284, 289 Eye Infections, 262, 289 F Family Health, 210, 289 Family Planning, 231, 289 Farnesyl, 13, 15, 289 Fat, 37, 57, 267, 270, 271, 273, 289, 303, 304, 305, 312, 319, 320, 331 Fatty acids, 263, 289, 304, 322 Feces, 273, 289, 332 Fenretinide, 48, 153, 289 Fetus, 57, 289, 339 Fibrinogen, 289, 318, 335 Fibrinolytic, 289, 302 Fibroblast Growth Factor, 14, 97, 191, 289 Fibroblasts, 31, 172, 279, 289, 300, 308 Fibronectin, 80, 289 Fibrosis, 236, 263, 289, 329 Flavopiridol, 114, 290 Flavoring Agents, 290, 317 Fluorescence, 23, 81, 87, 95, 101, 171, 288, 290 Fluorouracil, 73, 89, 97, 121, 156, 290, 303 Folate, 290 Fold, 7, 22, 31, 43, 47, 290 Folic Acid, 50, 290, 303 Food Additives, 181, 290 Food Coloring Agents, 290 Food Preservatives, 290 Fungi, 266, 279, 289, 290, 294, 307, 341 G Gallbladder, 261, 283, 290 Gallium, 28, 83, 224, 290 Gallium nitrate, 28, 83, 290 Gamma Rays, 290, 309, 325 Gamma-interferon, 290, 300 Ganglia, 261, 264, 269, 290, 310 Ganglioside, 56, 84, 291 Gas, 53, 264, 272, 275, 283, 291, 296, 309, 311 Gasoline, 269, 291 Gastric, 287, 291

Index 349

Gastrin, 291, 295 Gastrointestinal, 47, 159, 271, 272, 273, 276, 287, 291, 303, 318, 333, 335, 338 Gastrointestinal tract, 273, 291, 303, 338 Gelatin, 291, 293 Gels, 181, 291 Gene Amplification, 60, 81, 291 Gene Expression, 13, 20, 25, 29, 31, 39, 45, 48, 61, 87, 94, 107, 130, 168, 236, 291, 337 Genetic Code, 291, 312 Genetic Markers, 18, 20, 29, 37, 291 Genetic testing, 291, 320 Genetics, 13, 18, 26, 82, 97, 98, 114, 279, 281, 291, 315 Genistein, 130, 291 Genital, 276, 292, 294, 339 Genitourinary, 4, 28, 47, 115, 193, 204, 206, 210, 292, 339 Genomics, 44, 292 Genotype, 19, 25, 86, 116, 292, 317 Geriatric, 208, 292 Germ cell tumors, 56, 292 Germ Cells, 186, 292, 314, 331, 334 Gland, 292, 304, 314, 315, 318, 322, 329, 332, 333, 335 Glioblastoma, 62, 169, 292 Glomerular, 292, 302 Glomeruli, 292, 324 Glomerulonephritis, 210, 292 Glomerulus, 292, 310 Glucocorticoid, 272, 292 Glucose, 235, 267, 269, 271, 274, 275, 283, 292, 293, 295, 299 Glucuronic Acid, 292, 338 Glucuronides, 43, 292 Glutamic Acid, 290, 292, 321 Glutathione Peroxidase, 292, 329 Glutathione Transferase, 35, 293 Glycine, 172, 264, 269, 293, 329 Glycoprotein, 62, 79, 116, 126, 134, 138, 272, 289, 293, 302, 308, 335, 338 Glycosaminoglycan, 38, 185, 293 Glycoside, 264, 293 Glycosylation, 15, 293 Gonorrhoea, 293, 313 Governing Board, 293, 320 Grading, 26, 245, 293 Graft, 293, 296, 298 Graft Rejection, 293, 298 Grafting, 293, 298 Gram-negative, 274, 293, 324 Gram-positive, 274, 293, 309

Granulocytes, 294, 303, 330, 341 Granulomas, 191, 294 Grasses, 290, 294 Groin, 294, 299 Growth factors, 179, 182, 294 Guanylate Cyclase, 294, 311 Gynecology, 106, 210, 294 H Habitat, 294, 309 Hair Color, 294 Hair Dyes, 99, 218, 294 Hair follicles, 294, 341 Hairy cell leukemia, 19, 294 Half-Life, 294, 318 Haploid, 294, 318, 319 Hazardous Substances, 56, 294 Headache, 272, 294 Health Status, 289, 294 Hematuria, 184, 210, 240, 256, 294 Heme, 264, 270, 281, 294 Hemodialysis, 283, 294, 302 Hemoglobin, 40, 265, 287, 294, 295 Hemoglobin A, 40, 295 Hemoglobinuria, 235, 295 Hemorrhage, 285, 294, 295, 332 Hemostasis, 295, 300 Hepatic, 42, 56, 263, 295 Hepatitis, 202, 295 Hepatocytes, 295 Hereditary, 19, 20, 55, 295, 316, 327 Heredity, 261, 291, 295 Herpes, 282, 295 Heterodimers, 295, 299 Heterogenic, 295 Heterogenous, 179, 187, 295 Histiocytosis, 94, 295 Histology, 295, 315 Histone Deacetylase, 56, 295 Homogeneous, 102, 127, 179, 295 Homologous, 21, 201, 263, 280, 295, 323, 329, 333 Hormonal, 19, 50, 181, 268, 295 Hormone, 50, 177, 262, 270, 280, 282, 287, 291, 295, 296, 299, 309, 328, 330, 334, 335 Hormone therapy, 262, 296 Horseradish Peroxidase, 22, 296 Host, 177, 179, 192, 199, 268, 296, 297, 298, 303, 308, 328, 339, 340 Humoral, 293, 296, 297 Hyaluronidase, 38, 184, 296 Hybrid, 182, 296 Hybridization, 56, 83, 296

350

Bladder Cancer

Hybridomas, 296, 300 Hydrogen, 261, 264, 269, 272, 282, 289, 292, 296, 303, 308, 310, 312, 314, 317, 323 Hydrolysis, 269, 270, 274, 276, 296, 317, 320, 323, 337 Hydrophobic, 296, 301 Hydroxylysine, 277, 296 Hydroxyproline, 277, 296 Hypercalcemia, 290, 296 Hyperplasia, 9, 62, 208, 296 Hypertension, 210, 294, 296 Hyperthermia, 117, 138, 208, 296, 309 Hypertrophy, 269, 296 Hypoxia, 89, 297, 334 Hysterectomy, 211, 297 I Ibuprofen, 297, 302 Id, 118, 141, 240, 245, 246, 252, 254, 297 Ifosfamide, 28, 130, 150, 297 Ileal, 87, 100, 214, 297 Ileum, 297 Image Cytometry, 101, 297 Imaging procedures, 297, 336 Imidazole, 24, 297 Immune response, 60, 90, 93, 158, 163, 197, 262, 266, 293, 297, 298, 333, 339, 340 Immune system, 145, 157, 158, 162, 173, 266, 270, 297, 298, 303, 305, 339, 341 Immunity, 32, 60, 297 Immunization, 297, 298 Immunoassay, 26, 101, 297 Immunocompetence, 127, 297 Immunodeficiency, 235, 297 Immunogenic, 183, 297 Immunoglobulin, 185, 265, 297, 308 Immunohistochemistry, 7, 12, 16, 21, 42, 59, 101, 109, 297 Immunologic, 275, 297, 325 Immunology, 177, 262, 296, 297 Immunosuppressant, 263, 290, 298 Immunosuppressive, 281, 292, 297, 298 Immunosuppressive therapy, 298 Immunotherapy, 15, 58, 90, 92, 104, 193, 197, 198, 204, 216, 232, 270, 298, 309 Immunotoxin, 163, 298 Impairment, 268, 289, 298, 306 Implant radiation, 298, 300, 301, 325, 341 Implantation, 38, 44, 67, 70, 189, 279, 298 Impotence, 208, 210, 287, 298 In situ, 27, 45, 55, 81, 95, 174, 185, 232, 298 In Situ Hybridization, 55, 81, 95, 174, 298 Incision, 298, 301, 316, 322, 328

Incontinence, 77, 203, 207, 208, 209, 210, 256, 298 Incubation, 43, 298, 316 Indicative, 170, 171, 204, 298, 315, 339 Indolent, 38, 298 Indomethacin, 22, 298 Induction, 4, 22, 35, 45, 49, 54, 60, 90, 94, 106, 298 Infant, Newborn, 262, 298 Infarction, 269, 280, 298, 307, 309 Infertility, 210, 299, 339 Infiltration, 89, 292, 299 Informed Consent, 9, 20, 299 Ingestion, 29, 272, 294, 299, 319, 334 Inguinal, 209, 299 Inhalation, 25, 294, 299, 319 Initiation, 6, 22, 24, 32, 41, 43, 299 Inlay, 299, 327 Inorganic, 267, 275, 276, 299, 308 Inositol, 34, 299 Inotropic, 284, 299 Insecticides, 299, 317 Insight, 13, 42, 45, 55, 299 Instillation, 47, 60, 104, 174, 193, 232, 299 Insulin, 11, 34, 299 Insulin-dependent diabetes mellitus, 299 Insulin-like, 34, 299 Integrins, 9, 299 Intercellular Adhesion Molecule-1, 74, 96, 100, 300 Interferometry, 43, 300 Interferon, 4, 22, 34, 93, 94, 196, 202, 290, 300 Interferon-alpha, 300 Interleukin-6, 69, 78, 100, 300 Interleukin-8, 106, 300 Internal Medicine, 58, 286, 300, 306 Internal radiation, 300, 301, 325, 341 Interphase, 85, 300, 312 Interstitial, 32, 185, 190, 197, 203, 207, 208, 209, 210, 271, 289, 300, 301, 310, 314, 341 Intestinal, 273, 286, 300, 305 Intestine, 269, 271, 277, 286, 300, 302 Intoxication, 300, 339 Intracellular, 53, 61, 173, 176, 197, 202, 272, 298, 299, 300, 311, 322, 329, 330 Intravenous, 3, 125, 135, 244, 257, 300 Intravenous pyelogram, 244, 257, 300 Intrinsic, 262, 269, 300 Intubation, 273, 301 Involuntary, 208, 269, 288, 301, 309 Iodoacetic Acid, 202, 301

Index 351

Ionization, 24, 301 Ionizing, 263, 286, 301, 325 Ions, 269, 283, 285, 296, 301 Irinotecan, 154, 301 Irradiation, 138, 301, 341 Ischemia, 268, 291, 301 Isoflavones, 135, 181, 301 Isoprenoids, 116, 138, 301 Isothiocyanates, 35, 301 Isotonic, 183, 301, 307 J Joint, 184, 276, 301, 313, 333 K Kb, 172, 201, 230, 301 Keratinocytes, 300, 301 Keratosis, 191, 261, 302 Ketoconazole, 202, 302 Ketoprofen, 15, 302 Keyhole, 92, 162, 163, 183, 302 Keyhole limpet hemocyanin, 92, 163, 183, 302 Kidney Disease, 165, 210, 230, 236, 302 Kidney Failure, 210, 286, 302 Kidney Failure, Acute, 302 Kidney Failure, Chronic, 302 Kidney Pelvis, 302, 338 Kinetics, 47, 302 Kringles, 85, 302 L Labile, 43, 278, 302 Laminin, 269, 289, 302 Laparoscopes, 213, 302 Large Intestine, 277, 283, 300, 302, 326, 330 Latency, 14, 34, 302 Latent, 69, 303, 321 Lectin, 303, 307 Leishmaniasis, 202, 303, 316 Lesion, 9, 57, 170, 172, 303, 304 Lethal, 97, 173, 177, 191, 211, 303, 309 Leucocyte, 303 Leucovorin, 73, 303 Leukaemia, 116, 138, 303 Leukemia, 8, 19, 28, 56, 59, 98, 147, 153, 169, 202, 235, 284, 303, 321, 323 Leukocytes, 25, 126, 269, 271, 275, 286, 294, 298, 300, 303, 308, 316, 338 Leukotrienes, 267, 303 Levamisole, 202, 303 Library Services, 252, 303 Ligament, 303, 322 Ligands, 41, 173, 299, 303 Linkage, 19, 274, 291, 303

Linkage Disequilibrium, 19, 303 Lipid, 195, 275, 299, 303, 314 Lipid Peroxidation, 303, 314 Lipophilic, 23, 304, 319 Liposomal, 4, 304 Lipoxygenase, 13, 267, 303, 304 Liquor, 304, 324 Liver, 42, 43, 80, 169, 261, 263, 267, 269, 281, 283, 286, 289, 290, 292, 295, 304 Liver cancer, 169, 304 Localization, 7, 45, 53, 178, 297, 304 Localized, 50, 114, 131, 150, 151, 200, 285, 298, 302, 304, 318 Locomotion, 304, 318 Locoregional, 208, 304 Loss of Heterozygosity, 52, 75, 88, 304 Lumen, 45, 171, 188, 304 Lycopene, 50, 304 Lymph, 57, 90, 94, 171, 198, 209, 275, 286, 304, 305, 311, 326, 333 Lymph node, 90, 171, 198, 209, 275, 304, 305, 311, 326 Lymphadenectomy, 80, 209, 304 Lymphatic, 185, 286, 299, 304, 306, 331, 335 Lymphatic system, 304, 331, 335 Lymphocele, 209, 304 Lymphocyte, 94, 266, 305, 308 Lymphoid, 19, 265, 297, 303, 305 Lymphoma, 8, 200, 201, 202, 235, 305 Lymphoproliferative, 200, 201, 305 Lysine, 281, 296, 305, 337 M Macronutrients, 137, 305 Macrophage, 89, 113, 202, 305 Magnetic Resonance Imaging, 41, 198, 305 Maintenance therapy, 106, 305 Malabsorption, 235, 305 Malignancy, 43, 47, 58, 168, 197, 200, 201, 305 Malignant tumor, 47, 179, 189, 197, 273, 305, 308 Malnutrition, 263, 268, 305, 309 Mammary, 44, 305 Matrix metalloproteinase, 9, 29, 94, 305 Meat, 50, 305 Mediastinoscopy, 58, 305 Mediastinum, 305 Mediate, 22, 39, 51, 122, 284, 305 Mediator, 108, 305, 319 Medical Oncology, 4, 78, 79, 115, 116, 121, 306

352

Bladder Cancer

Medicament, 263, 306 MEDLINE, 231, 232, 234, 236, 306 Medullary, 210, 306 Megaloblastic, 290, 306 Melanin, 306, 317, 338 Melanocytes, 306 Melanoma, 5, 19, 29, 169, 191, 202, 235, 306 Menopause, 306, 321 Mental Disorders, 165, 306, 324 Mental Health, iv, 4, 165, 230, 233, 306, 324 Mephenytoin, 25, 306 Mercury, 56, 64, 306 Mesenchymal, 287, 306 Meta-Analysis, 91, 96, 306 Metabolite, 40, 43, 270, 303, 306, 321 Metastasize, 184, 306, 329 Metastatic cancer, 45, 306 Methylcholanthrene, 177, 307 MI, 14, 115, 179, 259, 307 Microbe, 307, 336 Microbiology, 261, 268, 307 Micronutrients, 137, 307 Microorganism, 277, 307, 315, 340 Micro-organism, 285, 307 Microscopy, 43, 269, 296, 307, 312 Microscopy, Polarization, 43, 307 Microtubules, 307, 314 Migration, 60, 187, 300, 307 Miscible, 189, 307 Mistletoe lectin, 128, 307 Mitochondria, 103, 143, 307, 313 Mitochondrial Swelling, 307, 309 Mitomycin, 46, 71, 76, 79, 91, 123, 132, 145, 156, 193, 224, 232, 307 Mitosis, 266, 267, 307 Mitotic, 189, 284, 288, 307, 334, 340 Mitotic inhibitors, 284, 307, 334 Mitoxantrone, 65, 224, 307 Modeling, 18, 21, 48, 308 Modification, 99, 209, 308, 324 Monitor, 8, 52, 61, 273, 308, 311 Monoclonal, 3, 42, 130, 157, 176, 178, 182, 187, 196, 296, 301, 308, 325, 337, 341 Monoclonal antibodies, 3, 157, 176, 182, 196, 308, 337 Monocyte, 96, 107, 308 Monocyte Chemoattractant Protein-1, 96, 308 Mononuclear, 308, 338 Monophosphate, 22, 308

Monotherapy, 208, 308 Morphological, 43, 143, 168, 179, 285, 306, 308 Morphology, 43, 54, 61, 109, 168, 308 Motility, 9, 53, 60, 180, 298, 308 Mucocutaneous, 303, 308 Mucolytic, 261, 308 Mucosa, 12, 49, 85, 184, 188, 258, 308 Mucositis, 308, 335 Mucus, 189, 308 Multicenter study, 65, 87, 308 Multidrug resistance, 79, 134, 308 Multiple Myeloma, 202, 308 Multivariate Analysis, 137, 309 Muscle Fibers, 309 Muscular Atrophy, 235, 309 Muscular Dystrophies, 285, 309 Mustard Gas, 309 Mutagen, 19, 269, 309 Mutagenic, 172, 263, 309, 311 Mycobacterium, 173, 184, 309, 337 Myocardial Ischemia, 280, 309 Myocardium, 307, 309 Myotonic Dystrophy, 235, 309 N Nasopharynx, 11, 309 Necrosis, 99, 267, 292, 298, 307, 309 Neoadjuvant Therapy, 102, 309 Neoplasia, 20, 27, 113, 235, 310, 322 Neoplasm, 180, 310, 315, 328, 338 Neoplastic, 123, 171, 178, 192, 265, 296, 304, 305, 310, 328 Nephritis, 210, 310 Nephropathy, 302, 310 Nephrosis, 310 Nephrotic, 210, 310, 327 Nephrotic Syndrome, 210, 310, 327 Nerve, 185, 262, 265, 268, 305, 310, 320, 327, 329, 332, 337 Nerve Growth Factor, 185, 310 Nervous System, 235, 274, 305, 310, 333 Networks, 297, 310 Neural, 96, 97, 171, 296, 297, 310 Neuroblastoma, 20, 169, 310 Neurogenic, 17, 185, 310 Neurologic, 292, 310 Neurology, 210, 310 Neurons, 290, 310, 311, 333 Neurophysiology, 17, 282, 310 Neurotransmitters, 308, 310 Neutrons, 263, 301, 310, 325 Neutrophil, 300, 311

Index 353

Niacinamide, 155, 311 Nickel, 64, 185, 311 Nicotine, 25, 36, 311 Nitric Oxide, 113, 311 Nitrogen, 42, 69, 189, 263, 264, 281, 289, 302, 311, 337 Nitrosamines, 63, 311 Node-negative, 198, 311 Nonmetastatic, 171, 311 Non-small cell lung cancer, 56, 311 Norepinephrine, 262, 284, 311 Nuclear Matrix, 7, 95, 96, 107, 168, 173, 311 Nuclear Pore, 311 Nuclear Proteins, 168, 311 Nuclei, 263, 279, 285, 305, 307, 310, 312, 323 Nucleic acid, 170, 197, 199, 281, 288, 291, 296, 298, 311, 312 Nucleic Acid Hybridization, 296, 312 Nucleoli, 168, 312 Nucleolus, 311, 312, 328 Nucleoproteins, 311, 312 Nucleus, 168, 267, 269, 275, 280, 281, 286, 288, 290, 308, 310, 311, 312, 323, 332, 334 Nutritive Value, 290, 312 O Observational study, 77, 312 Obstetrics, 69, 106, 210, 312 Occult, 14, 27, 178, 198, 312 Occupational Exposure, 56, 171, 312 Ocular, 312, 313 Odds Ratio, 312, 327 Odour, 267, 312 Ointments, 312, 315 Oliguria, 302, 313 Onchocerciasis, 202, 313 Oncogene, 66, 82, 89, 106, 172, 176, 186, 196, 235, 313 Oncogenic, 27, 44, 46, 172, 300, 313, 323 Opacity, 282, 313 Ophthalmology, 69, 210, 313 Orchitis, 105, 313 Orderly, 189, 313 Organ Culture, 313, 336 Organ Preservation, 133, 313 Organelles, 281, 306, 313 Ornithine, 281, 313 Osmotic, 263, 307, 313 Osteoarthritis, 302, 313, 318 Osteosarcoma, 313, 323 Otolaryngology, 210, 313

Outpatient, 131, 313 Ovalbumin, 33, 313 Ovarian epithelial cancer, 163, 314 Ovaries, 314, 327, 330 Ovary, 50, 191, 314 Overall survival, 38, 314 Oxalic Acid, 272, 314 Oxidation, 43, 261, 266, 267, 270, 281, 292, 303, 314 Oxidation-Reduction, 270, 314 Oxidative metabolism, 43, 262, 303, 314 Oxidative Stress, 9, 314 Oxides, 293, 314 P P53 gene, 26, 45, 78, 102, 162, 314, 323 Painful bladder syndrome, 203, 314 Palate, 309, 314 Palliative, 135, 314, 334 Pancreas, 50, 191, 200, 201, 261, 270, 283, 299, 314, 337, 338 Pancreatic, 19, 41, 44, 163, 169, 235, 287, 314 Pancreatic cancer, 19, 41, 44, 235, 287, 314 Papilla, 315 Papillary, 46, 61, 82, 171, 180, 186, 193, 198, 245, 315 Papillary tumor, 46, 180, 186, 245, 315 Papilloma, 89, 315 Paraffin, 39, 56, 75, 315 Parasite, 8, 315 Parathyroid, 64, 315, 334 Parathyroid Glands, 315 Parathyroid hormone, 64, 315 Paroxysmal, 235, 315, 316 Particle, 315, 336 Parturition, 312, 315 Passive transport, 91, 315 Pathogen, 298, 315 Pathogenesis, 19, 46, 56, 185, 315 Pathologic, 37, 73, 133, 198, 267, 270, 280, 315, 324, 340 Pathologic Processes, 267, 315 Patient Advocacy, 38, 315 Patient Education, 244, 250, 252, 259, 315 PDQ, 241, 242, 246, 315 Pelvic, 80, 99, 112, 125, 209, 211, 315, 322 Penicillin, 265, 316, 339 Penis, 209, 316, 327 Pentamidine, 202, 316 Peptide, 41, 55, 56, 286, 289, 316, 320, 323, 325 Perfusion, 297, 316, 336

354

Bladder Cancer

Perineal, 209, 316 Perineal prostatectomy, 209, 316 Perineum, 316 Perioperative, 99, 135, 139, 211, 316 Perioperative Care, 211, 316 Peripheral blood, 26, 300, 316 Peritoneal, 267, 283, 285, 316 Peritoneal Cavity, 267, 316 Peritoneal Dialysis, 283, 285, 316 Peroxidase, 22, 267, 303, 316 Peroxide, 292, 303, 316 Pertussis, 268, 316 Pesticides, 19, 98, 115, 299, 317 Petroleum, 291, 315, 317 PH, 62, 75, 89, 108, 126, 141, 177, 208, 210, 317 Pharmaceutic Aids, 290, 317 Pharmaceutical Preparations, 274, 291, 317 Pharmacodynamic, 47, 56, 317 Pharmacokinetic, 48, 317 Pharmacologic, 265, 268, 294, 317, 336 Pharynx, 309, 317 Phenotype, 19, 38, 62, 94, 168, 172, 191, 270, 278, 317 Phenylalanine, 317, 338 Phospholipases, 317, 330 Phospholipids, 289, 299, 302, 317 Phosphorus, 272, 315, 317 Phosphorylated, 90, 277, 317 Phosphorylating, 202, 317 Phosphorylation, 60, 202, 281, 282, 317, 323 Photocoagulation, 276, 317 Photodynamic therapy, 127, 136, 317 Physical Examination, 210, 275, 318 Physiologic, 45, 99, 262, 270, 294, 301, 307, 318, 322, 326 Physiology, 189, 203, 210, 245, 261, 270, 286, 294, 310, 318 Pigment, 270, 304, 306, 318 Pilot study, 16, 19, 49, 318 Piritrexim, 134, 318 Piroxicam, 67, 124, 127, 318 Pitch, 128, 318 Pituitary Gland, 289, 318 Plants, 33, 181, 263, 272, 275, 276, 292, 293, 303, 307, 308, 311, 314, 318, 320, 324, 328, 336 Plasma cells, 265, 308, 318 Plasma protein, 263, 302, 318 Plasmid, 291, 318, 340

Plasmin, 318, 319 Plasminogen, 85, 318 Plasminogen Activators, 318 Plasticity, 94, 319 Platelet Activation, 319, 330 Platelet Aggregation, 264, 311, 319, 335 Platelet Factor 4, 300, 319 Platelets, 267, 269, 311, 319, 329 Platinum, 276, 319 Ploidy, 47, 48, 74, 112, 126, 319 Podophyllotoxin, 288, 319 Point Mutation, 170, 201, 319 Poisoning, 272, 300, 306, 319 Polychlorinated Biphenyls, 56, 319 Polycystic, 210, 236, 319 Polymerase, 16, 55, 319 Polymerase Chain Reaction, 16, 55, 319 Polymers, 195, 200, 320, 323 Polymorphic, 51, 320 Polymorphism, 66, 67, 76, 86, 88, 93, 320 Polypeptide, 105, 264, 277, 287, 289, 296, 318, 320, 341 Polyposis, 20, 277, 320 Polysaccharide, 266, 274, 293, 320, 323, 338 Polyunsaturated fat, 320, 335 Polyvalent, 56, 320 Posterior, 161, 264, 268, 284, 314, 320 Postoperative, 130, 209, 211, 214, 318, 320 Postsynaptic, 320, 330, 333 Potentiate, 6, 320 Potentiation, 194, 320, 330 Practicability, 320, 337 Practice Guidelines, 233, 245, 320 Precancerous, 15, 261, 275, 320, 321 Preclinical, 22, 100, 124, 320 Precursor, 39, 267, 275, 281, 284, 285, 286, 289, 311, 317, 318, 320, 321, 322, 337, 338, 339 Predictive factor, 112, 126, 321 Predisposition, 20, 30, 195, 200, 321 Pregnancy Maintenance, 288, 321 Premalignant, 14, 39, 49, 172, 320, 321, 322 Premenopausal, 19, 321 Prevalence, 8, 9, 40, 175, 312, 321 Primary tumor, 40, 41, 49, 176, 196, 321 Probe, 194, 201, 218, 321 Prodrug, 58, 321 Progeny, 30, 279, 321 Prognostic factor, 3, 47, 87, 100, 106, 112, 121, 132, 133, 137, 184, 321 Progressive, 146, 158, 274, 276, 284, 287, 294, 302, 309, 313, 319, 321, 338

Index 355

Proliferating Cell Nuclear Antigen, 86, 321 Proline, 277, 296, 321 Promoter, 29, 42, 45, 46, 51, 83, 93, 143, 186, 321 Promyelocytic leukemia, 321, 337 Prophylaxis, 189, 321, 339 Propidium, 55, 321 Proportional, 291, 321 Prospective Studies, 50, 321 Prospective study, 11, 16, 38, 122, 137, 322 Prostaglandin, 22, 43, 49, 79, 322, 335 Prostaglandins A, 49, 298, 322 Prostaglandins D, 322 Prostate gland, 177, 276, 322 Prostatectomy, 322 Prostate-Specific Antigen, 176, 196, 322 Prostatic Hyperplasia, 62, 322 Prostatic Intraepithelial Neoplasia, 51, 322 Prostatitis, 104, 208, 210, 323 Prosthesis, 175, 323 Protease, 277, 323 Protein Binding, 323, 336 Protein C, 39, 53, 201, 263, 264, 268, 277, 323 Protein Isoforms, 263, 323 Protein p53, 103, 323 Protein S, 182, 185, 202, 206, 236, 268, 270, 291, 323, 328 Protein-Tyrosine Kinase, 291, 323 Proteinuria, 309, 310, 323 Proteoglycans, 269, 289, 323 Proteolytic, 173, 278, 286, 289, 318, 323 Protocol, 20, 26, 58, 97, 323 Protons, 263, 296, 301, 323, 325 Proto-Oncogene Proteins, 314, 323 Proto-Oncogene Proteins c-mos, 314, 323 Proto-Oncogenes, 170, 172, 323 Protozoa, 279, 303, 307, 324, 337 Proximal, 209, 284, 324 Pruritic, 285, 324 Pruritus, 313, 324 Pseudomonas, 174, 182, 324 Psoriasis, 191, 277, 309, 324, 337 Psychiatric, 270, 306, 324 Psychiatry, 210, 324 Psyllium, 181, 324 Public Health, 4, 6, 9, 25, 50, 56, 63, 207, 233, 269, 324 Public Policy, 231, 324 Publishing, 64, 209, 324 Puerperium, 312, 324

Pulmonary, 33, 58, 271, 275, 279, 302, 303, 324 Pulmonary Edema, 275, 302, 324 Pulse, 308, 324 Pyelonephritis, 210, 324 Pyogenic, 191, 324 Q Quality of Life, 50, 87, 100, 324, 333 R Race, 5, 63, 307, 325 Radioactive, 294, 296, 298, 300, 301, 308, 311, 313, 325, 338, 341 Radioimmunotherapy, 277, 325 Radioisotope, 325, 336 Radiolabeled, 301, 325, 341 Radiotherapy, 3, 15, 66, 73, 99, 104, 105, 116, 125, 126, 138, 258, 271, 301, 325, 341 Random Allocation, 325 Randomization, 37, 325 Ras gene, 45, 325 Reactive Oxygen Species, 173, 325 Reagent, 54, 275, 314, 326 Receptivity, 60, 326 Recombinant, 199, 326, 340 Recombination, 55, 201, 279, 291, 326 Reconstitution, 53, 326 Rectal, 211, 326 Rectum, 50, 99, 267, 271, 277, 283, 291, 298, 302, 322, 326 Recur, 45, 46, 59, 198, 244, 326 Recurrent cancer, 149, 154, 155, 326 Red blood cells, 287, 326 Red Nucleus, 268, 326 Reductase, 35, 193, 326 Refer, 1, 271, 278, 290, 295, 304, 311, 325, 326 Reflux, 210, 326 Refraction, 326, 331 Refractory, 28, 94, 121, 130, 136, 154, 177, 184, 198, 216, 285, 326 Regeneration, 289, 326 Regimen, 12, 28, 46, 125, 127, 129, 135, 148, 149, 152, 208, 285, 326 Regional lymph node, 198, 326 Relapse, 4, 50, 60, 108, 139, 148, 189, 326 Relative risk, 31, 326 Reliability, 29, 327 Remission, 305, 326, 327 Renal Artery, 210, 327 Renal cell cancer, 124, 327 Renal tubular, 281, 327 Renal vein thrombosis, 210, 327

356

Bladder Cancer

Reproductive cells, 292, 327 Reproductive system, 322, 327 Research Support, 20, 327 Residual disease, 56, 327 Respiration, 272, 308, 327 Restoration, 81, 326, 327, 341 Retina, 265, 327, 328 Retinoblastoma, 20, 25, 53, 70, 102, 235, 327 Retinoid, 48, 51, 55, 169, 327 Retinopathy, 69, 317, 327 Retropubic, 209, 322, 328 Retropubic prostatectomy, 209, 328 Retrospective, 9, 39, 45, 328 Retrospective Studies, 9, 328 Retrovirus, 61, 328 Rheumatoid, 302, 318, 328 Rheumatoid arthritis, 302, 318, 328 Ribonucleoproteins, 311, 328 Ribose, 262, 328, 335 Ribosome, 328, 337 Rigidity, 318, 328 Risk factor, 5, 8, 19, 25, 34, 35, 39, 50, 51, 52, 287, 322, 326, 328 Risk patient, 37, 328 Rod, 268, 324, 328 Rodenticides, 317, 328 S Saccharin, 220, 328 Saline, 200, 328 Salivary, 283, 314, 328, 333 Salivary glands, 283, 328 Salvage Therapy, 278, 328 Sapogenins, 181, 328 Saponin, 328 Sarcoma, 20, 163, 191, 313, 328 Sargramostim, 158, 329 Scatter, 180, 329 Sclerosis, 235, 329 Screening, 7, 41, 70, 80, 170, 171, 176, 179, 180, 199, 216, 218, 242, 246, 276, 315, 329, 339 Scrotum, 209, 316, 329, 334 Sebaceous, 329, 341 Secondary tumor, 210, 306, 329 Secretion, 261, 287, 299, 308, 329 Secretory, 323, 329, 333 Sediment, 9, 32, 52, 329, 339 Segregation, 27, 30, 268, 326, 329 Seizures, 292, 315, 329 Selenium, 5, 11, 29, 50, 51, 329 Semen, 322, 329

Semisynthetic, 272, 274, 288, 329 Senile, 261, 329 Sensor, 30, 329 Sequencing, 7, 15, 54, 172, 320, 329 Serine, 322, 323, 329, 337 Serologic, 297, 329 Serous, 69, 286, 330 Serum, 11, 23, 32, 34, 51, 52, 74, 100, 103, 170, 187, 263, 264, 278, 301, 302, 326, 329, 330, 338 Sessile, 245, 330 Sex Characteristics, 288, 330, 334 Sex Determination, 235, 330 Shock, 72, 87, 330, 337 Shunt, 175, 330 Side effect, 154, 200, 223, 245, 246, 262, 270, 281, 318, 330, 333, 336 Signal Transduction, 34, 201, 299, 330 Signs and Symptoms, 326, 327, 330 Single-agent, 56, 330 Skeletal, 97, 308, 309, 330 Skeleton, 168, 261, 301, 322, 330 Skull, 330, 334 Small cell lung cancer, 330 Small intestine, 285, 296, 297, 300, 330, 337 Smallpox, 330, 339 Smooth muscle, 263, 264, 268, 272, 279, 331, 333 Social Environment, 324, 331 Sodium, 7, 134, 174, 201, 202, 220, 331 Soft tissue, 271, 330, 331 Solid tumor, 21, 169, 179, 265, 284, 286, 331 Solvent, 269, 313, 331 Soma, 331 Somatic, 8, 186, 296, 307, 331, 334 Somatic cells, 186, 307, 331 Specialist, 247, 331 Specificity, 10, 15, 16, 40, 41, 44, 47, 58, 101, 177, 262, 267, 331, 336 Spectrum, 19, 197, 200, 208, 216, 280, 302, 331 Sperm, 276, 292, 327, 331, 334, 338 Spinal cord, 7, 64, 268, 274, 275, 310, 331 Spinal Cord Injuries, 7, 331 Spleen, 304, 331 Sporadic, 18, 55, 327, 331 Squamous, 5, 25, 30, 60, 64, 156, 176, 191, 192, 196, 287, 311, 331, 332 Squamous cell carcinoma, 25, 30, 64, 156, 191, 192, 287, 311, 331, 332 Squamous cells, 331, 332

Index 357

Staging, 3, 26, 41, 43, 46, 58, 184, 198, 209, 245, 246, 332, 336 Steel, 332, 339 Sterile, 315, 332 Sterility, 281, 299, 332 Steroid, 269, 280, 292, 328, 332 Stimulant, 272, 332, 339 Stimulus, 284, 300, 302, 332, 335 Stoma, 214, 332 Stomach, 11, 194, 261, 283, 287, 291, 296, 316, 317, 326, 330, 331, 332 Stool, 170, 298, 302, 332 Strand, 278, 319, 332 Stress, 208, 256, 273, 280, 314, 321, 328, 332 Stroke, 165, 230, 332 Stroma, 31, 332 Stromal, 10, 31, 332 Subacute, 299, 332 Subclinical, 298, 329, 332 Subcutaneous, 183, 285, 313, 332 Submaxillary, 287, 333 Subspecies, 331, 333, 339 Substance P, 306, 326, 329, 333 Substrate, 22, 38, 60, 173, 193, 202, 285, 333 Substrate Specificity, 38, 333 Sulfur, 289, 293, 333 Sulindac, 15, 333 Supportive care, 36, 315, 333 Suppression, 54, 62, 333 Suramin, 156, 161, 202, 333 Survival Rate, 170, 314, 333 Sympathomimetic, 284, 287, 311, 333 Symphysis, 322, 333 Synaptic, 311, 330, 333 Synaptic Transmission, 311, 333 Synergistic, 17, 55, 57, 333 Synthetic retinoid, 54, 289, 334 Syphilis, 313, 334 Systemic therapy, 130, 334 Systolic, 296, 334 T Taxanes, 31, 48, 334 Telangiectasia, 201, 235, 334 Telomerase, 53, 68, 72, 75, 104, 334 Telomere, 53, 334 Temporal, 5, 334 Teratogenic, 263, 334, 337 Terminator, 277, 334 Testicles, 329, 334 Testicular, 28, 140, 334 Testis, 28, 313, 334 Testosterone, 326, 334

Tetany, 315, 334 Thalamic, 268, 334 Thalamic Diseases, 268, 334 Therapeutics, 17, 36, 41, 127, 143, 225, 334 Thermal, 283, 310, 320, 335 Thiotepa, 46, 224, 232, 335 Thoracic, 57, 283, 335, 341 Thorax, 261, 305, 335 Threshold, 171, 296, 335 Thrombin, 289, 319, 323, 335 Thrombolytic, 318, 335 Thrombomodulin, 323, 335 Thrombosis, 269, 300, 323, 332, 335 Thromboxanes, 49, 267, 335 Thymidine, 72, 80, 103, 335 Thymidine Kinase, 72, 335 Thymidine Phosphorylase, 80, 103, 335 Thymidylate Synthase, 48, 335 Thymoma, 28, 335 Thymus, 24, 297, 304, 335 Thyroid, 176, 196, 315, 335, 338 Thyroid Gland, 315, 335 Thyroxine, 263, 317, 335 Tissue Culture, 44, 179, 335 Tissue Distribution, 19, 336 Tissue Polypeptide Antigen, 107, 336 Tomography, 43, 336 Tonic, 306, 336 Tonicity, 301, 336 Topical, 268, 277, 315, 336, 337 Topoisomerase inhibitors, 301, 336 Toxicity, 15, 28, 44, 47, 49, 56, 60, 91, 154, 161, 182, 194, 200, 202, 273, 284, 306, 336 Toxicologic, 23, 336 Toxicology, 40, 42, 63, 232, 336 Toxins, 182, 266, 292, 298, 308, 325, 336 Trace element, 5, 271, 275, 277, 311, 336 Tracer, 23, 296, 336 Trachea, 271, 305, 317, 335, 336 Transcriptase, 16, 55, 75, 328, 334, 336 Transcutaneous, 213, 336 Transduction, 58, 192, 268, 330, 336 Transfection, 6, 195, 270, 336 Transferases, 293, 336 Transgenes, 46, 337 Translation, 16, 32, 337 Translational, 4, 9, 10, 14, 18, 20, 36, 42, 337 Translocation, 20, 337 Transmitter, 261, 284, 305, 311, 337 Transplantation, 177, 276, 297, 302, 337

358

Bladder Cancer

Transurethral, 46, 77, 90, 92, 97, 125, 147, 183, 193, 197, 198, 232, 244, 245, 322, 337 Trastuzumab, 157, 337 Trauma, 175, 269, 294, 304, 309, 334, 337 Treatment Failure, 191, 337 Treatment Outcome, 232, 337 Tretinoin, 4, 337 Trypanosomiasis, 202, 316, 333, 337 Trypsin, 106, 179, 286, 337, 341 Tryptophan, 277, 337 Tuberculosis, 69, 279, 313, 337 Tuberous Sclerosis, 191, 235, 337 Tubulin, 48, 307, 338 Tumor marker, 31, 75, 78, 105, 270, 336, 338 Tumor model, 15, 183, 338 Tumor Necrosis Factor, 93, 173, 338 Tumor suppressor gene, 15, 27, 45, 52, 70, 176, 180, 186, 194, 196, 304, 314, 338 Tumorigenic, 54, 83, 338 Tumour, 89, 99, 105, 107, 117, 126, 139, 338 Tyrosine, 29, 60, 201, 202, 284, 323, 338 U Unconscious, 282, 297, 338 Unresectable, 132, 158, 338 Uracil, 47, 338 Uremia, 302, 338 Urethra, 175, 177, 188, 209, 210, 211, 269, 316, 322, 337, 338, 339 Urethral Obstruction, 177, 338 Urethritis, 203, 210, 293, 338 Uridine Diphosphate, 292, 338 Uridine Diphosphate Glucuronic Acid, 292, 338 Urinalysis, 210, 257, 339 Urinary tract, 77, 146, 148, 150, 154, 157, 161, 184, 208, 209, 210, 268, 339 Urinary tract infection, 77, 208, 209, 210, 268, 339 Urinate, 209, 339, 341 Urogenital, 292, 339 Uterus, 211, 275, 280, 286, 297, 314, 327, 339 V Vaccination, 339 Vaccine, 56, 158, 163, 188, 262, 302, 323, 339 Vaccinia, 183, 184, 339 Vaccinia Virus, 183, 184, 339 Vagina, 211, 259, 275, 283, 327, 339 Vaginal, 107, 209, 339 Valine, 172, 339

Vanadium, 56, 339 Variola, 339 Vascular, 15, 33, 37, 64, 108, 185, 263, 286, 298, 299, 311, 319, 335, 339 Vascular endothelial growth factor, 37, 108, 339 Vasodilatation, 178, 339 Vasodilation, 264, 339 Vasodilator, 271, 284, 340 Vasomotor, 185, 340 Vector, 59, 61, 77, 85, 86, 102, 200, 336, 339, 340 Vein, 300, 311, 340 Venous, 191, 269, 323, 340 Venules, 271, 272, 340 Verruca, 191, 340 Vertebrae, 331, 340 Vesicoureteral, 210, 340 Veterinary Medicine, 231, 340 Vinblastine, 28, 112, 113, 114, 116, 117, 121, 122, 123, 126, 128, 129, 132, 133, 137, 138, 139, 225, 338, 340 Vinca Alkaloids, 340 Vincristine, 115, 125, 135, 338, 340 Viral, 45, 185, 194, 196, 202, 261, 313, 323, 328, 336, 338, 340 Viral vector, 194, 340 Virulence, 268, 336, 340 Virus, 89, 103, 184, 268, 280, 282, 300, 330, 336, 339, 340 Viscera, 331, 340 Visceral, 303, 340 Viscosity, 189, 261, 296, 340 Vitamin A, 299, 327, 340 Vitro, 7, 8, 9, 12, 22, 29, 33, 41, 47, 48, 53, 55, 58, 60, 61, 62, 67, 72, 79, 88, 90, 92, 103, 109, 113, 114, 122, 123, 124, 126, 130, 134, 172, 177, 193, 195, 196, 202, 206, 298, 319, 335, 340 Vivo, 12, 22, 29, 33, 35, 41, 43, 47, 48, 53, 54, 58, 60, 61, 67, 79, 90, 109, 122, 123, 124, 134, 140, 179, 186, 196, 202, 206, 298, 333, 335, 341 Void, 81, 341 Volition, 301, 341 Vulgaris, 191, 341 W Wart, 302, 341 White blood cell, 110, 265, 294, 303, 304, 305, 308, 311, 318, 341 Windpipe, 317, 335, 341 Womb, 327, 339, 341

Index 359

Wound Healing, 265, 289, 300, 305, 341 Wounds, Gunshot, 331, 341 X Xenograft, 10, 265, 338, 341 X-ray, 149, 155, 156, 160, 279, 290, 300, 301, 309, 311, 325, 341

X-ray therapy, 301, 341 Y Yeasts, 290, 317, 341 Z Zygote, 279, 341 Zymogen, 323, 341

360

Bladder Cancer

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