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

A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2003 by ICON Group International, Inc. Copyright Ó2003 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., 1960Lung 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: 0-597-83712-0 1. Lung Cancer-Popular works. I. Title.

iii

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

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

iv

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on lung 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.

v

About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

vi

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

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON LUNG CANCER.......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lung Cancer.................................................................................. 5 E-Journals: PubMed Central ....................................................................................................... 65 The National Library of Medicine: PubMed ................................................................................ 70 CHAPTER 2. NUTRITION AND LUNG CANCER .............................................................................. 149 Overview.................................................................................................................................... 149 Finding Nutrition Studies on Lung Cancer .............................................................................. 149 Federal Resources on Nutrition ................................................................................................. 166 Additional Web Resources ......................................................................................................... 166 CHAPTER 3. ALTERNATIVE MEDICINE AND LUNG CANCER ....................................................... 171 Overview.................................................................................................................................... 171 National Center for Complementary and Alternative Medicine................................................ 171 Additional Web Resources ......................................................................................................... 206 General References ..................................................................................................................... 209 CHAPTER 4. DISSERTATIONS ON LUNG CANCER ......................................................................... 211 Overview.................................................................................................................................... 211 Dissertations on Lung Cancer ................................................................................................... 211 Keeping Current ........................................................................................................................ 213 CHAPTER 5. CLINICAL TRIALS AND LUNG CANCER .................................................................... 215 Overview.................................................................................................................................... 215 Recent Trials on Lung Cancer ................................................................................................... 215 Keeping Current on Clinical Trials ........................................................................................... 235 CHAPTER 6. PATENTS ON LUNG CANCER .................................................................................... 237 Overview.................................................................................................................................... 237 Patents on Lung Cancer ............................................................................................................ 237 Patent Applications on Lung Cancer......................................................................................... 260 Keeping Current ........................................................................................................................ 285 CHAPTER 7. BOOKS ON LUNG CANCER ........................................................................................ 287 Overview.................................................................................................................................... 287 Book Summaries: Federal Agencies............................................................................................ 287 Book Summaries: Online Booksellers......................................................................................... 288 The National Library of Medicine Book Index ........................................................................... 296 Chapters on Lung Cancer .......................................................................................................... 297 CHAPTER 8. MULTIMEDIA ON LUNG CANCER ............................................................................. 299 Overview.................................................................................................................................... 299 Video Recordings ....................................................................................................................... 299 Bibliography: Multimedia on Lung Cancer ............................................................................... 300 CHAPTER 9. PERIODICALS AND NEWS ON LUNG CANCER .......................................................... 303 Overview.................................................................................................................................... 303 News Services and Press Releases.............................................................................................. 303 Academic Periodicals covering Lung Cancer............................................................................. 307 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 309 Overview.................................................................................................................................... 309 U.S. Pharmacopeia..................................................................................................................... 309 Commercial Databases ............................................................................................................... 310 Researching Orphan Drugs ....................................................................................................... 311 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 315 Overview.................................................................................................................................... 315

viii Contents

NIH Guidelines.......................................................................................................................... 315 NIH Databases........................................................................................................................... 317 Other Commercial Databases..................................................................................................... 319 The Genome Project and Lung Cancer ...................................................................................... 319 APPENDIX B. PATIENT RESOURCES ............................................................................................... 325 Overview.................................................................................................................................... 325 Patient Guideline Sources.......................................................................................................... 325 Finding Associations.................................................................................................................. 335 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 337 Overview.................................................................................................................................... 337 Preparation................................................................................................................................. 337 Finding a Local Medical Library................................................................................................ 337 Medical Libraries in the U.S. and Canada ................................................................................. 337 ONLINE GLOSSARIES ................................................................................................................ 343 Online Dictionary Directories ................................................................................................... 343 LUNG CANCER DICTIONARY................................................................................................. 345 INDEX .............................................................................................................................................. 429

1

FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with lung 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 lung 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 lung 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 lung 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 lung 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 lung cancer. The Editors

1

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

3

CHAPTER 1. STUDIES ON LUNG CANCER Overview In this chapter, we will show you how to locate peer-reviewed references and studies on lung 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 lung 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 “lung 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: ·

Phytochemicals: The New Science of Eating Right Source: Fitness. p.108-110,112. April 1998. Summary: Kressy discusses phytochemicals, describing what they are and why some think they may help reduce the risk of heart disease, lung cancer, and other diseases, as well as assist in weight control. A chart lists the major phytochemicals and good sources for each. Several recipes are included.

·

Emerging Concepts in Immunology, Clinical Practice, and Research for Dental Hygiene Source: Access. 15(8): 42, 45-49. September-October 2001.

4

Lung Cancer

Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: The Surgeon General's report on 'Oral Health in America,' released in 2000, described and evaluated the relationship of oral health to general health and well being, throughout the lifespan in the context of changes in society. This article reviews emerging concepts in immunology, clinical practice, and research, as they have an impact on dental hygiene and the provision of dental care. The author notes that oral health care is in the process of making the transition from a 'repair' model of care to a 'wellness' model of care. Evidence based care; emphasis on the skills of cognition, synthesis and communication; and client satisfaction are becoming more important in oral health care delivery. Other topics covered are gender-specific medicine, cancer, autoimmune diseases, diabetes, systemic lupus erythematosus (SLE), HIV, and AIDS, pharmaceuticals (drug therapy), tobacco and lung cancer, musculoskeletal health, current research at the National Institutes of Health (NIH), and the National Center for Complementary and Alternative Medicine (NCCAM, one of the Institutes of Health). 3 figures. 41 references. ·

Apolipoprotein E4: A Genetic Risk Factor for Late-Onset Alzheimer's Disease Source: Caring. 13(8): 24-28. August 1994. Summary: This article discusses the results of genetic research on Alzheimer's disease (AD) at Duke University. Researchers have found the first genetic risk factor for the type of AD that begins after age 60. The gene is a specific version of apolipoprotein E (ApoE), a protein that carries cholesterol through the bloodstream. These scientists assert that the inheritance of a specific form of ApoE raises the odds of having AD to a level comparable to that associated with smoking, getting lung cancer, or having high blood pressure that leads to a stroke. According to the authors, people with two ApoE4 alleles (one of three ApoE versions) are much more likely to develop AD than those who have none or only one copy. Once discovery of the effects of this protein on the brain and its involvement in the cause of late-onset AD occurs, researchers can design and test preventive therapies for AD.

·

Vegetarian Diets: The Pluses and the Pitfalls Source: Rockville, MD: U.S. Department of Health and Human Services, Food and Drug Administration, Department of Agriculture, 4 p., 1994. Contact: Food and Drug Administration, Office of Consumer Affairs, 5600 Fishers Lane, HFE-50, Rockville, MD 20857. (301) 443-3170. Publication number (FDA) 93-2258. Summary: This article reviews the precautions that must be considered when adopting a vegetarian diet. The various reasons for choosing a vegetarian lifestyle include religious beliefs, expense, and personal beliefs. Vegetarians who abstain from dairy products or animal flesh face the greatest nutritional risks because some nutrients naturally occur mainly or almost exclusively in animal foods. These potential risks are explained. Next the health benefits of fruit and vegetable consumption are considered, including a lower risk of certain cancers, including prostate, breast, and colon cancer. Vegetarians are at lesser risk for obesity, atonic constipation, lung cancer, and alcoholism. Evidence is also good that risks for hypertension, coronary artery disease, diabetes, and gallstones are lower. It is generally agreed that to avoid intestinal discomfort, a person shouldn't switch to foods with large amounts of fiber all at once. The steps one should take for a gradual dietary change are considered. The article also includes a list of sources of nutrients of greatest concern for vegetarians who don't eat animal foods.

Studies

·

5

Smoking and Chewing in Young People: The Power of Prevention is in Our Hands Source: Postgraduate Medicine. 101(3): 13-18. March 1997. Summary: This commentary serves as an introduction to a series of articles about lung cancer and smoking cessation. The author reflects on the use of tobacco by young people and the role of health care providers in preventing such use. The author begins with a discussion of the government's role in regulating the tobacco industry, particularly the sale and distribution of cigarettes and smokeless (spit) tobacco to young people. The article includes a sidebar of statistical information about tobacco use, primarily among young people. The author outlines specific step-by-step instructions for health care providers who wish to participate in preventing tobacco use in young people. 1 table. 7 references.

·

National Cancer Institute's OCCAM Partners With NCCAM to Expand Research on Unconventional Cancer Source: Alternative Therapies in Health and Medicine. 5(4): 26-30. July 1999. Summary: This journal article discusses the recent establishment of the Office of Cancer Complementary and Alternative Medicine (OCCAM) within the National Cancer Institute (NCI), and its partnership with the National Center for Complementary and Alternative Medicine (NCCAM). Dr. J.D. White, director of the OCCAM, is the official liaison with other institutes and offices concerning alternative medicine research projects. Two cooperative NCI research projects involving complementary medicine had already been funded when the OCCAM was established. One is a phase III trial of the Gonzales protocol for pancreatic cancer, and the other is a phase II trial of shark cartilage for stages IIIA and IIIB lung cancer. To help advance additional high quality cancer research, Dr. White is working to develop the NCI's best case series, the process by which researchers submit their well-documented case reports for independent evaluation. The NCCAM's newly established Cancer Advisory Panel helps the OCCAM review the case studies of alternative cancer therapies, and makes recommendations about how to follow up on these evaluations. Areas of interest for future research projects include folk beliefs and practices and palliative care.

·

Transbronchial Needle Aspiration Source: Gastroenterology Nursing. 14(2): 80-84. October 1991. Summary: Transbronchial needle aspiration biopsy is an endoscopic pulmonary procedure used to diagnose a variety of pulmonary conditions including staging patients with lung cancer and identifying nodules, masses, and benign disorders such as sarcoidosis. Transbronchial needle aspiration biopsy is a safe procedure, performed primarily with local anesthesia combined with intravenous sedation. This article is intended to educate nurses and technicians about the procedure of transbronchial needle aspiration and the instruments used. Four charts present the specifications for different types of biopsy needles. 1 figure. 4 tables. 8 references. (AA-M).

Federally Funded Research on Lung Cancer The U.S. Government supports a variety of research studies relating to lung cancer. These studies are tracked by the Office of Extramural Research at the National Institutes of

6

Lung Cancer

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 lung 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 lung cancer. The following is typical of the type of information found when searching the CRISP database for lung cancer: ·

Project Title: A SIMULATION OF TOBACCO POLICY, SMOKING AND LUNG CANCER Principal Investigator & Institution: Levy, David T.; Professor; Pacific Institute for Res and Evaluation Calverton, Md 207053102 Timing: Fiscal Year 2002; Project Start 26-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant) Because over 85% of lung cancer is caused by smoking, we focus on the effect of tobacco policies on lung cancer. We will extend a previously developed macro-simulation model, known as SimSmoke, to predict smoking-attributable lung cancer the effect of tobacco control policies on those deaths. The first major aim of this project is extending SimSrnoke to estimate and predict smoking-attributable lung cancer deaths. The model will be programmed to estimate the number of smoking-attributable lung cancer deaths to smoker and non smokers during the past ten years and predict deaths over the next 35 years, and to distinguish the number of deaths by age, gender and by racial/ethnic group, and distinguish the effects of quantity smoked and smoking prevalence. We will also distinguish the effect on lung cancer of factors other than smoking, other such as other risks and the effects of treatment. We also propose to determine the impact of tobacco control interventions on observed trends in mortality; and to determine if the interventions are having their expected population impact. Specifically, SimSmoke will be used to estimate the number of smoking-attributable deaths in the United States averted as a result of policies implemented in the last ten years, and estimate the number of smoking deaths that have been averted as a result of policies implemented in the last ten years in three states with proactive tobacco control policy. We will also consider the potential impact of policies in the future. In examining the effect of tobacco control policies, we will distinguish their effects on smoker and non-smoker deaths, their effects by age, gender, and racial/ethnic group, and their effects in terms of quantity reduction and smoking cessation. We will also add a new module to examine the effect of new tobacco products (low tar and cigarettes without certain additives) and non-tobacco products (inhalers) which may reduce lung cancer risk, and a module to consider how improved lung cancer detection and treatment may reduce smoking-attributable lung cancer deaths, and how they might be coordinated with tobacco control policies. A final goal of this project will be to critically examine the methods that are traditionally used to project lung cancer deaths, and determine how the estimates depend on the sensitivity to key parameters.

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies

7

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

Project Title: ALLOGENEIC TGF-B ANTISENSE CELL VACCINE FOR LUNG CANCER Principal Investigator & Institution: Fakhrai, Habib A.; Novarx Corporation 8395 Camino Santa Fe, Ste a San Diego, Ca 92121 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (provided by applicant): The purpose of this study is to conduct a Phase II clinical trial in patients with incurable non-small cell lung cancer (NSCLC). Our aim is to induce antitumor immune responses by immunizing patients with an experimental vaccine comprised of four allogeneic NSCLC cell lines genetically modified with a TGFbeta 2 antisense vector. By blocking secretion of the immunosuppressive molecule TGF-beta in this manner we inhibit one of the major mechanisms by which tumor cells evade immune surveillance. Developing an effective therapy for the disease that accounts for 30 percent of all cancer-related deaths will benefit the approximately 180,000 new patients that develop lung cancer in the United States each year. In a previous clinical trial, we have shown that injections with gene-modified allogeneic tumor cells induced cellular immune responses to autologous tumor cells. In this trial, 18 patients will be randomized into three cohorts that will receive 1.25 x 10exp7, 2.5 x 10exp7, or 5 x 10exp7 TGF-beta antisensemodified vaccine cells. Following completion of this phase of the trial, an additional 48 patients will be enrolled in the two cohorts that demonstrate the best clinical responses. We anticipate that our treatment will induce measurable clinical responses in some of the treated patients. PROPOSED COMMERCIAL APPLICATIONS: The potential patient pool for this study is 180,000 patients annually in the United States. When considering other parts of the world, the potential patient pool is significantly larger. Once the Phase II clinical trial is completed, and the efficacy of our method is proved, we will perform the subsequent phases of our clinical trial phases, as well as the commercialization of our method in partnership with a pharmaceutical company that has the facility to mass produce and market our vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: ALTERATIONS OF THE HUMAN SWI/SNF COMPLEX IN LUNG CANCER Principal Investigator & Institution: Reisman, David N.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Candidate: The candidate is an Oncology fellow whose career goal is to become a translational researcher focusing on the molecular growth inhibitory pathways in lung cancer and the development of assays to detect neoplastic aberrance in these pathways both in vitro and in vivo. Research Plan: Lung cancer is the leading cause of cancer deaths in the United States. A reduction in the mortality will require the development of prognostic markers based on the understanding of growth inhibitory pathways. The SWI/SNF complex is a candidate to fill this critical need since it is likely required for function of the tumor suppressors, retinoblastoma (RB) and p130 (RB2). To understand how alterations in SWI/SNF may affect RB and p130 function, this proposal will determine the mechanisms for the downregulation of BRG and BRM (AIM 1), to clarify the role of BRG1 in RB mediated growth inhibition (AIM 2), to determine if BRG1 and BRM are lost or mutated in primary lung cancers (AIM 3), and to determine if BRG1 and BRM are important for p130 function

8

Lung Cancer

(AIM 4). It is the goal of this training period to provide an intense research experience whereby expertise in molecular biology is gained leading to a career as a dually trained independent researcher. Environment: The excellent research environment at the Lineberger Comprehensive Cancer Center will promote the accomplishment of these specific aims. The candidate?s training and development will be directed by the dedicated mentorship and guidance of a senior and accomplished scientist, Dr. Bernard Weissman. Dr. Beverly Mitchell, who has many years? experience in mentoring successful physician/scientists, will provide protected research time and translational research guidance. Thus, this K08 funding period will allow the acquisition of new skills resulting in a series of publications leading to an independent cancer research career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ANALYSIS OF ETHNIC ADMIXTURE IN LUNG CANCER Principal Investigator & Institution: Barnholtz-Sloan, Jill S.; Internal Medicine; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): This proposal describes a five-year plan developed for a Cancer Prevention, Control, Behavioral and Population Sciences Career Development Award. It outlines a program that integrates education, teaching and research to develop my skills in statistical genetics, molecular biology, cancer biology, human genetics and genetic epidemiology. My research plan consists of two projects: (l) higher level genetic modeling of early onset lung cancer cases and controls with admixture versus ethnicity as a covariate and (2) application of an admixture, population substructure and disequilibria testing procedure to early onset lung cancer cases, population-based controls and nuclear families. Project l uses data from a funded study on early onset lung cancer of African-Americans and Caucasians. Nine candidate loci believed to be involved in lung cancer risk along with 35 population specific markers (PSAs) for Africans and Europeans combined, are being typed for each case and a matched population and familial control. An admixture algorithm will be written, programmed and tested on cases, controls and parents to estimate individual and population admixture, using the PSAs. Logistic regression models and decision tree models (classification and regression tree) will be compared when modeling the genotypes of the candidate loci and other collected environmental/descriptive variables, in order to assess the difference between using an ethnicity variable versus an individual admixture estimate variable. Project 2 will build on the already developed admixture estimation algorithm (Project l). I will develop a complete procedure that will estimate individual and population admixture and within population substructure and will test for induced linkage disequilibrium (LD) and Hardy-Weinberg disequilibrium (HWD), for all cases, controls and nuclear families. This procedure will be tested in a computer-based simulation, using the early onset lung cancer data as a model, in order to estimate the statistical power and test characteristics such as false-positive and falsenegative rates. Linkage disequilibrium mapping will also be performed on the study data. Both of these projects will address epidemiological study design issues about ethnicity and using population-based versus familial based controls. From the studies proposed, a recommendation could be made on how to utilize individual admixture information in the choice of controls for epidemiological studies. These projects will give me experience in developing methodology in statistical genetics and genetic epidemiology, while also helping me to better understand etiology of disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

·

9

Project Title: AUTOANTIBODIES IN NSCLC AS MARKERS FOR DISEASE Principal Investigator & Institution: Hirschowitz, Edward A.; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 05-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): A variety of diagnostic and therapeutic strategies are being explored to change poor outcomes in lung cancer. Tumor markers, measured in peripheral blood, could complement the evolving clinical approach to lung cancer management. Autoantibodies to tumor-associated proteins may effectively expand the number and range of available serologic markers for lung cancer and be translated into a valuable test for lung cancer. Our preliminary data supports this hypothesis. We used phage-display and biopan techniques to identify multiple autoantibodies to known and unknown tumor-associated proteins in the serum of non-small cell lung cancer (NSCLC) patients. Using conventional immunochemical techniques and novel protein microarray we showed that autoantibodies to individual tumor-associated proteins are found in cancer patient sera and not in normals. Because no single antibody response is likely to be a comprehensive marker, we intend to build on these exciting data and develop an inclusive blood test for lung cancer by profiling sera for a variety of atuoantibodies. We have already identified 21 proteins recognized by autoantibodies in NSCLC patient sera and using these, plus additional proteins identified with these techniques; we will generate a comprehensive a panel of proteins used for antibody measurement. Fluorescent microarray technology, applied generally to gene discovery, is ideal for this purpose. Thus the primary goal of this proposal is to develop a novel blood test for NSCLC. To begin to expand the clinical relevance of this approach, a secondary goal is to show the association of autoantibody responses to tumor protein expression. The data shows feasibility and proof of concept that supports the rationale behind this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: BAYESIAN BIOMARKER MODELS FOR CANCER GENETICS STUDIES Principal Investigator & Institution: Thurston, Sarah W.; Biostatistics & Computational Biology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 13-SEP-2002; Project End 31-JUL-2005 Summary: (Taken from the Investigator?s Abstract) This proposal aims to develop statistical methods which incorporate biomarkers and genetic information to improve estimates of cancer risk. This methodology will be developed using data from an ongoing study of lung cancer, smoking history, asbestos exposure, DNA adducts (a biomarker of smoking exposure), and genes associated with adduct formation and DNA repair (including CYP1A1 MSP1, GSTM1 and XRCC1). Currently the study has 2800 subjects, approximately half of whom are cases. Genotyping for multiple genes is ongoing. Phenol-related adducts have been measured in nontumorous lung tissue for 69 cases and in mononuclear blood cells for 38 cases and 42 controls. Polycyclic aromatic hydrocarbon adducts have been measured in normal lung tissue for 143 cases. The Bayesian paradigm, which can incorporate information from prior studies, will be used throughout. This paradigm can easily handle missing data such as lung adduct counts which cannot be measured in controls. All models for lung cancer risk will allow for synergistic effects between smoking and asbestos exposure. The specific aims of the proposal are: (1) to develop a model for DNA adduct counts given genes and smoking, and to then use the predicted adduct counts in a logistic regression model for lung

10 Lung Cancer

cancer risk which corrects for the measurement error bias induced by using blood adducts instead of lung adducts in controls; (2) to develop a pharmacokinetic model for the number of blood adducts over time as a function of genes and changing smoking behavior, and to use the predicted cumulative adduct burden in a model for cancer risk; (3) by combining aims 1 and 2, to develop a model of cancer risk which both takes into account the changing adduct load over time and corrects for measurement error bias; (4) to extend the models in aims 1-3 to allow for nonlinear relationships between covariates and lung cancer risk using generalized additive models; (5) using new data, to compare the performance of the models developed in aims 1-4 to model which do not use biomarkers, and to assess the sensitivity of the outputs to both model and prior specification; and, (6) to develop guidelines on optimal sample sizes, sample selection and timing schemes for biomarker measurement, for future biomarker and exposuremediated cancer studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CANCER INTERVENTION AND SURVEILLANCE MODELING NETWORK Principal Investigator & Institution: Boer, Rob; Natural Scientist; Rand Corporation 1700 Main St Santa Monica, Ca 90401 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant) The proposed study is intended to develop a model for the comprehensive surveillance of population trends in lung cancer. This model will deliver estimates of the impact of cancer control interventions on: observed trends in incidence and/or mortality; the extent to which recommended interventions are having their expected population impact; the potential impact of new interventions on future national lung cancer trends; and the impact of targeted cancer control interventions on population outcome. The proposed model will be based on the Micro-simulation SCreening ANalysis (MISCAN) simulation model developed earlier for other cancer simulations and will be adapted to include an explicit model for the association between exposure to risk factors (smoking and diet) and risk for lung cancer as well as the time between exposure and effect. This risk-factor model will precede the comprehensive model for screening evaluation that includes the natural history of lung cancer, as well as exposure to screening and its health effects. This lung cancer screening evaluation model will be similar to MISCAN models that were previously successfully used for the evaluation of screening for breast, cervical, colorectal, and prostate cancer. As with other MISCAN models, the MISCAN-lung cancer model will simulate a full dynamic population, which makes it particularly suitable for surveillance of population trends. The model will be informed by the evidence from the literature, and it will be validated on several empirical longitudinal studies both on aspects concerning risk factors as well as screening. The proposed project will also develop a model for the evaluation of trends in survival from lung cancer that will optimally account for changes in reporting practice, in order to evaluate the impact of changes in therapy. This project provides a unique opportunity to integrate knowledge on all aspects of lung cancer that are relevant for the surveillance of population trends. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: CAREER DEVELOPMENT PROGRAM Principal Investigator & Institution: Roth, Michael D.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024

Studies

11

Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-DEC-2005 Summary: (provided by applicant): The Career Development Program will utilize dedicated funds to prepare postdoctoral fellows or junior faculty for careers in translational lung cancer research. In addition, in well-justified selected cases, senior investigators who are already established in another area of research will be eligible in another area of research will be eligible for support to re-direct their research focus to lung cancer. The Career Development Selection Committee members represent a broad array of lung cancer-related disciplines including Medical Oncology, Surgical Oncology, Radiology, Thoracic Surgery, Radiation Oncology, Pathology, Pulmonary Medicine, Immunology, and Molecular Genetics. Committee members have extensive experience in mentoring trainees at all levels. Selection of Postdoctoral Fellows: Fellowship applications will be accepted from M.D. or Ph.D. post-doctoral trainees to work with a senior mentor. The fellow applicants will be required to submit a five-page research proposal and biosketch to the committee. The application will require a statement of career plans by the applicant as well as three letters of recommendation. One of these letters will be written by the primary mentor. The criteria for selection of fellows will be: 1) Quality of the scientific proposal, 2) The fellow's potential for an independent lung cancer research career, 3) Potential impact of the research on the field of lung cancer and, 4) Relevance to the overall translational research mission of the lung cancer SPORE program. Selection of junior faculty: The selection criteria noted above will also apply for the selection of junior faculty. In addition, the junior faculty applicant's department will be required to submit a letter of support delineating the commitment the commitment and support for the candidate. The process for selecting candidates for this program: An announcement will e made to all cancer center members two times per year. Distribution will also be directed to all graduate departments, training grant directors and clinical department chairs. The program will place special emphasis on recruitment of qualified women and minorities. The prospective mentor pool will be comprised of all of the senior SPORE investigators. In addition to the primary mentor, each postdoctoral or junior faculty trainee will be assigned an advisory committee. The advisory committee will consist of at least two additional mentors who will be meeting regulatory with the trainee to review work in progress. The overall purpose of this program will be to train well- qualified investigators in translational lung cancer research in a highly structured, academic setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CAREGIVER COPING SKILLS TRAINING FOR LUNG CANCER Principal Investigator & Institution: Keefe, Francis J.; Professor and Associate Director; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 06-JUN-2002; Project End 31-MAY-2007 Summary: (provided by investigator): Symptoms such as pain, fatigue, paroxysmal coughing, and dyspnea are major concerns of lung cancer patients and their caregivers. The focus in management of such symptoms traditionally has been on the patient. Studies of caregivers, however, have documented that the psychosocial impact of providing care to family members with lung cancer is profound. The ultimate goal of this research is to develop more effective ways to help patients and caregivers cope more effectively with problematic symptoms experienced by lung cancer patients. The proposed study seeks to evaluate the efficacy of a new, caregiver assisted coping skills training protocol. 500 early stage lung cancer patients (Stages I to IIIA) and their caregivers will be randomly assigned to one of two conditions: 1) Caregiver-assisted coping skills training-systematically trains caregivers in methods for guiding the patient

12 Lung Cancer

in use of coping skills for symptom management (i.e. relaxation training, imagery, activity pacing, and communication skills), or 2) Cancer education and support-a comparison condition that provides patients and caregivers with information on the nature of lung cancer and treatment methods and controls for attention and contact. Assessment measures to be collected before and after treatment and at 4- and 14-months follow-up will include patient reports of major symptoms (pain, fatigue, coughing, and dyspnea), quality of life, depression, anxiety, self efficacy and quality of relationship with the caregiver and caregivers' ratings of mood, strain, and quality of relationship with the patient. If caregiver-assisted CST is effective, future studies could evaluate this training in other cancer populations (e.g. breast cancer, prostate cancer). Future studies could also identify the particular caregiver-assisted CST components (e.g. relaxation training, imagery training, or activity pacing methods) that contribute most to treatment effects. By isolating the active ingredients of training, one can streamline it, making it more cost-effective and more readily available to the larger population of patients having lung cancer. The proposed study rigorously evaluations methods for enhancing the effects of caregiver-assisted coping skills training in cancer patients and their caregivers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CHANGES IN DNA METHYLATION PATTERNS AS MARKER FOR CANCER Principal Investigator & Institution: Herman, James G.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Lung cancer is the most common cause of cancer death in the United States, accounting for more life lost than breast, prostate, colon and rectal cancer combined. Of the estimated 190,000 individuals who are diagnosed each year, over 180,000 succumb to the disease. Increasing insight into the molecular basis of lung cancer pathogenesis offers hope to combat this disease. Lung cancer development and progression involves the inactivation of tumor suppressor genes and activation of oncogenes. While the accumulation of genetic alterations has been shown to be involved in the progression of lung epithelial cells from hyperplasia, metaplasia, dysplasia, carcinoma in situ, invasive carcinoma, and finally metastatic carcinoma, recent work in the previous funding period of this SPORE project has demonstrated that epigenetic changes represent another important molecular change in lung cancer. With that background, the specific aims of the current proposal are: Specific aim 1. To utilize a newly derived microarray approach to identify novel hypermethylated genes which will help comprise methylation marker panels providing for full coverage of the non-small cell lung cancer genome. Specific aim 2. To utilize the marker panels from specific aim 1 to develop an epigenetic progression model based upon studies of precursor lesions and early stage lung cancer. Specific aim 3. To test the epigenetic marker panels for their efficacy as prognostic markers to identify patients with Stage I non-small cell lung cancer at very high risk for rapid disease recurrence. 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

Studies

13

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 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: COMPUTER AIDED DIAGNOSIS OF LUNG CANCER Principal Investigator & Institution: Chan, Heang-Ping; Professor; Radiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Lung cancer is the leading cause of cancer deaths in both men and women. A 70 percent five-year survival rate has been reported when the lung cancer is diagnosed at a local stage, compared to 2 percent when distant metastases are found. Recent studies indicate that helical CT may be an effective screening tool for lung cancer. The American College of Radiology Imaging Network (ACRIN) will begin a randomized controlled trial of helical CT for lung cancer screening to evaluate its efficacy. Analysis of CT images to detect lung nodules is a demanding task for radiologists. Some lung nodules will likely be overlooked because of the overwhelming amount of information to be interpreted. Characterization of detected nodules to reduce unnecessary biopsies will also become more important as the number of thoracic CT exams increases. Computer-aided diagnosis (CAD) can be a viable approach to improving the accuracy and efficiency of lung cancer detection in CT images. It will be particularly useful if lung cancer screening with CT is implemented. The goal of the

14 Lung Cancer

proposed project is to develop a CAD system for early detection of lung cancers on thoracic helical CT images. We hypothesize that an accurate CAD system (1) can be developed, (2) can be used as a second opinion to assist radiologists in interpretation of thoracic CT exams, and (3) will improve radiologists' accuracy for lung cancer detection. We will develop advanced computer vision techniques to automatically segment helical CT images, detect candidate pulmonary nodules, differentiate nodule and normal pulmonary structures, and estimate the likelihood of malignancy of the nodules. Computerized image segmentation and feature extraction techniques will be developed based on expert knowledge and image characteristics. Statistical classifiers, fuzzy classifiers, and artificial neural networks will be designed to differentiate nodules and normal structures, as well as to characterize malignant and benign nodules. Quantitative CT phantom studies will be performed to develop reliable methods for estimating the calcium concentration of nodules and estimating nodule volume on CT images so that these features can be used in our CAD system for malignancy detection. Observer performance studies using receiver operating characteristic (ROC) methodology will be conducted to evaluate the effects of CAD on radiologists' detection and classification of lung nodules in CT images. A large public database of helical CT cases to be collected by an NIH-supported consortium will be the main data source for the development of the computer vision techniques. The innovations of this project include: (1) developing region-specific computer vision method for detection of lung nodules; (2) eliminating the vascular tree in the helium for false positive reduction, (3) exploring interval change analysis for classification of malignant and benign nodules; (4) developing a quantitative method for measuring the calcium concentration of nodules for improved characterization of calcified nodules, and (5) performing ROC studies to evaluate CAD's ability to assist radiologists in the detection and characterization of lung nodules in CT studies. It is expected that the proposed studies will result in an effective CAD system for lung cancer diagnosis. When fully developed and clinically implemented, a CAD system for lung nodules will increase the efficacy of lung cancer screening with helical CT, improve early detection, and improve the chance of survival of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: COMPUTER-AIDED DIAGNOSIS TO ENHANCE THORACIC CT IMAGE Principal Investigator & Institution: Lure, Yuan-Ming F.; Caelum Research Corporation 1700 Research Blvd, Ste 100 Rockville, Md 208506121 Timing: Fiscal Year 2003; Project Start 01-MAY-2001; Project End 31-MAY-2005 Summary: (provided by applicant): In the US alone, it is estimated that lung cancer caused a total of 161,900 deaths in 2000. The 5-year survival rate in the US is 13% when all stages are considered. Substantial evidence suggests that early detection of lung cancer may reduce mortality for patients with stage T1 NxMx. High-resolution CT can detect lung nodules when they are still small. But it is currently difficult for radiologists to distinguish those that are malignant from those that are benign. We propose to develop a computer-aided diagnosis (CAD) system to assist radiologists in the diagnosis of lung cancer in thoracic computed tomography (CT). The CT-CAD system will enable radiologists to robustly measure and analyze the suspicious lesions, effectively visualize the region of interest, and improve differentiation between malignant and benign nodules. Specifically, this SBIR phase II effort includes (1) continuous development of dedicated lung cancer diagnostic tools, (2) development of a complete CT-CAD system for accurate analysis of small lung lesions, (3) evaluation of the proposed system functions and integration of them in a CAD-specific 3D visualization platform; and (4)

Studies

15

evaluation of the radiologists performance with and without using the CT-CAD system using the MRMC-ROC study protocol. The successful development of the proposed CTCAD system can significantly benefit the existing CT lung cancer diagnosis in two-fold: (a) improving sensitivity for lung cancer detection and (b) improving the accuracy of lung cancer diagnosis in CT and leading to reduction of unnecessary biopsies. We expect that this CT-CAD can facilitate remote reading by experts and will also increase radiologists' efficiency in reading large image arrays and reducing the observer variations in thoracic CT image interpretation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CORE--CLINICAL RESEARCH Principal Investigator & Institution: Sandler, Alan; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 28-JUN-2001; Project End 31-DEC-2006 Summary: (provided by applicant): The role of the Clinical Trials Core is to provide expertise in the development, implementation and coordination of all translational clinical trials resultant from the other SPORE projects that will ultimately lead to a better understanding of the biology of lung cancer. This improved understanding will ultimately lead to improvements in the treatment of lung cancer. To achieve this goal, the major responsibilities of the Clinical Trials Core will be 1) Provide expertise in the development and implementation of translational clinical trials related to the other SPORE projects 2) Accrual of patients to participate in SPORE initiated trials, 3) Timely and accurate collection of data, and 4) Accessibility of data for analysis by the various SPORE researchers at Vanderbilt university as well as researchers at other Lung SPORE sites. During the first year there will be at least seven translational trials open for accrual. These trials will serve to further the scientific knowledge regarding the role of 1) molecular fingerprinting and outcome analysis in resectable patients with lung cancer and 2) angiogenesis in lung cancer. More specifically, the impact of matrix metalloproteinases and their inhibition; the role of VEGF and its inhibition; the role of COX-2 and its inhibition on the outcomes of patients with lung cancer treated with either surgery, radiation, chemotherapy and/or their combination in patients with lung cancer. Over the five year course of the SPORE grant, trials will open and close. One of the goals of this SPORE is that the successful completion of these early pilot trials will ultimately lead on to larger scale, multi-institution trials for confirmation of our results. A second goal is that additional translational clinical trials will be designed based upon the results of the early pilot trials as well as the ongoing research of the participating SPORE investigators. The current pilot trials will thus serve as the template for further translational research in lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: CORE--TISSUE FACILITY Principal Investigator & Institution: Johnson, Joyce; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 28-JUN-2001; Project End 31-DEC-2006 Summary: (provided by applicant): The tissue resource and pathology core will provide high-quality tissue specimens and basic histology and pathology services in support of lung cancer research performed within the SPORE. The specimens, information, and services provided by the core will be carefully quality-controlled, and informed consent and patient confidentiality will be consistently maintained. The primary function of the

16 Lung Cancer

core will be to procure, archive, and distribute to SPORE investigators lung cancer tissue specimens and paired normal tissue which has been characterized histopathologically, along with relevant clinical data, if allowed by the specific protocol involved. Such tissue will be maintained in a variety of conditions to allow DNA, RNA, or protein studies, depending on the research requirements of individual investigators. The core will also provide laser capture micro-dissection technology. Data obtained from individual specimens will be maintained in the core's database. Establishment of the core functions will be facilitated by the prior existence of the Vanderbilt-Ingram Cancer Center's Human Tissue Acquisition and Pathology Shared Resource, established in 1993 and managed since its inception by Roy Jensen, MD, who is a co-Principal Investigator on this core. The specific aims of this core are: 1. To collect, accession, and store tissues removed from lung cancer patients and normal "control" lung as outlined in the appropriate research informed consent, and to preserve these tissues frozen, formalin-fixed and embedded, and on touch imprints, in order to support lung cancer SPORE projects. 2. To maintain a centralized, computerized database of all specimens with basic demographic and pathologic information to permit the integration of findings by SPORE investigator through molecular assays and other laboratory studies with risk factor data and follow-up. 3. To maintain the confidentiality and integrity of the database, through keyed numeric identifier assigned by the tissue core for each specimen. 4. To provide high quality control of all well-characterized tissues in both human and murine with respect to preservation and histopathologic characterization. 5. To provide micro-dissected lung tumor and matched control cell populations from paraffin and frozen section for appropriate projects (e.g. project 2). 6. To provide immunohistochemical evaluation and quantitation in both human lung and murine tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CREATION AND CHARACTERIZATION OF MOUSE MODELS OF HUMAN L Principal Investigator & Institution: Jacks, Tyler E.; Associate Investigator; Center for Cancer Research; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-MAR-2004 Summary: Lung cancer is the third most common cancer in the United States and is the leading cause of cancer related mortality for both men and women, with 171,500 new cases and 165,600 deaths projected for 1998 in this country. Although smoking cessation trends among adults may result in fewer lung cancer cases in the short to intermediate term, smoking rates among young adults seem to be on the rise. In addition, smoking rates in other parts of the world guarantee that lung cancer will remain a major public health problem worldwide for years to come. One reason for the poor rate of survival of individuals diagnosed with lung cancer is the frequently advanced stage of the disease upon presentation. Thus, there is a clear need to characterize markers associated with early-stage lung cancer to improve methods of diagnosis. Novel therapies for the treatment and prevention of the disease are also wanting. The mouse has been used to model human lung cancer extensively over the past several years in a variety of circumstances, including in spontaneous tumor models, chemically-induced models using a variety of agents, and in certain transgenic strains. Although these studies have confirmed that the mouse can be an adequate model of the early stages of human nonsmall cell lung cancer (NSCLC) (the predominant form of human lung cancer), the methods used in the derivation of these models (e.g., treatment with chemical carcinogens or transgenic expression of viral oncoproteins) and their limited stage of

Studies

17

progression has lessened enthusiasm somewhat. This MMHCC team proposes to create novel mouse models of human NSCLC and to characterize these strains in a variety of ways directed toward their proper validation. The strains will harbor targeted activating mutations in the K-ras oncogene (frequently mutated in human NSCLC) and constitutive or conditional loss-of-function mutations in the lung tumor suppressor genes p53 and the Ink4A locus. Existing and future mouse models of NSCLC will be examined by histological analysis in consultation with a veterinary and human clinical pathologist. Mouse tumors will be subjected to extensive DNA and RNA analysis, in part with reference to known molecular changes in human NSCLC and in part in an effort to identify changes that can then be screened for in human tumor samples. The mouse models of NSCLC will be used in cigarette smoke exposure studies and will be used to evaluate investigative chemotherapeutic and chemopreventative agents. A genetic modifier screen will be performed as part of the characterization of one of these strains. Finally, these mouse lung cancer models will be used in the development of novel non-invasive imaging protocols for primary lung tumors and metastatic lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DEFINING THE SENSITIVITY & SPECIFICITY OF BIOMARKERS Principal Investigator & Institution: Belinsky, Steven A.; Director Lung Cancer Program; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Lung cancer is the most common cause of cancer death in the United States, accounting for more life lost than breast, prostate, colon and rectal cancer combined. Of the estimated 190,000 individuals who are diagnosed each year, over 180,000 succumb to the disease. Increasing insight into the molecular basis of lung cancer pathogenesis offers hope to combat this disease. Lung cancer development and progression involves the inactivation of tumor suppressor genes and activation of oncogenes. While the accumulation of genetic alterations has been shown to be involved in the progression of lung epithelial cells from hyperplasia, metaplasia, dysplasia, carcinoma in situ, invasive carcinoma, and finally metastatic carcinoma, recent work in the previous funding period of this SPORE project has demonstrated that epigenetic changes represent another important molecular change in lung cancer. With that background, the specific aims of the current proposal are: Specific aim 1. To utilize a newly derived microarray approach to identify novel hypermethylated genes which will help comprise methylation marker panels providing for full coverage of the non-small cell lung cancer genome. Specific aim 2. To utilize the marker panels from specific aim 1 to develop an epigenetic progression model based upon studies of precursor lesions and early stage lung cancer. Specific aim 3. To test the epigenetic marker panels for their efficacy as prognostic markers to identify patients with Stage I non-small cell lung cancer at very high risk for rapid disease recurrence. case-control study comparing sputum samples from 33 incident cases and their matched controls was conducted. The presence of any of four methylation markers examined was associated with a 6.3-fold increase in the risk for lung cancer. Moderate atypia or worse in sputum was also associated with a 4.1-fold increase in the relative risk for lung cancer over this time period. Interestingly, the methylation markers and cytology were not highly correlated with each other, though each was predictive of lung cancer risk, hence the two biomarkers were synergistic in conveying a 13.8-fold increase in relative risk. Through this cohort and a Phase II chemoprevention trial, studies with appropriate power will be designed to test specific hypotheses related to prediction of cancer risk and monitoring of chemoprevention interventions. This project is an inter-SPORE collaboration with

18 Lung Cancer

Colorado that links clinical and epidemiologic findings with the development of promoter hypermethylation as molecular markers through the following three specific aims. Specific aim 1 will conduct a nested, case-control study within the Colorado cohort to evaluate longitudinally the ability to detect in sputum genes inactivated by methylation as biomarkers for predicting lung cancer risk either alone or in combination. Specific aim 2 will examine the dynamics of the field cancerization process by determining the concordance between methylation changes detected in sputum and bronchial biopsies from the same subject. Specific aim 3 will determine whether a panel of methylation markers can be used to predict the efficacy of the chemopreventive agent Iloprost in a randomized Phase II study through evaluation of bronchial biopsies and sputum collected at study entry and following completion of the intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DEVELOPMENTAL RESEARCH PROGRAM Principal Investigator & Institution: Strieter, Robert M.; Professor and Chief; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-DEC-2005 Summary: (provided by applicant): The UCLA Lung Cancer Spore Developmental Program will be used as a source of seed funding with two primary goals: 1) to encourage and explore innovative translational research ideas which focus on lung cancer research, and 2) to encourage successful researchers working in other fields to focus their expertise toward the development of innovative translational projects in lung cancer research, and 2) to encourage successful researchers working in other fields to focus their expertise toward the development of innovative ideas for funding will occur through a peer review mechanism. Announcements for developing funding opportunities will be made two times each year, using a highly successful organizational structure offered by the UCLA Jonsson Comprehensive Cancer Center. The request for applications will be posted by e-mail, regular mail and distribution of flyers of flyers to the more than 300 members of the Cancer Center. The Developmental Programs Committee will then meet to select the most meritorious Lung Cancer Research applications. The criteria for judging these applications will be: 1) scientific merit, 2) translational potential, 3) relevance to lung cancer, 4) potential for collaborative research and, 5) qualifications of the investigative team to perform the Committee, the Executive Committee will determine the factual funding line. The Internal and External Advisory Boards will review these funding decisions biannually. Applicants will be funded for a maximum of two years. Funding for the second year will be contingent on documented progress made during the first year of funding. Annual progress reports documenting research progress, publications and submission for additional outside funding will be required. Only those projects that demonstrate a productivity and clear translational potential will be funded for a second year. In addition, all Developmental Research Program funded investigators will be expected to present at least two times each year at the SPORE Review of Work in Progress meetings. This will provide the Executive Committee the opportunity to assess the progress of the investigators to be knowledgeable about on- going research. At the conclusion for additional NIH or other funding, or their project will be incorporated as a larger project within the SPORE. The Executive Committee will make the ultimate decisions regarding starting and stopping funding for individual projects after receiving input from the Developmental Programs Selection Committee. These decisions will be reviewed and critiqued by the Internal and External Advisory Boards. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

·

19

Project Title: DIET AND GENETIC RISKS FOR LUNG CANCER Principal Investigator & Institution: Patterson, Ruth E.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 05-MAR-2001; Project End 31-DEC-2002 Summary: (Applicant's Description) This proposal is for an investigation into the associations of diet, and interactions of diet and genetic polymorphisms, with the risk of lung cancer. Data are from 18,314 men and women enrolled in a chemoprevention trial of beta-carotene and retinol (CARET). After a mean of 7.4 years of follow up, CARET has endpoint data on almost 800 cases of lung cancer. Dietary intake was measured with a food frequency questionnaire. Serum micronutrient and genetic polymorphisms have been analyzed for 388 lung cancer cases and 753 controls. Our specific aims are: 1. To better understand the association of fruit and vegetable intake with the reduced risk of lung cancer. Fruit and vegetable intake will be measured as: (i) servings per day (total and grouped by phytochemical content), (ii) micronutrient associated with fruits and vegetables, including vitamins C and E, folate, and carotenoids, and (iii) serum carotenoids and vitamin E. 2. To examine whether the associations of fruit and vegetable intake with lung cancer risk are modified by genotypes of carcinogen metabolizing enzymes (i.e., CYP2D6, CYP2El, CYP1Al, GSTM1, GSTT1, and EH). We will conduct cohort analyses for dietary intake data and case control analyses for laboratory based studies. Although the baseline dietary data have been collected and the laboratory analyses (for serum micronutrients and genotypes) have been completed, there are no CARET investigators with expertise in nutrition science who are funded to conduct these analyses and write the associated manuscripts. Therefore, to meet the specific aims proposed above, we request support for nutritional epidemiologists, a statistician, molecular biologist, and the staff support needed to publish the findings. This work addresses important questions about the etiology and prevention of lung cancer, and can be completed with a modest amount of funding in addition to what has already been invested in this large chemoprevention trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: DNA CARCINOGENESIS

DOUBLE

STRAND

BREAK

REPAIR

IN

TOBACCO

Principal Investigator & Institution: Bedford, Joel S.; Professor; Environmental & Radiological Health Sciences; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Despite strong epidemiological data associating tobacco smoke to lung cancer, the mechanism of carcinogenesis by tobacco chemicals is not well understood. Among those exposed to tobacco smoke, only a certain portion develop lung cancer suggesting the involvement of genetic factor(s) in the susceptible population. A difference in DNA repair ability has been suggested for the explanation of the susceptibility. Of the various DNA repair pathways, a relationship between nucleotide excision repair and tobacco carcinogens (e.g. benzo[a]pyrene) has been well documented. However, DNA double strand break (DSB) repair, another important repair pathway, has rarely been studied with tobacco chemicals in mammalian systems. Since a recent study revealed a positive association between lung cancer and the reduced activity of a protein involved in DNA DSB repair, this application is initiated to confirm and extend the study on the role of DNA DSB repair in tobacco carcinogenesis. DNA DSB is the most destructive form of DNA damage and can lead to cell death, mutation and transformation if not repaired or mis-repaired. An efficient way to study

20 Lung Cancer

the role of DNA DSB repair is to use DNA DSB repair deficient mutant cell lines exposed to tobacco chemicals. Specific Aim 1 addresses: Various rodent and human DNA DSB repair deficient cell lines will be treated with several tobacco carcinogens and cigarette smoke condensate (CSC), and comparisons will be made to wild type cells with regard to cell survival and mutation frequency. This is to test the hypothesis "Mammalian cells utilize DNA DSB repair mechanism or protein(s) associated with DNA DSB repair in the recovery process of DNA damage induced by tobacco carcinogens". Further molecular studies are suggested based on the cell line studies. These studies have the potential to identify a new tobacco sensitive sub-population. The experiments in Specific Aim 2 are proposed based on our recent finding that lung cancer sensitive BALB/c mice showed a mild DNA DSB repair defect. Specific Aim 2 puts forward the studies on the cell viability, DNA DSB formation and chromosome rearrangements in alveolar macrophage (AM), lymphocytes and lung epithelial cells from BALB/c and C57BL/6 (control) mice exposed to tobacco carcinogens. Two hypotheses will be tested in this aim: (1) Cells from BALB/c mice show a higher level of chromosome misrejoining which is detected by a sensitive premature chromosome condensation (PCC) assay in interphase chromosomes combined with/without fluorescence in situ hybridization (FISH)." (2) There is a good correlation between the sensitivity data with lymphocytes and those with AM and/or lung epithelial cells. The proposed experiments not only provide new mechanistic insight on the initial step for tobacco carcinogenesis, but also help furnish sensitive diagnostic tools to identify lung cancer susceptible individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPIDEMIOLOGIC STUDIES OF LUNG CANCER RISKS IN NSAID USERS Principal Investigator & Institution: Zheng, Wei; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 28-JUN-2001; Project End 31-DEC-2006 Summary: (provided by applicant): Cumulative evidence from in vitro and animal studies suggests that the enzyme cyclooxygenase-2 (COX-2) is important in the development and progression of lung cancer. Epidemiologic studies evaluating the association between the use of aspirin (an inhibitor of COX-2) and the risk of lung cancer have been conflicting, and no study has been conducted to evaluate non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). Using pre-recorded drug prescription databases of the Tennessee Medicaid program and North Jutland County of Denmark, we propose to conduct two studies in these populations to examine the effect of NSAID use on the risk of lung cancer. The first is a retrospective cohort study of over 10,000 enrollees of the Tennessee Medicaid Program who were diagnosed with chronic obstructive pulmonary diseases (COPD) during the period of 1980 to 2002. The second is a population-based, retrospective cohort study of over 150,000 users of NSAIDs in the general population of North Jutland County during the period of 1991 to 2002. Within the Danish cohort will be a nested case-control study of 350 cases and 700 controls, in which relevant information will be obtained on over the counter (OTC) analgesic use, as well as cigarette smoking and other potential confounding factors. The two studies proposed here complement each other and provide for an international comparison of NSAIDs as possible lung cancer chemoprevention agents. Because the data on NSAID use have already been collected, the studies will be very cost-efficient. More importantly, the use of pre-recorded pharmacy records minimizes potential errors in exposure assessment and provides a major advantage over existing cohort studies in

Studies

21

evaluating the potential chemopreventive effect of NSAIDs. Given the high incidence and mortality of lung cancer and high prevalence of NSAID use, the results from our studies may have important public health implications in lung cancer prevention, and could set the stage for future randomized trials of COX-2 inhibitors in cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ETHNIC DISPARITIES, QUALITY OF LIFE AND MODE OF DEATH Principal Investigator & Institution: Fouad, Mona N.; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2006 Summary: Description This 3-year special project proposes to examine racial/ethnic variations in and associations between disease-specific symptoms, quality of life (QOL), and site of death during the terminal stages of lung cancer for newly diagnosed lung cancer cases enrolled by the Deep South CanCORS Consortium. Working closely with the Consortium, the special study will identify advanced lung cancer subjects (with tumor(s) inoperable for staging reasons), and follow them bimonthly by telephone until the subject's death or the end of the special study. Bimonthly follow-up is to include administration of at least two disease-specific instruments: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Specific Module (EORTC QLQ-LC13), which measures symptoms; and the Functional Assessment of Cancer Therapy lung cancer module(FACT-L), which assesses QOL. At least one general instrument is also proposed for use, SF-36, with physical functioning and role limitation subscales. Following the subject's death, staff will telephone and interview the nearest relative about the death using an investigator-developed, nineitem survey. Utilizing descriptive statistics and multi-variable models, investigators will test whether: African-Americans have lower QOL and worse symptom control than Caucasians; subjects with better symptom control have higher QOL; and subjects with higher QOL or better symptom control are more likely to die at home. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: EXISULIND FOR CHEMOPREVENTION OF LUNG CANCER Principal Investigator & Institution: Bepler, Gerold; Program Leader, Profesor of Medicine, On; H. Lee Moffitt Cancer Ctr & Research Ins and Research Institute, Inc. Tampa, Fl 336129497 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant) Lung cancer is the leading cause of cancer death in the United States. Cure rates from primary treatment are low (approximately 15%). There is an urgent need to develop compounds, which can prevent the disease in individuals with a history of cigarette smoking and other factors associated with increased lung cancer risk. A number of compounds have been tested but trials to date have not resulted in a decrease of lung cancer incidence. In fact, two large-scale chemoprevention trials that evaluated beta-carotene in active and former smokers, resulted in an increase of incidence and mortality from lung cancer. Recently, the focus of lung cancer chemoprevention has shifted towards investigations using inhibitors of inflammatory response pathways and inhibitors of growth factor signaling pathways. A novel class of agents has been developed that induce apoptosis. Exisulind (Aptosyn) is the first agent in this class, and it has shown promise in chemoprevention of colorectal carcinoma by reducing the number of size of adenomatous polyps in humans. In animal

22 Lung Cancer

studies, this agent has resulted in a reduction of carcinogen-induced lung cancer. To test the clinical utility of this agent in lung cancer prevention, we propose to perform a double-blind, placebo-controlled, randomized, clinical efficacy trial in former smokers. Participants will be stratified by lung cancer risk based on airway obstruction, prior history of completely resected stage I non-small cell lung cancer, and the histopathology of bronchial biopsies. They will be randomized 2:1 to drug vs. placebo. A surrogate marker of lung cancer, the proliferation marker Ki-67, will be used as the primary endpoint. Other markers previously and currently investigated by us and others (MCM2, hnRNP, apoptosis, cytokine response profiles, (epi) genetic alterations, morphology) will be explored as surrogate trial endpoints. Exisulind will be given orally at a dose of 500 mg daily for 6 months. With 93 evaluable participants randomized to exisulind, the study will have 80% power to detect a 50% or greater decrease in the mean Ki-67 labelling index as a result of treatment. Since we anticipate a 25% attrition rate, we are planning to enroll a total of 186 subjects over 4 years. Given the number of eligible subjects at our institution that already participate in early detection trials, we are confident that the goal of this proposed study can be achieved during the 5-years of funding. The data generated by these investigations will be important for future decisions on large-scale chemoprevention trials using disease incidence and mortality as endpoints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENE EXPRESSION INDICES IN CHEMORESISTANT LUNG CANCER Principal Investigator & Institution: Willey, James C.; Professor; Medicine; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-MAR-2004 Summary: Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer death in this country and it is poorly responsive to current chemotherapeutic regimens with an overall regression rate of only 30-50 percent. Histological categorization provides extremely limited information regarding biological behavior of a particular NSCLC tissue. Progress in the genome project and advances in high throughput measurement of gene expression are providing the opportunity to re-define diagnosis of NSCLC tissues on the basis of important phenotypes, such as chemoresistance, rather than on the basis of histology. The primary long-term objectives of the proposed investigation are to improve mechanistic understanding of NSCLC chemoresistance and to develop a method for predicting which NSCLC tumors will respond. The mechanisms of resistance likely to involve multiple gene products. For example, in other studies it was determined that indices comprising multiple independent gene expressions values measured in bronchial epithelial cells correlated better than individual gene expression values when phenotypes for malignancy (c-myc x E2F-1/p21) and risk for lung cancer (GSTP1 x mGST x GSHPx). In preliminary studies, the H1435 non-small cell lung cancer (NSCLC) cell line is 50-fold more resistant to carboplatin than H460. Evaluation of 20 genes putatively associated with carboplatin chemoresistance using standardized mixtures of competitive templates in quantitative RT-PCR revealed that glutathione transferase (GST) p1, Bax alpha, GADD45, ERCC3, glutathione peroxidase and mGST genes are expressed at 100, 20, 10, 6, 5, and 4-fold higher levels respectively in H1435. These genes and other putative chemoresistance genes may be effectively combined into gene expression indices to produce a better marker for the chemoresistant phenotype. The over-all hypothesis of this proposal is that patterns of individual gene expression and/or indices comprising the expression

Studies

23

values of multiple individual genes will provide an effective marker for chemoresistant NSCLC tumors. A National Cooperative Tumor Signature Group has assembled to test the hypothesis through completion of the following specific aims. AIM 1) Measure expression of putative chemoresistant genes in primary NSCLC tumor tissues then identify which, if any, correlate with resistant phenotype. AIM 2) Identify gene expression indices that correlate with NSCLC tumor chemoresistance AIM 3) Develop a standardized mixture of competitive templates that will allow inter-laboratory comparison of gene expression data. AIM 4) Automate the quantitative RT-PCR method. AIM 5) Develop an internet based databank for storage of the data acquired during this study and for storage of data acquired by other laboratories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENETIC SUSCEPTIBILITY TO LUNG CANCER Principal Investigator & Institution: Christiani, David C.; Professor; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 10-APR-1997; Project End 31-JAN-2003 Summary: (Adapted from Applicant's Abstract). The leading risk factor for lung cancer in the U.S. is cigarette smoking. The incidence of lung cancer remains alarmingly high and, despite the use of modern diagnostic and treatment modalities, the overall cure rate is low. Thus, preventive efforts, based upon the understanding of risk factors may be of paramount importance in controlling this deadly disease. A minority of smokers develops lung cancer, suggesting variability in disease susceptibility. Smoking itself may contribute to a causal complex along with other contributing factors such as genetic predisposition. Moreover, only a small proportion of all cancers is explained by simple monogenic inheritance. Several polymorphisms in the genes responsible for either activation or deactivation of carcinogens have been reported to be associated with lung cancer risk. To date, however, no studies have had sufficient statistical power to examine a number of complex gene-environment interactions in lung cancer (e.g., dietary and occupational contributions or gene-gene interactions). A large molecular epidemiologic study is proposed to examine six polymorphic traits in metabolism and lung cancer risk and how this risk may be modified by dietary or occupational exposures. The application posits that the combination of traits which enhance activation of carcinogenic metabolites and decrease detoxification of reactive products will confer excess risk in current and former smokers. Furthermore, it suggests that this risk will be modified by diet and occupational exposures. It is intended that a better understanding of these risks and their modification could lead to more effective preventive strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: GENETICS OF TOBACCO AND ALCOHOL RELATED CANCERS Principal Investigator & Institution: Brennan, Paul J.; World Hlth Org Intl Agcy Res on Cancer Int'l Agency for Res on Cancer Lyon, Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Even though lung and upper aero-digestive tract (UADT) cancers are predominantly caused by tobacco and alcohol, only a minority of heavy smokers and heavy drinkers will develop lung or UADT cancer. A possible explanation for this is that the metabolisation of carcinogenic products, the level of internal dose and subsequent DNA repair and cell cycle control mechanisms vary

24 Lung Cancer

widely between individuals because of genetic factors. The broad long-term goal of this project will be to investigate in two separate studies the role of 45 genes which are potentially involved in the susceptibility of lung and UADT cancers. The first is a study of lung and UADT cancers in Central Europe, involving approximately 2300 lung cancer cases, 1200 UADT cancer cases and 2800 controls. The second is a separate study of UADT cancer in South America involving approximately 2100 cases and 1700 controls. Both studies are conducted to an identical protocol involving the collection of high quality detailed information on lifestyle and occupational history, as well as blood collection for DNA extraction. Genotyping of 108 SNPs for the 45 genes will be conducted using automated and pre-validated DNA microarrays. The genes comprise those involved in the metabolism of tobacco products, alcohol and other potential carcinogens (e.g. CYPs, GSTs, ADH2, ADH3, MPO), as well as genes involved in DNA repair (e.g. XRCC1, XRCC3, XPD, XPF), tumour suppression (p53, p16, CCND1 ) and nicotine addiction (dopamine D2 and D4 receptor genes). Using these large sample sizes, we will accurately measure the overall effect of each gene in lung and UADT cancer. Subsequently, the effect of combinations of genes will be measured (gene-gene interaction), as well as the effect of individual genes in specific subgroups identified by alcohol and tobacco consumption and occupational history (gene-environment interaction). Statistical techniques will include haplotype reconstruction, empirical Bayes and semi-Bayes analysis to control for false positive results, and modeling of complex pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEDGEHOG PATHWAY INHIBITION BY CYCLOPAMINE IN CANCER Principal Investigator & Institution: Watkins, D Neil.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Lung cancer results in more deaths than colon, breast and prostate cancer combined. Conventional cytotoxic therapy of lung cancer is limited by side effects, and is rarely curative. Mechanism based therapies directed at tumor specific pathways offers hope for the development of novel treatments. With this in mind, we have studied activation of mammalian development pathways in human lung cancer to provide insights into how such interventions can be achieved. The morphogen sonic hedgehog (Shh), which signals to adjacent embryonic cells to specify morphogenic patterns and progenitor cell fates, is essential for lung development. In extensive preliminary studies, we provide compelling evidence that many human lung cancers activate Hedgehog (Hh) signaling. We demonstrate cell autonomous Hh signaling in small cell lung cancer (SCLC), whereas non-SCLC (NSCLC) sends a Shh signal to adjacent stromal cells. Moreover, we find that specific inhibition of Hh signaling by the Veratrum alkaloid cyclopamine inhibits the growth of SCLC cells exhibiting pathway activation both in vivo and in vivo. Although NSCLC cells express Shh, they are not sensitive to cyclopamine and do not demonstrate cell autonomous pathway activation in vivo. However, NSCLC cell lines which signal to adjacent fibroblasts in vivo are growth inhibited by cyclopamine in vivo, suggesting that tumorstromal interactions mediated by Shh promote malignant growth. These data show that activation of the Shh pathway promotes the malignant behavior of lung cancer, and that inhibition of this pathway may represent a novel mechanism-based therapy. Outside of studies in CNS tumors, this is the first direct demonstration of Hh pathway activation in any human cancer. Moreover, our studies show that this phenomenon is not a general

Studies

25

feature of carcinomas, but is restricted to epithelial systems in which Hh signaling plays a role in development. We propose to establish inhibitors of Hh signaling as clinically useful therapies in lung cancer using an approach integrating human tumor tissue arrays, molecular and cell biology studies, mouse models and basic pharmacology. First, we will identify the prevalence of Shh pathway activation in lung cancer and premalignant airway tissue using immunohistochemical markers. Then, using genetically engineered reporter cell lines and mouse models, we will study the pharmacologic effect of Hh pathway inhibitors on tumor growth, pathway activation and tumor-stromal interactions. Using these preclinical models, we will then perform delivery, dosing and toxicity studies as a rational basis for eventual phase one studies in humans. This research plan will firmly establish the importance of Shh signaling in lung cancer, and provide a rational, mechanism based approach for the treatment of lung cancer with inhibitors of the Shh pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HSP110-LUNG TUMOR ANTIGEN COMPLEX AS A CANCER VACCINE Principal Investigator & Institution: Subjeck, John R.; Professor; Corixa Corporation 1124 Columbia St, Ste 200 Seattle, Wa 98104 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JAN-2004 Summary: (provided by applicant): The objective of the research is to develop an effective vaccine for the treatment of lung cancer. The commercial value derives from the novelty of the lung cancer antigen, L523S, as well as the novelty of the molecular chaperone approach using hsp110. L523S is expressed in a large number of lung carcinomas and has been shown to be immunogenic. Hsp110 is a heat shock protein with strong chaperoning properties. This molecular chaperone is then naturally complexed with L523S by heat shock. Since heat shock proteins have natural immunological functions, this hsp110-L523 S vaccine may well provide an effective therapy in the treatment of lung cancer and correspondingly have significant commercial value. Two specific aims are defined. Aim 1 will be to manufacture active, recombinant hsp110 in large quantity, establish its chaperone and immune activity, and then to verify its proper binding to the 523S lung cancer antigen. Aim 2 will determine the ability of the hsp110-L523S natural chaperone complex to elicit antigen specific immune responses in mice and will compare the magnitude of these responses to conventional approaches. Effective vaccines against lung cancer have not been previously developed and the characterization of this approach could lead to highly marketable commercial product. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: IDENTIFYING GENES THAT CAUSE LUNG CANCER TO PROGRESS Principal Investigator & Institution: Debs, Robert J.; Senior Scientist; California Pacific Med Ctr-Pacific Camp San Francisco, Ca 94115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Recently, cDNA microarray studies have identified multiple different genes that are aberrantly-expressed in aggressive human lung cancers. However, to translate these microarray-based results into improved therapies for cancer patients, the critical genes whose aberrant expression actually controls metastatic spread must now be identified. To date, functional assays for identifying such

26 Lung Cancer

metastasis-controlling genes have been limited. Systemic gene transfer in adult, tumorbearing mice is a powerful new approach to this problem. We now propose to use new systemic gene transfer technologies to identify which of nine selected genes (already identified by cDNA microarray studies to be aberrantly-expressed in poor prognosis, primary human lung cancers) actually control the metastatic spread of two different murine lung cancer tumor lines, LLC-LM and LLC-HM, in tumor-bearing mice. Our three specific aims are: Aim 1: To maximize the level and duration of gene expression produced in tumor-bearing mice by PEI- and IV, CLDC-based gene delivery. We will identify the most efficient, durably-expressing systemic gene transfer approaches for transfecting LLC-LM and LLC-HM cells in tumor-bearing mice. To accomplish this, we will optimize the: A) DNA carrier system, B) plasmid DNA:carrier ratio and C) repetitive dosing schedule. Aim 2: To use systemic delivery of selected cDNAs and ribozymes to identify specific genes that control the metastatic spread of lung cancers in mice. We will identify specific genes whose blocked expression or over-expression significantly reduces the metastatic spread of LLC-LM and HM in mice. Specifically, we will use plasmid-based ribozymes to target the endogenous expression of the CD98, cathepsin L, prostaglandin E synthase or VEGF-C genes, and use plasmid-based cDNAs to over-express the p21, 14-3-3, TGF-beta, thymosin beta or diacylglycerol genes. Each of these nine genes has already been identified by cDNA microarray studies to be aberrantly-expressed specifically in poor prognosis human lung cancers, and has been linked to the malignant phenotype. Aim 3: To identify pairs of metastasis-controlling cDNAs and/or ribozymes that act synergistically. We will assess IV co-injection of pairs of plasmid-based ribozymes and/or cDNAs that produce significant metastasiscontrolling effects against murine lung cancer lines in Aim 2. We will assess multiple different dose combinations of each pair tested to determine whether there are specific interactions between each pair of genes. Overall, we will attempt to identify specific genes whose altered expression is functionally required for the metastatic spread of lung cancers. These critical metastasis-controlling genes can be specifically targeted by emerging small molecule-, protein- and gene-based therapeutic approaches; including those based on the more powerful systemic gene transfer approaches we have recently developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: IMAGING MDR CHEMOTHERAPY EFFECT IN SMALL CELL LUNG CANCER Principal Investigator & Institution: Piwnica-Worms, David; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 31-MAY-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Lung cancer is the leading cause of cancer related death in the United States. Approximately 20% of patients with newly diagnosed lung cancer have the small cell histological type (SCLC). Even though it is more responsive to chemotherapy, nearly all patients with extensive stage small cell lung cancer succumb to recurrent disease. Overexpression of the multidrug resistance gene (MDR1) and its protein product P-glycoprotein (Pgp) as well as the multidrug resistance-associated protein-1 (MRP1) have been shown to result in poor response to therapy and shorter survival in SCLC when compared to those whose tumors do not overexpress these MDR determinants. Because many of the drugs in current use are impacted by Pgp and MRP1 (i.e., etoposide, paclitaxel, anthracyclines, vincristine), it is conceivable that administration of these chemotherapeutic agents may contribute to the emergence of drug resistance clones, ultimately contributing to poor outcomes. Thus, functional

Studies

27

identification of Pgp, and perhaps MRP1, at the time of presentation could provide important information which could direct the choice of chemotherapeutic options. We have discovered that Tc-99m-Sestamibi, a commercially available radiopharmaceutical, is recognized as a transport substrate by the human MDR1 P-glycoprotein in vitro and in vivo and may be recognized by MRP1. Thus, Tc-99m-Sestamibi may serve as a molecular imaging agent enabling functional identification of transporter-mediated resistance by scintigraphy. However, single photon agents such as Tc-99m-Sestamibi, while yielding high quality images for analysis of superficial tissues such as breast tumors, are prone to attenuate artifacts when applied to lesions deep in the thorax such as lung tumors. At Washington University, the cyclotron Research Resource can produce a variety of non-standard isotopes, including Tc-94m, a novel isotope suitable for positron emission tomography (PET). Thus, the WU ICMIC has an unique opportunity to directly translate our extensive biochemical and clinical experience with Tc-99m-Sestamibi imaging of MDR into novel PET studies with Tc-94m-Sestamibi. Exploiting the quantitative advantages of PET in this project, we propose to use Tc-94mSestamibi PET to image patients with extensive stage SCLC. We propose to test the hypothesis that dynamic imaging of lung tumors with Tc-94m-Sestamibi will predict treatment failure in patients with extensive stage small cell lung cancer and determine whether Pgp and MRP1 together or independently impact Tc-94m-Sestamibi pharmacokinetics in lung tumors in vivo. Molecular imaging of the MDR phenotype with radiopharmaceuticals may provide a novel tool to rapidly characterize clinically relevant MDR in human tumors in vivo, target MDR modulators in vivo, and ultimately provide a means to direct patients to molecular-specific cancer therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: IMPACT OF SMOKING ON LUNG CANCER CHEMOPREVENTION Principal Investigator & Institution: Hong, Waun K.; Professor and Chairman; Head Neck & Thoracic Med Oncol; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 20-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant) Lung cancer is the leading cause of cancer death among both men and women in the United States today, and a rising public health problem throughout the world. Although we?ve seen some improvement using combined modality approaches, these have had little impact on survival. Chemoprevention is a highly promising new approach that has already shown enormous potential for the control of other epithelial solid tumors. However, numerous studies of lung cancer chemoprevention have shown no benefit, and some have shown actual harmful effects in current smokers. It seems clear that previously unsuspected adverse interactions exist between tobacco carcinogens and chemopreventive agents. Although further studies of lung cancer chemoprevention are warranted, a thorough investigation of these carcinogen/chemoprevention interactions is necessary before further large-scale randomized trials are implemented. The overall goals of this translational, multidisciplinary Program project are to elucidate the interactions between tobacco carcinogens and chemopreventive agents, investigate the potential of celecoxib for lung cancer chemoprevention, and validate intermediate markers of lung carcinogenesis. To accomplish our goals, we propose to carry out a clinical chemoprevention trial in humans, while performing genetic, molecular, and pharmacologic studies to understand the carcinogenic process and the interaction of carcinogens with chemopreventive agents through the following projects: Project 1: Clinical Trial of Celecoxib in Lung Cancer Chemoprevention Project 2: Lung Cancer

28 Lung Cancer

Prevention by COX-2 and 5-LOX Inhibitors, Retinoids, and Their Combinations Project 3: Molecular Alterations in Lung Carcinogenesis Project 4: The Role of Transcription Factor NF-kB in Lung Cancer Development and Chemoprevention Core components (Administration, Biostatistics and Data Management, Histology, and Pharmacology) are also included to provide the structure and expertise required for the successful integration and execution of these studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INTERNATIONAL CONFERENCES ON SCREENING FOR LUNG CANCER Principal Investigator & Institution: Henschke, Claudia I.; Professor; Radiology; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): The first study of the Early Lung Cancer Action Project (ELCAP), led by Dr. Caludia Henschke, Ph.D., M.D. of the Weill Medical College of Cornell university and New York) Presbyterian Hospital, demonstrated that annual low-dose chest computed tomography (CT) screening has the potential to markedly increase the diagnosis of small, early stage lung cancers. With such early diagnosis, the cure rate of individuals with lung cancer has been greater than 70%. As a result of the worldwide interest in CT screening for lung cancer, we held our initial conference entitled the "International Conference on Screening for Lung Cancer." It was partially supported by an NCI conference grant. We invited all investigators from around the globe involved in ongoing screening studies as well as those with proposed studies. We also invited participants to discuss imaging and molecular diagnostics for early detection of lung cancer, as well as innovative treatments and chemoprevention. Study design issues and health care policies are addressed in depth, offering the opportunity for medical professionals to exchange ideas and to collaborate on research activities. To date, six semi-annual conferences have been held with an enrollment totally more than 1200 participants. The increasing enrollment at each successive conference demonstrates that, in a short time, these conferences have become an important forum for lung cancer screening specialists. The broadest mission of these semi-annual conferences is the collective pursuit of avant-garde understanding of the issues surrounding early diagnosis and early treatment of lung cancer. Any given Conference focuses on issues that are particularly topical at the time. Lectures are devoted to these issues on one day with workshops being held on the second day and the development of a consensus on these issues during the third day. The consensus statement and particulars of the workshops are then published on the ICScreen.med.cornell.edu website. These conferences are open to all. At each conference we provide an update on the interim advances in both research and practice of early diagnosis and early treatment as well as an update on the results of screening trials, whether they are randomized controlled trials or not. We also review the progress of all collaborating worldwide institutions. New technologies and methodologies are continually being developed to refine measurements, data collections, and statistical evaluations, all of which are aimed at promoting further reductions in lung cancer morbidity and mortality. All viewpoints and types of methodologic issues inherent in screening evaluation are openly discussed by invited experts. As a result of the conferences, critical issues which might require further study will be addressed. Consensus reports will be developed. The advantage of such a consensus reports is that it will provide useful and up-to-date information about CT screening on which to base the national and international policies in a very timely and cost-efficient manner.

Studies

29

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

Project Title: IOWA AND MISSOURI RADON LUNG CANCER STUDIES Principal Investigator & Institution: Field, Robert W.; Epidemiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 17-JAN-2001; Project End 31-DEC-2005 Summary: Risk estimates, extrapolated from studies of underground miners, predict that residential radon progeny exposure accounts for approximately 19,000 lung cancer deaths each year in the United States. Previous case-control epidemiologic studies, which examined the relationship between residential radon exposure and lung cancer, lacked the ability to verify these risk estimates. Inaccurate dose assessment of radon exposure, a high percentage of proxy respondents, inadequate pathologic review, and low residential radon concentrations led to exposure misclassification and limited the interpretation of these studies. The Iowa Radon Lung Cancer Phase I study was designed to overcome many of these limitations. The Phase I study utilized advanced radon dose assessments, independent histologic review, and a study population that was characterized by geographic stability, high percentage of live cases, and potential for high radon exposure. The Phase I study demonstrated that exposure to residential radon gas increases the risk of developing lung cancer. To refine these estimates, we now propose Phase II studies that examine the association between residential radon product (progeny) exposure and the development of lung cancer. Because radon progeny deliver the actual radiation dose to the lung tissues, rather than radon gas itself, in order to reduce further the exposure misclassification, radon dose estimates need to take into account exposure to residential radon progeny. This requires measuring actual airborne radon progeny concentrations and integrating the exposure to radon progeny over time. The Phase II study will derive more accurate retrospective radon dose estimates by using a novel retrospective radon progeny integrating glass-based detector. Specific Aim I examines the hypothesis that exposure to residential radon progeny is associated with increased risk of developing lung cancer, after controlling for confounders. We will perform field calibration and laboratory validation of the retrospective radon "glass" detectors, and analyze the risk estimates by incorporating exposures to radon progeny, rather than exposures to radon gas. Specific Aim II will determine whether the shape of the dose response curve that best describes the relationship between residential radon progeny exposure and lung cancer risk is linear or nonlinear. Specific Aim III will examine whether exposure to radon progeny contributes to the development of adenocarcinoma, as well as other lung cancer histologic types. For Aims II and III we will use pooled analyses of exposure estimates that are derived from retrospective radon progeny "glass" detectors for subjects from the Iowa and Missouri Radon Lung Cancer Studies. The pooling of data between two largescale epidemiologic studies from a similar geographic area, Iowa and Missouri, will allow us to increase sample size and statistical power. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: LOCALIZED VITAMIN DEFICIENCIES AND RISK FOR LUNG CANCER Principal Investigator & Institution: Piyathilake, Chandrika J.; Nutrition Sciences; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2003

30 Lung Cancer

Summary: (Applicant's Description) Although there is substantial epidemiological and experimental evidence of a protective effect of a high intake of fruits and vegetables against lung cancer (LC), studies that have attempted to isolate specific nutrient effects have given variable results. One possible reason for the lack of consistency between studies of individual nutrients and fruits and vegetables is that the frequently studied components like beta-carotene and other antioxidants in fruits and vegetables may not be the only protective components. We advance the possibility that folate in fruits and vegetables is one of these relatively unstudied components. The potential mechanisms whereby deficiencies of folate and inter-related vitamin B-12, could lead to gene damage via DNA hypomethylation are well understood. Furthermore, chemical components of cigarette smoke have been shown to interact with folate and vitamin B-12, transforming them into biologically inactive compounds. That these chemical reactions may have physiologic significance is supported by the reports of lower circulating and buccal mucosal folate levels in smokers, and a response of bronchial metaplasia to folate/B-12 supplementation. We expect the effect of smoking to be greatest in the lung, where the potential for cigarette smoke to oxidize and destroy micronutrients should be most pronounced. Yet, the importance of folate and vitamin B-12 in LC prevention is not widely appreciated. There are no reports on the measurement of folate or vitamin B-12 levels in lung tissue. Although there are some reports on the epithelial lining fluid (ELF) levels of vitamins C and E, and their accumulation by alveolar macrophages (AM) of smokers, none of these studies has measured a battery of vitamins in the same sample, studied the significance of AM accumulation of vitamins, or most importantly, correlated those vitamins with the expression of intermediate endpoint biomarkers (IEB). The identification of IEB in LC has proceeded briskly, but studies of the chronology of early events are only in their infancy. Therefore, special emphasis will be given to the identification and validation of IEB in lung carcinogenesis since this is an inadequately documented but emerging area in cancer prevention research. This fiveyear Preventive Oncology Academic Award will provide the applicant with intensive training in IEB research under expert guidance to become an independent researcher in this area. Following this, the dietary intake and concentrations of folate, vitamins B-12, A, E, C, and beta-carotene in ELF, AM, bronchial biopsies, and blood will be measured along with global DNA hypomethylation and IEB in bronchial biopsies of smokers and non smokers matched for age, gender, and race. Along with identifying and validating IEB, the proposed studies will provide insight into the mechanisms for the welldocumented protective effects of fruits, vegetables, and antioxidant nutrients on the risk for lung cancer in smokers, and will provide much needed base-line data for the evaluation of chemopreventive applications of vitamins. These activities, along with advanced studies of epidemiology and statistical analysis and experience in teaching, will provide the expertise needed for a career as a successful, independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: LUNG CANCER Principal Investigator & Institution: Jett, James; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-JAN-1982; Project End 31-DEC-2005 Summary: Between 170-250 patients per year were enrolled on lung cancer treatment trials between January, 1996, and December, 1999. Additionally, 200 patients were enrolled on ancillary trials, as well as quality of life and cancer control trials. During this grant cycle, we have published 11 abstracts and 12 manuscripts related to NCCTG trials. Six other manuscripts are in preparations. Three major accomplishments were made

Studies

31

over this period: First, we have complete two phase III randomized trials with combined modality therapy that have evaluated the role of twice daily hyperfractionated radiotherapy. In these trails, patients received concurrent chemoradiotherapy. One trail was in small cell (SCLC) and the second in non-small cell lung cancer (NSCLC). These were important trials for scientifically evaluating hyperfractionated radiotherapy. Additionally, these trials further evaluated the evaluated the risks and benefits of concurrent chemoradiotherapy. We have learned that acutely concurrent therapy is somewhat more toxic, but tolerable, and results in improved survival for small cell lung cancer. However, hyperfractionated radiotherapy, when given with cycle 4 of chemotherapy, did not impact on survival versus concurrent chemoradiotherapy with once a day irradiation. The results of the impact on survival versus concurrent chemoradiotherapy with once a day irradiation. The results of the impact on survival versus concurrent chemoradiotherapy with once a day irradiation. The results of the impact on survival versus concurrent chemoradiotherapy with once a day irradiation. The results of the non- small cell lung cancer trial are pending. The small cell trial has resulted in a change in practice in the community with concurrent therapy becoming the standard. Second, our community-based oncologists and thoracic surgeons have successfully completed a neoadjuvant chemotherapy trial in early stage (stage I and II) lung cancer and participated in an adjuvant trial for resected stage II and IIIA non-small lung cancer. We have learned that neoadjuvant chemotherapy does not increase surgical morbidity and/or mortality. These trials have prepared us for participation in the current neoadjuvant phase III Intergroup trial (S9900) in early stage patients and Intergroup adjuvant trials in totally resected patients with more advanced disease. Third, new chemotherapy gents and combinations (LU103793, topotecan/paclitaxel topotecan/cisplatin) were tested in NSCLC and found not to be effective or associated with excessive toxicity. These are important negative findings. Additionally, topotecan/paclitaxel alternating with etoposide/cisplatin has been tested against small cell lung cancer with promising results. NCCTG was also a major contributor to the Intergroup surgical adjuvant trial for resected stage II/IIIA NSCLC (INT 0115). Future Plans. A new leadership team is now in place, and the group is focused on building on its strengths to advance the treatment of lung cancer. Accrual on phase III trials has not been adequate to conduct Phase III trials sorely within NCCTG in a timely fashion. Treatment trials within NCCTG in the next grant cycle will, therefore, be primarily phase II studies testing the role of novel chemotherapy agents and agents that will, therefore, be primarily phase II studies testing the role of novel chemotherapy agents and agents will target specific abnormalities. We will focus on novel agents that affect signal transduction pathways. Promising treatments will be brought forth for rapid testing in large phase III studies in the Intergroup setting. In addition to selected ancillary studies with treatment trials, translational research in the genetic epidemiology of lung cancer will be an area of emphasis. The third area of research will be the treatment of lung cancer in the elderly, who are increasingly represented in our patient population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: LUNG CONSORTIUM--IOWA

CANCER

CARE

OUTCOMES/SURVEILLANCE

Principal Investigator & Institution: Wallace, Robert B.; Professor; Epidemiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 20-SEP-2001; Project End 31-AUG-2006

32 Lung Cancer

Summary: We have assembled a team of multi-disciplinary investigators to study, on a population basis, the patterns of treatment initially and continuing for a representative sample of lung cancer patients in the state of Iowa. These patterns will be explored in terms of patient decision-making processes for short and long-term treatment, with follow-up for suitable outcomes including disease-free interval, quality-of-life measures, end of-life care and overall survivorship. Factors proposed for exploration include including patient demographic, economic and behavioral attributes, including traits such as the patient's cancer learning environment and fatalism, the influences of geographically-dispersed practitioners with varied clinical management approaches, practitioner continuing education and information sources, the application of treatments where optimal approaches are uncertain and the influence of spatial and fiscal access to care. Special features of this proposal include: a) a multi-disciplinary team of investigators including epidemiology, disease registration, biostatistics, health economics, behavioral science and thoracic oncology; b) proven ability to access approximately 2000 lung cancer patients per year and achieve long term follow-up rates of 98-99%, using the Iowa Cancer Registry (NCI SEER Program); c) the elaboration of an economics model to guide both theory and questionnaire design for patients and practitioners, and offered to understand patient decision-making and its relation to outcomes; and d) demonstrable high levels of community cooperation, from patients, cancer care practitioners and pathologists. The goal of the special study is to use Instrumental Variable (IV) techniques to assess whether patient survival rates can be increased by increasing adjuvant therapy treatment rates for early stage non-small cell lung cancer (ENSCLC) patients. If providers are accurately sorting patients by their expected treatment benefits, and only patients expected to benefit from adjuvant treatments actually receive them, we would expect that treatment benefits for patients on the extensive margin to be minimal. We hypothesize there will be little or no treatment survival benefits for patients on the ENSCLC patients provides the rationale for this study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: LUNG PREVENTION

CANCER

IN

THE

US:

PATHOGENESIS,

TRENDS,

Principal Investigator & Institution: Moolgavkar, Suresh H.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant)Using the SEER database, which covers more than 10% of the US population, lung cancer incidence trends over the period 1973-1998 will be investigated using extensions of age-cohort-period models. Specifically, it is proposed to develop models in which non-specific age effects are replaced by parametric hazard functions that acknowledge the multistage nature of carcinogenesis. At least formally, this procedure finesses the well known problem of arbitrary linear trends that plagues the traditional age-cohort-period models. Furthermore, analyses of carefully collected incidence data in large registries such as SEER using biologicallybased modelscan lead to insights in to the mechanisms underlying carcinogenesis in addition to shedding light on temporal trends. With respect to temporal trends, attempts will be made to relate trends in lung cancer incidence to trends in smoking habits in the US. Tobacco smoke contains both mutagens and agents that impact cell proliferation kinetics. Thus, tobacco smoke probably acts as both an initiator and a promoter in lung carcinogenesis. One goal of these analyses is to investigate whether non-specific and birth cohort and calendar year trends can be directly linked to specific

Studies

33

aspects of carcinogenesis, such as initiation, promotion and progression. This possibility will be investigated by incorporating tobacco consumption trends into the parameters of the multistage model. Because of the large size of the SEER database it should be possible to conduct these analyses separately by race, sex and histologic type. Finally, the estimated parameters of the optimal multistage model will be used to project lung cancer incidence trends into the future under various assumptions regarding changes in composition of cigarettes and smoking habits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: LUNG CANCER--ROLE OF PTHRP AND REGULATION BY TGFBETA Principal Investigator & Institution: Tannehill-Gregg, Sarah H.; Veterinary Biosciences; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (Applicant's Description): The overall goal of the K08 award is to permit Sarah Tannehill-Gregg, D.V.M. to devote full time for research training leading to a Ph.D. in experimental pathobiology, and for development into an independent scientist for a cancer in academia or biomedical research. Dr. Tannehill-Gregg has completed a residency in comparative pathology and one year of research training in the sponsor's laboratory. The research goals are to investigate the regulation of extracellular calcium and the role of transforming growth factor-beta in parathyroid hormone-related protein (PTHrP) expression and secretion by cancers of the lung. This will address an important medical question since PTHrP is expressed by many carcinomas and is responsible for inducing humoral hypercalcemia of malignancy. The action of TGFbeta may be a critical determinant in the overexpression of PTHrP by carcinomas and play an important role in the pathogenesis of cancer-associated hypercalcemia in human patients. The overall hypothesis to be tested is that TGFbeta production by lung carcinoma acts as an autocrine or paracrine against to stimulate PTHrP production by the carcinoma cells. Aim 1: Investigate expression of PTHrP, TGFbeta1-3 and TGFbeta receptors (I and II) and measure serum ionized calcium and PTHrP concentrations and urine excretion of calcium and phosphorus in humans with lung cancer. Aim 2: Investigate the regulation of PTHrP expression and secretion by TGFbeta in lung carcinomas in vitro using explant cultures from spontaneous human neoplasms and cultures of lung carcinoma cell lines. Aim 3: Investigate the molecular regulation of PTHrP mRNA steady state levels, stability, and alternate splicing by TGFbeta in vitro using lung carcinoma explants and cell lines. Dr. Tannehill-Gregg has developed preliminary data to support all three aims and a collaboration with Medical and Surgical Oncology to facilitate the in vivo studies. The cooperative efforts of Dr. Tannehill-Gregg, the sponsor, and co-investigators in the Department of Veterinary Biosciences, Comprehensive Cancer Center, James Cancer Research Hospital, Pulmonary Oncology and Thoracic Surgery Divisions, and Tissue Procurement Program at Ohio State University will provide a productive environment to complete this significant investigation. The studies will provide important new data on the function of PTHrP and TGFbeta in lung cancer in human patients. The combination of results from in vivo study, in vitro cultures, and mechanistic molecular experiments will contribute to the understanding of the role of PTHrP in lung cancer and provide insight into the pathogenesis of cancer-associated hypercalcemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

34 Lung Cancer

·

Project Title: NETWORK

LUNG/COLON

CANCER

OUTCOMES--CANCER

RESEARCH

Principal Investigator & Institution: Weeks, Jane C.; Assistant Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 18-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): We will accrue all patients with newly diagnosed lung or colon cancer receiving their care in one of five geographically diverse sites in the Cancer Research Network, an NCI-funded research consortium of HMOs. Automated data for all patients (2,058 patients with lung cancer over the two year enrollment period, and 1,732 patients with colon cancer over the two year enrollment period) will be supplemented with data obtained from complete medical record review and patient surveys for a sample of 1,424 patients with newly diagnosed lung cancer and 1,222 patients with newly diagnosed colon cancer. We will oversample African-Americans, Asians and Pacific Islanders, as well as Medicaid recipients. In addition, we will assemble an inception cohort of patients with newly diagnosed metastatic recurrences of colorectal cancer during the two-year enrollment period (projected at approximately 300 patients) for comprehensive data collection. We propose to lead analyses of CanCORSwide core data in order to (1) examine the effect of race and ethnicity on patterns of care, treatment choice, quality of life, symptom control, and satisfaction; (2) characterize the types of providers seen by patients and examine the associations between provider characteristics/attitudes and patterns of care and outcomes; (3) evaluate the relationship between the structure/function of cancer care in the health care delivery systems of participating patients and patient outcomes, including health status, patient satisfaction, and cost; and (4) generate estimates of utility weights and time- and out-of-pocket costs that are disease- and treatment-specific for use in future cost-effectiveness analyses. Finally, in a Special Research Study we will aggregate cost data for CRN CanCORS subjects in order to (1) determine cancer-attributable phase-specific and lifetime costs of care for colorectal and lung cancer; (2) determine the proportion of total cancerattributable costs that are spent on initial therapy versus second- and third line therapies for each cancer, stratified by stage at diagnosis; and (3) determine the relationship between type of initial therapy and the subsequent lifetime cancer-attributable costs of care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MATRIX METALLOPROTEINASES IN LUNG CANCER Principal Investigator & Institution: Matrisian, Lynn M.; Professor and Chair; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 28-JUN-2001; Project End 31-DEC-2006 Summary: (provided by applicant): Matrix metalloproteinases (MMPs) have been implicated in tumor growth, angiogenesis, invasion, and metastasis. There is extensive preclinical data that inhibition of MMP activity results in a reduction in tumor burden and prolongs the survival of treated animals. Synthetic MMP inhibitors (MMPIs) are currently in Phase III clinical trials in a variety of tumor types, and non-small cell lung cancer (NSCLC) trials in particular have been initiated with several different compounds. The results of the initial studies with the broad spectrum inhibitor marimastat (British Biotech) showed little benefit in advanced pancreatic and gastric cancer, but encouraging results in patients without overt metastases. Studies with the MMPI tanomastat (Bayer Corp.), however, were stopped when preliminary results from an adjuvant small cell lung cancer (SCLC) trial demonstrated that the MMPI was

Studies

35

performing worse than placebo. These results raised the realization that very little is known about the role of MMPs in lung cancer development and progression. This proposal is designed to test the hypothesis that MMPs are valid therapeutic targets for lung cancer, and to determine the MMP family members that represent the most appropriate targets for MMPIs in NSC and SC lung cancer. The following specific aims are proposed: 1) Determine the expression profile of MMP transcripts and protein in SCLC and NSCLC samples and associate the expression profile with response to MMPI treatment. 2) Determine if MMPIs inhibit MMP activity in lung cancer patients using an ex vivo MMP activity assay, and 3) Determine the efficacy of MMPIs in chemicallyinduced and orthotopic preclinical models of lung cancer. The availability of mice that are null for several MMP family members provides the opportunity to examine the role of specific MMP family members in these model systems. These studies represent translational research that will guide the selection and application of selective MMPIs to the treatment of lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MODELING INTERVENTIONS FOR LUNG CANCER MORTALITY Principal Investigator & Institution: Holford, Theodore R.; Professor; Epidemiology and Public Health; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant)The study of time trends in cancer incidence and mortality can provide valuable insights into the effect that a disease is having on the population. A model will be developed in which the effect that smoking cigarettes, a well know cause of this disease, has on population based lung cancer rates. Age-periodcohort models have offered one useful way of developing a statistical summary of temporal trends. In this case, age represents the effect of the aging process on a disease risk. Period and cohort, on the other hand, are likely to reflect changes in the exposure to import risk factors or in the surveillance system. While analytical epidemiologic studies offer the best way to estimate the effect of putative risk factors on disease risk, quantitative descriptions of the way in which changes in exposure can affect population rates can be much more challenging. The purpose of this research is to develop a model in which trends in risk factors for lung cancer incidence are used to describe observed trends in incidence and mortality for the disease. These will then be used to estimate the effect on lung cancer mortality of interventions designed to reduce cigarette smoking. The specific aims of this research are to: 1. Develop a model for lung cancer incidence trends among SEER registries and determine the extent to which available data on smoking trends can be used as explanatory variables; 2. Develop a compartment model that describes the relationship between lung cancer incidence and mortality using available data from SEER registries; 3. Develop a model that uses available state information on cigarette smoking trends to explain the variation in cancer mortality trends among contiguous states; and, 4. Use the model developed in aims1-3 to estimate the population effect of various anti-smoking campaign strategies on future lung cancer mortality trends. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: MODELING LUNG CANCER IN TELOMERASE NULL MICE Principal Investigator & Institution: Wong, Kwok-Kin; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008

36 Lung Cancer

Summary: (provided by applicant): Lung cancer is a major international health problem. In the United States alone, an estimated 157,000 people will die of this disease in 2001 and tobacco use accounts for 85% of all lung cancers. Despite recent advances in cytotoxic drug development, radiotherapy and surgical management, the cure rate for advanced lung cancer remains poor. Further, much remains unknown about the molecular and genetic events involved in initiation and progression of lung cancer. One important mechanism seen in the development of epithelial cancers (i.e., lung cancer) appears to be underlying chromosomal instability due to a loss in telomere function brought about by significant cell division in the face of insufficient telomerase activity. Our laboratory has proposed that a combination of age-dependent epithelial renewal, somatic mutations that drive clonal proliferation, and chronic injury can accelerate telomere erosion, this culminating in a chromosomal fusion-bridge-breakagetranslocation process. This process provides a mechanism for rapid and wholesale changes in cells, with rare cells incurring a threshold number of relevant changes to initiate the transformation process. Reactivation of telomerase or upregulation of alternative telomere maintenance mechanisms restabilizes the genome, allowing such initiated cells to expand and acquire changes resulting in a fully cancerous cell. I propose to build on the unique experimental attributes of the telomerase deficient mouse to develop a lung cancer model that is driven by mechanisms underlying the genesis of human lung cancer. A physiologic mouse model of lung cancer may be developed by exposing the telomerase deficient mice with shortened telomeres to chronic tobacco smoke: this will accelerate lung epithelial cell turnover and promote genome wide mutagenesis. Once validated, this model will be used to examine the role of telomerase activation during carcinogenesis, and as a tool for novel lung cancer gene discovery. The applicant is an M.D. who will have completed a residency in internal medicine with subspecialty training in adult medical oncology prior to the proposed start date. He also holds a Ph.D. in molecular biology and biophysics. The proposed research will be carried out in the laboratory of Dr. Ronald DePinho at the Dana Farber Cancer Institute. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MODELING LUNG CANCER: RISKS, PROGRESSION, AND SCREENING Principal Investigator & Institution: Kimmel, Marek; Professor; Statistics; Rice University 6100 S Main Houston, Tx 77005 Timing: Fiscal Year 2002; Project Start 18-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): We propose to construct a realistic statistical model of lung cancer risk and progression that will make it possible to relate current trends in lung cancer incidence and mortality to past trends in smoking in the US population. We depart from existing approaches by having the model include genetic and behavioral determinants of susceptibility, progression of the disease from precursor lesions through early localized tumors to disseminated disease, detection by various modalities, and medical intervention. Using model estimates as a foundation, we intend to predict mortality reduction caused by primary prevention, and early-detection and intervention programs, under different scenarios. This includes utilization of genetic indicators of susceptibility to lung cancer to define the highest-risk subgroups of the high-risk behavior population (smokers). To allow for uncertainty in the various sources of data we will develop parameter estimation techniques using simulation and Bayesian hierarchical modeling approaches. Along with developing new methodology, we will apply our techniques to a variety of data sets available to us, which will allow

Studies

37

calibration and validation of the model. To investigate and develop lung cancer susceptibility, we will use tobacco impact estimates developed at the University of California at San Diego, as well as case-control genetic data on lung cancer maintained by the Epidemiology Department at MD Anderson Cancer Center. To investigate incidence of lung cancer we will use public registry data of the SEER type. For disease progression, early detection and intervention, we will use data from the NCI lung cancer chest X-ray screening studies, and the recent ELCAP CT-scan screening study developed at Weill Medical College of Cornell University. The team assembled for the proposed work includes researchers at Rice University, MD Anderson Cancer Center, Weill Medical College of Cornell University and University of California at San Diego, whose documented expertise spans population studies, modeling of natural history of cancer, impact of screening, Bayesian techniques, genetic epidemiology, statistical genetics and risks analysis of smoking. Data used and generated by the project, as well as software, will be made available to CISNET members. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MOLECULAR ALTERATIONS IN LUNG CARCINOGENESIS Principal Investigator & Institution: Mao, Li; Associate Professor/Director; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 20-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Early lung tumorigenesis is poorly understood at the molecular level. Consequently, no validated molecular marker is currently available for lung cancer risk assessment or evaluation of therapeutic efficacy. We previously demonstrated that certain genetic alterations commonly found in lung cancers might occur in normal-appearing bronchial epithelium of smokers. Altered expression patterns of tumor suppressor genes/oncogenes could also be detected in the bronchial epithelium of smokers. Recently, we found that DNA methylation status in promoter regions of genes involved in tumorigenesis could be altered, not only in lung tumors but also in the bronchial cells of smokers without cancer, resulting in transcriptional repression or activation of these genes. Recent advances in human genome project and high-throughput technologies provide opportunity to accelerate discovery of biomarkers for cancer risk assessment and evaluation of therapeutic efficacy. We hypothesize that substantial molecular alterations occur in airway of smokers, which causes "field defect" and associates with an increased lung cancer risk in this population. As a result, these molecular alterations critical in the initiation of transformation and early progression may predict lung cancer risk and can be used as intermediate endpoints to assess efficacy of chemopreventive agents. Three specific aims are proposed: (1) To identify molecular alterations in smoking damaged lungs and determine their role in assessing efficacy of chemopreventive agents. We will focus on molecular abnormalities that involve critical pathways and can be frequently detected in the bronchial epithelial cells in smokers. Potential differences between current and former smokers will also be analyzed. (2) To determine the role of easily accessible tissues as surrogate materials in evaluating lung damages and chemopreventive effects in the lung. We will determine molecular alterations in sputum and oral brushes in smokers and more importantly to see if potential drug effects in these specimens may reflect those in lung bronchial epithelium. (3) To identify novel biomarkers for risk assessment and evaluation of effects of chemoprevention. In this exploratory aim, we will identify proteins abnormally expressed in carcinogen damaged lungs with high risk to develop lung cancer as well as proteins modulated by chemopreventive agents. We believe that the success of this project will significantly improve our understanding of

38 Lung Cancer

early lung carcinogenesis at the molecular level and provide useful molecular markers for lung chemoprevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MOLECULAR CLONING OF A T(15;19) IN LUNG CANCER CELL LINE Principal Investigator & Institution: Dang, Thao P.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: This is an application for a K08 award for Thao Dang, M.D. designed to support five-years of laboratory training to further develop her skills in molecular genetics and to explore a novel mechanism of carcinogenesis. Malignant transformation is the result of an accumulation of genetic abnormalities. Specific chromosomal translocations are a major mechanism for oncogene activation in hematopoietic malignancies, but have not been described in the much more common epithelial tumors. We have established a cell line, HCC2429, from an aggressive, metastatic lung cancer that has a normal karyotype except for a single translocation between chromosomes 15q and 19p. Using positional cloning we demonstrated that the breakpoint on chromosome 19 lies approximately 40 kb upstream from the start site of Notch3, a member of the Notch proto- oncogene family. This translocation is associated with massive overexpression of Notch3, supporting the hypothesis that the t(15;19) translocation results in the deregulation of this putative cellular proto-oncogene. Furthermore, we have also demonstrated Notch3 over-expression in a panel of lung cancer cell lines and shown that it is highly correlated with translocations involving 19p. We have therefore identified a novel recurring mechanism for oncogene activation in lung cancer as well as a putative oncogene not previously known to be involved in human cancer. Under the mentorship of Dr. David Carbone, Dr. Dang will complete the molecular characterization of the identified t(15;19) translocation, determine the spectrum of the Notch3 receptor and ligand expression in lung cancer and normal tissues, and perform studies to characterize the transforming nature of Notch3 and its effects on downstream signaling pathways in lung cancer. The research environment at the Vanderbilt Ingram Cancer Center is of exceptional caliber and will provide Dr. Dang with the opportunity to interact with experienced molecular biologists as well as geneticists. The support given by this K08 award will allow Dr. Dang to build on her existing knowledge and promote her transition to an independent investigator in a highly competitive environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: MOLECULAR EPIDEMIOLOGY OF SECONDARY LUNG CANCER Principal Investigator & Institution: Shields, Peter G.; Professor & Chief; V T Lombardi Cancer Res Center; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Several studies indicate that women with breast cancer who undergo radiotherapy are susceptible to secondary lung cancer, whether they are smokers or nonsmokers. However, all studies to date have methodological limitations and have been small. Also, none have used molecular markers, which can improve exposure assessments or elucidate mediating mechanisms. Over time, radiotherapy methods have changed and doses to the lung have lessened. On the other hand, prevalence of smoking has increased among women in the western world. The

Studies

39

identification of lung cancer risk is important in the context of the debates for benefits of radiation therapy in good prognosis tumors or older women. Thus, a study of breast and secondary lung cancer is needed to improve dosimetry assessments for radiation induced lung cancer, with and without an interactive effect of smoking. Also, studying a unique population of women who have had both breast and lung cancer can provide new insights into carcinogeneis and cancer risk. In order to do this, we are proposing a population-based study using the Swedish Cancer Registry (SCR) and determination of radiation doses to the whole lung and side of the lung where the tumor subsequently develops. Reliable smoking data will be available. Our specific aims are to: 1) determine risk factors for secondary lung cancer in women treated with radiotherapy for breast cancer using complementary nested case-control and case-only study designs (n=559 cases and 559 matched controls); 2) to determine p53 inactivation pathways, (i.e., mutational spectra and loss of heterozygosity) in lung tumors of women with a prior history of breast cancer (n=402) and; 3) to determine the frequency of p53 inactivation pathways in breast tumors of women who did and did not develop lung cancer, and compare them to the frequency of p53 inactivation pathways in the lung tumors (n=342 cases and 342 controls). The first aim will allow us to identify risks. The second aim will provide information about the mechanistic relationship of radiotherapy to lung cancer and may identify a unique spectrum for radiation-related lung cancer. The third aim considers the combined occurrence of breast and lung cancer in a woman as phenotype of susceptibility for multiple primary cases. This study provides unique opportunities. Using the SCR and the unparalleled ability to obtain tissue blocks dating back to the 1950's, we can provide new data to understand risk in the context of molecular markers, especially because we will be able to retrieve the tumor blocks from both the breast and lung cancer from the same women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MOLECULAR STAGING AND SCREENING OF LUNG CANCER Principal Investigator & Institution: Ahrendt, Steven A.; Surgery; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 31-MAY-2003 Summary: (Applicant's Description): Lung cancer is the leading cause of cancer related deaths among both males and females in the United States. Surgical resection remains the only curative therapy for patients with non-small cell lung cancer (NSCLC). Despite undergoing curative resection, a large percentage of patients (30 to 40%) with stage I (node-negative) NSCLC develop recurrent disease. Improvements in adjuvant therapy and in the ability to identify those patients most likely to benefit from adjuvant therapy are essential to improving survival in patients with NSCLC. The proposed study uses common molecular genetic events in the neoplastic progression of NSCLC to improve the ability to assign pathological stage, determine prognosis, and to detect disease recurrence in patients with early stage disease. The influence of p53 and K-ras gene mutations on disease-free and overall survival will be examined in patients with nodenegative NSCLC. Molecular techniques will be used to determine the presence of micrometastatic disease in regional lymph nodes in patients undergoing surgical resection. The influence of micrometastatic disease on clinical outcome will be determined for patients with stage I NSCLC. In addition, tumor-specific p53 and K-ras gene mutations and/or microsatellite alterations will be identified in the serum DNA of patients with early-stage NSCLC and their presence correlated with clinical outcome. Completion of the research project will enable the candidate, an Assistant Professor in General Surgery with a strong interest in surgical oncology, to learn state-of-the-art

40 Lung Cancer

molecular techniques with previously demonstrated clinical utility in the staging and screening of patients with cancer. The mentor's laboratory is an ideal place to pursue this project having made substantial contributions in this field. In addition, the wider network of investigators in the field of cancer genetics at the candidate's institution provides a constructive setting for critical review and support of ongoing research in this field. Completion of the proposed mentored training period will provide the candidate with an excellent foundation for pursuing his long-term goals in academic surgical oncology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MOUSE MODELS OF LUNG CANCER Principal Investigator & Institution: Boivin, Gregory P.; Pathology and Lab Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Dr. Boivins's immediate career objectives are to excel in primary and collaborative research efforts, to start a fellowship program in Mouse Pathology, and a training program in Laboratory Animal Medicine. This proposal will alleviate service work so that the fellowship and training program can be pursued and will provide funding for developing a primary research focus. Training and mentoring of high school students, undergraduates, graduate students, postdoctoral fellows, and faculty members will also continue to be performed in two general categories: unstructured or one-on-one time and structured time spent in courses or classes. Alleviation of service work will allow expansion in these areas. Lung cancer is the most common malignant tumor worldwide and is subsequently the greatest cause of cancerrelated mortality. The identification of genes mutated in lung cancer has pointed to some of the signal transduction abnormalities, such as changes in RAS signaling, that occur in the establishment of these tumors. Additionally, mouse-modeling experiments have shown that transgenic mice over expressing Fgf-7, Fgf-10, or activated K-Ras in lung epithelium exhibit epithelial hyperplasia, adenoma, and carcinoma, respectively. Preliminary data have shown that tumor formation in the mouse can be promoted by altering the genotype of mice at the BIm locus. The experiments proposed here will establish and validate mouse models of lung cancer by manipulating the genetic background of the mouse to increase the expression of tumor-promoting factors by increasing somatic recombination and mutation. Tumors will be characterized genomically and by transcription profiling in order to identify other genes altered in the lung tumor formation. This work will test the hypothesis that haploinsufficiency of BIm will increase tumor progression in transgenic mouse models of lung tumorigenesis by increasing mutation rates. The long term aims are to establish in vivo models of lung neoplasia in the mouse in order to identify and characterize the signaling pathways and genes that are disrupted in the development of these tumors, to use these models to identify early markers of tumor development in the lung, and to identify therapeutic targets for human lung cancer therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: MUTATION AND ENVIRONMENTAL EXPOSURES Principal Investigator & Institution: Hunt, Jay D.; Professor; Biochem and Molecular Biology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2001; Project Start 03-APR-2001; Project End 31-MAR-2004

Studies

41

Summary: (Provided by Applicant) Elevated mortality rates of lung cancer along the Mississippi River in Louisiana have been documented for 50 years and are among the highest in the nation. The Lower Mississippi River interagency Cancer Study (LMRICS, Elizabeth T. H. Fontham, Dr. P. H., PI) is funded by the EPA to conduct a populationbased case-control study of lung cancer in the river parishes. LMRICS will collect tumor samples and exposure data for analysis. The ACS has funded Jay D. Hunt, III, Ph.D. to test the hypothesis that the elevated incidence of lung cancer in the river parishes is associated with chronic exposure to occupational and environmental chemical carcinogens, in addition to tobacco carcinogens, in susceptible individuals as defined by specific phase I and phase II genetic polymorphisms resulting in mutations in key regulatory genes in somatic cells. This funded project will provide the necessary research experience for Dr. Hunt's career development as a molecular epidemiologist. Dr. Elizabeth Fontham will serve as Dr. Hunt's mentor. This application proposes a structured approach to Dr. Hunt obtaining formal training in epidemiology and biostatistics. With this formal training in epidemiology and biostatistics, he will be able to obtain his long-term goals of integrating his training in molecular genetics with molecular epidemiology. Dr. Hunt's long-term career goals are: (1) to continue in his academic, full- time tenure-track position conducting basic and translational molecular genetics studies of non-small cell lung cancer and stomach cancer; (2) to integrate the findings at the bench to develop new biomarkers of prognosis and progression in lung cancer and stomach cancer; and (3) to further develop a molecular epidemiology program in cancer for the Stanley S. Scott Cancer Center at LSUHSC-New Orleans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: NEW STRATEGIES FOR CHEMOPREVENTION OF LUNG CANCER Principal Investigator & Institution: Biswal, Shyam S.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This new SPORE project seeks to take promising laboratory leads for lung cancer prevention, beginning with animal models, to proof of principle clinical studies. Our first efforts will explore electrophiles generated after metabolic activation of chemical carcinogens as well as reactive oxygen species. Both are major causes of malignancy. Cancer chemoprevention by induction of protective phase II proteins to counteract the effects of these carcinogens has gained considerable attention. Isothiocyanates have proved to be potent inducers of phase II proteins and compelling epidemiological evidence suggests that dietary isothiocyanates are linked with decreased incidence of lung cancer. Deciphering the downstream targets of isothiocyanates can help in developing these compounds for cancer chemoprevention. The genes for phase II proteins contain the antioxidant or electrophile response element (ARE), which regulate their basal and/or inducible expression. Nrf2, a member of the basic leucine zipper family plays a central role in activation of these genes by binding to ARE in response to its activation by chemopreventive agents. Our studies have shown that Sulforaphane, a naturally occurring isothiocyanate, acts as a potent activator of Nrf2. In this work, we used a microarray approach to identify Nrf2 targets in intestine, which included enzymes that detoxify a wide spectrum of electrophiles and tobacco specific carcinogens. The strategy of activation of Nrf2 for induction of phase II proteins recently has been shown to be effective among former smokers in a phase II b trial using anethole dithiolethione in lowering progression of pre-existing dysplastic lesions and appearance of new lesions. This proposal will focus on the hypothesis that activation of Nrf2 in lungs by Sulforaphane can lead to protection against lung cancer with the

42 Lung Cancer

ultimate goal of developing this agent for clinical trials. The downstream targets of Nrf2 activation in lungs, identified using a genomics approach, will serve as biomarkers to monitor the efficacy of Sulforaphane for lung cancer chemoprevention in the NNK inducible A/J mouse lung cancer model. A small clinical trial will evaluate the efficacy of broccoli sprout extract, optimized for high amount Sulforaphane, to activate the Nrf2 pathway in individuals at high risk for lung cancer. Success in these studies will justify larger controlled studies in current and former smokers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: NF KAPPA B MEDIATED CHEMORESISTANCE IN HUMAN LUNG CANCER Principal Investigator & Institution: Jones, David R.; Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 05-AUG-2000; Project End 31-JUL-2005 Summary: Lung cancer is the most common cause of cancer death in both men and women. Eighty percent of all newly diagnosed lung cancers are non-small cell lung cancers (NSCLC), and over 75 percent present with advanced stage disease. For this reason as well as the predilection for distant recurrence after complete resection, most patients are treated with chemotherapy alone or in combination with other modalities. Unfortunately, the majority of NSCLC are chemoresistant despite treatment regimens with second or third generation of chemotherapeutic agents. Tumor chemoresistance has been attributed to the ability of cells to overcome programmed cell death (apoptosis). Recently, it has been established that chemotherapy upregulates the NFkappaB transcription factor and this is associated with cellular resistance to chemotherapy-induced apoptosis. With this understanding, experiments were performed to determine whether NF-kappaB provided a similar cell survival signal in NSCLC cell lines following the addition of gemcitabine and cisplatin, two genotoxic agents commonly used to treat NSCLC. Preliminary data demonstrates that these chemotherapeutic agent induce NF-kappaB transcriptional activity. More importantly, the loss of NF- kappaB sensitizes NSCLC cell lines to chemotherapy-induced apoptosis. Although cell death induced by chemotherapy involves death receptor pathways in certain cell types, chemotherapy- induced apoptosis in NSCLC cells did not involve either Fas- or caspase-8-dependent death receptor pathways. In contrast, NF- kappaB was required to overcome mitochondrial-mediated apoptosis following chemotherapy addition. In addition, ceramide has recently been shown to inhibit the anti-apoptotic P13K/Akt pathway as well as activate NFkappaB. Since the loss of NF- kappaB activity sensitizes NSCLC cells to chemotherapy-induced apoptosis, the major goal of this proposal is to examine the cell signaling mechanisms governing apoptosis and chemoresistance following the addition of chemotherapy. To achieve this objective, we will use established (by the P.I.) cell lines which lack NF-kappaB activity and compare them to controls. These cells will be exposed to chemotherapeutic agents and apoptotic and anti-apoptotic signaling pathways will be examined in vitro. The specific aims of the proposal are to: 1) establish whether chemotherapy kills NSCLC cells through mitochondrial-dependent mechanisms, 2) determine whether the redox status of the cell is responsible for modulating NF-kappaB-dependent cell survival in response to chemotherapy, and 3) determine the role of ceramide as both a pro- and anti-apoptotic mediator following chemotherapy. These studies will provide important insight into how chemotherapy activates apoptotic pathways, as well as mechanisms by which tumors become chemoresistant through upregulation of NF-kappaB. The ultimate goal

Studies

43

of this study is to provide the necessary background for the initiation of novel treatment strategies designed to treat patients with advanced lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ONCOGENESIS IN RETROVIRUS-INDUCED LUNG CANCER Principal Investigator & Institution: Palmarini, Massimo; Med Microbiol & Parasitology; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): The object of this proposal is to study the mechanisms of oncogenesis in ovine pulmonary carcinoma (OPC), a naturally occurring lung cancer of sheep. OPC is caused by a retrovirus known as Jaagsiekte sheep retrovirus (JSRV). OPC has strikingly similarities with human bronchioalveolar carcinoma (BAC), a lung tumor that is only weakly associated with cigarette smoking and now represents a quarter of all lung cancers in the U.S. Animal models of retrovirus-induced neoplams have given insight into the genetic basis of cancer and have led to the discovery of oncogenes. Thus, OPC is a unique model to investigate lung carcinogenesis and the only viral-induced pulmonary neoplasm in domestic animals. The causal association between JSRV and OPC has been demonstrated by the isolation of an infectious and pathogenic molecular clone (JSRV2 1) but the mechanisms used by JSRV to induce cell transformation are not known and are the object of this proposal. The expression of the JSRV envelope is sufficient to induce transformation of rodent fibroblasts in classical transformation assays. These results suggest a novel mechanism in retroviral-induced oncogenesis. Preliminary results show that the antiapoptotic cell signaling pathway initiated by phosphoinositide-3 kinase (Pl-3K) is constitutively active in JSRV-transformed NIH3T3 but not in the parental cell line. In addition, replication competent JSRV mutants that have lost the ability to transform rodent fibroblasts in vitro have been obtained. These mutants have a single a single point mutation in a tyrosine of the cytoplasmic tail of the transmembrane region of the JSRV envelope altering a putative docking site for PI-3K. These results create an exciting rationale for this proposal whose aim is to dissect and understand the mechanisms of JSRV-induced carcinogenesis both in vitro and in vivo in its natural host. Aim 1 is to dissect the signal transduction pathway initiated by the JSRV envelope in rodent fibroblasts and in cell lines obtained from naturally occurring OPC tumor. However, the mechanisms of carcinogenesis in vivo are likely to be more complex that those followed by JSRV to transform immortalized cell lines. In Aim 2, newborn lambs will be inoculated with JSRV-based vectors and mutants that will determine whether the expression of the viral envelope and the activation of the PI-3K signaling cascade are necessary and/or sufficient to induce lung carcinogenesis. Aim 3 is to look for further mechanisms contributing to oncogenesis in OPC by analyzing the viral insertion sites in naturally occurring OPC-cases. The completion of these experiments will clarify the molecular mechanisms of JSRV-induced pulmonary carcinogenesis and might furnish an intellectual framework to unravel the pathogenesis of some forms of human lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: PHARMACODYNAMIC PHASE II BREAST, LUNG AND OVARY TRIALS Principal Investigator & Institution: Doroshow, James H.; Associate Director for Clinical Research; City of Hope National Medical Center Duarte, Ca 91010

44 Lung Cancer

Timing: Fiscal Year 2001; Project Start 30-JUN-1994; Project End 31-JUL-2001 Summary: The objective of this proposal is to develop novel, laboratory-based chemotherapeutic treatment strategies for patients with cancers of the breast, lung, and ovary. This goal will be pursued through the formation of a consortium of molecular pharmacologists and clinical investigators from two NCI-designated Cancer Centers and a large University Hospital who will utilize the extensive patient resources of the City of Hope National Medical Center (COH), the Kenneth Norris, Jr. Comprehensive Cancer Center at the University of Southern California (USC), and the University of California, Davis Cancer Center (UCD) to perform pharmacologically-guided Phase II clinical trials that focus on: a) novel high-dose chemotherapies with peripheral blood progenitor cell reinfusion, the molecular pharmacodynamics of the folatefluoropyrimidine interaction, and combination anthracycline resistance modulation studies for patients with advanced breast cancer; b) modification of intrinsic platinum resistance, chemotherapy dose intensification, new agent development, and clinical radiation sensitization for individuals suffering from small cell and non- small cell lung cancer; and c) targeted intraperitoneal and high-dose chemotherapy investigations for women with cancer of the ovary. This application formalizes an ongoing series of collaborative interactions among these three institutions that have existed since the mid1980's. Based on the availability of over 6,250 new cancer patients per year (including 710 with breast cancer, 594 with lung cancer, and 157 with ovarian cancer in 1991), and on the major strengths of the consortium in the areas of bone marrow transplantation, the clinical pharmacodynamics of the fluoropyrimidines and the antifols, as well as pioneering experience in the quantitation of relative gene expression from small amounts of human tumor tissue, the biochemical pharmacology of the anthracyclines and platinum compounds, and clinical research strengths in regional chemotherapy, the development of novel treatment regimens, and biostatistics and data management, the COH-USC-UCD Phase II Consortium is well-positioned to utilize its clinical research expertise to perform complex, laboratory-supported investigations of both new agents and new strategies to enhance therapeutic outcomes for patients with cancers of the breast, lung, and ovary. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PHASE I/II TRIAL OF ZD1839 AND CELECOXIB IN EX-SMOKERS Principal Investigator & Institution: Kelley, Michael J.; Associate Professor of Medicine; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Cigarette smoking is causally associated with development of cancer of the lung, head & neck region, esophagus, bladder, and other sites by overwhelming epidemiological and biologic evidence. Cessation of smoking results in a slow decline in risk of cancer development that remains elevated compared to never smokers beyond 15 years after smoking cessation. Thus, strategies to reduce the impact of lung cancer in former smokers are needed. The epidermal growth factor receptor (EGFR) and cyclo-oxygenase II (COX-2) have been implicated in the development and maintenance of lung cancer. Clinical trials of the EGFR tyrosine kinase inhibitor, ZD1839, in patients with established cancer have demonstrated biological and anti-tumor effects. In the first part of this application, a Phase I, openlabel, dose escalation clinical trial will be conducted to determine the maximal tolerable dose of ZD1839, and the associated effect on EGFR signaling, when used as a chemopreventive agent in former smokers. Former smokers treated with curative intent for early stage lung or head and neck cancer will be treated in cohorts of escalating

Studies

45

doses of ZD1839. Measures of drug effect (EGFR, c-fos, apoptosis) and biomarkers of lung cancer risk will be measured in bronchial epithelium before and after taking drug for 12 weeks. Potential efficacy of EGFR and/or COX-2 inhibition (using ZD1839 and Celecoxib, respectively) will then be assessed in a Phase II, placebo-controlled, clinical trial assessing effect on bronchial epithelial genetic loss and other surrogate biomarkers of lung cancer risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PILOT -- PSYCHOLOGICAL SUPPORT BY TELEPHONE: PILOT OF A NOVEL PSYCHOTHERAPY Principal Investigator & Institution: Holland, James F.; Professor and Chairman; SloanKettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Presently in the US, 58% of people diagnosed with cancer are 65 years or older (163). Illness is an added burden to other existing or anticipated losses: loss of spouse, friends, family, loss of hearing, sight, and mobility, and reduced independence all further compromise the ability to cope with cancer and its treatment. Colon and lung cancer are more often seen in older age. In fact, 76% of people who have colon cancer and the majority of those who have lung cancer are 65 years or older (163). Lung cancer patients have the highest distress levels (43.5%), and those with colon cancer, 31.6% (162). However, many elderly patients who are severely distressed go unrecognized in the busy clinics and their distress remains undiagnosed and untreated. (165-168). Additionally, it is often difficult for patients with advanced stages of cancer to receive psychological treatment due to physical limitations and inability to come to outpatient clinics. A pilot of a study of telephone counseling for older patients is proposed to provide psychological support. It will examine the delivery over the telephone of a newly developed integrative psychotherapy with patients age 65 and older who have diagnoses of stage IV colon or stage IIIB/IV lung cancer. The psychotherapeutic model is an integrative intervention influenced by the work of Folkman (169). She found that people facing life-threatening events often coped better by finding a tolerable meaning to the event (167). Patients who complete informed consent will receive a telephone counseling intervention that includes 10 counseling sessions across approximately 10 weeks. A pre-and post-assessment will be administered before and following the intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

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

46 Lung Cancer

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

Project Title: RADIODIAGNOSIS & RADIOTHERAPY OF LUNG CANCER METASTASES Principal Investigator & Institution: Kassis, Amin I.; Professor/Director; Radiology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2004 Summary: Lung cancer claims approximately 150,000 lives each year in the USA and its incidence is increasing globally. Early diagnosis of this disease is difficult to obtain. The five-year survival rate of patients with lung cancer is approximately 14 percent and has not changed over the past several decades. The purpose of the proposed research is to establish the potential of the thymidine analog 5-iodo-2'-deoxyuridine (IUdR) radiolabeled with the gamma-emitting isotope iodine-123 (I-123) for the scintigraphic detection of lung cancer and radiolabeled with either the Auger electron-emitting isotope iodine-125 or the beta-emitting isotope iodine-131 for the therapy of lung cancer. To this end, experiments have been designed to examine the specific uptake of radiolabeled IUdR in nude mice bearing cancer cells growing within the lungs. The approaches described should provide an opportunity for the selective targeting of dividing cancerous cells within the lungs and lead to methods for scintigraphic detection of lung cancer as well as development of an effective/adjuvant therapeutic approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: RAS/RAF/RHO DIFFERENTIATION

IN

LUNG

CANCER

GROWTH

AND

Principal Investigator & Institution: Nelkin, Barry D.; Associate Professor; Oncology Center; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006

Studies

47

Summary: (provided by applicant) This project will continue our long term interest in investigating the mechanisms of control of lung cancer cell behavior, focusing on ras/raf-mediated signal transduction pathways. We have shown that raf activation can induce growth arrest in small cell lung cancer (SCLC), but not in non small cell lung cancer (NSCLC), This growth arrest is accompanied by induction of cyclin dependent kinase inhibitor expression; in at least some cell lines, p27Kip1 is induced by translational control. We hypothesize!) that raf activation may mediate growth arrest via translational control in SCLC cells, 2) that this growth arrest can be blocked by activation of rho family protein signal transduction, which may be more active in NSCLC than in SCLC cells, and 3) raf effects on SCLC cells may be mediated in part by autocrine or paracrine mechanisms. The level of activation of the rho family signal transduction pathway will be examined in SCLC and NSCLC cells. In a complementary series of studies, the effect of activating or inhibiting rho family signal transduction in SCLC cells will be investigated, focusing on the effects of rho family members on rafmediated growth arrest. The mechanism of induction of p27kip1 by translational activation during raf-mediated growth arrest in SCLC cells will be investigated. The role of the translation initiation factor eIF4E will be examined. The ability of translational activation to induce cyclin dependent kinase inhibitors and cell cycle arrest in SCLC cells will be determined. The role of autocrine ligands in mediating the effects of raf activation in SCLC cells will be investigated. Identification of two raf-induced autocrine lung cancer derived factors, LCDF I and LCDF2, will be completed. LCDF 1 induces Phosphorylation of MAPK and accumulation of p27, and LCDF2 induces morphological changes in SCLC cells. The ability of LCDF I to promote growth arrest will be determined. The receptor for LCDF 1 will be isolated, and its signal transduction pathways will be identified. The expression patterns for LCDF 1 and its receptor, and LCDF2, will be determined in lung cancer cell lines and primary tumors. The factors responsible for raf-mediated induction of LCDF 1 in SCLC cells will be identified. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RECEPTOR TYROSINE KINASE INHIBITION AND RADIATION Principal Investigator & Institution: Hallahan, Dennis E.; Professor and Chairman; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 28-JUN-2001; Project End 31-DEC-2006 Summary: (provided by applicant): We have identified a novel survival pathway within tumor vascular endothelium that enhances the therapeutic effects of ionizing radiation. Considering that radiation therapy is the primary modality of treatment for unresectable lung carcinoma, improving the efficacy of this treatment is important to improve the cure rate of lung cancer patients. In this regard, we have collaborated with several pharmaceutical companies that are developing small compounds that inhibit specific enzymes within the tumor endothelium. We will only investigate compounds that have entered or will enter clinical studies within the next 3 years. These compounds include SU5416 and SU6668 (Sugen) and PTK87/2K222584 (Novartis). These compounds inhibit receptor tyrosine kinases and downregulate the survival pathway within the tumor endothelium. These compounds will also enter clinical studies through the clinical core in this lung cancer SPORE application. An example of the success in this endeavor is the clinical protocol investigating SU5416 with radiation in a neoadjuvant lung cancer study. We anticipate additional studies with other compounds and future phase III trials. In addition to this translational approach, we will also investigate the mechanisms by which Flk-1 antagonists enhance the therapeutic effects of radiation. We will study the PI3 kinase and Akt/PKB signal transduction pathways. Our preliminary findings

48 Lung Cancer

indicate that inhibition of this pathway enhances radiation-induced apoptosis in the vascular endothelium. We have entered into a material transfer agreement with ICOS, Inc. ICOS has identified several small compounds that inhibit specific isoforms of PI3 kinase. We will determine which of these compounds is most effective in enhancing the therapeutic effects of radiation in lung cancer models in mice. These compounds will then be developed at ICOS to enhance the pharmacokinetics and minimize toxicity. The same approach will be taken with Akt inhibitors as they are developed. In summary, findings from these preclinical studies will assist us in the design of phase I and feasibility studies in the clinic through the clinical core in this SPORE application. In addition, our close collaboration with pharmaceutical companies will ensure that these compounds move rapidly into clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: REGULATION OF TELOMERASE BY CERAMIDE IN LUNG CANCER Principal Investigator & Institution: Ogretmen, Besim; Biochem and Molecular Biology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Lung cancer remains to be the leading cause of cancer related deaths in the United States with poor prognosis. Telomerase, which is upregulated in about 85 percent of lung cancers and not detected in normal lung tissues, is extremely important in cellular proliferation and tumor development. Telomerase elongates telomeres at the end of chromosomes. Thus, it is believed that the modulation of telomerase activity, and telomere length may be a potential therapeutic modality for the treatment of lung cancers. However, molecular mechanisms involved in the regulation of telomerase and telomere length in human lung cancers are not known. The sphingolipid ceramide is known as a tumor suppressor lipid, which mediates antiproliferative biological responses in human cancer cells. Preliminary results by the PI show that ceramide can regulate telomerase activity, independent of apoptosis or necrosis. Therefore, this proposal focuses on identifying the molecular mechanisms and function of ceramide in the regulation of telomerase activity, and telomere length in human lung cancer cells. Specifically, this proposal aims at: 1) Defining the role of ceramide in the inhibition of telomerase activity in human lung cancer cells. This will be achieved by determining: a) the effects of exogenous C6-ceramide, its biologically inactive analog dihydro-C6-ceramide, and analyzing the effects of overexpression of glucosylceramide synthase, which attenuates ceramide, and b) the effects of increased generation of endogenous ceramide by over-expression of serine palmitoyl transferase, and bacterial sphingomyelinase on telomerase activity in lung cancer cell lines. 2) Determining molecular mechanisms and signaling pathways by which ceramide inhibits telomerase activity in human lung cancer cell lines. This will be done by: a) examining the role of ceramide in the transcription of hTERT (the catalytic subunit of telomerase) via determining its role on the stability of hTERT mRNA, regulation of hTERT promoter activity, and c-Myc protein stability and ubiquitination, and b) determining if ceramide induces the inhibition of telomerase through phosphatase activation, since PP2A which is a downstream target of ceramide has been shown to alter telomerase activity by dephosphorylating hTERT, and 3) Analyzing the mechanisms by which ceramide mediates rapid shortening of telomere length. This will be done by a) analyzing the effects of ceramide on telomere length, b) examining the role of ceramide on the activity of recently identified telomere end-binding proteins, TEF-42 and hPot1, which are potential regulators of telomere length in human lung cancer cells, and c) identification and cloning of TEF-42 protein. The long-term objective of this proposal is to better

Studies

49

understand the molecular mechanisms of telomerase regulation, which will then help develop novel and mechanism-driven therapeutic strategies for the treatment of human lung cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RELEVANCE OF FISH OIL DERIVED PGE3 TO LUNG CANCER Principal Investigator & Institution: Newman, Robert A.; Chief, Section of Pharmacology; Clinical Investigation; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): We hypothesize that the fish oils, EPA and DHA, can serve as effective chemopreventive agents against lung cancer and that this protective effect is mediated by selective alteration of arachidonate metabolism through cyclooxygenase enzymes to favor production of PGE3 rather than PGE2. The beneficial effect of PGE3 (i.e. inhibition of tumor cell proliferation vs stimulation produced by PGE2) is at present a poorly understood phenomenon. The research proposed in this application will help us determine the efficacy of fish oil against human lung cancer and obtain insight into the pharmacodynamic activity of EPA and DHA on normal and malignant lung epithelial cells. The specific aims of this proposed project are as follows: 1. To compare the time and concentration-dependent inhibitory effect of EPA and DHA alone or in combination on growth of human lung tumor cells, including cells expressing high and low levels of COX-2. 2. To determine changes in eicosanoid metabolism in human normal and cancer lung cells resulting from exposure of cells to EPA and DHA. The relative effect of these fish oils will also be examined against purified human recombinant COX-1 or COX-2 enzymes using our new and highly specific LC/MS/MS method that simultaneously and rapidly determines prostaglandins (e.g. PGE2 and PGE3) as well as selected lipoxygenase enzyme products (5-, 8-, 11-, 12-, and 15-HETE as well as specific leukotrienes such as LTB4 and LTB5). 3. To compare the relative effect of PGE2 and PGE3 at physiological and pharmacological concentrations on lung cell proliferation and mobility. 4. To study the relationship of PGE2 and PGE3 on cell proliferation and motility relative to activation of the cAMPPKA signaling pathway through prostanoid receptors in human normal and cancer cells, and 5. To evaluate the relative efficacy of EPA, DHA and fish oil (containing both fatty acids) in prevention of tumor growth and its correlation to alteration of eicosanoid metabolism in a mouse model of human lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: RESOURCE AND QOL CONSEQUENCES OF LUNG CANCER SCREENING Principal Investigator & Institution: Byrne, Margaret M.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 08-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The primary purpose of this proposal is to provide the candidate with the means, mentorship and structure to achieve the following goals. The intermediate goal is to measure the psychological, quality of life and resource effects of screening for lung cancer using low dose spiral computed tomography (CT), as well as factors affecting adherence to follow up recommendations. The long term goal is to become an independent health services researcher focusing on evaluation of cancer screening programs and promotion of individual decision making in cancer screening.

50 Lung Cancer

The candidate will further develop and utilize research skills in psychological measurement and analysis, cancer epidemiology and cancer screening techniques, and assessment of health care resource utilization through medical claims databases. The career development program will incorporate formal course work, tutorials with experts in specific methodological fields, clinical training through preceptorships and the National Cancer Institute Cancer Prevention and Control summer course, conferences and seminars, and research. The major goal of the proposed research is to measure the psychological and resource utilization consequences for individuals participating in a lung cancer screening program, and adherence to follow up recommendations from screening. The clinical benefits of screening lung CT are as yet uncertain. However, screening CT detects abnormalities in approximately 40% of all screened individuals. To evaluate and improve screening lung CT programs, and to promote informed decision making concerning screening, it is essential to determine the non-clinical effects of screening. The proposed research will recruit patients from an NCI-funded SPORE project on the clinical outcomes of screening lung CT (Joel Weissfeld, P.I., Pittsburgh Lung Screening Study). Self-administered surveys of psychological characteristics and medical care use, medical claims data, and data from the PLuSS study will be collected over time. The proposed K07 research will determine 1) the psychological and resource effects of participating in lung cancer screening, 2) how these effects vary with screening results and individual characteristics, and 3) whether individuals adherence to recommended follow up after screening and what factors affect non-adherence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RETINOIC ACID RESPONSE IN HUMAN LUNG CANCER Principal Investigator & Institution: Zhang, Xiao-Kun; Associate Professor; Burnham Institute 10901 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-AUG-1993; Project End 31-JUL-2003 Summary: Lung cancer is the leading cause of cancer death in the United States. Therefore, more effective methods to prevent and treat lung cancer are urgently needed. Epidemiological and animal studies have demonstrated that vitamin A and its natural and synthetic derivatives, retinoids, are promising agents in preventing the development of lung cancer. However, clinical trials have found no preventative effects of vitamin A against lung cancer development, suggesting that retinoid responses may be impaired in lung cancer cells. The effects of retinoids are mainly mediated by two classes of nuclear receptors, the retinoic acid receptors (RARs) and retinoid X receptors (RXRs), both of which are encoded by three distinct genes, alpha, beta, and gamma. In our previous study, we found that retinoid responses are impaired in a majority of lung cancer cells and that loss of RARbeta is primarily responsible for the defect. In addition, we observed that loss of RARbeta can be attributed to abnormal regulation of a RA responsive element (beta RARE) in the RARbeta promoter, due to low levels of COUPTF that is required to maintain retinoid sensitivity and/or elevated levels of orphan receptor nur77 which inhibits RXR and COUP-TF activities through heterodimers. The loss of RARbeta could also be attributed to low binding activity of a pEA3 binding site in the RARbeta promoter. Furthermore, we demonstrated that nur77 can induce lung cancer cell apoptosis depending on its stimulus. In the proposed study, we will first study the anti-cancer effects of RARbeta by identifying its specific DNA binding sequences and interacting proteins as well as genes mediating its growth inhibition and apoptosis inducing effects. We will then analyze and clone protein that actively binds to pEA3 site and regulates RARbeta promoter activity. In addition, we will study the mechanism by which COUP-TF sensitizes RAREs and their responsiveness to trans-RA.

Studies

51

Finally, we will investigate how phosphorylation of nur77 regulates its DNA binding and heterodimerization specificity and their involvement in determining the effects of nur77 on trans-RA resistance and induction of apoptosis, and identify genes responsible for its apoptosis inducing effects. Results from these studies will contribute to our understanding of the mechanism by which RARbeta exerts its anti-cancer activities and how the activities are lost in lung cancer cells, and may provide means to increase retinoid sensitivity in lung cancer cells, thereby enhancing the anti-cancer efficacy and spectrum of retinoids against this diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RISK POLYMORPHISMS

MODELS:ENVIRONMENT

VERSUS

METABOLIC

Principal Investigator & Institution: Etzel, Carol; Epidemiology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): My career goal is to become an established researcher in molecular epidemiology with expertise in genetic epidemiology of cancer. This goal builds upon my previous training in statistical science and statistical genetics, but requires further training in molecular techniques and epidemiology. At the end of this training period, I will be an established researcher in cancer prevention. I have developed a comprehensive education and reentering plan. My education plan will provide intensive instruction in the areas of genetics, cancer biology and epidemiotogic methodologies. I have chosen three mentors who will supervise specific portions of my training. Dr. Xifeng Wu will mentor me in molecular epidemiology; Dr. Christopher Amos will supervise the development and application of the statistical methods; and Dr. Margaret Spitz will provide guidance in cancer epidemiology and cancer prevention and control methodologies. My research proposal will focus on developing risk models for lung cancer. I propose to capitalize on the availability of epidemiologic and genetic marker data from an ongoing case-control study (R01 CA55679) under the direction of Dr. Margaret Spitz. This study currently includes over 2700, mostly Caucasian, lung cancer cases and controls, matched on sex, age, ethnicity and smoking status. I will also utilize data from her completed study involving an additional 597 Mexican- and African-American lung cases and controls. My research goal is to construct robust risk models to characterize the most important genetic and environmental risk factors for lung cancer. I aim to investigate lung cancer risk by simultaneously analyzing genetic and epidemiologic data. The specific aims are: 1. To investigate the effect of missing genotypic data on risk modeling and apply methodology to deal with missing data in the assessment of risk for cancer. This is a real deficiency in many studies and I will investigate approaches to handle missing data. I propose a simulation study to investigate the validity of imputation methods in a case/control framework. As a result of this simulation study I will be able to identify the pros and cons of imputation of missing genetic data. Only after an optimal method to impute missing marker values has been identified will I implement imputation in the lung study data. 2. To build a risk model that simultaneously includes available susceptibility markers and epidemiologic data, including gene-environment and gene-gene interactions. I will employ the methods of multiple logistic regression and CART to model lung cancer as a function of genetic and epidemiologic variables, I will incorporate gene-environment and gene-gene interactions cited in the risk assessment literature as welt as those identified from CART into the risk model, I will explore techniques to compare the models obtained by these two methods in order to arrive at an optimal risk model.

52 Lung Cancer

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

Project Title: ROLE OF COX2 IN LUNG CANCER ANGIOGENESIS AND METASTASIS Principal Investigator & Institution: Johnson, David H.; Professor of Medical and Surgical Oncolo; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 28-JUN-2001; Project End 31-DEC-2006 Summary: (provided by applicant): Upregulation of cyclooxygenase-2 (COX-2) has been shown to be an early event in colon carcinogenesis. Multiple lines of evidence suggest that COX-2 upregulation is also an early event in the development of non-small cell lung cancer (NSCLC). In humans, COX-2 expression is upregulated in about one-third of atypical adenomatous hyperplasias and carcinoma in situ specimens obtained from lung, and in 70 percent-90 percent of invasive adenocarcinomas of the lung. The proportion of adenocarcinoma cells with increased COX-2 expression is much greater in lymph node metastases than in the corresponding primary tumors. Preclinical data indicate tumors with upregulation of COX-2 synthesize high levels of prostaglandin E2 (PGE2). High PGE2 levels are associated with increased production of proangiogenic factors and enhanced metastatic potential. These findings suggest that an increase in COX-2 expression may play a significant role in the development and growth of NSCLC and possibly with the acquisition of an invasive and metastatic phenotype. Specific inhibitors of COX-2 are now available and may prove useful in understanding the role of eicosanoids in lung cancer pathogenesis as well as in the management of established malignancies and possibly as chemopreventive agents. However, there are limited data on the function of tumor overexpression of COX-2 in lung cancer patients, and no data on whether selective inhibitors actually affect COX-2 activity within the targeted tumor in vivo. We propose to study the effects of specific inhibitors of COX-2 on COX-2 expression, serum VEGF levels and urinary metabolites of PGE2 in patients with lung cancer. Our results will serve as a prelude to clinical trials in which these agents are employed therapeutically. Our preliminary data suggest inhibitors of COX-2 rapidly reduce enzyme activity as determined by measurements of urinary metabolites of prostaglandin and assessment of enzyme activity within the tumor itself. These experiments will expand upon these preliminary results. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: ROLE OF PROTEIN KINASE C IN LUNG CANCER Principal Investigator & Institution: Xiao, Lei; Shands Cancer Center; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: The overall objectives of the current proposal are to investigate the cell typespecific regulatory mechanisms that control the expression of protein kinase C-epsilon (PKC-epsilon) in human lung cancer cells and to define what role the phenotypespecific expression of PKC-epsilon may play in the control of cell growth, transformation, and cellular response to drug treatment. Specifically, the proposed studies are designed to extend preliminary results which indicate that induction of PKCepsilon expression may, in part, contribute to development of a drug resistant phenotype during tumor progression of small cell lung cancer (SCLC). A strategy of direct targeting PKC-epsilon expression using antisense technology as well as expression of wild type and mutant forms of PKC-epsilon will be used. A striking differential expression profile of PKC-epsilon but not other PKC isoforms, is found in

Studies

53

human lung cancer cell lines. PKC-epsilon is expressed in all of the non-SCLC cell lines tested, but none of the SCLC cell lines. Further, its expression is induced when H82 human SCLC cell line is transformed to a non- SCLC phenotype. This transformation is accompanied with changes in drug sensitivity. Therefore, the molecular mechanisms underlying phenotype-specific expression of the PKC-epsilon isoform will be investigated in detail. The information obtained from the proposed studies should provide a better understanding of the biology of lung cancer at the molecular level. More importantly, the results may provide insight into the molecular basis of developing drug resistance, which may lead to novel antineoplastic strategies. Finally, it is expected that a more precise understanding of the regulatory mechanism of PKCepsilon gene expression will help in the basic understanding of the role(s) PKC may play in human tumor cell proliferation, and how specific interference with PKCmediated signaling pathways may be therapeutically exploited in the treatment of human cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SELENIUM AND LUNG CANCER RISK IN ASBESTOS WORKERS Principal Investigator & Institution: Gottschall, Eva B.; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2001; Project Start 21-AUG-2000; Project End 31-JUL-2005 Summary: (Applicant's Description) Lung cancer accounts for more cancer deaths in the United States than breast, prostate and colorectal cancer combined. Efforts to improve early detection, develop successful screening programs and find effective chemopreventive agents are desirable. Selenium has shown promise as a cancer chemopreventive agent in animal and human studies. A putative mechanism of selenium's anticarcinogenic activity is its integral part in cellular antioxidant systems. Asbestos-exposed workers have a well established increased incidence of lung cancer, and asbestos carcinogenesis is thought to involve activated oxygen species. In a crosssectional study of asbestos-exposed workers, a large number of individuals were found to have moderate sputum atypia (28 percent), a marker of lung cancer risk. The major hypothesis of this proposal is that asbestos-exposed workers treated with oral seleniumrich yeast (200gg/day) will show significant improvement in intermediate end-point biomarkers of lung cancer risk compared to placebo; and furthermore, changes in markers of lung cancer will be accompanied by decreases in markers of oxidative cellular damage. The study design is a randomized, placebo-controlled, double blind trial of asbestos-exposed construction trades workers using high selenium yeast supplementation. Markers of lung cancer risk to be examined include sputum cytologic atypia, endobronchial metaplasia/dysplasia, and nuclear morphometry of sputum and endobronchial biopsy specimens. The mechanism of action of selenium will be investigated using markers of oxidative cellular damage, including 8hydroxydeoxyguanosine (a marker of DNA damage), malondialdehyde (a marker of lipid peroxidation), and 8-iso-prostaglandine F2, (a marker of lipid peroxidation), before and after the intervention. The proposed study will assess whether selenium is effective in reversing premalignant lesions indicative of increased lung cancer risk and elucidate potential mechanisms of action of selenium. As such, this study will provide a critical foundation to further establish selenium as a potential chemopreventive agent for human lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

54 Lung Cancer

·

Project Title: SELENIUM PREVENTION OF TOBACCO SMOKE-INDUCED LUNG CANCER Principal Investigator & Institution: Fan, Teresa W.; None; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant) The long-term objectives of the proposed work are to understand the biochemical mechanism(s) of supranutritional Se in chemoprevention and to utilize this information for mechanistic clinical studies. A chemopreventive role of selenium (Se) in cancers has been implicated in several clinical and numerous animal studies but whether Se is effective against tobacco smoke (TS)-induced lung cancers is unknown. Nor is it clear in general on the form(s) of Se that are chemopreventive. Lung cancer is a leading cause of cancer death and TS-induced lung cancer may be on the rise worldwide due to growing smoking habit. Thus, the specific aims of this proposal are: 1) To examine whether dietary Se supplement in the form of selenized yeast (Se-yeast) or its major component selenomethionine (Se-Met) is chemopreventive for mice that have "quit" smoking; 2) To characterize biomarkers of Se action such as apoptotic markers and selenoproteins that have been established in other chemoprevention studies so that Se chemoprevention can be understood better at the molecular level; 3) To investigate whether a synergism exists between Se and other chemopreventive agents such as the glucocorticoid hormone budesonide and retinoid isotretinoin in TS induction of lung cancers. To fulfill these aims, the A/J mice model which is the only animal model for TS-induced lung cancer will be employed. Mice will be pre-exposed to tobacco smoke to induce lung tumors during the recovery phase. The effect of dietary Se-yeast or Se-Met supplement during the recovery phase on tumor incidence and/or multiplicity will be measured to see if Se supplement is effective in reducing tumor formation and if additional Se form(s) in Se-yeast may be active. Major Se metabolites present in Se-yeast in addition to Se-Met will be characterized by a combination of NMR and HPLC coupled to mass spectrometry. The Se action will be characterized both immunocytochemically and in lung extracts by a series of apoptotic markers including cytochrome c release, activation of caspases, production of caspase cleavage products, and DNA fragmentation will be measured, along with the activation of selenoprotein, thioredoxin reductase. These biomarkers are known to be elicited in other Se chemoprevention studies. A similar approach will be used to investigate any interactive effect of Se-yeast supplement and budesonide or isotretinoin administered via inhalation; the latter two agents are also known to cause apoptosis. Biomarker characterization should reveal whether synergism is mediated via apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: SLC/6CKINE IMMUNOTHERAPY FOR CANCER Principal Investigator & Institution: Sharma, Sherven; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 13-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Lung cancer is the number one cause of cancer death in the United States. Lung cancers express tumor antigens but are ineffective as antigen presenting cells. We will utilize secondary lymphoid chemokine (SLC) to localize DC at the tumor site where they can function to present an array of antigenic epitopes. This approach to stimulate specific T cell immune responses would not exclude patients on the basis of HLA phenotype or because of lack of expression of a particular tumor antigen. Thus, this therapy would be available to all lung cancer

Studies

55

patients in the appropriate clinical setting. We hypothesize that SLC therapy will lead to co-localization of dendritic cells (DC) and Th1 cytokine-expressing lymphocytes. We anticipate that DC will traffick to the tumor site where they will be positioned to process and present autologous tumor antigen (Ag) thus providing access to the entire repertoire of available antigens in situ, both increasing the likelihood of a response and reducing the potential for phenotypic modulation. The overall goal of this proposal is to use murine models to determine the mechanisms of SLC-mediated restoration of antitumor immune responses. Utilizing transplantable murine lung cancer models, different modes of SLC delivery will be evaluated that ultimately may have clinical relevance. The following modes of intratumoral SLC delivery will be assessed: 1) injection of recombinant SLC, 2) injection of irradiated SLC transduced tumor cells, and 3) injection of adenovirus vector expressing SLC. A spontaneous murine lung cancer model will be utilized to evaluate the antitumor efficacy of these modes of SLC delivery by intradermal, axillary lymph node region and systemic i.p. injections. Each of these systems will be evaluated because each has potential advantages in the development of immune based therapy for lung cancer. Specific Aims: 1. To identify the mechanisms of anti-tumor responses in secondary lymphoid chemokine (SLC) therapy. (A) The capacity of SLC to enhance the generation of tumor-specific CTL will be investigated. Tumor infiltrating lymphocytes (TIL), splenic T cells and lymph node derived lymphocytes (LNDL) will be evaluated for cytolytic activity and cytokine release against specific and non-specific tumor targets. (B) The importance of cytokines IFN gamma, IL10, GM-CSF, IL-12, MIG and IP10 in SLC- mediated anti-tumor responses will be assessed. 2. To identify the T cell subsets and cytokines important for the memory phenotype following SLC mediated tumor eradication. (A) Mice having rejected their tumors following SLC therapy will be treated with anti-CD3, anti-CD4, anti-CD8 antibodies before rechallenge with 3LL parental tumors, T cell subsets from mice having rejected their tumors following SLC therapy will be transferred to naive mice before challenge with 3LL parental tumors. (B) The importance of cytokines IFN gamma, IL-10, GM-CSF and IL-12 will be assessed in the memory phenotype after SLC mediated tumor eradication. 3. To evaluate the efficacy of different modes and routes of SLC therapy in a spontaneous murine lung cancer model. Dr. Sharma, has the requisite attributes that predict successful academic independence. He is in an excellent scientific environment and will spend 100 percent effort to this endeavor. Work resulting in this environment will prepare Dr. Sharma for a successful independent career in basic cancer research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SPHINGOLIPIDS AND CHEMOTHERAPY-INDUCED APOPTOSIS Principal Investigator & Institution: Hannun, Yusuf A.; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The sphingolipid ceramide, a bioeffector lipid, is known to regulate anti-proliferative responses in various human cell lines. In particular, it has been shown that various anti-cancer agents cause the elevation of endogenous ceramide levels accompanied by apoptotic cell death in human cancer cells. Preliminary results from this program demonstrate that: i) Treatment of A549 human lung adenocarcinoma cells with chemotherapeutic agents results in the formation of endogenous long-chain ceramide via either the de novo pathway or the hydrolysis of sphingomyelin through the action of sphingomyelinase (SMase); ii) Agents that cause ceramide generation via these two distinct pathways have synergistic cytotoxic effects; iii) Downstream targets of ceramides that are generated via the two distinct pathways

56 Lung Cancer

are distinct. These data lead us to the HYPOTHESIS that there are two distinct mechanisms of ceramide formation, namely the de novo pathway and the hydrolysis of sphingomyelin, which function independently and synergistically in mediating apoptosis and growth suppression in human lung cancer cells. As a corollary, we believe that prevention of ceramide clearance should augment chemotherapy action in lung cancer treatment. Therefore, two specific aims are proposed: 1) To determine whether the two distinct mechanisms of ceramide generation act synergistically in mediating apoptotic cell death and/or growth suppression in lung cancer cells. A) Determine which chemotherapeutic agents activate which of the two pathways; B) establish the synergistic effects of anti-cancer agents which activate neutral sphingomyelinase (NSMase) or the de novo pathway, respectively; C) determine the role of ceramide, generated from each pathway, in mediating the action of chemotherapeutic agents by inhibiting each pathway, and D) establish the synergistic effects of activating the two pathways, by overexpression of SMase and serinepalmitoyl transferase (SPT). 2) To identify the mechanisms by which ceramides generated by the two different pathways act synergistically in mediating apoptosis and/or growth suppression. A) Determine the compartmentalization of these pathways, and analyze whether the sub-cellular compartments in which these two pathways are activated are important for their synergistic action; B) test the corollary that clearance of ceramide attenuates the synergistic effects of ceramides in different sub-cellular compartments; and C) determine the down stream targets of ceramides generated via these two pathways. These studies will offer mechanism-based targets for the development of novel cancer therapeutics involving these two distinct ceramide pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SPORE IN LUNG CANCER Principal Investigator & Institution: Carbone, David P.; Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 28-JUN-2001; Project End 31-DEC-2006 Summary: (provided by applicant) This Lung Cancer SPORE application is a new application submitted by the Vanderbilt-Ingram Cancer Center and its affiliated institutions. In this proposal, we apply the translational research strengths of the Vanderbilt-Ingram Cancer Center toward reducing the incidence, morbidity, and mortality of lung cancer, by focusing on the discovery and validation of molecular targets for prevention and therapy. In project 1 we are studying the role of specific matrix metalloproteinases and targeted inhibitors in the development and behavior of lung cancer. In Project 2 we are applying sophisticated cDNA microarray and protein mass spectrometry techniques to the identification of molecular fingerprints of lung cancer. These fingerprints could ultimately be used to guide patient care or discover novel molecular targets for therapy. Project 3 studies a new potential molecular target, Notch3, that we identified by mapping a balanced chromosome translocation. This also represents a completely new mechanism for gene activation in lung cancer. Receptor tyrosine kinase inhibitors are an exciting new class of molecularly targeted reagents, and in Project 4 we study their effects on downstream signaling pathways and their use in combination with radiation therapy in anti-angiogenic tumor therapy. In projects 5 and 6 we investigate the role cyclooxygenase 2 (COX2) in the therapy (Project 5) and prevention (Project 6) of lung cancer. We have unique facilities for the analysis of COX2 metabolites and intend to study eicosanoid production by human lung cancer tumors in situ, its association with tumor angiogenesis, and its response to treatment with specific inhibitors in vivo. For Project 6 we propose to use two cohorts with previously collected

Studies

57

pharmacy data to study the impact of long term COX2 inhibitors on the incidence of lung cancer. The first is a retrospective cohort study over 10,000 enrollees of the Tennessee Medicaid Program who were diagnosed with chronic obstructive pulmonary diseases (COPD) during the period of 1980 to 2002. The second is a population-based cohort and nested case-control studies of over 150,000 users of NSAIDs in North Jutland County, Denmark during the period of 1991 to 2002. In order to accomplish these research goals, we propose 4 cores: administrative, tissue, clinical, and biostatistical. The proposed career development and developmental research programs are tightly integrated with established institutional initiatives with documented track records of identifying and funding promising projects and individuals. We will use these established mechanisms to fund lung cancer-targeted career development and research projects. We believe that these projects, cores, and pilot and career development awards could lead to major improvements in the prevention, diagnosis, and treatment of lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SPORE IN LUNG CANCER Principal Investigator & Institution: Baylin, Stephen B.; Professor of Oncology; Oncology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAY-2003 Summary: The Johns Hopkins SPORE program for lung cancer, functioning as a major element of the Johns Hopkins Comprehensive Cancer Center, would represent a multidisciplinary and highly collaborative translational research effort to develop new strategies for early detection, prevention and treatment of lung cancer. Included will be an emphasis upon enhancing entry of new investigators into careers in lung cancer research -- and encouragement of novel research approaches through funding of pilot projects. The work scope of the SPORE addresses most of the research imperatives defined at the 1991 Annapolis Lung Cancer Workshop. A major emphasis is devoted to defining, at a molecular level, the earliest steps in lung cancer evolution. The goal is to develop markers which will be tested for efficacy in predicting and/or detecting early lung cancer and which will serve as new tools for guiding prevention and early treatment strategies. Unique tissue acquisition efforts of a Core Tissue Resource will allow isolated fresh and cultured human bronchial epithelium to be studied for timing of genetic (allelic losses, gene mutations) and epigenetic (changes in DNA methylation, neuroendocrine differentiation, signal transduction events, monoclonal antibody recognition) abnormalities in lung cancer progression. The research will include studies of unique patient cohorts for lung cancer risk, including uranium miners and individuals at genetic risk, and studies of unique rodent models for lung cancer induction. Novel treatment strategies for lung cancer, based on molecular targets defined in the laboratory, will be evaluated in focused clinical trials. Included will be molecular biology and biochemical assays to predict and monitor responses. Novel polyamine analogues active, through a newly defined gene induction event, against non-small cell lung cancer (NSCLC) will receive an initial clinical trial. The observation that retinoids can block a tumor progression step for small cell lung cancer cells, in a laboratory model, will be translated into a clinical trial to prevent, or delay, drug resistance for this cancer. In summary, this SPORE program represents an exciting collaborative opportunity for basic and clinical investigators to translate understanding of fundamental biology into new means to prevent, detect and treat lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

58 Lung Cancer

·

Project Title: STRATEGIES

TARGETING

EARLY

CHANGES

FOR

NEW

SCREENING

Principal Investigator & Institution: Sidransky, David; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Lung cancer is the leading cause of cancer related deaths in males and females in the United States. Surgical resection remains the only curative therapy for patients with non-small cell lung cancer (NSCLC). Identifying highrisk patients likely to develop cancer within a defined period of time is a clinical and biologic challenge for improving survival in patients with NSCLC. This study aims to use the power of molecular biology to develop and test promising new molecular markers for the identification of patients at risk of developing non-small cell lung cancer. Molecular studies have shown that clonal genetic alterations, e.g. 9p21 deletions, are often present in the lung epithelia of smokers and patients with a previous lung malignancy. This study will examine lung epithelium in smokers with a previous history of lung cancer and controls for the presence of specific chromosomal losses using state of the art techniques. New molecular markers will be developed and confirmed by genome wide SNP microarray analysis in normal appearing, preneoplastic, and malignant lung epithelium. The identified genetic markers will be used to test mucosa at risk in a unique population and develop a profile of genetic changes that predict progression to invasive cancer over a defined period of time. Genetic alterations at critical chromosome loci have been shown to be able to predict the progression of oral precursor lesions to invasive cancer. Our studies will pave the way for the development of similar markers in lung cancer and rapid translation into the clinical setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: TARGETING FATTY ACID SYNTHASE FOR LUNG CANCER TREATMENT Principal Investigator & Institution: Gabrielson, Edward W.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This project will target the enzyme, fatty acid synthase (FAS), for the treatment of lung cancer. Our preliminary studies have found that the vast majority of non-small cell lung cancers express high levels of this enzyme compared to normal tissues. This increased expression of FAS is significant because inhibition of this enzyme in cancer cells leads to a metabolic imbalance and cellular apoptosis. In a series of in vivo experiments, we found that treatment of orthotopic xenografts of human mesothelioma cells with an agent that inhibits FAS essentially abolished the growth of established tumors. Furthermore, in preliminary experiments, we found a promising anti-tumoral response of lung cancer orthotopic xenografts (in nude rats) treated with an FAS inhibitory compound. Importantly, these treatments did not result in any recognizable damage to normal tissue but did lead to dose-limiting anorexia. The proposed studies will further develop the use of FAS inhibitory therapy for lung cancer treatment. In the first phase of our preclinical studies, we will compare several novel FAS inhibitory agents, using in vivo and in vivo experimental systems, to identify a lead compound with high level of activity against lung cancer cells and tolerable levels of toxicity/anorexia. In the second phase of the preclinical studies, we will optimize dosing protocols for the treatment of lung cancer orthotopic xenografts

Studies

59

using this compound. This optimization of treatment protocols could be useful for designing treatment protocols to be applied in the clinical setting. The third pre-clinical aim of this project is to examine the effects of the FAS inhibitory compound when used in combination with other agents, such as those currently used to treat lung cancer or being evaluated for treatment of lung cancer. Because the FAS target represents a pathway distinct from those targeted by other compounds, there is a significant potential that such combinations could have synergistic antineoplastic activity, thus allowing reduction of doses of the respective agents. The final aim of this project is to initiate a phase I clinical trial for a compound identified by the preclinical studies to have the best potential for lung cancer treatment. Successful completion of this phase I trial and the preclinical modeling studies will provide a framework for further evaluation of an FAS inhibitory compound in the treatment of lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: THE BIOLOGY FLUOROTHYMIDINE PET

OF

LUNG

CANCER--

FDG

AND

Principal Investigator & Institution: Vesselle, Hubert J.; Assistant Professor; Radiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 12-JAN-2000; Project End 31-DEC-2004 Summary: The objective of the proposed studies is to investigate quantitative [F18]fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) as a measure of non-small cell lung cancer (NSCLC) aggressiveness in vivo (i.e. grading) and to make comparisons with patients' outcomes and with specimen-derived measures of cellular proliferation previously shown to predict poor outcome (S-phase fraction, Ki-67 index). We postulate that, in clinically resectable NSCLC patients, pre-operative FDG PET will show that tumors with higher FDG uptake: (a) will recur sooner after surgical resection than same stage tumors with low uptake; (b) are more likely to have mediastinal or distal metastatic disease than tumors of the same clinical stage but low uptake; (c) have higher S-phase fraction of Ki-67 scores in their resected specimen. The specific aims of the proposal are: (1) Perform whole-body pre- operative FDG PET imaging and correlate FDG uptake in primary NSCLC with outcome. FDG uptake will be quantified by the following methods that will be compared. Standardized Uptake Value (SUV) and SKMFDGMR (FDG Metabolic Rate determined by a Simplified Kinetic Method). (2) Perform whole-body pre-operative FDG PET imaging and correlate FDG uptake (quantified as SUV and SKM-FDGMR) in primary NSCLC with disease extent as demonstrated by PET and surgical staging. (3) Correlate pre-operative FDG uptake in primary NSCLC with markers of cellular proliferation measured from the resected specimen and previously shown to predict poor outcome. Outcome will be measured by recurrence-free survival, time-to recurrence and survival. In summary, by studying NSCLC patients preoperatively, prior to any form of chemotherapy or radiotherapy, we will gain valuable information about the biology of lung cancer, the leading cause of cancer death in the United States. By performing a biologic grading of resectable NSCLC with FDG PET, we will predict which patients will have a worse outcome. This information will allow individualized therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: TRANSCRIPTION DEVELOPMENT

FACTOR

NFKB

IN

LUNG

CANCER

Principal Investigator & Institution: Aggarwal, Bharat B.; Professor of Medicine; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030

60 Lung Cancer

Timing: Fiscal Year 2001; Project Start 20-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Cigarette smoke (CS) causes approximately 80-90 percent of lung cancer in the United States, but the mechanism by which CS mediates its effects is not fully understood. One factor may be transcription factor NF-kB, which regulates the expression of various genes involved in tumor initiation, promotion, and metastasis. We hypothesize that NF-kB activation by CS is an important factor in lung cancer development, and that inhibition of NF-kB activation or the activity of NF-kB regulated gene products (such as cyclooxygenase-2) could prevent lung cancer development. To test this hypothesis, we propose the following specific aims: Specific Aim 1: Determine if NF-kB is activated in biopsies containing bronchial epithelial cells from former and current cigarette smokers before and after celecoxib treatment. Specific Aim 2: Determine if cigarette smoke activates NF-kB and induces the NF-kB dependent gene expression in selected normal, premalignant and malignant lung cancer cell lines. Specific Aim 3: Determine if the cigarette smoke-induced NF-kB activation blocks apoptosis. Specific Aim 4: Determine if celecoxib downregulates cigarette smokeinduced NF-kB activation and overcomes cigarette smoke-induced resistance to apoptosis. Through these studies, we will determine: 1) whether cigarette smoking in humans leads to NF-kB activation and if it is modulated by celecoxib; 2) whether cigarette smoke activates NF-kB and induces NF-kB-dependent gene expression in bronchial epithelial lung cells; 3) whether CS-induced NF-kB results in suppression of apoptosis; and, 4) whether celecoxib can induce apoptosis through suppression of CSinduced NF-kB activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: TUMOR SUSCEPTIBILITY /GENETIC MUTATION /LUNG CANCER RISK Principal Investigator & Institution: Zhang, Zuo-Feng; Director/Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-DEC-2005 Summary: This proposal is built upon an ongoing population-based case-control study on marijuana use and the risk of lung and UAT cancers funded by NIH. The objectives are to better understand the molecular mechanisms for the risk of lung cancer. We propose that the development of lung cancer is an interactive process involving previous environmental exposures such as active and passive tobacco smoking, marijuana smoking; intrinsic host susceptibility such as polymorphisms and methylations of the GST P1 and polymorphisms of the TP53 gene and genetic instability including TP53 and mutations and p16 methylations an and other alterations. The study will be based on 600 cases and 600 controls interviewed by the parent study. Among those, we project 420 lung cancer patients with have their tumor tissue available for the analysis and 488 case and 488 controls will have their buccal cell samples for this proposed study, according to our pilot study. Epidemiological factors will be obtained by face-to-face interview. Our study is designed Our study is designed to fulfill these specific aims. (1) We will assay polymorphisms and hypermethylations of GST P1 in 488 cases and 488 controls, to evaluate will have their buccal cell samples for this proposed study, according to our pilot study. Epidemiological factors will be obtained by face-toface interview. Our study is designed to fulfill these specific aims. (1) We will assay polymorphisms and hypermethylations of GST P1 in 488 cases and 488 controls, to evaluate the effects of those alterations on the risk of lung cancer, and explore geneenvironment interaction between GSTP1 and environmental exposures. Other metabolic genes involved in PAH metabolism such as GSTM1 and P450A1 will be assayed. (2) We

Studies

61

will measure polymorphisms of TP53 gene in 488 cases and 488 controls and examine the effects of polymorphisms of TP53 gene by a case-control study. We will measure TP53 mutations by PCR-SSCP and sequencing to test the hypothesis that cases with lung cancer with and without p53 mutations are etiologically distinctive groups with regard to major risk factors such as active and passive tobacco smoking, occupational exposure, etc. (3) We will measure p16 methylations and other alterations including mutations, homozygous deletions, and microsatellite instability, and correlate these alterations with tobacco smoking and occupational exposures. The result of this study may provide insight into lung carcinogenesis. It may assist us to identify high-risk individuals for intervention and may have translational potential to screening, early detection and prognostic prediction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: UCLA SPORE IN LUNG CANCER Principal Investigator & Institution: Dubinett, Steven M.; Professor of Medicine; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-DEC-2005 Summary: The UCLA Jonsson Comprehensive Cancer Center has designed a Specialized Program of Research Excellence (SPORE) in lung cancer. This multidisciplinary, translational research program addresses critical questions in a broad based research effort to enhance our understanding of lung cancer biology and develop more effective methods for the prevention diagnosis, and treatment of lung cancer. The UCLA Lung Cancer SPORE is led by experienced lung cancer researchers who have organized investigative teams to develop highly interactive research programs with a strong translational focus. These scientific programs will focus on: 1) Tumor Susceptibility, Genetic Mutations, and Risk of Lung Cancer; 2) A Combined CT-PET Approach to Optimize in vivo Lung Nodule Characterization; 3) Neuropeptide Signaling Antagonists for SCLC Therapy; 4) Genetic Immunotherapy for Lung Cancer; and 5) Chemokine Regulation of Angiogenesis in Lung Cancer. The translational focus of this research will be maintained in each scientific section by teams of both basic and applied investigators. A Developmental Research Program will award 3-5 new grants each years for highly innovative translational research. The selection and progress of these developmental programs will be monitored by the Developmental Programs and Executive Committees, as well as the Internal and External Advisory Boards. A Lung Cancer SPORE Career Development Program designed for both fellows and faculty will be implemented for the career development of translational lung cancer investigators. To promote the strong translational research emphasis we have instituted a Clinical Trials Core that will be responsible for initiating clinical trials that are based on the preclinical investigations in each of the laboratories. Additional cores for pathology, informatics and administration will serve to support all of the research programs within the SPORE. In addition to research based at UCLA, our Lung Cancer SPORE Program is designed to foster collaborative interactions regionally and nationally. Accordingly, we have selected an external advisory board comprised of cancer center directions within our region as well as nationally recognized translational lung cancer researchers. In collaboration with the Lung Cancer SPORE leadership, the Internal and External Advisory Boards will continually assess the progress of all aspects of the program. The UCLA Lung Cancer SPORE is designed for maximum flexibility so that resources can be focused on the most promising investigations with the greatest translational potential.

62 Lung Cancer

The UCLA Lung Cancer SPORE constitutes a highly collaborative, multi-disciplinary translational research program designed to make a significant impact on lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: USE OF BETA-LAPACHONE FOR LUNG CANCER CHEMOTHERAPY Principal Investigator & Institution: Boothman, David A.; Professor and Director of Basic Research; Radiation Oncology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Lung cancer is the leading cause of death by cancer in the U.S. Non-small cell lung cancer (NSCLC) comprises over 75 percent of lung cancers diagnosed. Current chemotherapeutic regimens are not effective against NSCLC, with five-year survival rates hovering at a mere 14 percent. Regimens that exploit cancer-specific targets, specifically in and increase therapeutic indices, should enhance the survival rates of patients. We hypothesize that Beta-lapachone (beta-lap), a drug that selectively kills cancer cells with elevated levels of the two-electron reductase, NAD(P)H:quinone oxidoreductase 1 (NQOI), will be an effective agent for use against NSCLC cells that specifically over-express this bioactivating enzyme. Cell death caused by beta-lap is not dependent on cell cycle status, not dependent on p53, pRb, or caspases, and downstream cell death events are consistent with calpain-mediated apoptosis. More importantly, cell death by beta-lap is dependent on NQO1 expression, where NQO1-deficient cells are resistant to the drug, correction of cells with NQO1 restores lethality, and co-administration of dicumarol (an NQO1 inhibitor) prevents lethality. NQOI is typically elevated 4- to greater than 100-fold in human NSCLC, indicating the use of beta-lap for treatment of this disease. Recent development of novel drug delivery methods make it feasible to administer this drug to determine efficacy against NSCLC in animal models. Three aims will test this hypothesis: Aim 1: Evaluate the role of NQO1 in beta-lap-mediated cell death in NSCLC cells, and develop lab correlates for use in future therapy. (Years 1-3). Aim 2: Develop drug vehicles for betalap that either deliver the drug locally to the lung, or utilize systemic delivery schemes that allow accumulation of the vehicle-drug complexes within the lung, while offering simultaneous treatment for metastatic disease. (Years 1-5). Aim 3: Compare beta-lapencoded microparticles developed in Aim 2 for specific delivery to the lung to systemic delivery (i.p.) of HP-beta-cyclodextrin-beta-lap complexes for NQOl-specific lung tumor responses. We will combine these therapies with systemic dicumarol administration for normal tissue protection. (Years 1-5). We have assembled a strong research team with the needed experience to develop novel drug vehicles, image the deposition and delivery of both beta-lap and the vehicle in the lung, and test the hypothesis that betalap should be an efficacious agent against NSCLC due to tumor-specific elevation of NQO 1, a bioactivating enzyme specifically needed for novel calpain-mediated cell death responses elicited by beta-lapachone. We will examine the possibility that coadministration of dicumarol can act as an antidote, increasing the anti-tumor efficacy of beta-lap. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: USE OF RADIATION IN STAGE IV NON-SMALL CELL LUNG CANCER Principal Investigator & Institution: Hayman, James A.; Assistant Professor; Radiation Oncology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274

Studies

63

Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2004 Summary: (provided by applicant): The primary objective of this project is to examine factors associated with the utilization of radiation therapy in a sample of patients with Stage IV (i.e., metastatic) non-small cell lung cancer diagnosed in selected regions of the U.S. during a period ranging from 1991 to 1996. Anecdotal reports suggest that the use of radiation therapy to palliate symptoms associated with metastatic cancer is common and that there may be substantial variation in the intensity of treatment (i.e., number of treatments). This has important cost and quality implications because studies published over the last decade suggest that shorter courses of radiation treatment may be as effective as longer courses. Although this remains controversial in the U.S., as early as 1994 clinical guidelines in the U.S. began to endorse shorter courses of therapy. We propose to use the population-based linked SEER-Medicare data set to examine patterns and determinants of the utilization of palliative radiation therapy in patients age 65 or greater diagnosed with metastatic non-small cell lung cancer between 1991 and 1996. Created by researchers at the National Cancer Institute, this data set contains clinical data on almost all patients aged 65 and older diagnosed with cancer in the eleven SEER regions that have been linked to their respective Medicare claims data. Specifically, we plan to use SEER data to identify incident cases of metastatic non-small cell lung cancer and then use the Medicare claims data to identify those patients who received radiation therapy and quantify the intensity with which they were treated. We then propose to use this information to identify factors associated with the use and intensity of treatment with radiation including patient predisposing/enabling factors, clinical factors, organizational factors and physician factors. Lastly, we plan to examine whether the frequency and intensity of the administration of treatment with palliative radiation in this patient population has changed over time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: VIRTUAL TRUE-COLOR BRONCHOSCOPY TO DETECT LUNG CANCER Principal Investigator & Institution: Mclennan, Geoffrey; Associate Professor of Medicine; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Lung cancer is the most common cause of cancer death in both men and women in the United States. Reliable generalizable methods to detect early cancer within the bronchoscopically visible (central) airways are urgently needed. This development needs to occur concurrently with other efforts already underway to identify early peripheral lung cancers. The characteristics of early cancer within the human airway are thickening of the airway mucosa, and a change of color of the mucosal surface. At an earlier stage there will likely be protein and molecular changes, but these are so far poorly described. However, the expectation is that within several years there will be fluorescent markers that could be used to identify cancer changes within the human airway at this early stage. Recently there have been major advances in human imaging hardware and software. The first true color CCD bronchoscopes have been commercially introduced within the last 12 months. The digital output provides better color and spatial resolution. CT scanning has also benefited in speed and resolution through the introduction of multislice spiral scanners. One problem with these technologies is that the richness of the digital information further compounds the substantial human observer error rate in reporting on abnormalities. The purpose of this phased innovation award application is to develop digital analytic color detection and analysis of the human airway mucosa with images

64 Lung Cancer

from the CCD color bronchoscope; to develop digital analysis and display of the airway mucosa from high resolution/high speed volumetric CT scan data; and to integrate these two complimentary modalities into a single generalizable early cancer detection tool. At the completion of the project we will have developed this integrated automated and analytic tool, and evaluated this in a human population at high risk for lung cancer. We will be able to define the characteristics of the normal human airway, and the human airway in smoking subjects at high risk of lung cancer. We will know the positive and negative predicted values for airway mucosal lesions determined by CT scan (thickening and abnormal topography), and by abnormal airway color, both separately and collectively against a pathologic gold standard. In the future, we expect this technology to be easily used and generally available for undertaking effective screening for lung cancer within the bronchoscopically visible airways. Such technology will be useful for the evaluation of molecular probes as they are developed, and in promoting image guided airway cancer treatment. Lung cancer is the most common cause of cancer death in both men and women in the United States. Reliable generalizable methods to detect early cancer within the bronchoscopically visible (central) airways are urgently needed. This development needs to occur concurrently with other efforts already underway to identify early peripheral lung cancers. The characteristics of early cancer within the human airway are thickening of the airway mucosa, and a change of color of the mucosal surface. At an earlier stage there will likely be protein and molecular changes, but these are so far poorly described. However, the expectation is that within several years there will be fluorescent markers that could be used to identify cancer changes within the human airway at this early stage. Recently there have been major advances in human imaging hardware and software. The first true color CCD bronchoscopes have been commercially introduced within the last 12 months. The digital output provides better color and spatial resolution. CT scanning has also benefited in speed and resolution through the introduction of multislice spiral scanners. One problem with these technologies is that the richness of the digital information further compounds the substantial human observer error rate in reporting on abnormalities. The purpose of this phased innovation award application is to develop digital analytic color detection and analysis of the human airway mucosa with images from the CCD color bronchoscope; to develop digital analysis and display of the airway mucosa from high resolution/high speed volumetric CT scan data; and to integrate these two complimentary modalities into a single generalizable early cancer detection tool. At the completion of the project we will have developed this integrated automated and analytic tool, and evaluated this in a human population at high risk for lung cancer. We will be able to define the characteristics of the normal human airway, and the human airway in smoking subjects at high risk of lung cancer. We will know the positive and negative predicted values for airway mucosal lesions determined by CT scan (thickening and abnormal topography), and by abnormal airway color, both separately and collectively against a pathologic gold standard. In the future, we expect this technology to be easily used and generally available for undertaking effective screening for lung cancer within the bronchoscopically visible airways. Such technology will be useful for the evaluation of molecular probes as they are developed, and in promoting image guided airway cancer treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

65

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 “lung 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 lung cancer in the PubMed Central database: ·

3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region. by Sithanandam G, Latif F, Duh FM, Bernal R, Smola U, Li H, Kuzmin I, Wixler V, Geil L, Shrestha S.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231067

·

A Gene in the Chromosomal Region 3p21 with Greatly Reduced Expression in Lung Cancer is Similar to the Gene for Ubiquitin-Activating Enzyme. by Kok K, Hofstra R, Pilz A, van den Berg A, Terpstra P, Buys CH, Carritt B.; 1993 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46869

·

A Vasoactive Intestinal Peptide Antagonist Inhibits Non-Small Cell Lung Cancer Growth. by Moody TW, Zia F, Draoui M, Brenneman DE, Fridkin M, Davidson A, Gozes I.; 1993 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46507

·

Aberrant methylation of p16 INK4a is an early event in lung cancer and a potential biomarker for early diagnosis. by Belinsky SA, Nikula KJ, Palmisano WA, Michels R, Saccomanno G, Gabrielson E, Baylin SB, Herman JG.; 1998 Sep 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21736

·

Altered HOX and WNT7A expression in human lung cancer. by Calvo R, West J, Franklin W, Erickson P, Bemis L, Li E, Helfrich B, Bunn P, Roche J, Brambilla E, Rosell R, Gemmill RM, Drabkin HA.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18840

·

An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer. by Brichory FM, Misek DE, Yim AM, Krause MC, Giordano TJ, Beer DG, Hanash SM.; 2001 Aug 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55537

·

Antiproliferative and Apoptotic Activities of Ketonucleosides and Keto-C-Glycosides against Non-Small-Cell Lung Cancer Cells with Intrinsic Drug Resistance. by Paterson J, Uriel C, Egron MJ, Herscovici J, Antonakis K, Alaoui-Jamali MA.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105541

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.

66 Lung Cancer

·

Assessment of whether in-hospital mortality for lobectomy is a useful standard for the quality of lung cancer surgery: retrospective study. by Treasure T, Utley M, Bailey A.; 2003 Jul 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164918

·

Bradykinin antagonist dimer, CU201, inhibits the growth of human lung cancer cell lines by a "biased agonist" mechanism. by Chan D, Gera L, Stewart J, Helfrich B, Verella-Garcia M, Johnson G, Baron A, Yang J, Puck T, Bunn P Jr.; 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123695

·

Conservation of the Drosophila lateral inhibition pathway in human lung cancer: A hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression. by Chen H, Thiagalingam A, Chopra H, Borges MW, Feder JN, Nelkin BD, Baylin SB, Ball DW.; 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24682

·

Cyclin D1 Overexpression vs. Retinoblastoma Inactivation: Implications for Growth Control Evasion in Non-Small Cell and Small Cell Lung Cancer. by Schauer IE, Siriwardana S, Langan TA, Sclafani RA.; 1994 Aug 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44495

·

Dying of lung cancer or cardiac failure: prospective qualitative interview study of patients and their carers in the community. by Murray SA, Boyd K, Kendall M, Worth A, Benton TF, Clausen H.; 2002 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130056

·

Effects of Renal Function on Pharmacokinetics of Recombinant Human Granulocyte Colony-Stimulating Factor in Lung Cancer Patients. by Fukuda M, Oka M, Ishida Y, Kinoshita H, Terashi K, Fukuda M, Kawabata S, Kinoshita A, Soda H, Kohno S.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90583

·

EPA links diesel exhaust, lung cancer. by Weir E.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=126532

·

Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer. by Moghal N, Neel BG.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230634

·

Genomic approaches to research in lung cancer. by Gabrielson E.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59540

·

Gleevec (STI-571) inhibits lung cancer cell growth (A549) and potentiates the cisplatin effect in vitro. by Zhang P, Gao WY, Turner S, Ducatman BS.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149413

·

Hemoptysis as an Unusual Presenting Symptom of Invasion of a Descending Thoracic Aortic Aneurysmal Dissection by Lung Cancer. by Tsui P, Lee JH, MacLennan G, Capdeville M.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116743

·

Human lung cancer and p53: The interplay between mutagenesis and selection. by Rodin SN, Rodin AS.; 2000 Oct 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17326

Studies

67

·

Human Semaphorins A(V) and IV Reside in the 3p21.3 Small Cell Lung Cancer Deletion Region and Demonstrate Distinct Expression Patterns. by Sekido Y, Bader S, Latif F, Chen J, Duh F, Wei M, Albanesi JP, Lee C, Lerman MI, Minna JD.; 1996 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39497

·

Immediate versus delayed palliative thoracic radiotherapy in patients with unresectable locally advanced non-small cell lung cancer and minimal thoracic symptoms: randomised controlled trial. by Falk SJ, Girling DJ, White RJ, Hopwood P, Harvey A, Qian W, Stephens RJ.; 2002 Aug 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119441

·

Increased Cytosine DNA-Methyltransferase Activity is Target-Cell-Specific and an Early Event in Lung Cancer. by Belinsky SA, Nikula KJ, Baylin SB, Issa JJ.; 1996 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39484

·

Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. by Tomizawa Y, Sekido Y, Kondo M, Gao B, Yokota J, Roche J, Drabkin H, Lerman MI, Gazdar AF, Minna JD.; 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61148

·

Isolation of DNA Sequences Deleted in Lung Cancer by Genomic Difference Cloning. by Wieland I, Bohm M, Bogatz S.; 1992 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50201

·

Jaagsiekte Sheep Retrovirus Is Necessary and Sufficient To Induce a Contagious Lung Cancer in Sheep. by Palmarini M, Sharp JM, de las Heras M, Fan H.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112782

·

Molecular characteristics of non-small cell lung cancer. by Nacht M, Dracheva T, Gao Y, Fujii T, Chen Y, Player A, Akmaev V, Cook B, Dufault M, Zhang M, Zhang W, Guo M, Curran J, Han S, Sidransky D, Buetow K, Madden SL, Jen J.; 2001 Dec 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65007

·

Molecular Determinants of AHPN (CD437)-Induced Growth Arrest and Apoptosis in Human Lung Cancer Cell Lines. by Li Y, Lin B, Agadir A, Liu R, Dawson MI, Reed JC, Fontana JA, Bost F, Hobbs PD, Zheng Y, Chen GQ, Shroot B, Mercola D, Zhang XK.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109058

·

Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer. by Bredin M, Corner J, Krishnasamy M, Plant H, Bailey C, A'Hern R.; 1999 Apr 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27809

·

MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer. by Nishioka M, Kohno T, Tani M, Yanaihara N, Tomizawa Y, Otsuka A, Sasaki S, Kobayashi K, Niki T, Maeshima A, Sekido Y, Minna JD, Sone S, Yokota J.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129434

68 Lung Cancer

·

Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer cell lines. by Missale C, Codignola A, Sigala S, Finardi A, Paez-Pereda M, Sher E, Spano P.; 1998 Apr 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20267

·

Neuropeptide Stimulation of Calcium Flux in Human Lung Cancer Cells: Delineation of Alternative Pathways. by Bunn PA Jr, Dienhart DG, Chan D, Puck TT, Tagawa M, Jewett PB, Braunschweiger E.; 1990 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53646

·

New transformation tricks from a barnyard retrovirus: Implications for human lung cancer. by Rosenberg N.; 2001 Apr 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33321

·

Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer. by Minna JD.; 2003 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151841

·

Nonconventional Opioid Binding Sites Mediate Growth Inhibitory Effects of Methadone on Human Lung Cancer Cells. by Maneckjee R, Minna JD.; 1992 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48410

·

Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial. by Moore S, Corner J, Haviland J, Wells M, Salmon E, Normand C, Brada M, O'Brien M, Smith I.; 2002 Nov 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133453

·

Opioid and Nicotine Receptors Affect Growth Regulation of Human Lung Cancer Cell Lines. by Maneckjee R, Minna JD.; 1990 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53886

·

Plasma PGE-2 levels and altered cytokine profiles in adherent peripheral blood mononuclear cells in non-small cell lung cancer (NSCLC). by Hidalgo GE, Zhong L, Doherty DE, Hirschowitz EA.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149408

·

Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews. by Silvestri G, Pritchard R, Welch HG.; 1998 Sep 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28665

·

Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. by Meert AP, Paesmans M, Berghmans T, Martin B, Mascaux C, Vallot F, Verdebout JM, Lafitte JJ, Sculier JP.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34096

·

Quality of life in lung cancer patients: does socioeconomic status matter? by Montazeri A, Hole DJ, Milroy R, McEwen J, Gillis CR.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165601

·

Rapid p53 sequence analysis in primary lung cancer using an oligonucleotide probe array. by Ahrendt SA, Halachmi S, Chow JT, Wu L, Halachmi N, Yang SC, Wehage S, Jen J, Sidransky D.; 1999 Jun 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22094

Studies

69

·

Reanalysis of epidemiological evidence on lung cancer and passive smoking. by Copas JB, Shi JQ.; 2000 Feb 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27286

·

Recent changes in lung cancer incidence for south Asians: a population based register study. by Smith LK, Peake MD, Botha JL.; 2003 Jan 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139937

·

Reconstituted Basement Membrane (Matrigel) and Laminin can Enhance the Tumorigenicity and the Drug Resistance of Small Cell Lung Cancer Cell Lines. by Fridman R, Giaccone G, Kanemoto T, Martin GR, Gazdar AF, Mulshine JL.; 1990 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54604

·

Reduction in receptors for bombesin and epidermal growth factor in xenografts of human small-cell lung cancer after treatment with bombesin antagonist RC-3095. by Halmos G, Schally AV.; 1997 Feb 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19621

·

Regular aspirin use and lung cancer risk. by Moysich KB, Menezes RJ, Ronsani A, Swede H, Reid ME, Cummings KM, Falkner KL, Loewen GM, Bepler G.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138809

·

Relation between socioeconomic status and tumour stage in patients with breast, colorectal, ovarian, and lung cancer: results from four national, population based studies. by Brewster DH, Thomson CS, Hole DJ, Black RJ, Stroner PL, Gillis CR.; 2001 Apr 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30560

·

Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics. by Goncalves A, Braguer D, Kamath K, Martello L, Briand C, Horwitz S, Wilson L, Jordan MA.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58799

·

Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer. by Gure AO, Stockert E, Scanlan MJ, Keresztes RS, Jager D, Altorki NK, Old LJ, Chen YT.; 2000 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18195

·

Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. by Peto R, Darby S, Deo H, Silcocks P, Whitley E, Doll R.; 2000 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27446

·

The exogenous form of Jaagsiekte retrovirus is specifically associated with a contagious lung cancer of sheep. by Palmarini M, Cousens C, Dalziel RG, Bai J, Stedman K, DeMartini JC, Sharp JM.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189985

·

Three Tumor-Suppressor Regions on Chromosome 11p Identified by HighResolution Deletion Mapping in Human Non-Small-Cell Lung Cancer. by Bepler G, Garcia-Blanco MA.; 1994 Jun 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44026

70 Lung Cancer

·

Tumor-Suppressive Effect of the Retinoic Acid Receptor [beta] in Human Epidermoid Lung Cancer Cells. by Houle B, Rochette-Egly C, Bradley WE.; 1993 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45795

·

Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo. by Maruno K, Absood A, Said SI.; 1998 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24380

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

A 63-year-old man with suspected lung cancer and acute renal failure. Author(s): Papagiannis A, Xafenias A, Kourtoglou G, Zarogoulidis K. Source: Chest. 2003 June; 123(6): 2140-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796200&dopt=Abstract

·

A case-case study comparing the usefulness of serum trace elements (Cu, Zn and Se) and tumor markers (CEA, SCC and SLX) in non-small cell lung cancer patients. Author(s): Oyama T, Kawamoto T, Matsuno K, Osaki T, Matsumoto A, Isse T, Nakata S, Ozaki S, Sugaya M, Yasuda M, Yamashita T, Takenoyama M, Sugio K, Yasumoto K. Source: Anticancer Res. 2003 January-February; 23(1B): 605-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680155&dopt=Abstract

·

A meta-analysis of asthma and risk of lung cancer (United States). Author(s): Santillan AA, Camargo CA Jr, Colditz GA. Source: Cancer Causes & Control : Ccc. 2003 May; 14(4): 327-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846363&dopt=Abstract

6

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

Studies

71

·

A new irradiation system for lung cancer combining linear accelerator, computed tomography, patient self-breath-holding, and patient-directed beam-control without respiratory monitoring devices. Author(s): Onishi H, Kuriyama K, Komiyama T, Tanaka S, Sano N, Aikawa Y, Tateda Y, Araki T, Ikenaga S, Uematsu M. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 May 1; 56(1): 14-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694819&dopt=Abstract

·

A novel bisphosphonate minodronate (YM529) specifically inhibits osteolytic bone metastasis produced by human small-cell lung cancer cells in NK-cell depleted SCID mice. Author(s): Zhang H, Yano S, Miki T, Goto H, Kanematsu T, Muguruma H, Uehara H, Sone S. Source: Clinical & Experimental Metastasis. 2003; 20(2): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705636&dopt=Abstract

·

A novel method for sentinel lymph node mapping using magnetite in patients with non-small cell lung cancer. Author(s): Nakagawa T, Minamiya Y, Katayose Y, Saito H, Taguchi K, Imano H, Watanabe H, Enomoto K, Sageshima M, Ueda T, Ogawa J. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 August; 126(2): 563-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928659&dopt=Abstract

·

A phase II single-institution study of neoadjuvant stage IIIA/B chemotherapy and radiochemotherapy in non-small cell lung cancer. Author(s): Granetzny A, Striehn E, Bosse U, Wagner W, Koch O, Vogt U, Froeschle P, Klinke F. Source: The Annals of Thoracic Surgery. 2003 April; 75(4): 1107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683546&dopt=Abstract

·

A population-based study of glutathione S-transferase M1, T1 and P1 genotypes and risk for lung cancer. Author(s): Nazar-Stewart V, Vaughan TL, Stapleton P, Van Loo J, Nicol-Blades B, Eaton DL. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 247-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781423&dopt=Abstract

·

A prospective study of indications for mediastinoscopy in lung cancer with CT findings, tumor size, and tumor markers. Author(s): Kimura H, Iwai N, Ando S, Kakizawa K, Yamamoto N, Hoshino H, Anayama T. Source: The Annals of Thoracic Surgery. 2003 June; 75(6): 1734-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822608&dopt=Abstract

72 Lung Cancer

·

A prospective study of infections in lung cancer patients admitted to the hospital. Author(s): Berghmans T, Sculier JP, Klastersky J. Source: Chest. 2003 July; 124(1): 114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853512&dopt=Abstract

·

A prospective study of the impact of weight loss and the systemic inflammatory response on quality of life in patients with inoperable non-small cell lung cancer. Author(s): Scott HR, McMillan DC, Brown DJ, Forrest LM, McArdle CS, Milroy R. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 295-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781428&dopt=Abstract

·

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery. Author(s): Endo C, Saito Y, Iwanami H, Tsushima T, Imai T, Kawamura M, Kondo T, Koike K, Handa M, Kanno R, Fujimura S; North-east Japan Study Group for Lung Cancer Surgery. Source: Lung Cancer (Amsterdam, Netherlands). 2003 May; 40(2): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711119&dopt=Abstract

·

Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer. Author(s): Virmani A, Rathi A, Sugio K, Sathyanarayana UG, Toyooka S, Kischel FC, Tonk V, Padar A, Takahashi T, Roth JA, Euhus DM, Minna JD, Gazdar AF. Source: International Journal of Cancer. Journal International Du Cancer. 2003 August 20; 106(2): 198-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800194&dopt=Abstract

·

Acetone extract of Bupleurum scorzonerifolium inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing telomerase activity. Author(s): Cheng YL, Chang WL, Lee SC, Liu YG, Lin HC, Chen CJ, Yen CY, Yu DS, Lin SZ, Harn HJ. Source: Life Sciences. 2003 September 19; 73(18): 2383-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941440&dopt=Abstract

·

Adenoviral melanoma differentiation-associated gene 7 induces apoptosis in lung cancer cells through mitochondrial permeability transition-independent cytochrome c release. Author(s): Pataer A, Chada S, Hunt KK, Roth JA, Swisher SG. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 June; 125(6): 1328-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830052&dopt=Abstract

Studies

73

·

Adjuvant chemotherapy for non-small-cell lung cancer: the end of the beginning. Author(s): Johnson BE. Source: Journal of the National Cancer Institute. 2003 October 1; 95(19): 1422-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519741&dopt=Abstract

·

Adjuvant therapy in completely resected non-small-cell lung cancer. Author(s): Scagliotti GV, Novello S. Source: Current Oncology Reports. 2003 July; 5(4): 318-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781075&dopt=Abstract

·

Adoptive cellular immunotherapy for non-small cell lung cancer: a pilot study. Author(s): Chan B, Lee W, Hu CX, Ng P, Li KW, Lo G, Ho G, Yeung DW, Woo D. Source: Cytotherapy. 2003; 5(1): 46-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745587&dopt=Abstract

·

Aggressive treatment for the fit elderly with non-small-cell lung cancer? Yes! Author(s): Sequist LV, Lynch TJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3186-8. Epub 2003 July 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874267&dopt=Abstract

·

Allelic loss of DNA locus of the RET proto-oncogene in small cell lung cancer. Author(s): Futami H, Egawa S, Takasaki K, Tsukada T, Shiraishi M, Yamaguchi K. Source: Cancer Letters. 2003 May 30; 195(1): 59-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767512&dopt=Abstract

·

Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin 3B in non-small cell lung cancer. Author(s): Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Williams NN, Kaiser LR, Croce CM. Source: Cancer Research. 2003 June 15; 63(12): 3352-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810670&dopt=Abstract

·

Alu profiling of primary and metastatic nonsmall cell lung cancer. Author(s): Furmaga WB, Ryan JL, Coleman WB, Cole SR, Tsongalis GJ. Source: Experimental and Molecular Pathology. 2003 June; 74(3): 224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782008&dopt=Abstract

·

An overview of lung cancer. Author(s): Sachs S, Fiore JJ. Source: Respir Care Clin N Am. 2003 March; 9(1): 1-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820710&dopt=Abstract

74 Lung Cancer

·

Analysis of NQO1, GSTP1, and MnSOD genetic polymorphisms on lung cancer risk in Taiwan. Author(s): Lin P, Hsueh YM, Ko JL, Liang YF, Tsai KJ, Chen CY. Source: Lung Cancer (Amsterdam, Netherlands). 2003 May; 40(2): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711112&dopt=Abstract

·

Angiogenesis in the progression of lung cancer. Author(s): Yano S, Goto H, Yamamoto A, Kanematsu T, Sone S. Source: Intern Med. 2003 March; 42(3): 305-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705807&dopt=Abstract

·

Appraising the economic efficiency of cancer treatment: an exploratory analysis of lung cancer. Author(s): Chirikos TN. Source: Health Care Management Science. 2003 May; 6(2): 87-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733612&dopt=Abstract

·

Assessment of whether in-hospital mortality for lobectomy is a useful standard for the quality of lung cancer surgery: retrospective study. Author(s): Treasure T, Utley M, Bailey A. Source: Bmj (Clinical Research Ed.). 2003 July 12; 327(7406): 73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855523&dopt=Abstract

·

Association between glutathione S-transferase p1 polymorphisms and lung cancer risk in Caucasians: a case-control study. Author(s): Wang Y, Spitz MR, Schabath MB, Ali-Osman F, Mata H, Wu X. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 25-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660004&dopt=Abstract

·

Association between self-reported environmental tobacco smoke exposure and lung cancer: modification by GSTP1 polymorphism. Author(s): Miller DP, De Vivo I, Neuberg D, Wain JC, Lynch TJ, Su L, Christiani DC. Source: International Journal of Cancer. Journal International Du Cancer. 2003 May 10; 104(6): 758-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640684&dopt=Abstract

·

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk. Author(s): Gsur A, Zidek T, Schnattinger K, Feik E, Haidinger G, Hollaus P, MohnStaudner A, Armbruster C, Madersbacher S, Schatzl G, Trieb K, Vutuc C, Micksche M. Source: British Journal of Cancer. 2003 August 18; 89(4): 702-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915882&dopt=Abstract

Studies

75

·

Autocrine motility factor-receptor gene expression in lung cancer. Author(s): Takanami I, Takeuchi K. Source: Jpn J Thorac Cardiovasc Surg. 2003 August; 51(8): 368-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962414&dopt=Abstract

·

Balance between cell division and cell death as predictor of survival in patients with non-small-cell lung cancer. Author(s): Puglisi F, Minisini AM, Aprile G, Barbone F, Cataldi P, Artico D, Damante G, Beltrami CA, Di Loreto C. Source: Oncology. 2002; 63(1): 76-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187075&dopt=Abstract

·

Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf. Author(s): Fedorov LM, Tyrsin OY, Papadopoulos T, Camarero G, Gotz R, Rapp UR. Source: Cancer Research. 2002 November 1; 62(21): 6297-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414660&dopt=Abstract

·

Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299. Author(s): Jang MH, Shin MC, Lim S, Han SM, Park HJ, Shin I, Lee JS, Kim KA, Kim EH, Kim CJ. Source: Journal of Pharmacological Sciences. 2003 February; 91(2): 95-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686753&dopt=Abstract

·

Benefits of chemotherapy for quality of life in patients with advanced nonsmall-cell lung cancer. Author(s): Paesmans M. Source: Current Opinion in Oncology. 2002 July; 14(4): 389-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12130921&dopt=Abstract

·

Beryllium and lung cancer: a reanalysis of a niosh cohort mortality study. Author(s): Levy PS, Roth HD, Hwang PM, Powers TE. Source: Inhalation Toxicology. 2002 October; 14(10): 1003-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396408&dopt=Abstract

·

Best supportive care versus palliative chemotherapy in nonsmall-cell lung cancer. Author(s): Medley L, Cullen M. Source: Current Opinion in Oncology. 2002 July; 14(4): 384-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12130920&dopt=Abstract

76 Lung Cancer

·

Biological markers in non-small cell lung cancer. Retrospective study of 10 year follow-up after surgery. Author(s): Carbognani P, Tincani G, Crafa P, Sansebastiano G, Pazzini L, Zoni R, Bobbio A, Rusca M. Source: The Journal of Cardiovascular Surgery. 2002 August; 43(4): 545-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124571&dopt=Abstract

·

Biology of lung cancer with implications for new therapies. Author(s): Aberle MF, McLeskey SW. Source: Oncology Nursing Forum. 2003 March-April; 30(2): 273-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692661&dopt=Abstract

·

Bleomycin-induced chromosome breaks as a risk marker for lung cancer: a casecontrol study with population and hospital controls. Author(s): Zheng YL, Loffredo CA, Yu Z, Jones RT, Krasna MJ, Alberg AJ, Yung R, Perlmutter D, Enewold L, Harris CC, Shields PG. Source: Carcinogenesis. 2003 February; 24(2): 269-74. Erratum In: Carcinogenesis. 2003 August; 24(8): 1425. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584177&dopt=Abstract

·

Blood glutathione as a surrogate marker of cancer tissue glutathione S-transferase activity in non-small cell lung cancer and squamous cell carcinoma of the head and neck. Author(s): Ferruzzi E, Franceschini R, Cazzolato G, Geroni C, Fowst C, Pastorino U, Tradati N, Tursi J, Dittadi R, Gion M. Source: European Journal of Cancer (Oxford, England : 1990). 2003 May; 39(7): 1019-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706373&dopt=Abstract

·

Blood hemoglobin as an independent prognostic factor in surgically resected stages I and II non-small cell lung cancer patients. Author(s): Watine J. Source: The Annals of Thoracic Surgery. 2002 June; 73(6): 2034-5; Author Reply 2035. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078827&dopt=Abstract

·

Blood pressure, smoking, and the incidence of lung cancer in hypertensive men in North Karelia, Finland. Author(s): Lindgren A, Pukkala E, Nissinen A, Tuomilehto J. Source: American Journal of Epidemiology. 2003 September 1; 158(5): 442-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936899&dopt=Abstract

·

Bone metastasis as the first manifestation of lung cancer. Author(s): Kagohashi K, Satoh H, Ishikawa H, Ohtsuka M, Sekizawa K. Source: Int J Clin Pract. 2003 April; 57(3): 184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723721&dopt=Abstract

Studies

77

·

BRAF and RAS mutations in human lung cancer and melanoma. Author(s): Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A, Roth JA, Albelda SM, Davies H, Cox C, Brignell G, Stephens P, Futreal PA, Wooster R, Stratton MR, Weber BL. Source: Cancer Research. 2002 December 1; 62(23): 6997-7000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460918&dopt=Abstract

·

Brain metastasis as the first manifestation of lung cancer. Author(s): Kagohashi K, Satoh H, Yamashita YT, Sekizawa K. Source: The American Journal of Medicine. 2003 April 1; 114(5): 420. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714137&dopt=Abstract

·

Breast and lung cancer are associated with a decrease in blood cell amino acid content. Author(s): Proenza AM, Oliver J, Palou A, Roca P. Source: The Journal of Nutritional Biochemistry. 2003 March; 14(3): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742540&dopt=Abstract

·

Bronchial hyperresponsiveness in patients with squamous cell lung cancer. Author(s): Inoue R, Nishimura Y, Kado T, Yokoyama M. Source: Respirology (Carlton, Vic.). 2002 December; 7(4): 339-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421242&dopt=Abstract

·

Bronchioloalveolar lung cancer: occurrence, surgical treatment and survival. Author(s): Furak J, Trojan I, Szoke T, Tiszlavicz L, Morvay Z, Eller J, Balogh A. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 May; 23(5): 818-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754039&dopt=Abstract

·

Bronchopleural fistula prevention after major pulmonary resection for primary lung cancer. Author(s): Bazzocchi R, Bini A, Grazia M, Petrella F. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 July; 22(1): 160. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12103397&dopt=Abstract

78 Lung Cancer

·

Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer. Author(s): Lardinois D, Brack T, Gaspert A, Spahr T, Schneiter D, Steinert HC, Weder W. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 May; 23(5): 824-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754040&dopt=Abstract

·

Bronchoscopic treatment of patients with intraluminal microinvasive radiographically occult lung cancer not eligible for surgical resection: a follow-up study. Author(s): Vonk-Noordegraaf A, Postmus PE, Sutedja TG. Source: Lung Cancer (Amsterdam, Netherlands). 2003 January; 39(1): 49-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499094&dopt=Abstract

·

Case-control study of lung cancer during 1994-1997 in the birth cohort in Tasmania, Australia, with an excess of female cases during 1983-1992. Author(s): Blizzard L, Dwyer T. Source: Cancer Causes & Control : Ccc. 2003 March; 14(2): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749717&dopt=Abstract

·

Changes in hemodynamics in patients who underwent extended mediastinal lymphadenectomy through median sternotomy for primary lung cancer. Author(s): Hirata T, Koizumi K, Tanaka S. Source: Jpn J Thorac Cardiovasc Surg. 2003 May; 51(5): 178-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776948&dopt=Abstract

·

Chemoprevention in lung cancer. Author(s): Reddy SC, Khuri FR. Source: J Med Assoc Ga. 2003 Winter-Spring; 92(1): 27-33. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743903&dopt=Abstract

·

Chemotherapy options for the elderly patient with advanced non-small cell lung cancer. Author(s): Hennessy BT, Hanrahan EO, Breathnach OS. Source: The Oncologist. 2003; 8(3): 270-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773749&dopt=Abstract

·

Chemotherapy versus best supportive care in the management of lung cancer. Author(s): Shajeem O, Behera D, Aggarwal AN. Source: J Assoc Physicians India. 2003 March; 51: 261-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839347&dopt=Abstract

Studies

79

·

Chilean pilot study on the risk of lung cancer associated with codon 72 polymorphism in the gene of protein p53. Author(s): Irarrazabal CE, Rojas C, Aracena R, Marquez C, Gil L. Source: Toxicology Letters. 2003 September 15; 144(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919725&dopt=Abstract

·

Chronic Chlamydophila pneumoniae infection in lung cancer, a risk factor: a casecontrol study. Author(s): Kocazeybek B. Source: Journal of Medical Microbiology. 2003 August; 52(Pt 8): 721-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867569&dopt=Abstract

·

Clinical efficacy and toxicity of gefitinib in patients with lung cancer. Author(s): Teramoto S, Yamamoto H, Ouchi Y. Source: Lancet. 2003 June 7; 361(9373): 1992-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801775&dopt=Abstract

·

Clinical efficacy and toxiciy of gefitinib in patients with lung cancer. Author(s): Mitsui H, Nakajima J, Maruyama T, Hanajiri K, Omata M. Source: Lancet. 2003 June 7; 361(9373): 1993. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801776&dopt=Abstract

·

Clinical equivalence of two cytokeratin markers in mon-small cell lung cancer: a study of tissue polypeptide antigen and cytokeratin 19 fragments. Author(s): Buccheri G, Torchio P, Ferrigno D. Source: Chest. 2003 August; 124(2): 622-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907552&dopt=Abstract

·

Clinical significance of co-expression of VEGF-C and VEGFR-3 in non-small cell lung cancer. Author(s): Li Q, Dong X, Gu W, Qiu X, Wang E. Source: Chin Med J (Engl). 2003 May; 116(5): 727-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875690&dopt=Abstract

·

Clinical value of CEA and CA125 regarding relapse and metastasis in resectable nonsmall cell lung cancer. Author(s): Gaspar MJ, Diez M, Rodriguez A, Ratia T, Martin Duce A, Galvan M, Granell J, Coca C. Source: Anticancer Res. 2003 July-August; 23(4): 3427-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926084&dopt=Abstract

80 Lung Cancer

·

Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non-small-cell lung cancer. Author(s): Feliu J, Martin G, Madronal C, Rodriguez-Jaraiz A, Castro J, Rodriguez A, Checa T, Bolano M, Casado E, Gonzalez-Baron M. Source: Cancer Chemotherapy and Pharmacology. 2003 September; 52(3): 247-52. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783203&dopt=Abstract

·

Combined modality therapy of early stage nonsmall cell lung cancer. Author(s): Pisters KM. Source: Respir Care Clin N Am. 2003 June; 9(2): 191-205. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911289&dopt=Abstract

·

Combined therapy with topotecan and gemcitabine in patients with inoperable or metastatic non-small cell lung cancer. Author(s): Dabrow MB, Francesco MR, Gilman PB, Cantor R, Rose L, Meyer TJ. Source: Cancer Investigation. 2003; 21(4): 517-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14533441&dopt=Abstract

·

Combined treatment for limited small cell lung cancer. Author(s): Komaki R. Source: Seminars in Oncology. 2003 August; 30(4 Suppl 9): 56-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908137&dopt=Abstract

·

Computed tomographic screening for lung cancer: home run or foul ball? Author(s): Swensen SJ, Jett JR, Midthun DE, Hartman TE. Source: Mayo Clinic Proceedings. 2003 September; 78(9): 1187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962174&dopt=Abstract

·

Concordant expression of the telomerase-associated genes in non-small cell lung cancer. Author(s): Hsu CP, Miaw J, Hsia JY, Shai SE, Chen CY. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 September; 29(7): 594-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943625&dopt=Abstract

·

Concurrent chemoradiotherapy for inoperable stage III non-small-cell lung cancer. Author(s): MacRae R, Choy H. Source: Current Oncology Reports. 2003 July; 5(4): 313-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781074&dopt=Abstract

Studies

81

·

Conditional survival of patients with the four major histologic subgroups of lung cancer in Denmark. Author(s): Skuladottir H, Olsen JH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 15; 21(16): 3035-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915592&dopt=Abstract

·

Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer. Author(s): Tsang KW, Lam CL, Yan C, Mak JC, Ooi GC, Ho JC, Lam B, Man R, Sham JS, Lam WK. Source: Respiratory Medicine. 2003 June; 97(6): 618-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814145&dopt=Abstract

·

Correlation between perioperative blood transfusion and prognosis of patients subjected to surgery for stage I lung cancer. Author(s): Nosotti M, Rebulla P, Riccardi D, Baisi A, Bellaviti N, Rosso L, Santambrogio L. Source: Chest. 2003 July; 124(1): 102-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853510&dopt=Abstract

·

Cost-effectiveness and lung cancer clinical trials. Author(s): Du W, Reeves JH, Gadgeel S, Abrams J, Peters WP. Source: Cancer. 2003 October 1; 98(7): 1491-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508837&dopt=Abstract

·

Cost-effectiveness of screening for lung cancer. Author(s): Chirikos TN, Hazelton T, Tockman M, Clark R. Source: Jama : the Journal of the American Medical Association. 2003 May 14; 289(18): 2358; Author Reply 2358-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746351&dopt=Abstract

·

Cost-effectiveness of screening for lung cancer. Author(s): Petty TL. Source: Jama : the Journal of the American Medical Association. 2003 May 14; 289(18): 2357; Author Reply 2358-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746350&dopt=Abstract

·

Cost-effectiveness of screening for lung cancer. Author(s): Reich J. Source: Jama : the Journal of the American Medical Association. 2003 May 14; 289(18): 2357; Author Reply 2358-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746349&dopt=Abstract

82 Lung Cancer

·

CT screening for lung cancer. Author(s): Yankelevitz D. Source: Ajr. American Journal of Roentgenology. 2003 June; 180(6): 1736-7; Author Reply 1737. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760953&dopt=Abstract

·

Current concepts in the mediastinal lymph node staging of nonsmall cell lung cancer. Author(s): Kramer H, Groen HJ. Source: Annals of Surgery. 2003 August; 238(2): 180-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894010&dopt=Abstract

·

Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population. Author(s): Qiuling S, Yuxin Z, Suhua Z, Cheng X, Shuguang L, Fengsheng H. Source: Carcinogenesis. 2003 September; 24(9): 1499-503. Epub 2003 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807740&dopt=Abstract

·

Cyclin D1 overexpression in bronchial epithelia of patients with lung cancer is associated with smoking and predicts survival. Author(s): Ratschiller D, Heighway J, Gugger M, Kappeler A, Pirnia F, Schmid RA, Borner MM, Betticher DC. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 1; 21(11): 2085-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775733&dopt=Abstract

·

Cyclooxygenase-2 in lung cancer. Author(s): Dubinett SM, Sharma S, Huang M, Dohadwala M, Pold M, Mao JT. Source: Prog Exp Tumor Res. 2003; 37: 138-62. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795053&dopt=Abstract

·

CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian nonsmokers: a pooled analysis. Author(s): Hung RJ, Boffetta P, Brockmoller J, Butkiewicz D, Cascorbi I, Clapper ML, Garte S, Haugen A, Hirvonen A, Anttila S, Kalina I, Le Marchand L, London SJ, Rannug A, Romkes M, Salagovic J, Schoket B, Gaspari L, Taioli E. Source: Carcinogenesis. 2003 May; 24(5): 875-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771031&dopt=Abstract

·

CYP3A5*1 is an inhibitory factor for lung cancer in Taiwanese. Author(s): Yeh KT, Chen JC, Chen CM, Wang YF, Lee TP, Chang JG. Source: Kaohsiung J Med Sci. 2003 May; 19(5): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822676&dopt=Abstract

Studies

83

·

Daily activities: exploring their spectrum and prognostic impact in older, chemotherapy-treated lung cancer patients. Author(s): Jatoi A, Hillman S, Stella PJ, Mailliard JA, Sloan J, Vanone S, Cannon MW, Kutteh L, Kanard A, Jett JR. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 July; 11(7): 460-4. Epub 2003 March 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505160&dopt=Abstract

·

Daily low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer. Author(s): Takata I, Ueoka H, Kiura K, Tabata M, Takigawa N, Katayama H, Takemoto M, Hiraki Y, Harada M, Tanimoto M. Source: Acta Medica Okayama. 2002 October; 56(5): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530510&dopt=Abstract

·

DEC1 (STRA13) protein expression relates to hypoxia- inducible factor 1-alpha and carbonic anhydrase-9 overexpression in non-small cell lung cancer. Author(s): Giatromanolaki A, Koukourakis MI, Sivridis E, Turley H, Wykoff CC, Gatter KC, Harris AL. Source: The Journal of Pathology. 2003 June; 200(2): 222-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754744&dopt=Abstract

·

Declining sex differences in mortality from lung cancer in high-income nations. Author(s): Pampel FC. Source: Demography. 2003 February; 40(1): 45-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647513&dopt=Abstract

·

Defining the need for radiotherapy for lung cancer in the general population: a criterion-based, benchmarking approach. Author(s): Barbera L, Zhang-Salomons J, Huang J, Tyldesley S, Mackillop W. Source: Medical Care. 2003 September; 41(9): 1074-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972847&dopt=Abstract

·

Dendritic cells efficiently acquire and present antigen derived from lung cancer cells and induce antigen-specific T-cell responses. Author(s): Zhou Y, McEarchern JA, Howard E, Pestano G, Salgaller ML, Bosch ML. Source: Cancer Immunology, Immunotherapy : Cii. 2003 July; 52(7): 413-22. Epub 2003 February 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835918&dopt=Abstract

84 Lung Cancer

·

Depression and psychological distress in patients during the year after curative resection of non-small-cell lung cancer. Author(s): Uchitomi Y, Mikami I, Nagai K, Nishiwaki Y, Akechi T, Okamura H. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 1; 21(1): 69-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506173&dopt=Abstract

·

Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at distal 17p13.3 in human lung cancer. Author(s): Konishi H, Sugiyama M, Mizuno K, Saito H, Yatabe Y, Takahashi T, Osada H, Takahashi T. Source: Oncogene. 2003 March 27; 22(12): 1892-905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660825&dopt=Abstract

·

Detection of loss of heterozygosity by high-resolution fluorescent system in nonsmall cell lung cancer: association of loss of heterozygosity with smoking and tumor progression. Author(s): Yoshino I, Fukuyama S, Kameyama T, Shikada Y, Oda S, Maehara Y, Sugimachi K. Source: Chest. 2003 February; 123(2): 545-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576379&dopt=Abstract

·

Detection of lung cancer with volatile markers in the breath. Author(s): Phillips M, Cataneo RN, Cummin AR, Gagliardi AJ, Gleeson K, Greenberg J, Maxfield RA, Rom WN. Source: Chest. 2003 June; 123(6): 2115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796197&dopt=Abstract

·

Detection of telomerase activity in bronchial lavage as an adjunct to cytological diagnosis in lung cancer. Author(s): Dikmen E, Kara M, Dikmen G, Cakmak H, Dogan P. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 February; 23(2): 194-9; Discussion 199-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559342&dopt=Abstract

·

Detection of telomerase expression in mediastinal lymph nodes of patients with lung cancer. Author(s): Wallace MB, Block M, Hoffman BJ, Hawes RH, Silvestri G, Reed CE, Mitas M, Ravenel J, Fraig M, Miller S, Jones ET, Boylan A. Source: American Journal of Respiratory and Critical Care Medicine. 2003 June 15; 167(12): 1670-5. Epub 2003 February 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615614&dopt=Abstract

Studies

85

·

Development of brain metastasis 5 years before the appearance of the primary lung cancer: “messenger metachronous metastasis”. Author(s): Furak J, Trojan I, Tiszlavicz L, Micsik T, Puskas LG. Source: The Annals of Thoracic Surgery. 2003 March; 75(3): 1016-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645740&dopt=Abstract

·

Diagnosis and management of lung cancer: ACCP evidence-based guidelines. American College of Chest Physicians. Author(s): American College of Chest Physicians; Health and Science Policy Committee. Source: Chest. 2003 January; 123(1 Suppl): D-G, 1S-337S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527560&dopt=Abstract

·

Diagnosis of lung cancer: the guidelines. Author(s): Rivera MP, Detterbeck F, Mehta AC; American College of Chest Physicians. Source: Chest. 2003 January; 123(1 Suppl): 129S-136S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527572&dopt=Abstract

·

Diagnostic challenges in patients with tumors: case 2. Staphylococcal scalded-skin syndrome in a patient with extended small-cell lung cancer. Author(s): Longo R, Amici S, Carillio G, Gasparini G. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 October 1; 21(19): 3702-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512404&dopt=Abstract

·

Diagnostic value of plasma vascular endothelial growth factor as a tumor marker in patients with non-small cell lung cancer. Author(s): Tamura M, Ohta Y, Nakamura H, Oda M, Watanabe G. Source: Int J Biol Markers. 2002 October-December; 17(4): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521132&dopt=Abstract

·

Dietary carotenoids, vegetables, and lung cancer risk in women: the Missouri women's health study (United States). Author(s): Wright ME, Mayne ST, Swanson CA, Sinha R, Alavanja MC. Source: Cancer Causes & Control : Ccc. 2003 February; 14(1): 85-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708729&dopt=Abstract

·

Different measures of asbestos exposure in estimating risk of lung cancer and mesothelioma among construction workers. Author(s): Koskinen K, Pukkala E, Martikainen R, Reijula K, Karjalainen A. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2002 December; 44(12): 1190-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500463&dopt=Abstract

86 Lung Cancer

·

Different risk relations with smoking for non-small-cell lung cancer: comparison of TP53 and TP73 genotypes. Author(s): Hiraki A, Matsuo K, Hamajima N, Ito H, Hatooka S, Suyama M, Mitsudomi T, Tajima K. Source: Asian Pac J Cancer Prev. 2003 April-June; 4(2): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875622&dopt=Abstract

·

Diffuse alveolar damage after ZD1839 therapy in a patient with non-small cell lung cancer. Author(s): Okamoto I, Fujii K, Matsumoto M, Terasaki Y, Kihara N, Kohrogi H, Suga M. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 339-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781434&dopt=Abstract

·

Diffusely increased uptake by thoracic vertebrae on bone scintigraphy in midcourse of lung cancer irradiation: a case report. Author(s): Shih WJ, Gross K. Source: Journal of Nuclear Medicine Technology. 2003 June; 31(2): 79-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777458&dopt=Abstract

·

Dihydropyrimidine dehydrogenase levels in nonsmall-cell lung cancer tissues. Author(s): Yano T, Koga T, Ninomiya S, Takeo S. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2002 December; 7(6): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494252&dopt=Abstract

·

Direct treatment costs for patients with lung cancer from first recurrence to death in france. Author(s): Braud AC, Levy-Piedbois C, Piedbois P, Piedbois Y, Livartovski A, Le Vu B, Tredaniel J, Reboul F, Brewer Y, Talbi S, Blanchon F, Paschen B, Durand-Zaleski I. Source: Pharmacoeconomics. 2003; 21(9): 671-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807368&dopt=Abstract

·

Discrepancy between Tc-99m HMDP bone scan and F-18 FDG positron emission tomographic images in a patient with small cell lung cancer. Author(s): Fukuchi K, Yamaguchi M, Hayashida K, Ishida Y. Source: Clinical Nuclear Medicine. 2003 March; 28(3): 232-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592136&dopt=Abstract

·

Disseminated Actinomyces meyeri infection resembling lung cancer with brain metastases. Author(s): Colmegna I, Rodriguez-Barradas M, Rauch R, Clarridge J, Young EJ. Source: The American Journal of the Medical Sciences. 2003 September; 326(3): 152-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501233&dopt=Abstract

Studies

87

·

DNA repair activity for oxidative damage and risk of lung cancer. Author(s): Paz-Elizur T, Krupsky M, Blumenstein S, Elinger D, Schechtman E, Livneh Z. Source: Journal of the National Cancer Institute. 2003 September 3; 95(17): 1312-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953085&dopt=Abstract

·

Do newly diagnosed lung cancer patients feel their concerns are being met? Author(s): Hill KM, Amir Z, Muers MF, Connolly CK, Round CE. Source: European Journal of Cancer Care. 2003 March; 12(1): 35-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641555&dopt=Abstract

·

Does HIV adversely influence the outcome in advanced non-small-cell lung cancer in the era of HAART? Author(s): Powles T, Thirwell C, Newsom-Davis T, Nelson M, Shah P, Cox S, Gazzard B, Bower M. Source: British Journal of Cancer. 2003 August 4; 89(3): 457-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888811&dopt=Abstract

·

Dose-comparative monotherapy trials of ZD1839 in previously treated non-small cell lung cancer patients. Author(s): Herbst RS. Source: Seminars in Oncology. 2003 February; 30(1 Suppl 1): 30-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644982&dopt=Abstract

·

Dose-escalation with CHARTWEL (continuous hyperfractionated accelerated radiotherapy week-end less) combined with neo-adjuvant chemotherapy in the treatment of locally advanced non-small cell lung cancer. Author(s): Saunders MI, Rojas A, Lyn BE, Wilson E, Phillips H. Source: Clin Oncol (R Coll Radiol). 2002 October; 14(5): 352-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555873&dopt=Abstract

·

Downregulation of plasma membrane expression/cytoplasmic accumulation of betacatenin predicts shortened survival in non-small cell lung cancer. A clinicopathologic study of 100 cases. Author(s): Kren L, Hermanova M, Goncharuk VN, Kaur P, Ross JS, Pavlovsky Z, Dvorak K. Source: Cesk Patol. 2003 January; 39(1): 17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673938&dopt=Abstract

88 Lung Cancer

·

Early detection of lung cancer: role of biomarkers. Author(s): Brambilla C, Fievet F, Jeanmart M, de Fraipont F, Lantuejoul S, Frappat V, Ferretti G, Brichon PY, Moro-Sibilot D. Source: Eur Respir J Suppl. 2003 January; 39: 36S-44S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572700&dopt=Abstract

·

Early lung cancer action project pathology protocol. Author(s): Vazquez M, Flieder D, Travis W, Carter D, Yankelevitz DF, Miettinen OS, Henschke CI. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 231-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581579&dopt=Abstract

·

Economic status, smoking, occupational exposure to rubber, and lung cancer: a casecohort study. Author(s): Li K, Yu S. Source: Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews. 2002 May; 20(1): 21-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734051&dopt=Abstract

·

Economic, legal, and ethical rationales for the ACRIN national lung screening trial of CT screening for lung cancer. Author(s): Hillman BJ; ACRIN. Source: Academic Radiology. 2003 March; 10(3): 349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643562&dopt=Abstract

·

Effect of epoxide hydrolase polymorphisms on chromosome aberrations and risk for lung cancer. Author(s): Cajas-Salazar N, Au WW, Zwischenberger JB, Sierra-Torres CH, Salama SA, Alpard SK, Tyring SK. Source: Cancer Genetics and Cytogenetics. 2003 September; 145(2): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12935919&dopt=Abstract

·

Effect of number of lymph nodes sampled on outcome in patients with stage I nonsmall-cell lung cancer. Author(s): Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 15; 21(6): 1029-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637467&dopt=Abstract

Studies

89

·

Effect of radioisotope sentinel node mapping in patients with cT1 N0 M0 lung cancer. Author(s): Sugi K, Kaneda Y, Sudoh M, Sakano H, Hamano K. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 August; 126(2): 56873. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928660&dopt=Abstract

·

Effect of temporal subtraction technique on the diagnosis of primary lung cancer with chest radiography. Author(s): Matsuda T, Yasuhara Y, Kano A, Mochizuki T, Ikezoe J. Source: Radiat Med. 2003 May-June; 21(3): 112-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868859&dopt=Abstract

·

Efficacy and safety of zoledronic acid in the treatment of bone metastases associated with lung cancer and other solid tumors. Author(s): Rosen LS. Source: Seminars in Oncology. 2002 December; 29(6 Suppl 21): 28-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584692&dopt=Abstract

·

Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. Author(s): Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Source: Jama : the Journal of the American Medical Association. 2003 October 22; 290(16): 2149-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570950&dopt=Abstract

·

Efficacy of neoadjuvant strategies with gemcitabine and other chemotherapy in resectable non-small cell lung cancer: a combined modality approach. Author(s): Scagliotti GV, Novello S. Source: Seminars in Oncology. 2003 August; 30(4 Suppl 10): 13-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917816&dopt=Abstract

·

Elevated levels of intracellular Ca2+ and apoptosis in human lung cancer cells given heat-shock. Author(s): Hashimoto T, Shibata MA, Ito Y, Nakao KI, Sasaki S, Otsuki Y. Source: International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2003 March-April; 19(2): 178-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623640&dopt=Abstract

90 Lung Cancer

·

Elevated serum epidermal growth factor receptor level is correlated with lymph node metastasis in lung cancer. Author(s): Sasaki H, Yukiue H, Mizuno K, Sekimura A, Konishi A, Yano M, Kaji M, Kiriyama M, Fukai I, Yamakawa Y, Fujii Y. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 April; 8(2): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720099&dopt=Abstract

·

Elevated serum periostin levels in patients with bone metastases from breast but not lung cancer. Author(s): Sasaki H, Yu CY, Dai M, Tam C, Loda M, Auclair D, Chen LB, Elias A. Source: Breast Cancer Research and Treatment. 2003 February; 77(3): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602924&dopt=Abstract

·

En-bloc chest wall and lung resection for non-small cell lung cancer. Predictors of 60day non-cancer related mortality. Author(s): Martin-Ucar AE, Nicum R, Oey I, Edwards JG, Waller DA. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 June; 23(6): 859-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829058&dopt=Abstract

·

Environmental exposure and lung cancer among nonsmokers: an example of Taiwanese female lung cancer. Author(s): Wen Cheng Y, Lee H. Source: Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews. 2003 May; 21(1): 1-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826030&dopt=Abstract

·

Epidemiological associations among lung cancer, radon exposure and elevation above sea level--a reassessment of Cohen's county level radon study. Author(s): Van Pelt WR. Source: Health Physics. 2003 October; 85(4): 397-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678279&dopt=Abstract

·

Epidemiology of lung cancer. Author(s): Kollarova H, Janout V, Cizek L. Source: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2002 December; 146(2): 103-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572908&dopt=Abstract

Studies

91

·

Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases. Author(s): Milas I, Komaki R, Hachiya T, Bubb RS, Ro JY, Langford L, Sawaya R, Putnam JB, Allen P, Cox JD, McDonnell TJ, Brock W, Hong WK, Roth JA, Milas L. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 March; 9(3): 1070-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631609&dopt=Abstract

·

Erlotinib: a new therapeutic approach for non-small cell lung cancer. Author(s): Bonomi P. Source: Expert Opinion on Investigational Drugs. 2003 August; 12(8): 1395-401. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882624&dopt=Abstract

·

Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Author(s): Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ. Source: British Journal of Cancer. 2003 September 15; 89(6): 1028-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966420&dopt=Abstract

·

Evaluation of different markers in non-small cell lung cancer: prognostic value of clinical staging, tumour cell detection and tumour marker analysis for tumour progression and overall survival. Author(s): Kasimir-Bauer S, Schleucher N, Weber R, Neumann R, Seeber S. Source: Oncol Rep. 2003 March-April; 10(2): 475-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579292&dopt=Abstract

·

Evidence that phosphatidylinositol 3-kinase- and mitogen-activated protein kinase kinase-4/c-Jun NH2-terminal kinase-dependent Pathways cooperate to maintain lung cancer cell survival. Author(s): Lee HY, Srinivas H, Xia D, Lu Y, Superty R, LaPushin R, Gomez-Manzano C, Gal AM, Walsh GL, Force T, Ueki K, Mills GB, Kurie JM. Source: The Journal of Biological Chemistry. 2003 June 27; 278(26): 23630-8. Epub 2003 April 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714585&dopt=Abstract

·

Evidence-based follow-up of lung cancer patients. Author(s): Smith TJ. Source: Seminars in Oncology. 2003 June; 30(3): 361-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870137&dopt=Abstract

92 Lung Cancer

·

Evidence-based prevention (EBP): approach to lung cancer prevention based on cytochrome 1A1 and cytochrome 2E1 polymorphism. Author(s): Oyama T, Matsumoto A, Isse T, Kim YD, Ozaki S, Osaki T, Sugio K, Yasumoto K, Kawamoto T. Source: Anticancer Res. 2003 March-April; 23(2C): 1731-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820449&dopt=Abstract

·

Examining the effects of false positive lung cancer screening results on subsequent lung cancer screening adherence. Author(s): Ford ME, Havstad SL, Flickinger L, Johnson CC. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 January; 12(1): 28-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540500&dopt=Abstract

·

Expression of aphidicolin-induced fragile sites and their relationship between genetic susceptibility in breast cancer, ovarian cancer, and non-small-cell lung cancer patients. Author(s): Dhillon VS, Husain SA, Ray GN. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 2003; Suppl 1: 35-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616595&dopt=Abstract

·

Expression of apoptosis-related proteins and morphological changes in a rat tumor model of human small cell lung cancer prior to and after treatment with radiotherapy, carboplatin, or combined treatment. Author(s): Fokkema E, De Vries EG, Groen HJ, Meijer C, Timens W. Source: Virchows Archiv : an International Journal of Pathology. 2003 April; 442(4): 34955. Epub 2003 February 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715170&dopt=Abstract

·

Expression of constitutively activated EGFRvIII in non-small cell lung cancer. Author(s): Okamoto I, Kenyon LC, Emlet DR, Mori T, Sasaki J, Hirosako S, Ichikawa Y, Kishi H, Godwin AK, Yoshioka M, Suga M, Matsumoto M, Wong AJ. Source: Cancer Science. 2003 January; 94(1): 50-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708474&dopt=Abstract

·

Expression of endoplasmic reticulum molecular chaperon GRP94 in human lung cancer tissues and its clinical significance. Author(s): Wang Q, An L, Chen Y, Yue S. Source: Chin Med J (Engl). 2002 November; 115(11): 1615-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609072&dopt=Abstract

Studies

93

·

Expression of surface protein receptors in lung cancer. Author(s): Esposito V, Groeger AM, De Luca L, Di Marino M, Santini D, Marchei P, Baldi F, Wolner E, Baldi A. Source: Anticancer Res. 2002 November-December; 22(6C): 4039-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553029&dopt=Abstract

·

Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer. Author(s): Funakoshi T, Tachibana I, Hoshida Y, Kimura H, Takeda Y, Kijima T, Nishino K, Goto H, Yoneda T, Kumagai T, Osaki T, Hayashi S, Aozasa K, Kawase I. Source: Oncogene. 2003 February 6; 22(5): 674-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569360&dopt=Abstract

·

Expression, proliferation activity and clinical significance of cathepsin B and cathepsin L in operated lung cancer. Author(s): Kayser K, Richter N, Hufnagl P, Kayser G, Kos J, Werle B. Source: Anticancer Res. 2003 May-June; 23(3C): 2767-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926111&dopt=Abstract

·

Extension of the “hygiene hypothesis” to the association of occupational endotoxin exposure with lower lung cancer risk. Author(s): Lange JH, Rylander R, Fedeli U, Mastrangelo G. Source: The Journal of Allergy and Clinical Immunology. 2003 July; 112(1): 219-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847509&dopt=Abstract

·

Extracts of lung cancer cells reveal antitumour antibodies in sera of patients with lung cancer. Author(s): Bazhin AV, Savchenko MS, Shifrina ON, Chikina SY, Goncharskaia, Jaques G, Chuchalin AG, Philippov PP. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 February; 21(2): 342-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608451&dopt=Abstract

·

Factors influencing the use of thoracic radiotherapy in lung cancer--an analysis of the 1995 Scottish lung cancer audit. Author(s): Erridge SC, Thomson CS, Davidson J, Jones RD, Price A; Scottish Cancer Trials Lung Group and The Scottish Cancer Therapy Network. Source: Clin Oncol (R Coll Radiol). 2002 June; 14(3): 219-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109826&dopt=Abstract

94 Lung Cancer

·

Failure of T stage to predict survival in patients with non-small-cell lung cancer treated by radiotherapy with or without concomitant chemotherapy. Author(s): Ball D, Smith J, Wirth A, Mac Manus M. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 November 15; 54(4): 1007-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419426&dopt=Abstract

·

Failure to diagnose lung cancer: anatomy of a malpractice trial. Author(s): Berlin L. Source: Ajr. American Journal of Roentgenology. 2003 January; 180(1): 37-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490474&dopt=Abstract

·

Farnesol for aerosol inhalation: nebulization and activity against human lung cancer cells. Author(s): Wang Z, Chen HT, Roa W, Finlay W. Source: Journal of Pharmacy & Pharmaceutical Sciences [electronic Resource] : a Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques. 2003 January-April; 6(1): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753732&dopt=Abstract

·

FDA announces fast track approval of new drug for lung cancer. Author(s): Dyer O. Source: Bmj (Clinical Research Ed.). 2003 May 10; 326(7397): 1004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742913&dopt=Abstract

·

FDG-PET imaging in lung cancer: how sensitive is it for bronchioloalveolar carcinoma? Author(s): Yap CS, Schiepers C, Fishbein MC, Phelps ME, Czernin J. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 September; 29(9): 1166-73. Epub 2002 June 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192561&dopt=Abstract

·

FDG-PET-detected extracranial metastasis in patients with non-small cell lung cancer undergoing staging for surgery or radical radiotherapy--survival correlates with metastatic disease burden. Author(s): MacManus MR, Hicks R, Fisher R, Rischin D, Michael M, Wirth A, Ball DL. Source: Acta Oncologica (Stockholm, Sweden). 2003; 42(1): 48-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665331&dopt=Abstract

Studies

95

·

Feasibility of induction chemotherapy using bronchial arterial infusion for locally advanced non-small cell lung cancer: a pilot study. Author(s): Osaki T, Oyama T, Takenoyama M, Taga S, So T, Yamashita T, Nakata S, Nakanishi R, Yasumoto K. Source: Surgery Today. 2002; 32(9): 772-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203053&dopt=Abstract

·

Fluorescent microsatellite analysis in bronchial lavage as a potential diagnostic tool for lung cancer. Author(s): Field JK, Liloglou T. Source: Methods in Molecular Medicine. 2003; 75: 251-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407745&dopt=Abstract

·

Focus on lung cancer. Author(s): Minna JD, Roth JA, Gazdar AF. Source: Cancer Cell. 2002 February; 1(1): 49-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086887&dopt=Abstract

·

Follow-up and surveillance of the lung cancer patient following curative-intent therapy. Author(s): Colice GL, Rubins J, Unger M; American College of Chest Physicians. Source: Chest. 2003 January; 123(1 Suppl): 272S-283S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527585&dopt=Abstract

·

Food groups and risk of lung cancer in Uruguay. Author(s): De Stefani E, Brennan P, Ronco A, Fierro L, Correa P, Boffetta P, DeneoPellegrini H, Barrios E. Source: Lung Cancer (Amsterdam, Netherlands). 2002 October; 38(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367786&dopt=Abstract

·

Fractional allele loss is a valuable marker for human lung cancer detection in sputum. Author(s): Arvanitis DA, Papadakis E, Zafiropoulos A, Spandidos DA. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 55-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660007&dopt=Abstract

·

Fractionated irradiation of H69 small-cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2, and topoisomerase IIalpha expression. Author(s): Henness S, Davey MW, Harvie RM, Davey RA. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 November 1; 54(3): 895-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377343&dopt=Abstract

96 Lung Cancer

·

Fragile histidine triad protein expression in nonsmall cell lung cancer and correlation with Ki-67 and with p53. Author(s): Mascaux C, Martin B, Verdebout JM, Meert AP, Ninane V, Sculier JP. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 May; 21(5): 753-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765416&dopt=Abstract

·

Frequent hypermethylation of the 5' CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer. Author(s): Corn PG, Summers MK, Fogt F, Virmani AK, Gazdar AF, Halazonetis TD, ElDeiry WS. Source: Carcinogenesis. 2003 January; 24(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538348&dopt=Abstract

·

From CHART to CHARTWEL in non-small cell lung cancer: clinical radiobiological modelling of the expected change in outcome. Author(s): Bentzen SM, Saunders MI, Dische S. Source: Clin Oncol (R Coll Radiol). 2002 October; 14(5): 372-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555876&dopt=Abstract

·

From clinical and pathologic to molecular staging of lung cancer. Author(s): Massion PP, Carbone DP. Source: American Journal of Respiratory and Critical Care Medicine. 2003 June 15; 167(12): 1587-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796051&dopt=Abstract

·

Functional cloning of a tumor suppressor gene, TSLC1, in human non-small cell lung cancer. Author(s): Murakami Y. Source: Oncogene. 2002 October 7; 21(45): 6936-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362275&dopt=Abstract

·

Functional genomics in lung cancer and biomarker detection. Author(s): Rom WN, Tchou-Wong KM. Source: American Journal of Respiratory Cell and Molecular Biology. 2003 August; 29(2): 153-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878582&dopt=Abstract

Studies

97

·

Fuzzy logic-based tumor marker profiles including a new marker tumor M2-PK improved sensitivity to the detection of progression in lung cancer patients. Author(s): Schneider J, Peltri G, Bitterlich N, Neu K, Velcovsky HG, Morr H, Katz N, Eigenbrodt E. Source: Anticancer Res. 2003 March-April; 23(2A): 899-906. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820320&dopt=Abstract

·

Fuzzy logic-based tumor-marker profiles improved sensitivity in the diagnosis of lung cancer. Author(s): Schneider J, Bitterlich N, Velcovsky HG, Morr H, Katz N, Eigenbrodt E. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2002 June; 7(3): 145-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109515&dopt=Abstract

·

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

·

Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC. Author(s): Cappuzzo F, Gregorc V, Rossi E, Cancellieri A, Magrini E, Paties CT, Ceresoli G, Lombardo L, Bartolini S, Calandri C, de Rosa M, Villa E, Crino L. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 July 15; 21(14): 2658-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860941&dopt=Abstract

·

Gefitinib in recurrent non-small-cell lung cancer: an IDEAL trial? Author(s): Johnson DH, Arteaga CL. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 15; 21(12): 2227-9. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748243&dopt=Abstract

·

Gelatinolytic activity of matrix metalloproteinase in lung cancer studied using film in situ zymography stamp method. Author(s): Kaji M, Moriyama S, Sasaki H, Saitoh Y, Kiriyama M, Fukai I, Yamakawa Y, Mitsui A, Toyama T, Nemori R, Fujii Y. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 125-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581563&dopt=Abstract

98 Lung Cancer

·

Gelsolin suppresses tumorigenicity through inhibiting PKC activation in a human lung cancer cell line, PC10. Author(s): Sagawa N, Fujita H, Banno Y, Nozawa Y, Katoh H, Kuzumaki N. Source: British Journal of Cancer. 2003 February 24; 88(4): 606-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592377&dopt=Abstract

·

Gemcitabine (Gemzar)-based induction chemotherapy in non-small-cell lung cancer. Author(s): Scagliotti GV, Novello S. Source: Lung Cancer (Amsterdam, Netherlands). 2002 November; 38 Suppl 2: S13-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431824&dopt=Abstract

·

Gemcitabine and carboplatin in patients with locally advanced or metastatic nonsmall cell lung cancer: a prospective phase II study. Author(s): Kortsik C, Albrecht P, Elmer A. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660012&dopt=Abstract

·

Gemcitabine and cisplatin as induction chemotherapy for patients with unresectable Stage IIIA-bulky N2 and Stage IIIB nonsmall cell lung carcinoma: an Italian Lung Cancer Project Observational Study. Author(s): Cappuzzo F, Selvaggi G, Gregorc V, Mazzoni F, Betti M, Rita Migliorino M, Novello S, Maestri A, De Marinis F, Darwish S, De Angelis V, Nelli F, Bartolini S, Scagliotti GV, Tonato M, Crino L. Source: Cancer. 2003 July 1; 98(1): 128-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833465&dopt=Abstract

·

Gemcitabine as single agent chemotherapy in elderly patients with stages III-IV nonsmall cell lung cancer (NSCLC): a phase II study. Author(s): Bianco V, Rozzi A, Tonini G, Santini D, Magnolfi E, Vincenzi B, D'Angelillo R, Marchei P. Source: Anticancer Res. 2002 September-October; 22(5): 3053-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530041&dopt=Abstract

·

Gemcitabine in the treatment of advanced non-small cell lung cancer: report of one case. Author(s): Liu AH, Wang XS, Zhou Y, Duan EY, Wu YX. Source: Di Yi June Yi Da Xue Xue Bao. 2002 January; 22(1): 94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390863&dopt=Abstract

Studies

99

·

Gemcitabine plus cisplatin in the treatment of patients with advanced non-small cell lung cancer: a phase II study. Author(s): Bretti S, Manzin E, Loddo C, Berruti A, Bombaci S, Vellani G, Celano A. Source: Anticancer Res. 2002 September-October; 22(5): 3039-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530039&dopt=Abstract

·

Gemcitabine/carboplatin in advanced non-small cell lung cancer. Author(s): Zatloukal P, Petruzelka L. Source: Lung Cancer (Amsterdam, Netherlands). 2002 November; 38 Suppl 2: S33-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431827&dopt=Abstract

·

Gemzar platinum combinations: phase III trials in non-small cell lung cancer. Author(s): Crino L, Calandri C. Source: Lung Cancer (Amsterdam, Netherlands). 2002 November; 38 Suppl 2: S9-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431823&dopt=Abstract

·

Gene and peptide analyses of newly defined lung cancer antigens recognized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes. Author(s): Yamada A, Kawano K, Koga M, Takamori S, Nakagawa M, Itoh K. Source: Cancer Research. 2003 June 1; 63(11): 2829-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782588&dopt=Abstract

·

Gene therapy for lung cancer. An introduction. Author(s): Haura EB, Sotomayor E, Antonia SJ. Source: Methods in Molecular Medicine. 2003; 75: 529-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407762&dopt=Abstract

·

Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk. Author(s): Ratnasinghe DL, Yao SX, Forman M, Qiao YL, Andersen MR, Giffen CA, Erozan Y, Tockman MS, Taylor PR. Source: Anticancer Res. 2003 January-February; 23(1B): 627-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680158&dopt=Abstract

·

Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer. Author(s): Osada H, Takahashi T. Source: Oncogene. 2002 October 21; 21(48): 7421-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379883&dopt=Abstract

100 Lung Cancer

·

Genetic alterations responsible for metastatic phenotypes of lung cancer cells. Author(s): Yokota J, Nishioka M, Tani M, Kohno T. Source: Clinical & Experimental Metastasis. 2003; 20(3): 189-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741677&dopt=Abstract

·

Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers. Author(s): Ariyoshi N, Miyamoto M, Umetsu Y, Kunitoh H, Dosaka-Akita H, Sawamura Y, Yokota J, Nemoto N, Sato K, Kamataki T. 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): 890-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223434&dopt=Abstract

·

Genetic polymorphisms and lung cancer susceptibility: a review. Author(s): Kiyohara C, Otsu A, Shirakawa T, Fukuda S, Hopkin JM. Source: Lung Cancer (Amsterdam, Netherlands). 2002 September; 37(3): 241-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234692&dopt=Abstract

·

Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility. Author(s): Stucker I, Hirvonen A, de Waziers I, Cabelguenne A, Mitrunen K, Cenee S, Koum-Besson E, Hemon D, Beaune P, Loriot MA. Source: Carcinogenesis. 2002 September; 23(9): 1475-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189190&dopt=Abstract

·

Genetic susceptibility to lung cancer: implications for smoking cessation. Author(s): Houfek JF, Atwood JR. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 2003 February; 12(1): 45-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619599&dopt=Abstract

·

Genetic testing for lung cancer risk: if physicians can do it, should they? Author(s): Marcy TW, Stefanek M, Thompson KM. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2002 December; 17(12): 946-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472931&dopt=Abstract

·

Geographical inequalities in lung cancer management and survival in South East England: evidence of variation in access to oncology services? Author(s): Jack RH, Gulliford MC, Ferguson J, Moller H. Source: British Journal of Cancer. 2003 April 7; 88(7): 1025-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671698&dopt=Abstract

Studies 101

·

Glass-based radon-exposure assessment and lung cancer risk. Author(s): Lagarde F, Falk R, Almren K, Nyberg F, Svensson H, Pershagen G. Source: Journal of Exposure Analysis and Environmental Epidemiology. 2002 September; 12(5): 344-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198583&dopt=Abstract

·

Glucocorticoids inhibit lung cancer cell growth through both the extracellular signalrelated kinase pathway and cell cycle regulators. Author(s): Greenberg AK, Hu J, Basu S, Hay J, Reibman J, Yie TA, Tchou-Wong KM, Rom WN, Lee TC. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 September; 27(3): 320-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12204894&dopt=Abstract

·

Glutathione S-transferase M1 polymorphism and the risk of lung cancer. Author(s): Mohr LC, Rodgers JK, Silvestri GA. Source: Anticancer Res. 2003 May-June; 23(3A): 2111-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894585&dopt=Abstract

·

Growth and molecular profile of lung cancer cells expressing ectopic LKB1: downregulation of the phosphatidylinositol 3'-phosphate kinase/PTEN pathway. Author(s): Jimenez AI, Fernandez P, Dominguez O, Dopazo A, Sanchez-Cespedes M. Source: Cancer Research. 2003 March 15; 63(6): 1382-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649203&dopt=Abstract

·

GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk. Author(s): Lewis SJ, Cherry NM, Niven RM, Barber PV, Povey AC. Source: Cancer Letters. 2002 June 28; 180(2): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175548&dopt=Abstract

·

Guidelines for the use of spiral computed tomography in screening for lung cancer. Author(s): Henschke CI, Yankelevitz DF, McCauley DI, Libby DM, Pasmantier MW, Smith JP. Source: Eur Respir J Suppl. 2003 January; 39: 45S-51S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572701&dopt=Abstract

·

Guidelines on treatment of stage IIIB non-small cell lung cancer. Author(s): Jett JR, Scott WJ, Rivera MP, Sause WT; American College of Chest Physicians. Source: Chest. 2003 January; 123(1 Suppl): 221S-225S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527581&dopt=Abstract

102 Lung Cancer

·

GVAX (GMCSF gene modified tumor vaccine) in advanced stage non small cell lung cancer. Author(s): Nemunaitis J. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2003 August 28; 91(1-2): 225-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932654&dopt=Abstract

·

Has lung cancer in the elderly different characteristics at presentation? Author(s): Montella M, Gridelli C, Crispo A, Scognamiglio F, Ruffolo P, Gatani T, Boccia V, Maione P, Fabbrocini G. Source: Oncol Rep. 2002 September-October; 9(5): 1093-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168079&dopt=Abstract

·

Health perceptions and risk behaviors of lung cancer survivors. Author(s): Evangelista LS, Sarna L, Brecht ML, Padilla G, Chen J. Source: Heart & Lung : the Journal of Critical Care. 2003 March-April; 32(2): 131-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734536&dopt=Abstract

·

Healthcare outcomes: gemcitabine cost-effectiveness in the treatment of non-small cell lung cancer. Author(s): Szczepura A. Source: Lung Cancer (Amsterdam, Netherlands). 2002 November; 38 Suppl 2: S21-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431825&dopt=Abstract

·

Health-related quality of life in non-small-cell lung cancer: methodologic issues in randomized controlled trials. Author(s): Bottomley A, Efficace F, Thomas R, Vanvoorden V, Ahmedzai SH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 1; 21(15): 2982-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885819&dopt=Abstract

·

Hedgehog signaling: progenitor phenotype in small-cell lung cancer. Author(s): Watkins DN, Berman DM, Baylin SB. Source: Cell Cycle (Georgetown, Tex.). 2003 May-June; 2(3): 196-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734424&dopt=Abstract

·

Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Author(s): Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Source: Nature. 2003 March 20; 422(6929): 313-7. Epub 2003 Mar 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629553&dopt=Abstract

Studies 103

·

Helical computed tomography for lung cancer screening. Author(s): Elwood M, Campbell DA, de Campo MP. Source: The Medical Journal of Australia. 2003 August 4; 179(3): 125-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885278&dopt=Abstract

·

Hematogenous dissemination of lung cancer cells during surgery: quantitative detection by flow cytometry and prognostic significance. Author(s): Dong Q, Huang J, Zhou Y, Li L, Bao G, Feng J, Sha H. Source: Lung Cancer (Amsterdam, Netherlands). 2002 September; 37(3): 293-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234699&dopt=Abstract

·

Hemoptysis as an unusual presenting symptom of invasion of a descending thoracic aortic aneurysmal dissection by lung cancer. Author(s): Tsui P, Lee JH, MacLennan G, Capdeville M. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 2002; 29(2): 136-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075873&dopt=Abstract

·

High dose rate endobronchial brachytherapy effectively palliates symptoms due to inoperable lung cancer. Author(s): Celebioglu B, Gurkan OU, Erdogan S, Savas I, Kose K, Kurtman C, Gonullu U. Source: Japanese Journal of Clinical Oncology. 2002 November; 32(11): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499415&dopt=Abstract

·

High pretreatment serum concentration of basic fibroblast growth factor is a predictor of poor prognosis in small cell lung cancer. Author(s): Ruotsalainen T, Joensuu H, Mattson K, Salven P. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1492-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433733&dopt=Abstract

·

High-dose chemotherapy in small cell lung cancer. Author(s): Pasini F, Pelosi G, De Manzoni G, Rosti G. Source: Tumori. 2002 May-June; 88(3): 179-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195754&dopt=Abstract

·

High-dose chemotherapy in small-cell lung cancer. Author(s): Pasini F, Durante E, De Manzoni D, Rosti G, Pelosi G. Source: Anticancer Res. 2002 November-December; 22(6B): 3465-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552940&dopt=Abstract

104 Lung Cancer

·

High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial. Author(s): Rosenman JG, Halle JS, Socinski MA, Deschesne K, Moore DT, Johnson H, Fraser R, Morris DE. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 October 1; 54(2): 348-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243807&dopt=Abstract

·

HIV-related lung cancer in the era of highly active antiretroviral therapy. Author(s): Bower M, Powles T, Nelson M, Shah P, Cox S, Mandelia S, Gazzard B. Source: Aids (London, England). 2003 February 14; 17(3): 371-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556691&dopt=Abstract

·

Hormonal factors and risk of lung cancer among women? Author(s): Kreuzer M, Gerken M, Heinrich J, Kreienbrock L, Wichmann HE. Source: International Journal of Epidemiology. 2003 April; 32(2): 263-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714547&dopt=Abstract

·

How quality of life data contribute to our understanding of cancer patients' experiences? A study of patients with lung cancer. Author(s): Montazeri A, Milroy R, Hole D, McEwen J, Gillis CR. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2003 March; 12(2): 157-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639062&dopt=Abstract

·

How to optimize staging in early non-small cell lung cancer. Author(s): Jett JR. Source: Lung Cancer (Amsterdam, Netherlands). 2002 October; 38(1): S13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367808&dopt=Abstract

·

HPV infections and lung cancer. Author(s): Syrjanen KJ. Source: Journal of Clinical Pathology. 2002 December; 55(12): 885-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461047&dopt=Abstract

·

hTERT expression is a prognostic factor of survival in patients with stage I non-small cell lung cancer. Author(s): Wang L, Soria JC, Kemp BL, Liu DD, Mao L, Khuri FR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 September; 8(9): 2883-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231532&dopt=Abstract

Studies 105

·

Hypermethylation of RASSF1A promoter is associated with the age at starting smoking and a poor prognosis in primary non-small cell lung cancer. Author(s): Kim DH, Kim JS, Ji YI, Shim YM, Kim H, Han J, Park J. Source: Cancer Research. 2003 July 1; 63(13): 3743-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839968&dopt=Abstract

·

Hypoxia enhances the expression of plasminogen activator inhibitor-1 in human lung cancer cells, EBC-1. Author(s): Kimura D, Imaizumi T, Tamo W, Sakai T, Ito K, Hatanaka R, Yoshida H, Tsushima T, Satoh K, Fukuda I. Source: The Tohoku Journal of Experimental Medicine. 2002 April; 196(4): 259-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086154&dopt=Abstract

·

Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer. Author(s): Chen Y, Petersen S, Pacyna-Gengelbach M, Pietas A, Petersen I. Source: Oncology. 2003; 64(4): 450-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759545&dopt=Abstract

·

Identification of nuclear proteins of small cell lung cancer cell line H82: An improved procedure for the analysis of silver-stained proteins. Author(s): Gonzalez LJ, Castellanos-Serra L, Badock V, Diaz M, Moro A, Perea S, Santos A, Paz-Lago D, Otto A, Muller EC, Kostka S, Wittmann-Liebold B, Padron G. Source: Electrophoresis. 2003 January; 24(1-2): 237-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652596&dopt=Abstract

·

Identification of TDE2 gene and its expression in non-small cell lung cancer. Author(s): Player A, Gillespie J, Fujii T, Fukuoka J, Dracheva T, Meerzaman D, Hong KM, Curran J, Attoh G, Travis W, Jen J. Source: International Journal of Cancer. Journal International Du Cancer. 2003 November 1; 107(2): 238-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949800&dopt=Abstract

·

Identification of tumor suppressor loci on the long arm of chromosome 15 in primary small cell lung cancer. Author(s): Kee HJ, Shin JH, Chang J, Chung KY, Shin DH, Kim YS, Kim SK, Kim SK. Source: Yonsei Medical Journal. 2003 February; 44(1): 65-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619177&dopt=Abstract

106 Lung Cancer

·

Identifying patients at risk of early postoperative recurrence of lung cancer: a new use of the old CEA test. Author(s): Buccheri G, Ferrigno D. Source: The Annals of Thoracic Surgery. 2003 March; 75(3): 973-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645726&dopt=Abstract

·

Immune cells in bronchoalveolar lavage in peripheral lung cancer--analysis of 140 cases. Author(s): Domagala-Kulawik J, Guzman J, Costabel U. Source: Respiration; International Review of Thoracic Diseases. 2003 January-February; 70(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584390&dopt=Abstract

·

Impact of treatment interruptions due to toxicity on outcome of patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. Author(s): Jeremic B, Shibamoto Y, Milicic B, Dagovic A, Nikolic N, Aleksandrovic J, Acimovic L, Milisavljevic S. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 317-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781431&dopt=Abstract

·

Impact of ZD1839 on non-small cell lung cancer-related symptoms as measured by the functional assessment of cancer therapy-lung scale. Author(s): Cella D. Source: Seminars in Oncology. 2003 February; 30(1 Suppl 1): 39-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644983&dopt=Abstract

·

Improving surgical resection rates in lung cancer without a two stop service. Author(s): Bowen EF, Anderson JR, Roddie ME. Source: Thorax. 2003 April; 58(4): 368. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668811&dopt=Abstract

·

In regard to Rosenman et al., high-dose conformal radiotherapy for treatment of stage III A/B non-small-cell lung cancer: technical issues and results of a phase I/II trial. IJROBP 2002;54:348-356. Author(s): Senan S, Lagerwaard FJ. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 April 1; 55(5): 1458-9; Author Reply 1459-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654460&dopt=Abstract

Studies 107

·

In regard to Tsujino et al.: predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. IJROBP 2003;55:110-115. Author(s): Seppenwoolde Y, De Jaeger K, Lebesque JV. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 July 15; 56(4): 1208-9; Author Reply 1209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829167&dopt=Abstract

·

In vitro effects of combinations of cis-amminedichloro (2-methylpyridine) platinum (II) (ZD0473) with other novel anticancer drugs on the growth of SBC-3, a human small cell lung cancer cell line. Author(s): Kanzawa F, Akiyama Y, Saijo N, Nishio K. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 325-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781432&dopt=Abstract

·

In vivo transglutaminase type 1 expression in normal lung, preinvasive bronchial lesions, and lung cancer. Author(s): Martinet N, Bonnard L, Regnault V, Picard E, Burke L, Siat J, Grosdidier G, Martinet Y, Vignaud JM. Source: American Journal of Respiratory Cell and Molecular Biology. 2003 April; 28(4): 428-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654631&dopt=Abstract

·

Increased expression of the LGALS3 (galectin 3) gene in human non-small-cell lung cancer. Author(s): Yoshimura A, Gemma A, Hosoya Y, Komaki E, Hosomi Y, Okano T, Takenaka K, Matuda K, Seike M, Uematsu K, Hibino S, Shibuya M, Yamada T, Hirohashi S, Kudoh S. Source: Genes, Chromosomes & Cancer. 2003 June; 37(2): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696064&dopt=Abstract

·

Independent predictive value of the overall number of metastatic N1 and N2 stations in lung cancer. Author(s): Ueda K, Kaneda Y, Sakano H, Tanaka T, Hayashi M, Li TS, Hamano K. Source: Jpn J Thorac Cardiovasc Surg. 2003 July; 51(7): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892460&dopt=Abstract

·

Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer. Author(s): Pelosi G, Pastorino U, Pasini F, Maissoneuve P, Fraggetta F, Iannucci A, Sonzogni A, De Manzoni G, Terzi A, Durante E, Bresaola E, Pezzella F, Viale G. Source: British Journal of Cancer. 2003 February 24; 88(4): 537-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592367&dopt=Abstract

108 Lung Cancer

·

Individually different “weights” of quality of life assessment in patients with advanced nonsmall-cell lung cancer. Author(s): Morita S, Ohashi Y, Kobayashi K, Matsumoto T, Eguchi K, Shibuya M, Yamaji Y, Fukuoka M, Nagao K, Niitani H; West and East CPT-11 Lung Cancer Study Groups. Source: Journal of Clinical Epidemiology. 2003 August; 56(8): 744-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954466&dopt=Abstract

·

Induction chemotherapy in early-stage non-small-cell lung cancer. Author(s): Pisters KM. Source: Current Oncology Reports. 2003 July; 5(4): 307-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781072&dopt=Abstract

·

Induction of apoptosis by combined treatment with differentiation-inducing agents and interferon-alpha in human lung cancer cells. Author(s): Yamamoto-Yamaguchi Y, Okabe-Kado J, Kasukabe T, Honma Y. Source: Anticancer Res. 2003 May-June; 23(3B): 2537-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894538&dopt=Abstract

·

Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer. Author(s): Sridhar SS, Seymour L, Shepherd FA. Source: The Lancet Oncology. 2003 July; 4(7): 397-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850190&dopt=Abstract

·

Intentional limited pulmonary resection for peripheral T1 N0 M0 small-sized lung cancer. Author(s): Koike T, Yamato Y, Yoshiya K, Shimoyama T, Suzuki R. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 April; 125(4): 924-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698157&dopt=Abstract

·

Interleukin-10 expression is closely correlated with the expression of granulocytemacrophage colony-stimulating factor in non-small cell lung cancer. Author(s): Kamiya T, Hatanaka H, Abe Y, Kijima H, Yamazaki H, Ohnishi Y, Inoue H, Ueyama Y, Osamura Y, Nakamura M. Source: Anticancer Res. 2003 May-June; 23(3C): 2909-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926133&dopt=Abstract

·

Intrathecal gemcitabine chemotherapy for non-small cell lung cancer patients with meningeal carcinomatosis--a case report. Author(s): Chen YM, Chen MC, Tsai CM, Perng RP. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 99-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660014&dopt=Abstract

Studies 109

·

Intrathoracic staging in non small cell lung cancer: re-do mediastinoscopy revisited. Author(s): Cesario A, Margaritora S, Porziella V, Granone P, Trodella L, D'Angelillo RM. Source: Lung Cancer (Amsterdam, Netherlands). 2003 May; 40(2): 227-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711126&dopt=Abstract

·

Investigation of anticancer mechanism of thiadiazole-based compound in human non-small cell lung cancer A549 cells. Author(s): Chou JY, Lai SY, Pan SL, Jow GM, Chern JW, Guh JH. Source: Biochemical Pharmacology. 2003 July 1; 66(1): 115-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818371&dopt=Abstract

·

JAMA patient page. Lung cancer. Author(s): Parmet S, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2003 January 15; 289(3): 380. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532974&dopt=Abstract

·

Joint action of smoking and asbestos exposure on lung cancer. Author(s): Liddell FD. Source: Occupational and Environmental Medicine. 2002 July; 59(7): 494-5; Author Reply 495-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107302&dopt=Abstract

·

Joint effects of radiation and smoking on lung cancer risk among atomic bomb survivors. Author(s): Pierce DA, Sharp GB, Mabuchi K. Source: Radiation Research. 2003 April; 159(4): 511-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643796&dopt=Abstract

·

Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. Author(s): Nguyen TT, Tran E, Ong CK, Lee SK, Do PT, Huynh TT, Nguyen TH, Lee JJ, Tan Y, Ong CS, Huynh H. Source: Journal of Cellular Physiology. 2003 October; 197(1): 110-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942547&dopt=Abstract

·

Ki-67 expression and prognosis for smokers with resected stage I non-small cell lung cancer. Author(s): Haga Y, Hiroshima K, Iyoda A, Shibuya K, Shimamura F, Iizasa T, Fujisawa T, Ohwada H. Source: The Annals of Thoracic Surgery. 2003 June; 75(6): 1727-32; Discussion 1732-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822607&dopt=Abstract

110 Lung Cancer

·

L523S, an RNA-binding protein as a potential therapeutic target for lung cancer. Author(s): Wang T, Fan L, Watanabe Y, McNeill PD, Moulton GG, Bangur C, Fanger GR, Okada M, Inoue Y, Persing DH, Reed SG. Source: British Journal of Cancer. 2003 March 24; 88(6): 887-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644826&dopt=Abstract

·

Lack of evidence for a role of Epstein-Barr virus in the increase of lung cancer in idiopathic pulmonary fibrosis. Author(s): Hayakawa H, Shirai M, Uchiyama H, Imokawa S, Suda T, Chida K, Muro H. Source: Respiratory Medicine. 2003 March; 97(3): 281-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645836&dopt=Abstract

·

Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Author(s): Koukourakis MI, Giatromanolaki A, Sivridis E, Bougioukas G, Didilis V, Gatter KC, Harris AL; Tumour and Angiogenesis Research Group. Source: British Journal of Cancer. 2003 September 1; 89(5): 877-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942121&dopt=Abstract

·

Liver metastases from lung cancer: is surgical resection justified? Author(s): Di Carlo I, Grasso G, Patane' D, Russello D, Latteri F. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 291-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842567&dopt=Abstract

·

Liver metastasis at the time of initial diagnosis of lung cancer. Author(s): Kagohashi K, Satoh H, Ishikawa H, Ohtsuka M, Sekizawa K. Source: Medical Oncology (Northwood, London, England). 2003; 20(1): 25-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665681&dopt=Abstract

·

Long-term changes in pulmonary function tests after definitive radiotherapy for lung cancer. Author(s): Miller KL, Zhou SM, Barrier RC Jr, Shafman T, Folz RJ, Clough RW, Marks LB. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 July 1; 56(3): 611-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788165&dopt=Abstract

·

Loss of heterozygosity on the long arm of chromosome 21 in non-small cell lung cancer. Author(s): Lee EB, Park TI, Park SH, Park JY. Source: The Annals of Thoracic Surgery. 2003 May; 75(5): 1597-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735585&dopt=Abstract

Studies 111

·

Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. Author(s): Chen Y, Knosel T, Kristiansen G, Pietas A, Garber ME, Matsuhashi S, Ozaki I, Petersen I. Source: The Journal of Pathology. 2003 August; 200(5): 640-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898601&dopt=Abstract

·

Low lung function and incident lung cancer in the United States: data From the First National Health and Nutrition Examination Survey follow-up. Author(s): Mannino DM, Aguayo SM, Petty TL, Redd SC. Source: Archives of Internal Medicine. 2003 June 23; 163(12): 1475-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824098&dopt=Abstract

·

Lung cancer * 8: Management of malignant mesothelioma. Author(s): Parker C, Neville E. Source: Thorax. 2003 September; 58(9): 809-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947146&dopt=Abstract

·

Lung cancer 5: state of the art radiotherapy for lung cancer. Author(s): Price A. Source: Thorax. 2003 May; 58(5): 447-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728171&dopt=Abstract

·

Lung cancer 7: management of lung cancer in elderly patients. Author(s): Booton R, Jones M, Thatcher N. Source: Thorax. 2003 August; 58(8): 711-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885992&dopt=Abstract

·

Lung cancer and related risk factors: an update of the literature. Author(s): Ruano-Ravina A, Figueiras A, Barros-Dios JM. Source: Public Health. 2003 May; 117(3): 149-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825464&dopt=Abstract

·

Lung cancer and Rosai-Dorfman's disease. A clinicopathological study. Author(s): Lutterbach J, Henne K, Pagenstecher A, Bohm J. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 2003 July; 179(7): 486-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835886&dopt=Abstract

112 Lung Cancer

·

Lung cancer associated with diffuse pulmonary fibrosis: CT-pathologic correlation. Author(s): Sakai S, Ono M, Nishio T, Kawarada Y, Nagashima A, Toyoshima S. Source: Journal of Thoracic Imaging. 2003 April; 18(2): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700479&dopt=Abstract

·

Lung cancer associated with sarcoidosis. Author(s): Sato Y, Sasano S, Oyama K, Sakuraba M, Onuki T, Nitta S. Source: Jpn J Thorac Cardiovasc Surg. 2003 January; 51(1): 21-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645151&dopt=Abstract

·

Lung cancer in elderly patients. Author(s): Hey JC. Source: Clinics in Geriatric Medicine. 2003 February; 19(1): 139-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735119&dopt=Abstract

·

Lung cancer in heavy equipment operators and truck drivers with diesel exhaust exposure in the construction industry. Author(s): Jarvholm B, Silverman D. Source: Occupational and Environmental Medicine. 2003 July; 60(7): 516-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819286&dopt=Abstract

·

Lung cancer incidence among Norwegian nickel-refinery workers 1953-2000. Author(s): Grimsrud TK, Berge SR, Martinsen JI, Andersen A. Source: Journal of Environmental Monitoring : Jem. 2003 April; 5(2): 190-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729252&dopt=Abstract

·

Lung cancer mortality among chromate production workers. Author(s): Luippold RS, Mundt KA, Austin RP, Liebig E, Panko J, Crump C, Crump K, Proctor D. Source: Occupational and Environmental Medicine. 2003 June; 60(6): 451-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771398&dopt=Abstract

·

Lung cancer patterns of care in south western Sydney, Australia. Author(s): Vinod SK, Delaney GP, Bauman AE, Barton MB. Source: Thorax. 2003 August; 58(8): 690-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885986&dopt=Abstract

·

Lung cancer risk in germline p53 mutation carriers: association between an inherited cancer predisposition, cigarette smoking, and cancer risk. Author(s): Hwang SJ, Cheng LS, Lozano G, Amos CI, Gu X, Strong LC. Source: Human Genetics. 2003 August; 113(3): 238-43. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802680&dopt=Abstract

Studies 113

·

Lung cancer risk in white and black Americans. Author(s): Stellman SD, Chen Y, Muscat JE, Djordjevic MV, Richie JP Jr, Lazarus P, Thompson S, Altorki N, Berwick M, Citron ML, Harlap S, Kaur TB, Neugut AI, Olson S, Travaline JM, Witorsch P, Zhang ZF. Source: Annals of Epidemiology. 2003 April; 13(4): 294-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684197&dopt=Abstract

·

Lung cancer risk in workers exposed to poly(vinyl chloride) dust: a nested casereferent study. Author(s): Mastrangelo G, Fedeli U, Fadda E, Milan G, Turato A, Pavanello S. Source: Occupational and Environmental Medicine. 2003 June; 60(6): 423-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771394&dopt=Abstract

·

Lung cancer screening with low-dose computed tomography. Author(s): Hartman TE, Swensen SJ. Source: Semin Roentgenol. 2003 January; 38(1): 34-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698589&dopt=Abstract

·

Lung cancer screening. Author(s): Truong MT, Munden RF. Source: Current Oncology Reports. 2003 July; 5(4): 309-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781073&dopt=Abstract

·

Lung cancer treatment present and future. Author(s): Cho JK. Source: Hawaii Med J. 2003 March; 62(3): 61-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703177&dopt=Abstract

·

Lung cancer. 6: The case for limited surgical resection in non-small cell lung cancer. Author(s): Sugarbaker DJ. Source: Thorax. 2003 July; 58(7): 639-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832686&dopt=Abstract

·

Lung cancer. 9: Molecular biology of lung cancer: clinical implications. Author(s): Fong KM, Sekido Y, Gazdar AF, Minna JD. Source: Thorax. 2003 October; 58(10): 892-900. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514947&dopt=Abstract

114 Lung Cancer

·

Lung cancer: the importance of seeing a respiratory physician. Author(s): Fergusson RJ, Thomson CS, Brewster DH, Brown PH, Milroy R; Scottish Cancer Trials Lung Group; Scottish Cancer Therapy Network. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 April; 21(4): 606-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762343&dopt=Abstract

·

Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: role in angiogenesis and prognosis. Author(s): White ES, Flaherty KR, Carskadon S, Brant A, Iannettoni MD, Yee J, Orringer MB, Arenberg DA. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 February; 9(2): 853-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576459&dopt=Abstract

·

Major conceptual change required to improve lung cancer: see a respiratory physician. Author(s): Field JK, Brambilla C. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 April; 21(4): 565-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762336&dopt=Abstract

·

MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Author(s): Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, Thomas M, Berdel WE, Serve H, Muller-Tidow C. Source: Oncogene. 2003 September 11; 22(39): 6087-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970751&dopt=Abstract

·

Malignant status at surgical margin of limited-resected non-small cell lung cancer: a crucial finding for predicting local relapse. Author(s): Sawabata N. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 August; 126(2): 610-1; Author Reply 611. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928675&dopt=Abstract

·

Management for chest wall implantation of non-small cell lung cancer after fineneedle aspiration biopsy. Author(s): Kim JH, Kim YT, Lim HK, Kim YH, Sung SW. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 May; 23(5): 828-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754041&dopt=Abstract

Studies 115

·

Management of the irradiated bronchus after lobectomy for lung cancer. Author(s): Greason KL, Miller DL, Clay RP, Deschamps C, Johnson CH, Allen MS, Trastek VF, Pairolero PC. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 180-5; Discussion 185-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842536&dopt=Abstract

·

MDR-1 C3435T genetic polymorphism and tobacco-related lung cancer. Author(s): Sinues B, Fanlo A, Bernal ML, Mayayo E, Bello S, Rubio E, Isla D. Source: Oncology. 2003; 64(2): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566917&dopt=Abstract

·

Measurement of chemoresistance markers in patients with stage III non-small cell lung cancer: a novel approach for patient selection. Author(s): Brooks KR, To K, Joshi MB, Conlon DH, Herndon JE 2nd, D'Amico TA, Harpole DH Jr. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 187-93; Discussion 193. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842538&dopt=Abstract

·

Mechanisms of metastasis as related to receptor tyrosine kinases in small-cell lung cancer. Author(s): Jafri NF, Ma PC, Maulik G, Salgia R. Source: Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer. 2003; 22(3): 14765. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529091&dopt=Abstract

·

Mechanisms of proteasome inhibitor PS-341-induced G(2)-M-phase arrest and apoptosis in human non-small cell lung cancer cell lines. Author(s): Ling YH, Liebes L, Jiang JD, Holland JF, Elliott PJ, Adams J, Muggia FM, Perez-Soler R. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 March; 9(3): 1145-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631620&dopt=Abstract

·

Mediastinoscopy in patients with clinical stage I non-small cell lung cancer. Author(s): Choi YS, Shim YM, Kim J, Kim K. Source: The Annals of Thoracic Surgery. 2003 February; 75(2): 364-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607640&dopt=Abstract

116 Lung Cancer

·

Menstrual and reproductive factors and risk of lung cancer among Chinese women, Eastern Gansu Province, 1994-1998. Author(s): Brenner AV, Wang Z, Kleinerman RA, Lei S, Metayer C, Wang W, Lubin JH. Source: J Epidemiol. 2003 January; 13(1): 22-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587610&dopt=Abstract

·

Menthol cigarettes and risk of lung cancer. Author(s): Brooks DR, Palmer JR, Strom BL, Rosenberg L. Source: American Journal of Epidemiology. 2003 October 1; 158(7): 609-16; Discussion 617-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14507595&dopt=Abstract

·

Metastatic lung cancer in pregnancy. Author(s): Wong CM, Lim KH, Liam CK. Source: Respirology (Carlton, Vic.). 2003 March; 8(1): 107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856752&dopt=Abstract

·

Methylation patterns and K-ras mutations in tumor and paired serum of resected nonsmall-cell lung cancer patients. Author(s): Ramirez JL, Sarries C, de Castro PL, Roig B, Queralt C, Escuin D, de Aguirre I, Sanchez JM, Manzano JL, Margeli M, Sanchez JJ, Astudillo J, Taron M, Rosell R. Source: Cancer Letters. 2003 April 25; 193(2): 207-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706879&dopt=Abstract

·

Minimal alteration of pulmonary function after lobectomy in lung cancer patients with chronic obstructive pulmonary disease. Author(s): Sekine Y, Iwata T, Chiyo M, Yasufuku K, Motohashi S, Yoshida S, Suzuki M, Iizasa T, Saitoh Y, Fujisawa T. Source: The Annals of Thoracic Surgery. 2003 August; 76(2): 356-61; Discussion 362. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902063&dopt=Abstract

·

Mitochondrial DNA mutation correlates with stage progression and prognosis in non-small cell lung cancer. Author(s): Matsuyama W, Nakagawa M, Wakimoto J, Hirotsu Y, Kawabata M, Osame M. Source: Human Mutation. 2003 April; 21(4): 441-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655558&dopt=Abstract

·

Molecular and cellular biology of small cell lung cancer. Author(s): Sattler M, Salgia R. Source: Seminars in Oncology. 2003 February; 30(1): 57-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635090&dopt=Abstract

Studies 117

·

Monocyte-derived microparticles may be a sign of vascular complication in patients with lung cancer. Author(s): Kanazawa S, Nomura S, Kuwana M, Muramatsu M, Yamaguchi K, Fukuhara S. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 145-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581566&dopt=Abstract

·

Mortality due to silico-tuberculosis and lung cancer among 200 whetstone cutters. Author(s): Ogawa S, Imai H, Ikeda M. Source: Ind Health. 2003 July; 41(3): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916753&dopt=Abstract

·

Mortality trend of lung cancer in Japan: 1960-2000. Author(s): Marugame T, Mizuno S. Source: Japanese Journal of Clinical Oncology. 2003 March; 33(3): 148-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710458&dopt=Abstract

·

Multidetector-row CT of lung cancer screening. Author(s): Jacobson FL. Source: Semin Roentgenol. 2003 April; 38(2): 168-75. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854440&dopt=Abstract

·

Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. Author(s): Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Feyereislova A, Dong RP, Baselga J. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 15; 21(12): 2237-46. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748244&dopt=Abstract

·

Multi-slice/helical computed tomography for lung cancer screening. Author(s): Banerjee S. Source: Issues Emerg Health Technol. 2003 June; (48): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812212&dopt=Abstract

·

Mutational analysis of the transforming growth factor beta receptor type I gene in primary non-small cell lung cancer. Author(s): Zhang HT, Fei QY, Chen F, Qi QY, Zou W, Wang JC, Zhang RM, Tao SH, Chen XF, Luo ZW. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 281-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781426&dopt=Abstract

118 Lung Cancer

·

Negative aspects of preoperative delay in early stage non-small cell lung cancer. Author(s): Sortini A, Sortini D, Carrella G. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 August; 126(2): 60910; Author Reply 610. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928674&dopt=Abstract

·

Neoadjuvant and adjuvant therapy of non-small cell lung cancer. Author(s): Rajdev L, Keller SM. Source: Surgical Oncology. 2002 December; 11(4): 243-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450560&dopt=Abstract

·

Neoadjuvant chemotherapy and chemoradiotherapy for non-small cell lung cancer: current status and future prospects. Author(s): Edelman MJ. Source: Expert Opinion on Pharmacotherapy. 2003 June; 4(6): 843-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783581&dopt=Abstract

·

Neoadjuvant chemotherapy with gemcitabine and cisplatin in stage IIIA/B non-small cell lung cancer. Author(s): Van Kooten M, Rosenberg M, Orlando M, Morero J, Vilanova M, Rojas O, Vicente H, Bagnes C, Silva C, Chacon RD. Source: Investigational New Drugs. 2002 November; 20(4): 439-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448663&dopt=Abstract

·

Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients. Author(s): Nakashima T, Huang C, Liu D, Kameyama K, Masuya D, Kobayashi S, Kinoshita M, Yokomise H. Source: British Journal of Cancer. 2003 June 2; 88(11): 1727-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771988&dopt=Abstract

·

Neuroendocrine alterations in lung cancer patients. Author(s): Mazzoccoli G, Carughi S, De Cata A, La Viola M, Giuliani A, Tarquini R, Perfetto F. Source: Neuroendocrinol Lett. 2003 February-April; 24(1-2): 77-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743538&dopt=Abstract

·

Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer. Author(s): Pujol JL, Quantin X, Jacot W, Boher JM, Grenier J, Lamy PJ. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581564&dopt=Abstract

Studies 119

·

New approaches for biomarker discovery in lung cancer. Author(s): Valle RP, Chavany C, Zhukov TA, Jendoubi M. Source: Expert Rev Mol Diagn. 2003 January; 3(1): 55-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528364&dopt=Abstract

·

New approaches in the treatment of non-small cell lung cancer: taxanes in the treatment of NSCLC: pathways to progress. Author(s): Kris MG, Tonato M. Source: Lung Cancer (Amsterdam, Netherlands). 2002 December; 38 Suppl 4: 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480188&dopt=Abstract

·

New model predicts risk of developing lung cancer. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 April 18; 14(8): 9-10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854531&dopt=Abstract

·

New potentials of radiotherapy in non-small cell lung cancer: stereotactic therapy and IMRT. Author(s): Van Houtte P. Source: Current Problems in Cancer. 2003 January-February; 27(1): 60-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569353&dopt=Abstract

·

New prognostic indicator for non-small-cell lung cancer, quantitation of thymidylate synthase by real-time reverse transcription polymerase chain reaction. Author(s): Shintani Y, Ohta M, Hirabayashi H, Tanaka H, Iuchi K, Nakagawa K, Maeda H, Kido T, Miyoshi S, Matsuda H. Source: International Journal of Cancer. Journal International Du Cancer. 2003 May 10; 104(6): 790-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640689&dopt=Abstract

·

New targeted therapies for lung cancer: expectations and reality. Author(s): Bunn PA Jr. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 August 5; 4(3): 12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466755&dopt=Abstract

·

New targets for the treatment of advanced non-small cell lung cancer. Author(s): Massarelli E, Onn A, Zinner R, Khuri FR, Kim ES, Herbst RS. Source: Cancer Chemother Biol Response Modif. 2002; 20: 717-61. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703232&dopt=Abstract

120 Lung Cancer

·

New techniques for early detection of lung cancer. Author(s): Sutedja G. Source: Eur Respir J Suppl. 2003 January; 39: 57S-66S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572703&dopt=Abstract

·

Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer. Author(s): Minna JD. Source: The Journal of Clinical Investigation. 2003 January; 111(1): 31-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511585&dopt=Abstract

·

No association between the p21 codon 31 serine-arginine polymorphism and lung cancer risk. Author(s): Su L, Liu G, Zhou W, Xu LL, Miller DP, Park S, Lynch TJ, Wain JC, Christiani DC. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 February; 12(2): 174-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582031&dopt=Abstract

·

Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Author(s): Toloza EM, Harpole L, McCrory DC. Source: Chest. 2003 January; 123(1 Suppl): 137S-146S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527573&dopt=Abstract

·

Nonradioactive iodide effectively induces apoptosis in genetically modified lung cancer cells. Author(s): Zhang L, Sharma S, Zhu LX, Kogai T, Hershman JM, Brent GA, Dubinett SM, Huang M. Source: Cancer Research. 2003 August 15; 63(16): 5065-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941836&dopt=Abstract

·

Non-small cell lung cancer staging techniques and endoscopic ultrasound: tissue is still the issue. Author(s): LeBlanc JK, Espada R, Ergun G. Source: Chest. 2003 May; 123(5): 1718-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740292&dopt=Abstract

Studies 121

·

Non-small cell lung cancer with chest wall invasion: evolution of surgical treatment and prognosis in the last 3 decades. Author(s): Roviaro G, Varoli F, Grignani F, Vergani C, Pagano C, Maciocco M, Romanelli A. Source: Chest. 2003 May; 123(5): 1341-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740245&dopt=Abstract

·

Non-small cell lung cancer with chest wall involvement. Author(s): Karmy-Jones R, Vallieres E. Source: Chest. 2003 May; 123(5): 1323-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740237&dopt=Abstract

·

Non-small cell lung cancer-derived soluble mediators enhance apoptosis in activated T lymphocytes through an I kappa B kinase-dependent mechanism. Author(s): Batra RK, Lin Y, Sharma S, Dohadwala M, Luo J, Pold M, Dubinett SM. Source: Cancer Research. 2003 February 1; 63(3): 642-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566308&dopt=Abstract

·

Novel therapies for lung cancer. Author(s): Hoang T, Traynor AM, Schiller JH. Source: Surgical Oncology. 2002 December; 11(4): 229-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450559&dopt=Abstract

·

Novel therapies for the treatment of non-small cell lung cancer. Author(s): Johnson DH, Schiller JH. Source: Cancer Chemother Biol Response Modif. 2002; 20: 763-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703233&dopt=Abstract

·

Nuclear accumulation of p53 is a potential marker for the development of squamous cell lung cancer in smokers. Author(s): Piyathilake CJ, Frost AR, Manne U, Weiss H, Heimburger DC, Grizzle WE. Source: Chest. 2003 January; 123(1): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527620&dopt=Abstract

·

Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial. Author(s): Moore S, Corner J, Haviland J, Wells M, Salmon E, Normand C, Brada M, O'Brien M, Smith I. Source: Bmj (Clinical Research Ed.). 2002 November 16; 325(7373): 1145. Erratum In: Bmj 2002 December 14; 325(7377): 1386. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433764&dopt=Abstract

122 Lung Cancer

·

Nurse practitioners' knowledge, practice and attitudes about tobacco cessation & lung cancer screening. Author(s): Lawvere S, Mahoney MC, Englert JJ, Murphy JM, Hyland A, Klein SB, Loewen GM. Source: Journal of the American Academy of Nurse Practitioners. 2003 August; 15(8): 376-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509103&dopt=Abstract

·

Nursing assessment and management of dyspneic patients with lung cancer. Author(s): Inzeo D, Tyson L. Source: Clinical Journal of Oncology Nursing. 2003 May-June; 7(3): 332-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793341&dopt=Abstract

·

Oat cell lung cancer diagnosed following metastasis to the skin. Author(s): Senen D, Adanali G, Tuncel A, Erdogan B. Source: Plastic and Reconstructive Surgery. 2003 January; 111(1): 510-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496648&dopt=Abstract

·

Observation-only management of inoperable lung cancer: do not do that: a loud and clear radiographic point of view! Author(s): Jeremic B, Classen J, Bamberg M. Source: Chest. 2003 January; 123(1): 313-4; Author Reply 314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527646&dopt=Abstract

·

Occupation and smoking as risk factors for lung cancer: a population-based casecontrol study. Author(s): Ruano-Ravina A, Figueiras A, Barreiro-Carracedo MA, Barros-Dios J. Source: American Journal of Industrial Medicine. 2003 February; 43(2): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541269&dopt=Abstract

·

Occupational exposures and lung cancer in New Caledonia. Author(s): Menvielle G, Luce D, Fevotte J, Bugel I, Salomon C, Goldberg P, BillonGalland MA, Goldberg M. Source: Occupational and Environmental Medicine. 2003 August; 60(8): 584-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883019&dopt=Abstract

·

Older people with non small cell lung cancer in clinical stage IIIA and co-morbid conditions. Is curative irradiation feasible? Final results of a prospective study. Author(s): Pergolizzi S, Santacaterina A, Renzis CD, Settineri N, Gaeta M, Frosina P, Russi EG, Altavilla G. Source: Lung Cancer (Amsterdam, Netherlands). 2002 August; 37(2): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140143&dopt=Abstract

Studies 123

·

On the origin of G --> T transversions in lung cancer. Author(s): Pfeifer GP, Hainaut P. Source: Mutation Research. 2003 May 15; 526(1-2): 39-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714181&dopt=Abstract

·

One from column A: choosing between CT, positron emission tomography, endoscopic ultrasound with fine-needle aspiration, transbronchial needle aspiration, thoracoscopy, mediastinoscopy, and mediastinotomy for staging lung cancer. Author(s): Silvestri GA, Hoffman B, Reed CE. Source: Chest. 2003 February; 123(2): 333-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576346&dopt=Abstract

·

ONS participates in American College of Chest Physicians Lung Cancer Guidelines Project. Author(s): Cooley ME. Source: Ons News / Oncology Nursing Society. 2003 January; 18(1): 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12599863&dopt=Abstract

·

Organ heterogeneity of host-derived matrix metalloproteinase expression and its involvement in multiple-organ metastasis by lung cancer cell lines. Author(s): Shiraga M, Yano S, Yamamoto A, Ogawa H, Goto H, Miki T, Miki K, Zhang H, Sone S. Source: Cancer Research. 2002 October 15; 62(20): 5967-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384564&dopt=Abstract

·

Outcome and prognostic factors for patients with non-small-cell lung cancer and severe radiation pneumonitis. Author(s): Wang JY, Chen KY, Wang JT, Chen JH, Lin JW, Wang HC, Lee LN, Yang PC. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 November 1; 54(3): 735-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377325&dopt=Abstract

·

Outcome in patients with lung cancer found on lung cancer mass screening roentgenograms, but who did not subsequently consult a doctor. Author(s): Kashiwabara K, Koshi S, Itonaga K, Nakahara O, Tanaka M, Toyonaga M. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660008&dopt=Abstract

·

Outcome of patients admitted to the intensive care unit with newly diagnosed small cell lung cancer. Author(s): Jennens RR, Rosenthal MA, Mitchell P, Presneill JJ. Source: Lung Cancer (Amsterdam, Netherlands). 2002 December; 38(3): 291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445751&dopt=Abstract

124 Lung Cancer

·

Overexpression of CCR7 mRNA in nonsmall cell lung cancer: correlation with lymph node metastasis. Author(s): Takanami I. Source: International Journal of Cancer. Journal International Du Cancer. 2003 June 10; 105(2): 186-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673677&dopt=Abstract

·

Overexpression of WISP-1 down-regulated motility and invasion of lung cancer cells through inhibition of Rac activation. Author(s): Soon LL, Yie TA, Shvarts A, Levine AJ, Su F, Tchou-Wong KM. Source: The Journal of Biological Chemistry. 2003 March 28; 278(13): 11465-70. Epub 2003 January 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529380&dopt=Abstract

·

Overview of clinical trials with epidermal growth factor receptor inhibitors in advanced non-small cell lung cancer. Author(s): Thomas M. Source: Semin Oncol Nurs. 2002 November; 18(4 Suppl 4): 20-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534150&dopt=Abstract

·

Overview of methodology for lung cancer evidence review and guideline development. Author(s): McCrory DC, Colice GL, Lewis SZ, Alberts WM, Parker S. Source: Chest. 2003 January; 123(1 Suppl): 3S-6S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527561&dopt=Abstract

·

p53 gene mutations in non-small cell lung cancer detected by polymerase chain reaction single-strand conformation polymorphism analysis. Author(s): Zhao Y, Wu D, Xiang X, Zhang B, Zhou N, Hu Y. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 1999 September; 14(3): 134-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903811&dopt=Abstract

·

p53 mutations and survival in stage I non-small-cell lung cancer: results of a prospective study. Author(s): Ahrendt SA, Hu Y, Buta M, McDermott MP, Benoit N, Yang SC, Wu L, Sidransky D. Source: Journal of the National Cancer Institute. 2003 July 2; 95(13): 961-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837832&dopt=Abstract

Studies 125

·

Paraneoplastic sensory neuronopathy and spontaneous regression of small cell lung cancer. Author(s): Gill S, Murray N, Dalmau J, Thiessen B. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 August; 30(3): 269-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945955&dopt=Abstract

·

Persistent excess mortality from lung cancer in patients with stage I non-small-cell lung cancer, disease-free after 5 years. Author(s): Pasini F, Verlato G, Durante E, de Manzoni G, Valduga F, Accordini S, Pedrazzani C, Terzi A, Pelosi G. Source: British Journal of Cancer. 2003 June 2; 88(11): 1666-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771977&dopt=Abstract

·

Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study. Author(s): Soo RA, Lim HL, Wang LZ, Lee HS, Millward MJ, Tok LT, Lee SC, Lehnert M, Goh BC. Source: Cancer Chemotherapy and Pharmacology. 2003 August; 52(2): 153-8. Epub 2003 May 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750842&dopt=Abstract

·

Phase I/II study of daily carboplatin, 5-fluorouracil and concurrent radiation therapy for locally advanced non-small-cell lung cancer. Author(s): Yoshizawa H, Tanaka J, Kagamu H, Maruyama Y, Miyao H, Ito K, Sato T, Iwashima A, Suzuki E, Gejyo F. Source: British Journal of Cancer. 2003 September 1; 89(5): 803-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942108&dopt=Abstract

·

Physical activity and the risk of lung cancer in Canada. Author(s): Mao Y, Pan S, Wen SW, Johnson KC; Canadian Cancer Registries Epidemiology Research Group. Source: American Journal of Epidemiology. 2003 September 15; 158(6): 564-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965882&dopt=Abstract

·

Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States). Author(s): Le Marchand L, Guo C, Benhamou S, Bouchardy C, Cascorbi I, Clapper ML, Garte S, Haugen A, Ingelman-Sundberg M, Kihara M, Rannug A, Ryberg D, Stucker I, Sugimura H, Taioli E. Source: Cancer Causes & Control : Ccc. 2003 May; 14(4): 339-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846365&dopt=Abstract

126 Lung Cancer

·

Population- and community-based recruitment of African Americans and Latinos: the San Francisco Bay Area Lung Cancer Study. Author(s): Cabral DN, Napoles-Springer AM, Miike R, McMillan A, Sison JD, Wrensch MR, Perez-Stable EJ, Wiencke JK; San Francisco Bay Area Lung Cancer Study. Source: American Journal of Epidemiology. 2003 August 1; 158(3): 272-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882950&dopt=Abstract

·

Positive reactions for both Cyfra21-1 and CA125 indicate worst prognosis in nonsmall cell lung cancer. Author(s): Ando S, Kimura H, Iwai N, Yamamoto N, Iida T. Source: Anticancer Res. 2003 May-June; 23(3C): 2869-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926125&dopt=Abstract

·

Products of oxidative DNA damage and repair as possible biomarkers of susceptibility to lung cancer. Author(s): Gackowski D, Speina E, Zielinska M, Kowalewski J, Rozalski R, Siomek A, Paciorek T, Tudek B, Olinski R. Source: Cancer Research. 2003 August 15; 63(16): 4899-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941813&dopt=Abstract

·

Prognostic factors for the survival of surgically treated patients for non-small cell lung cancer. Author(s): Fernandes OJ, Almgren SO, Thaning L, Filbey D, Helsing M, Karlsson M, Magnusson A, Souza D. Source: Acta Oncologica (Stockholm, Sweden). 2003; 42(4): 338-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899506&dopt=Abstract

·

Prognostic significance of bcl-2 expression in resected pN2 non-small cell lung cancer. Author(s): Tomita M, Matsuzaki Y, Edagawa M, Shimizu T, Hara M, Onitsuka T. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 October; 29(8): 654-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511612&dopt=Abstract

·

Prognostic significance of mutant p53 protein, P-glycoprotein and glutathione Stransferase-pi in patients with unresectable non-small cell lung cancer. Author(s): Miyatake K, Gemba K, Ueoka H, Nishii K, Kiura K, Tabata M, Shibayama T, Takigawa N, Kawaraya M, Tanimoto M. Source: Anticancer Res. 2003 May-June; 23(3C): 2829-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926120&dopt=Abstract

Studies 127

·

Prognostic value of cytokeratin-positive cells in the bone marrow and lymph nodes of patients with resected nonsmall cell lung cancer: a multicenter prospective study. Author(s): Yasumoto K, Osaki T, Watanabe Y, Kato H, Yoshimura T. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 194-201; Discussion 202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842539&dopt=Abstract

·

Prophylactic cranial irradiation for patients with locally advanced non-small-cell lung cancer. Author(s): Gore EM. Source: Oncology (Huntingt). 2003 June; 17(6): 775-9; Discussion 779-80, 784, 787 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846122&dopt=Abstract

·

Proteomic patterns of tumour subsets in non-small-cell lung cancer. Author(s): Yanagisawa K, Shyr Y, Xu BJ, Massion PP, Larsen PH, White BC, Roberts JR, Edgerton M, Gonzalez A, Nadaf S, Moore JH, Caprioli RM, Carbone DP. Source: Lancet. 2003 August 9; 362(9382): 433-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927430&dopt=Abstract

·

Pulmonary embolism with cavity formation, spontaneous pneumothorax, and highoutput air leak in a patient with non-small-cell lung cancer. Author(s): Pavlakis G, Siafakas K, Gorgogiannis D, Sakorafas GH. Source: N Z Med J. 2003 July 11; 116(1177): 2P Following U500. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866506&dopt=Abstract

·

Pulmonary paragonimiasis mimicking lung cancer on FDG-PET imaging. Author(s): Watanabe S, Nakamura Y, Kariatsumari K, Nagata T, Sakata R, Zinnouchi S, Date K. Source: Anticancer Res. 2003 July-August; 23(4): 3437-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926086&dopt=Abstract

·

Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer. Author(s): Langendijk JA, Aaronson NK, de Jong JM, ten Velde GP, Muller MJ, Slotman BJ, Wouters EF. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 July 15; 53(4): 847-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095549&dopt=Abstract

·

Quality of life after lung cancer surgery: a forgotten outcome measure. Author(s): Chen JC, Johnstone SA. Source: Chest. 2002 July; 122(1): 4-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114328&dopt=Abstract

128 Lung Cancer

·

Quality of life following lung cancer resection: video-assisted thoracic surgery vs thoracotomy. Author(s): Li WW, Lee TW, Lam SS, Ng CS, Sihoe AD, Wan IY, Yim AP. Source: Chest. 2002 August; 122(2): 584-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171836&dopt=Abstract

·

Quality of life following lung cancer surgery. Author(s): Myrdal G, Valtysdottir S, Lambe M, Stahle E. Source: Thorax. 2003 March; 58(3): 194-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612291&dopt=Abstract

·

Quality of life of long-term survivors of non-small-cell lung cancer. Author(s): Sarna L, Padilla G, Holmes C, Tashkin D, Brecht ML, Evangelista L. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 July 1; 20(13): 2920-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089220&dopt=Abstract

·

Quality trials and quality of life in non-small-cell lung cancer. Author(s): Harper P, Plunkett T, Khayat D. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 15; 21(16): 3007-8. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837809&dopt=Abstract

·

Quantification of macrophage migration inhibitory factor mRNA expression in nonsmall cell lung cancer tissues and its clinical significance. Author(s): Tomiyasu M, Yoshino I, Suemitsu R, Okamoto T, Sugimachi K. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 December; 8(12): 3755-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473586&dopt=Abstract

·

Quantitative O(6)-methylguanine DNA methyltransferase methylation analysis in curatively resected non-small cell lung cancer: associations with clinical outcome. Author(s): Brabender J, Usadel H, Metzger R, Schneider PM, Park J, Salonga D, TsaoWei DD, Groshen S, Lord RV, Takebe N, Schneider S, Holscher AH, Danenberg KD, Danenberg PV. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 January; 9(1): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538473&dopt=Abstract

Studies 129

·

RA175, which is the mouse ortholog of TSLC1, a tumor suppressor gene in human lung cancer, is a cell adhesion molecule. Author(s): Fujita E, Soyama A, Momoi T. Source: Experimental Cell Research. 2003 July 1; 287(1): 57-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799182&dopt=Abstract

·

Racial differences pertaining to a belief about lung cancer surgery: results of a multicenter survey. Author(s): Margolis ML, Christie JD, Silvestri GA, Kaiser L, Santiago S, Hansen-Flaschen J. Source: Annals of Internal Medicine. 2003 October 7; 139(7): 558-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530226&dopt=Abstract

·

Radiation pneumonitis following treatment of non-small-cell lung cancer with continuous hyperfractionated accelerated radiotherapy (CHART). Author(s): Jenkins P, D'Amico K, Benstead K, Elyan S. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 June 1; 56(2): 360-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738310&dopt=Abstract

·

Radiation therapy of changes secondary to lung cancer and pneumonectomy on bone and Tc-99m depreotide imaging. Author(s): Shih WJ, Kiefer V. Source: Clinical Nuclear Medicine. 2003 May; 28(5): 419-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702946&dopt=Abstract

·

Radiologic screening for lung cancer. Author(s): Bastarrika G, Pueyo JC, Mulshine JL. Source: Expert Rev Anticancer Ther. 2002 August; 2(4): 385-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647981&dopt=Abstract

·

Radiotherapy for medically inoperable non-small cell lung cancer at clinical stage I and II. Author(s): Yamada K, Soejima T, Ota Y, Sasaki R, Yoden E, Kanaoka N, Maruta T, Sugimura K. Source: Tumori. 2003 January-February; 89(1): 75-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729366&dopt=Abstract

130 Lung Cancer

·

RASSF1A gene inactivation in non-small cell lung cancer and its clinical implication. Author(s): Endoh H, Yatabe Y, Shimizu S, Tajima K, Kuwano H, Takahashi T, Mitsudomi T. Source: International Journal of Cancer. Journal International Du Cancer. 2003 August 10; 106(1): 45-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794755&dopt=Abstract

·

Re: “Differential association of body mass index and fat distribution with three major histologic types of lung cancer: evidence from a cohort of older women”. Author(s): Kabir Z. Source: American Journal of Epidemiology. 2003 August 1; 158(3): 288; Author Reply 289. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882952&dopt=Abstract

·

Re: “Dose specific meta-analysis and sensitivity analysis of the relation between alcohol consumption and lung cancer risk”. Author(s): Bandera EV, Potter JD. Source: American Journal of Epidemiology. 2003 March 15; 157(6): 569-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631550&dopt=Abstract

·

Re: Beta-carotene and lung cancer: a lesson for future chemoprevention investigations? Author(s): Stram DO, Wu AH. Source: Journal of the National Cancer Institute. 2003 May 21; 95(10): E4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759404&dopt=Abstract

·

Re: Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. Author(s): VanAudenrode M. Source: Journal of the National Cancer Institute. 2003 May 21; 95(10): 761-2; Author Reply 762-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759400&dopt=Abstract

·

Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to Bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells. Author(s): Ling YH, Liebes L, Zou Y, Perez-Soler R. Source: The Journal of Biological Chemistry. 2003 September 5; 278(36): 33714-23. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821677&dopt=Abstract

Studies 131

·

Recurrent small cell lung cancer: update. Author(s): Glisson BS. Source: Seminars in Oncology. 2003 February; 30(1): 72-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635091&dopt=Abstract

·

Reduced expression of the neuron restrictive silencer factor permits transcription of glycine receptor alpha1 subunit in small-cell lung cancer cells. Author(s): Gurrola-Diaz C, Lacroix J, Dihlmann S, Becker CM, von Knebel Doeberitz M. Source: Oncogene. 2003 August 28; 22(36): 5636-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944912&dopt=Abstract

·

Reduction of cisplatin-induced anemia by the pineal indole 5-methoxytryptamine in metastatic lung cancer patients. Author(s): Lissoni P, Malugani F, Bukovec R, Bordin V, Perego M, Mengo S, Ardizzoia A, Tancini G. Source: Neuroendocrinol Lett. 2003 February-April; 24(1-2): 83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743539&dopt=Abstract

·

Remarks about usefulness of videothoracoscopic intrapericardial examination of pulmonary vessels to assess the resectability of clinical T4 lung cancer. Author(s): Wurtz AJ. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 342; Author Reply 342. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842588&dopt=Abstract

·

Right lung cancer with right aortic arch. Author(s): Suzuki S, Miyamoto A, Aikawa H, Tabata T, Matsumura Y, Kondo T. Source: Jpn J Thorac Cardiovasc Surg. 2003 September; 51(9): 469-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529170&dopt=Abstract

·

Risk factors associated with lung cancer in Hong Kong. Author(s): Chan-Yeung M, Koo LC, Ho JC, Tsang KW, Chau WS, Chiu SW, Ip MS, Lam WK. Source: Lung Cancer (Amsterdam, Netherlands). 2003 May; 40(2): 131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711113&dopt=Abstract

·

Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of environmental tobacco smoke and lung cancer: a case-control study in Japanese nonsmoking women. Author(s): Kiyohara C, Wakai K, Mikami H, Sido K, Ando M, Ohno Y. Source: International Journal of Cancer. Journal International Du Cancer. 2003 October 20; 107(1): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925969&dopt=Abstract

132 Lung Cancer

·

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis. Author(s): Martin B, Paesmans M, Berghmans T, Branle F, Ghisdal L, Mascaux C, Meert AP, Steels E, Vallot F, Verdebout JM, Lafitte JJ, Sculier JP. Source: British Journal of Cancer. 2003 July 7; 89(1): 55-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838300&dopt=Abstract

·

Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer. Author(s): Prenzel KL, Monig SP, Sinning JM, Baldus SE, Gutschow CA, Grass G, Schneider PM, Holscher AH. Source: Journal of Surgical Oncology. 2003 April; 82(4): 256-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672010&dopt=Abstract

·

Role of targeted therapy in non-small cell lung cancer: hype or hope? Author(s): Langer CJ. Source: Expert Rev Anticancer Ther. 2003 August; 3(4): 443-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934657&dopt=Abstract

·

Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer. Author(s): Miller KL, Marks LB, Sibley GS, Clough RW, Garst JL, Crawford J, Shafman TD. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 June 1; 56(2): 355-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738309&dopt=Abstract

·

Scientists report progress against non-small cell lung cancer. Author(s): McCarthy M. Source: Lancet. 2003 June 14; 361(9374): 2055. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814725&dopt=Abstract

·

Screening for lung cancer: a systematic review and meta-analysis of controlled trials. Author(s): Manser RL, Irving LB, Byrnes G, Abramson MJ, Stone CA, Campbell DA. Source: Thorax. 2003 September; 58(9): 784-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947138&dopt=Abstract

·

Screening for lung cancer: an old idea revisited. Author(s): Sachs S. Source: Respir Care Clin N Am. 2003 March; 9(1): 27-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820711&dopt=Abstract

Studies 133

·

Second-line chemotherapy for non-small cell lung cancer. Author(s): Shepherd FA. Source: Expert Rev Anticancer Ther. 2003 August; 3(4): 435-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934656&dopt=Abstract

·

Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Author(s): Liang G, Xing D, Miao X, Tan W, Yu C, Lu W, Lin D. Source: International Journal of Cancer. Journal International Du Cancer. 2003 July 10; 105(5): 669-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740916&dopt=Abstract

·

Sequential chemoradiotherapy versus radiotherapy in the management of locally advanced non-small-cell lung cancer. Author(s): Sharma S, Sharma R, Bhowmik KT. Source: Adv Ther. 2003 January-February; 20(1): 14-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772814&dopt=Abstract

·

Serial-measured versus estimated creatinine clearance in patients with non-small cell lung cancer receiving cisplatin-based chemotherapy. Author(s): Chang GC, Yang TY, Shih CM, Lin LY, Lee HS, Chiang CD. Source: J Formos Med Assoc. 2003 April; 102(4): 257-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833190&dopt=Abstract

·

Small-cell cancers, and an unusual reaction to chemotherapy. Case 2. Synchronous renal cell carcinoma and limited-stage small-cell lung cancer. Author(s): Massarweh S, Lewitton M, Popat U, Lynch GR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 15; 21(12): 2439-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805345&dopt=Abstract

·

Smoking, DNA repair capacity and risk of nonsmall cell lung cancer. Author(s): Shen H, Spitz MR, Qiao Y, Guo Z, Wang LE, Bosken CH, Amos CI, Wei Q. Source: International Journal of Cancer. Journal International Du Cancer. 2003 October 20; 107(1): 84-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925960&dopt=Abstract

·

Some unusual paraneoplastic syndromes. Case 4. Paraneoplastic nephrotic syndrome in a patient with lung cancer. Author(s): Ebert B, Shaffer K, Rennke H. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 July 1; 21(13): 2624-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829687&dopt=Abstract

134 Lung Cancer

·

Staging of non-small-cell lung cancer with integrated PET and CT. Author(s): Pravinkumar E. Source: The New England Journal of Medicine. 2003 September 18; 349(12): 1188-90; Author Reply 1188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14503543&dopt=Abstract

·

Staging of non-small-cell lung cancer with integrated PET and CT. Author(s): Miles KA. Source: The New England Journal of Medicine. 2003 September 18; 349(12): 1188-90; Author Reply 1188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14503542&dopt=Abstract

·

Staging of non-small-cell lung cancer with integrated PET and CT. Author(s): Comans EF. Source: The New England Journal of Medicine. 2003 September 18; 349(12): 1188-90; Author Reply 1188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14503541&dopt=Abstract

·

Staging of non-small-cell lung cancer with integrated PET and CT. Author(s): Schirrmeister H, Hetzel M, Buck A. Source: The New England Journal of Medicine. 2003 September 18; 349(12): 1188-90; Author Reply 1188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679538&dopt=Abstract

·

Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. Author(s): Lardinois D, Weder W, Hany TF, Kamel EM, Korom S, Seifert B, von Schulthess GK, Steinert HC. Source: The New England Journal of Medicine. 2003 June 19; 348(25): 2500-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815135&dopt=Abstract

·

Stereotactic single-dose radiotherapy of stage I non-small-cell lung cancer (NSCLC). Author(s): Hof H, Herfarth KK, Munter M, Hoess A, Motsch J, Wannenmacher M, Debus J J. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 June 1; 56(2): 335-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738306&dopt=Abstract

·

Strategies in lung cancer detection. Achieving early identification in patients at high risk. Author(s): Bechtel JJ, Petty TL. Source: Postgraduate Medicine. 2003 August; 114(2): 20-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926174&dopt=Abstract

Studies 135

·

Strong association between the GSTM1-null genotype and lung cancer in a Turkish population. Author(s): Pinarbasi H, Silig Y, Cetinkaya O, Seyfikli Z, Pinarbasi E. Source: Cancer Genetics and Cytogenetics. 2003 October 15; 146(2): 125-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14553946&dopt=Abstract

·

Study of lung cancer in MMVF workers. Author(s): Boffetta P, Kjaerheim K, Hansen J, Cherrie J, Chang-Claude J, Olsen JH, Saracci R, Westerholm P, Andersen A. Source: International Journal of Occupational and Environmental Health : Official Journal of the International Commission on Occupational Health. 2003 April-June; 9(2): 169-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848246&dopt=Abstract

·

Surgical considerations with lung cancer screening. Author(s): Warner EE, Mulshine JL. Source: Journal of Surgical Oncology. 2003 September; 84(1): 1-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949983&dopt=Abstract

·

Surgical management of cerebral metastases from non-small cell lung cancer. Author(s): Koutras AK, Marangos M, Kourelis T, Partheni M, Dougenis D, Iconomou G, Vagenakis AG, Kalofonos HP. Source: Tumori. 2003 May-June; 89(3): 292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908786&dopt=Abstract

·

Surgical viewpoints for the definitive treatment of lung cancer. Author(s): Bilfinger TV. Source: Respir Care Clin N Am. 2003 June; 9(2): 141-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911287&dopt=Abstract

·

Survival among Chinese women with lung cancer in Singapore: a comparison by stage, histology and smoking status. Author(s): Tan YK, Wee TC, Koh WP, Wang YT, Eng P, Tan WC, Seow A. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 237-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781422&dopt=Abstract

·

Survival and prognostic factors of surgically resected T4 non-small cell lung cancer. Author(s): Osaki T, Sugio K, Hanagiri T, Takenoyama M, Yamashita T, Sugaya M, Yasuda M, Yasumoto K. Source: The Annals of Thoracic Surgery. 2003 June; 75(6): 1745-51; Discussion 1751. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822610&dopt=Abstract

136 Lung Cancer

·

Survivin gene expression in early-stage non-small cell lung cancer. Author(s): Falleni M, Pellegrini C, Marchetti A, Oprandi B, Buttitta F, Barassi F, Santambrogio L, Coggi G, Bosari S. Source: The Journal of Pathology. 2003 August; 200(5): 620-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898598&dopt=Abstract

·

Synchronous solitary fibrous tumor of the pleura and lung cancer. Author(s): Watanabe S, Nakamura Y, Sakasegawa K, Kariatsumari K, Yotsumoto D, Sakata R, Gezima K. Source: Anticancer Res. 2003 May-June; 23(3C): 2881-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926128&dopt=Abstract

·

Targeted therapy for lung cancer. Author(s): Kukunoor R, Shah J, Mekhail T. Source: Current Oncology Reports. 2003 July; 5(4): 326-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781076&dopt=Abstract

·

Targeted therapy in combination with gemcitabine in non-small cell lung cancer. Author(s): Rosell R, Crino L, Danenberg K, Scagliotti G, Bepler G, Taron M, Alberola V, Provencio M, Camps C, De Marinis F, Sanchez JJ, Penas R. Source: Seminars in Oncology. 2003 August; 30(4 Suppl 10): 19-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917817&dopt=Abstract

·

Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965). Author(s): Dziadziuszko R, Ardizzoni A, Postmus PE, Smit EF, Price A, Debruyne C, Legrand C, Giaccone G; EORTC Lung Cancer Group. Source: European Journal of Cancer (Oxford, England : 1990). 2003 June; 39(9): 1271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763216&dopt=Abstract

·

The cost-effectiveness of low-dose CT screening for lung cancer: preliminary results of baseline screening. Author(s): Wisnivesky JP, Mushlin AI, Sicherman N, Henschke C. Source: Chest. 2003 August; 124(2): 614-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907551&dopt=Abstract

·

The emerging role of pemetrexed (Alimta) and gemcitabine in non-small cell lung cancer. Author(s): Le Chevalier T. Source: Seminars in Oncology. 2003 August; 30(4 Suppl 10): 37-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947960&dopt=Abstract

Studies 137

·

The impact of cardiovascular comorbidity on the outcome of surgery for stage I and II non-small-cell lung cancer. Author(s): Ambrogi V, Pompeo E, Elia S, Pistolese GR, Mineo TC. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 May; 23(5): 811-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754038&dopt=Abstract

·

The natural history of recurrence after bronchoplastic procedures for non-small cell lung cancer. Author(s): Hollaus PH, Wurnig PN, Pridun NS. Source: The Annals of Thoracic Surgery. 2003 August; 76(2): 363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902065&dopt=Abstract

·

The Patterns of Care Study and Regional Cancer Registry for non-small-cell lung cancer in Japan. Author(s): Sugiyama H, Teshima T, Ohno Y, Inoue T, Takahashi Y, Oshima A, Sumi M, Uno T, Ikeda H; Japanese PCS Working Subgroup for Lung Cancer. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 July 15; 56(4): 1005-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829136&dopt=Abstract

·

The rationale and potential of combining novel biologic therapies with radiotherapy: focus on non-small cell lung cancer. Author(s): Herbst RS, O'Reilly MS. Source: Seminars in Oncology. 2003 August; 30(4 Suppl 9): 113-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908142&dopt=Abstract

·

The re-emergence of aerosol gene delivery: a viable approach to lung cancer therapy. Author(s): Densmore CL. Source: Current Cancer Drug Targets. 2003 August; 3(4): 275-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871058&dopt=Abstract

·

The relationship of pain, uncertainty, and hope in Taiwanese lung cancer patients. Author(s): Hsu TH, Lu MS, Tsou TS, Lin CC. Source: Journal of Pain and Symptom Management. 2003 September; 26(3): 835-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967732&dopt=Abstract

·

The role of chemotherapy in the treatment of unresectable stage III and IV nonsmall cell lung cancer. Author(s): Socinski MA. Source: Respir Care Clin N Am. 2003 June; 9(2): 207-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911290&dopt=Abstract

138 Lung Cancer

·

The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature. Author(s): Meert AP, Martin B, Paesmans M, Berghmans T, Mascaux C, Verdebout JM, Delmotte P, Lafitte JJ, Sculier JP. Source: British Journal of Cancer. 2003 September 15; 89(6): 959-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966408&dopt=Abstract

·

The role of mediastinoscopy in the evaluation of thoracic disease and lung cancer. Author(s): Hsu HS, Wang LS, Hsieh CC, Wang CY, Wu YC, Huang BS, Hsu WH, Huang MH. Source: J Chin Med Assoc. 2003 April; 66(4): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854875&dopt=Abstract

·

The role of mismatch repair in small-cell lung cancer cells. Author(s): Hansen LT, Thykjaer T, Orntoft TF, Rasmussen LJ, Keller P, Spang-Thomsen M, Edmonston TB, Schmutte C, Fishel R, Petersen LN. Source: European Journal of Cancer (Oxford, England : 1990). 2003 July; 39(10): 1456-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826050&dopt=Abstract

·

The role of radiotherapy and chemotherapy for curative management of medically inoperable and stage III nonsmall cell lung cancer, and radiotherapy for palliation of symptomatic disease. Author(s): Turrisi AT 3rd, Bogart J, Sherman C, Silvestri G. Source: Respir Care Clin N Am. 2003 June; 9(2): 163-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911288&dopt=Abstract

·

The sequence of vessel interruption during lobectomy for non-small cell lung cancer: is it indeed important? Author(s): Refaely Y, Sadetzki S, Chetrit A, Simansky DA, Paley M, Modan B, Yellin A. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 June; 125(6): 1313-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830050&dopt=Abstract

·

The use of surgery to treat lung cancer in elderly patients. Author(s): Jaklitsch MT, Mery CM, Audisio RA. Source: The Lancet Oncology. 2003 August; 4(8): 463-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901960&dopt=Abstract

·

The XRCC1 codon 399 Gln allele is associated with adenine to guanine p53 mutations in non-small cell lung cancer. Author(s): Casse C, Hu YC, Ahrendt SA. Source: Mutation Research. 2003 July 25; 528(1-2): 19-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873719&dopt=Abstract

Studies 139

·

Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study. Author(s): Tan D, Li Q, Deeb G, Ramnath N, Slocum HK, Brooks J, Cheney R, Wiseman S, Anderson T, Loewen G. Source: Human Pathology. 2003 June; 34(6): 597-604. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827614&dopt=Abstract

·

Transoesophageal echocardiography and lung cancer staging. Author(s): Maskill JM, Rother A, Seevanayagam S. Source: Thorax. 2003 August; 58(8): 735. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886001&dopt=Abstract

·

Treatment of relapsed small-cell lung cancer--a focus on the evolving role of topotecan. Author(s): Rocha Lima CM, Chiappori A. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 229-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781421&dopt=Abstract

·

Treatment options for brain metastases in patients with non-small-cell lung cancer. Author(s): Taimur S, Edelman MJ. Source: Current Oncology Reports. 2003 July; 5(4): 342-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781078&dopt=Abstract

·

Treatment planning for lung cancer: traditional homogeneous point-dose prescription compared with heterogeneity-corrected dose-volume prescription. Author(s): Frank SJ, Forster KM, Stevens CW, Cox JD, Komaki R, Liao Z, Tucker S, Wang X, Steadham RE, Brooks C, Starkschall G. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 August 1; 56(5): 1308-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873675&dopt=Abstract

·

Trends in histopathology of lung cancer in Alberta. Author(s): Hatcher J, Dover DC. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 2003 July-August; 94(4): 292-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873089&dopt=Abstract

·

Tumor implantation after pneumonectomy for lung cancer. Author(s): Raja V, Bessman D. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 1; 21(15): 2998-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885823&dopt=Abstract

140 Lung Cancer

·

Ubiquitination of tissue transglutaminase is modulated by interferon alpha in human lung cancer cells. Author(s): Esposito C, Marra M, Giuberti G, D'Alessandro AM, Porta R, Cozzolino A, Caraglia M, Abbruzzese A. Source: The Biochemical Journal. 2003 February 15; 370(Pt 1): 205-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401132&dopt=Abstract

·

Uncommon syndromes and treatment manifestations of malignancy: Case 2. Metastatic non-small-cell lung cancer presenting with leukocytosis. Author(s): Ganti AK, Potti A, Mehdi S. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 1; 21(1): 168-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506187&dopt=Abstract

·

Unsuspected residual disease at the resection margin after surgery for lung cancer: fate of patients after long-term follow-up. Author(s): Lequaglie C, Conti B, Brega Massone PP, Giudice G. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 February; 23(2): 229-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559347&dopt=Abstract

·

Unusual presentations of lung cancer: Case 1. Diabetes insipidus as the initial manifestation of non-small-cell lung cancer. Author(s): Reddy P, Kalemkerian GP. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 1; 20(23): 4597-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454118&dopt=Abstract

·

Unusual presentations of lung cancer: Case 2. Adrenal insufficiency as the initial manifestation of non-small-cell lung cancer. Author(s): Sirachainan E, Kalemkerian GP. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 1; 20(23): 4598-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454119&dopt=Abstract

·

Unusual presentations of lung cancer: Case 3. Paraneoplastic digital necrosis in a patient with small-cell lung cancer. Author(s): Iamandi C, Dietemann A, Grosshans E, Pauli G, Quoix E. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 1; 20(23): 4600-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454120&dopt=Abstract

Studies 141

·

Unusual presentations of lung cancer: Case 4. Palliative radiotherapy in eyelid nonHodgkin's lymphoma. Author(s): Galeazzi G, Di Russo A, Boffi R, De Conno F. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 1; 20(23): 4601-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454121&dopt=Abstract

·

Unusual problems in breast cancer and a rare lung cancer case. Case 1. Clinical complete response of breast cancer metastases after trastuzumab-based immunotherapy. Author(s): Tonini G, Vincenzi B, Santini D, Avvisati G, La Cesa A, Baldi A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 1; 21(11): 2215-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775749&dopt=Abstract

·

Unusual problems in breast cancer and a rare lung cancer case. Case 2. Aggressive fibromatosis of the chest wall arising near a breast prosthesis. Author(s): Khanfir K, Guinebretiere JM, Vanel D, Barreau-Pouhaer L, Bonvalot S, Le Cesne A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 1; 21(11): 2216-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775750&dopt=Abstract

·

Unusual problems in breast cancer and a rare lung cancer case. Case 3. Simultaneous and synchronous bilateral inflammatory breast cancer. Author(s): Agrawal BL, Nath AR, Glynn TP Jr, Velazco D, Garnett RF Jr. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 1; 21(11): 2218-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784818&dopt=Abstract

·

Unusual problems in breast cancer and a rare lung cancer case. Case 4. Primary lymphoepithelioma-like carcinoma of the lung. Author(s): Irie HY, Jaklitsch MT, Shaffer K, Weinstein M, Salgia R. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 1; 21(11): 2220-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775751&dopt=Abstract

·

Update on gemcitabine/carboplatin in patients with advanced non-small cell lung cancer. Author(s): Harper P. Source: Seminars in Oncology. 2003 August; 30(4 Suppl 10): 2-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917815&dopt=Abstract

142 Lung Cancer

·

Update on the systemic treatment of lung cancer. Author(s): Giaccone G, Smit EF. Source: Cancer Chemother Biol Response Modif. 2002; 20: 697-716. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703231&dopt=Abstract

·

Up-regulation of ALG-2 in hepatomas and lung cancer tissue. Author(s): la Cour JM, Mollerup J, Winding P, Tarabykina S, Sehested M, Berchtold MW. Source: American Journal of Pathology. 2003 July; 163(1): 81-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819013&dopt=Abstract

·

Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Author(s): Chen JJ, Yao PL, Yuan A, Hong TM, Shun CT, Kuo ML, Lee YC, Yang PC. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 February; 9(2): 729-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576442&dopt=Abstract

·

Uptake rates of 18F-fluorodeoxyglucose and 11C-choline in lung cancer and pulmonary tuberculosis: a positron emission tomography study. Author(s): Hara T, Kosaka N, Suzuki T, Kudo K, Niino H. Source: Chest. 2003 September; 124(3): 893-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970014&dopt=Abstract

·

Use of a dual-head coincidence camera and 18F-FDG for detection and nodal staging of non-small cell lung cancer: accuracy as determined by 2 independent observers. Author(s): Stevens H, Bakker PF, Schlosser NJ, van Rijk PP, de Klerk JM. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 March; 44(3): 336-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620997&dopt=Abstract

·

Use of antisense oligonucleotides for therapy. Manipulation of apoptosis inhibitors for destruction of lung cancer cells. Author(s): Leech SH, Olie RA, Zangemeister-Wittke U. Source: Methods in Molecular Medicine. 2003; 75: 655-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407770&dopt=Abstract

·

Use of ICD-9 coding as a proxy for stage of disease in lung cancer. Author(s): Thomas SK, Brooks SE, Mullins CD, Baquet CR, Merchant S. Source: Pharmacoepidemiology and Drug Safety. 2002 December; 11(8): 709-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512248&dopt=Abstract

Studies 143

·

Use of nucleotide excision repair-deficient mice as a model for chemically induced lung cancer. Author(s): Cheo DL, Friedberg EC. Source: Methods in Molecular Medicine. 2003; 74: 481-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415716&dopt=Abstract

·

Use of technetium-99m tin colloid for sentinel lymph node identification in nonsmall cell lung cancer. Author(s): Nomori H, Horio H, Naruke T, Orikasa H, Yamazaki K, Suemasu K. Source: The Journal of Thoracic and Cardiovascular Surgery. 2002 September; 124(3): 486-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202864&dopt=Abstract

·

Usefulness of bone markers for detection of bone metastases in lung cancer patients. Author(s): Alatas F, Alatas O, Metintas M, Colak O, Erginel S, Harmanci E. Source: Clinical Biochemistry. 2002 June; 35(4): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135691&dopt=Abstract

·

Usefulness of low-dose spiral CT of the chest in regular follow-up of postoperative non-small cell lung cancer patients: Preliminary report. Author(s): Chiu CH, Chern MS, Wu MH, Hsu WH, Wu YC, Huang MH, Chang SC. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 June; 125(6): 1300-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830048&dopt=Abstract

·

Using multiple imputation methods to estimate relative risks in small EPIC lung cancer subsets. Author(s): Altenburg HP, Agudo A, Berrino F, Boshuizen HC, Bueno-de-Mesquita HB, Janzon L, Le Marchand L, Linseisen J, Lukanova A, Rasmuson T, Vineis P, Riboli E, Miller A; EPIC Working Group on Lung Cancer. Source: Iarc Sci Publ. 2002; 156: 53-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484123&dopt=Abstract

·

Validation of the Charlson comorbidity index in patients with operated primary nonsmall cell lung cancer. Author(s): Birim O, Maat AP, Kappetein AP, van Meerbeeck JP, Damhuis RA, Bogers AJ. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 January; 23(1): 30-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493500&dopt=Abstract

144 Lung Cancer

·

Variations in lung cancer risk among smokers. Author(s): Bach PB, Kattan MW, Thornquist MD, Kris MG, Tate RC, Barnett MJ, Hsieh LJ, Begg CB. Source: Journal of the National Cancer Institute. 2003 March 19; 95(6): 470-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644540&dopt=Abstract

·

Vascular endothelial growth factor expression in non-small cell lung cancer. Author(s): O'Byrne KJ, Goddard J, Giatromanolaki A, Koukourakis MI. Source: Methods in Molecular Medicine. 2003; 74: 357-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415708&dopt=Abstract

·

Vegetables and fruits and lung cancer. Author(s): Miller AB; EPIC Working Group on Lung Cancer. Source: Iarc Sci Publ. 2002; 156: 85-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484133&dopt=Abstract

·

Video-assisted thoracic surgery (VATS) resection for lung cancer. Author(s): Swanson SJ, Batirel HF. Source: The Surgical Clinics of North America. 2002 June; 82(3): 541-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371584&dopt=Abstract

·

Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer. Author(s): Perez JE, Machiavelli MR, Romero AO, Romero Acuna LA, Dominguez ME, Fasce H, Flores Acosta L, Marrone N, Romero Acuna JM, Langhi MJ, Amato S, Bologna F, Ortiz EH, Leone BA, Lacava JA, Vallejo CT. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 August; 25(4): 383-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151970&dopt=Abstract

·

Visceral pleura invasion and pleural lavage tumor cytology by lung cancer: a prospective appraisal. Author(s): Riquet M, Badoual C, Le Pimpec Barthes F, Lhote FM, Souilamas R, Hubsch JP, Danel C. Source: The Annals of Thoracic Surgery. 2003 February; 75(2): 353-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607638&dopt=Abstract

·

Wegener disease mimicking central lung cancer. Author(s): Cesario A, Meacci E, Mule A, Margaritora S. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 October; 22(4): 626. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297184&dopt=Abstract

Studies 145

·

What happens to patients undergoing lung cancer surgery? Outcomes and quality of life before and after surgery. Author(s): Handy JR Jr, Asaph JW, Skokan L, Reed CE, Koh S, Brooks G, Douville EC, Tsen AC, Ott GY, Silvestri GA. Source: Chest. 2002 July; 122(1): 21-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114334&dopt=Abstract

·

What margins are necessary for incorporating mediastinal nodal mobility into involved-field radiotherapy for lung cancer? Author(s): van Sornsen de Koste JR, Lagerwaard FJ, Nijssen-Visser MR, SchuchhardSchipper R, Joosten H, Senan S. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 August 1; 53(5): 1211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12128122&dopt=Abstract

·

Whole-body 18F-2-deoxyglucose positron emission tomography in primary staging small cell lung cancer. Author(s): Shen YY, Shiau YC, Wang JJ, Ho ST, Kao CH. Source: Anticancer Res. 2002 March-April; 22(2B): 1257-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168935&dopt=Abstract

·

Why are lung cancer rate trends so different in the United States and United kingdom? Author(s): Lee PN, Forey BA. Source: Inhalation Toxicology. 2003 August; 15(9): 909-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872179&dopt=Abstract

·

Will differential culturing of circulating human lung cancer cells aid in understanding metastasis? Author(s): Onuigbo WI. Source: Medical Hypotheses. 2002 June; 58(6): 552-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12323131&dopt=Abstract

·

Will sewage workers with endotoxin related symptoms have the benefit of reduced lung cancer? Author(s): Lange JH, Mastrangelo G, Thomulka KW. Source: Occupational and Environmental Medicine. 2003 February; 60(2): 144-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554846&dopt=Abstract

146 Lung Cancer

·

WNT7a induces E-cadherin in lung cancer cells. Author(s): Ohira T, Gemmill RM, Ferguson K, Kusy S, Roche J, Brambilla E, Zeng C, Baron A, Bemis L, Erickson P, Wilder E, Rustgi A, Kitajewski J, Gabrielson E, Bremnes R, Franklin W, Drabkin HA. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 September 2; 100(18): 10429-34. Epub 2003 August 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937339&dopt=Abstract

·

Wortmannin inhibits growth of human non-small-cell lung cancer in vitro and in vivo. Author(s): Boehle AS, Kurdow R, Boenicke L, Schniewind B, Faendrich F, Dohrmann P, Kalthoff H. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2002 October; 387(5-6): 234-9. Epub 2002 September 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410360&dopt=Abstract

·

WW domain containing oxidoreductase gene expression is altered in non-small cell lung cancer. Author(s): Yendamuri S, Kuroki T, Trapasso F, Henry AC, Dumon KR, Huebner K, Williams NN, Kaiser LR, Croce CM. Source: Cancer Research. 2003 February 15; 63(4): 878-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591741&dopt=Abstract

·

XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Author(s): Wu X, Zhao H, Wei Q, Amos CI, Zhang K, Guo Z, Qiao Y, Hong WK, Spitz MR. Source: Carcinogenesis. 2003 March; 24(3): 505-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663511&dopt=Abstract

·

ZD 1839 in patients with brain metastases from non-small-cell lung cancer (NSCLC): report of four cases. Author(s): Cappuzzo F, Calandri C, Bartolini S, Crino L. Source: British Journal of Cancer. 2003 July 21; 89(2): 246-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865910&dopt=Abstract

·

ZD0473 treatment in lung cancer: an overview of the clinical trial results. Author(s): Treat J, Schiller J, Quoix E, Mauer A, Edelman M, Modiano M, Bonomi P, Ramlau R, Lemarie E. Source: European Journal of Cancer (Oxford, England : 1990). 2002 December; 38 Suppl 8: S13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645908&dopt=Abstract

Studies 147

·

ZD1839 (Iressa) in non-small cell lung cancer. Author(s): Herbst RS, Kies MS. Source: The Oncologist. 2002; 7 Suppl 4: 9-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202783&dopt=Abstract

·

ZD1839 (Iressa): for more than just non-small cell lung cancer. Author(s): Ranson M. Source: The Oncologist. 2002; 7 Suppl 4: 16-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202784&dopt=Abstract

·

ZD1839, a novel, oral epidermal growth factor receptor-tyrosine kinase inhibitor, as salvage treatment in patients with advanced non-small cell lung cancer. Experience from a single center participating in a compassionate use program. Author(s): Pallis AG, Mavroudis D, Androulakis N, Souglakos J, Kouroussis C, Bozionelou V, Vlachonikolis IG, Georgoulias V. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 301-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781429&dopt=Abstract

·

Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial-the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. Author(s): Rosen LS, Gordon D, Tchekmedyian S, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, de Souza P, Zheng M, Urbanowitz G, Reitsma D, Seaman JJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 15; 21(16): 3150-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915606&dopt=Abstract

149

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

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

7

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

150 Lung Cancer

The following is a typical result when searching for recently indexed consumer information on lung cancer: ·

A case-control study of lung cancer in Polish women. Author(s): Epidemiology Unit, Centre of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow, Poland. [email protected] Source: Rachtan, J Neoplasma. 2002; 49(2): 75-80 0028-2685

·

A cohort study of dietary carotenoids and lung cancer risk in women (Canada). Author(s): Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA. [email protected] Source: Rohan, T E Jain, M Howe, G R Miller, A B Cancer-Causes-Control. 2002 April; 13(3): 231-7 0957-5243

·

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer. Author(s): Southampton Health Technology Assessments Centre, Wessex Institute for Health Research and Development, University of Southampton, UK. Source: Clegg, A Scott, D A Sidhu, M Hewitson, P Waugh, N Health-Technol-Assess. 2001; 5(32): 1-195 1366-5278

·

Aberrant promoter methylation in Chinese patients with non-small cell lung cancer: patterns in primary tumors and potential diagnostic application in bronchoalevolar lavage. Author(s): University Department of Medicine, Queen Mary Hospital, Hong Kong. Source: Chan, E C Lam, S Y Tsang, K W Lam, B Ho, J C Fu, K H Lam, W K Kwong, Y L Clin-Cancer-Res. 2002 December; 8(12): 3741-6 1078-0432

·

Angiogenesis inhibitors in lung cancer. Author(s): Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 432, Houston 77030, USA. [email protected] Source: Kim, Edward S Herbst, Roy S Curr-Oncol-Repage 2002 July; 4(4): 325-33 15233790

·

Apoptosis of human highly metastatic lung cancer cell line 95-D induced by acutiaporberine, a novel bisalkaloid derived from Thalictrum acutifolium. Source: Chen, Q. Peng, W. Qi, S. Xu, A. Planta-med. Stuttgart : Georg Thieme Verlag,. June 2002. volume 68 (6) page 550-553. 0032-0943

·

Bradykinin antagonist dimer, CU201, inhibits the growth of human lung cancer cell lines in vitro and in vivo and produces synergistic growth inhibition in combination with other antitumor agents. Author(s): Lung Cancer Program of the University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver 80262, USA. [email protected] Source: Chan, D C Gera, L Stewart, J M Helfrich, B Zhao, T L Feng, W Y Chan, K K Covey, J M Bunn, P A Jr Clin-Cancer-Res. 2002 May; 8(5): 1280-7 1078-0432

·

Chemoprevention strategies for non-small cell lung cancer. Author(s): Netherlands Cancer Institute, Amsterdam, The Netherlands. [email protected] Source: van Zandwijk, Nico Hirsch, Fred R Curr-Opin-Oncol. 2002 March; 14(2): 185-90 1040-8746

Nutrition 151

·

Chemotherapy for small cell lung cancer. Author(s): Departments of Thoracic Oncology and Hematology/Oncology, Vanderbilt University, Nashville, TN 37232, USA. Source: Sandler, A B Semin-Oncol. 2003 February; 30(1): 9-25 0093-7754

·

Chemotherapy of non-small cell lung cancer in elderly patients. Author(s): Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy. [email protected] Source: Gridelli, C Maione, P Colantuoni, G Rossi, A Curr-Med-Chem. 2002 August; 9(16): 1487-95 0929-8673

·

Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Author(s): University of Minnesota Cancer Center, Minneapolis, MN 55455, USA. [email protected] Source: Hecht, Stephen S Lancet-Oncol. 2002 August; 3(8): 461-9 1470-2045

·

Comparison of unidimensional and bidimensional measurements in metastatic nonsmall cell lung cancer. Author(s): Department of Oncology, Clinica Universitaria de Navarra, Avenida de Pio XII, 36, 31008 Pamplona, Spain. [email protected] Source: Cortes, J Rodriguez, J Diaz Gonzalez, J A Garzon, C Gurpide, A Arbea, L Gil Bazo, I Navarro, V Cambeiro, M Nicolas, A I Martin Algarra, S Garcia Foncillas, J Calvo, E Br-J-Cancer. 2002 July 15; 87(2): 158-60 0007-0920

·

Concurrent administration of Docetaxel and Stealth liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection. Author(s): Tumour and Angiogenesis Research Group, PO Box 12, Democritus University of Thrace, Alexandroupolis 68100, Greece. [email protected] Source: Koukourakis, M I Romanidis, K Froudarakis, M Kyrgias, G Koukourakis, G V Retalis, G Bahlitzanakis, N Br-J-Cancer. 2002 August 12; 87(4): 385-92 0007-0920

·

Cost-effectiveness of chemotherapy for nonsmall-cell lung cancer. Author(s): Cancer Care Ontario, Toronto, Canada. Source: Dranitsaris, G Cottrell, W Evans, W K Curr-Opin-Oncol. 2002 July; 14(4): 375-83 1040-8746

·

Current role of irinotecan in the treatment of non-small-cell lung cancer. Author(s): Division of Medical Oncology, University of Colorado Health Sciences Center, Denver 80262, USA. [email protected] Source: Kelly, K Oncology-(Huntingt). 2002 September; 16(9): 1153-62, 1165; discussion 1165-6 passim 0890-9091

·

Dietary habits and lung cancer risk among Polish women. Author(s): Epidemiology Unit, Centre of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow, Poland. [email protected] Source: Rachtan, J Acta-Oncol. 2002; 41(4): 389-94 0284-186X

·

Docetaxel followed by gemcitabine in the treatment of advanced non-small cell lung cancer: a phase I study. Author(s): Department of Medical Oncology, Pierantoni Hospital, Forli, Italy. Source: Frassineti, Giovanni Luca Ibrahim, Toni Zoli, Wainer Monti, Manuela Ricotti, Luca Nanni, Oriana Amadori, Dino Tumori. 2002 Mar-April; 88(2): 99-103 0300-8916

152 Lung Cancer

·

Docetaxel in combination with platinums (cisplatin or carboplatin) in advanced and metastatic non-small cell lung cancer. Author(s): Lung and Thoracic Cancer Program, University of Pittsburgh Cancer Institute, PA. Source: Belani, Chandra P Semin-Oncol. 2002 June; 29(3 Suppl 12): 4-9 0093-7754

·

Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer. Author(s): First Department of Internal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. [email protected] Source: Yamada, M Kudoh, S Fukuda, H Nakagawa, K Yamamoto, N Nishimura, Y Negoro, S Takeda, K Tanaka, M Fukuoka, M Br-J-Cancer. 2002 July 29; 87(3): 258-63 0007-0920

·

Early results of a randomized phase III trial of platinum-containing doublets versus a nonplatinum doublet in the treatment of advanced non-small cell lung cancer: European Organization for Research and Treatment of Cancer 08975. Author(s): Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. Source: Giaccone, Giuseppe Semin-Oncol. 2002 June; 29(3 Suppl 9): 47-9 0093-7754

·

Epidemiology, etiology, and prevention of lung cancer. Author(s): Department of Medicine, University of California San Francisco at Fresno, University Medical Center, Fresno, California, USA. [email protected] Source: Bilello, Kathryn Smith Murin, Susan Matthay, Richard A Clin-Chest-Med. 2002 March; 23(1): 1-25 0272-5231

·

Exisulind in combination with docetaxel inhibits growth and metastasis of human lung cancer and prolongs survival in athymic nude rats with orthotopic lung tumors. Author(s): University of Colorado Cancer Center, Department of Medicine, Preventive Medicine and Biostatistics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Source: Chan, Daniel C Earle, Keith A Zhao, Tom L M Helfrich, Barbara Zeng, Chan Baron, Anna Whitehead, Clark M Piazza, Gary Pamukcu, Rifat Thompson, W Joseph Alila, Hector Nelson, Peter Bunn, Paul A Jr Clin-Cancer-Res. 2002 March; 8(3): 904-12 1078-0432

·

Familial cancer aggregation and the risk of lung cancer. Author(s): Department of Epidemiology, Public Health School, University of Sao Paulo, Sao Paulo, Brazil. [email protected] Source: Wunsch Filho, V Boffetta, P Colin, D Moncau, J E Sao-Paulo-Med-J. 2002 March 7; 120(2): 38-44 1516-3180

·

GEM 231, a second-generation antisense agent complementary to protein kinase A RIalpha subunit, potentiates antitumor activity of irinotecan in human colon, pancreas, prostate and lung cancer xenografts. Author(s): Hybridon, Inc., Cambridge, MA 02139, USA. [email protected] Source: Agrawal, S Kandimalla, E R Yu, D Ball, R Lombardi, G Lucas, T Dexter, D L Hollister, B A Chen, S F Int-J-Oncol. 2002 July; 21(1): 65-72 1019-6439

Nutrition 153

·

Identification of a novel synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9dien-28-oate, that potently induces caspase-mediated apoptosis in human lung cancer cells. Author(s): Department of Thoracic/Head and Neck Medical Oncology, Box 432, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Source: Kim, K B Lotan, R Yue, P Sporn, M B Suh, N Gribble, G W Honda, T Wu, G S Hong, W K Sun, S Y Mol-Cancer-Ther. 2002 January; 1(3): 177-84 1535-7163

·

Incorporation of pemetrexed (Alimta) into the treatment of non-small cell lung cancer (thoracic tumors). Author(s): Lung Cancer Program and Department of Medicine, University of Colorado Cancer Center and University of Colorado Health Sciences Center, Denver, CO 80262, USA. Source: Bunn, Paul A Jr Semin-Oncol. 2002 June; 29(3 Suppl 9): 17-22 0093-7754

·

Insulin-like growth factor-I inhibits cell growth in the a549 non-small lung cancer cell line. Author(s): Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia. Source: Kodama, Y Baxter, R C Martin, J L Am-J-Respir-Cell-Mol-Biol. 2002 September; 27(3): 336-44 1044-1549

·

Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer. Author(s): Center for Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-5671, USA. Source: Wu, H G Choy, H Oncology-(Huntingt). 2002 September; 16(9 Suppl 9): 13-8 0890-9091

·

Irinotecan in the treatment of small cell lung cancer. Author(s): Department of Respiratory Disease, Otemae Hospital, 1-5-34 Otemae, Chuoku, Osaka, Osaka, 540-0008, Japan. Source: Masuda, N Fukuoka, M Expert-Rev-Anticancer-Ther. 2001 August; 1(2): 187-95 1473-7140

·

Irinotecan plus cisplatin in small-cell lung cancer. Author(s): Division of Medical Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-5536, USA. [email protected] Source: Sandler, A Oncology-(Huntingt). 2002 September; 16(9 Suppl 9): 39-43 0890-9091

·

Irinotecan therapy for small-cell lung cancer. Author(s): Vanderbilt University, Medical Center, Nashville, Tennessee 37232, USA. Source: Sandler, A Oncology-(Huntingt). 2002 April; 16(4): 419-25, 428, 433; discussion 433-4, 437-8 0890-9091

·

Long-term follow-up of patients treated with paclitaxel/carboplatin-based chemotherapy for advanced non-small-cell lung cancer: sequential phase II trials of the Minnie Pearl Cancer Research Network. Author(s): Sarah Cannon Cancer Center and Tennessee Oncology, PLLC, Nashville, TN 37203, USA. Source: Hainsworth, John D Gray, James R Morrissey, Lisa H Kalman, Leonard A Hon, Jeremy K Greco, F Anthony J-Clin-Oncol. 2002 July 1; 20(13): 2937-42 0732-183X

154 Lung Cancer

·

Lung cancer prevention with (-)-epigallocatechin gallate using monitoring by heterogeneous nuclear ribonucleoprotein B1. Author(s): Saitama Cancer Center, Ina, Kitaadachi-gun 362-0806, Japan. Source: Fujimoto, Nobukazu Sueoka, Naoko Sueoka, Eisaburo Okabe, Sachiko Suganuma, Masami Harada, Mine Fujiki, Hirota Int-J-Oncol. 2002 June; 20(6): 1233-9 1019-6439

·

Mechanism of vinorelbine-induced radiosensitization of human small cell lung cancer cells. Author(s): Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan. Source: Fukuoka, Kazuya Arioka, Hitoshi Iwamoto, Yasuo Fukumoto, Hisao Kurokawa, Hirokazu Ishida, Tomoyuki Tomonari, Akira Suzuki, Toshihiro Usuda, Jitsuo Kanzawa, Fumihiko Kimura, Hiroshi Saijo, Nagahiro Nishio, Kazuto Cancer-ChemotherPharmacol. 2002 May; 49(5): 385-90 0344-5704

·

New treatment approaches for lung cancer and impact on survival. Author(s): Oncology Department, Hospital Universitario, Madrid, Spain. Source: Cortes Funes, Hernan Semin-Oncol. 2002 June; 29(3 Suppl 8): 26-9 0093-7754

·

Paclitaxel and carboplatin plus megestrol acetate in the treatment of advanced nonsmall cell lung cancer. Author(s): Department of Medicine, Faculty of Medicine, Chiang Mai University, Thailand. Source: Thongprasert, Sumitra Cheewakriangkrai, Rattiya Euathrongchit, Juntima Thaikla, Kanittha J-Med-Assoc-Thai. 2002 April; 85(4): 424-32 0125-2208

·

Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-smallcell lung cancer: a phase III randomized trial. Author(s): Second Medical Oncology Department, Hygeia Hospital, Athens, Greece. [email protected] Source: Kosmidis, P Mylonakis, N Nicolaides, C Kalophonos, C Samantas, E Boukovinas, J Fountzilas, G Skarlos, D Economopoulos, T Tsavdaridis, D Papakostas, P Bacoyiannis, C Dimopoulos, M J-Clin-Oncol. 2002 September 1; 20(17): 3578-85 0732183X

·

Pemetrexed as a single agent in the therapy of advanced lung cancer. Author(s): Department of Pulmonary Diseases, Vrije Universiteit, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. Source: Postmus, Pieter E Bunn, Paul A Jr Semin-Oncol. 2002 April; 29(2 Suppl 5): 17-22 0093-7754

·

Pemetrexed combination therapy in the treatment of non-small cell lung cancer. Author(s): Medical Oncology Service, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. Source: Rosell, Rafael Crino, Lucio Semin-Oncol. 2002 April; 29(2 Suppl 5): 23-9 00937754

·

Pemetrexed in the treatment of non-small cell lung cancer. Author(s): University of Toronto and the Princess Margaret Hospital, Toronto, ON, Canada. Source: Shepherd, F A Semin-Oncol. 2002 December; 29(6 Suppl 18): 43-8 0093-7754

Nutrition 155

·

Perspectives and opportunities: Docetaxel in the current and future treatment of nonsmall cell lung cancer. Author(s): Department of Medicine, Medical University of South Carolina, Charleston 29425, USA. Source: Green, Mark R Semin-Oncol. 2002 June; 29(3 Suppl 12): 17-21 0093-7754

·

Phase I/II study of gemcitabine plus vinorelbine in non-small cell lung cancer. Author(s): Medical Oncology Department, Hospital Central de Asturias, Oviedo, Spain. [email protected] Source: Esteban, E Fra, J Corral, N Valle, M Carrasco, J Sala, M Puerta, J Estrada, E Palacio, I Vieitez, J M Buesa, J M Lacave, A J Invest-New-Drugs. 2002 February; 20(1): 73-82 0167-6997

·

Phase II and pharmacologic study of weekly oral paclitaxel plus cyclosporine in patients with advanced non-small-cell lung cancer. Author(s): Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Source: Kruijtzer, C M Schellens, J H Mezger, J Scheulen, M E Keilholz, U Beijnen, J H Rosing, H Mathot, R A Marcus, S van Tinteren, H Baas, P J-Clin-Oncol. 2002 December 1; 20(23): 4508-16 0732-183X

·

Phase II neoadjuvant trial of paclitaxel by 96-hour continuous infusion (CIVI) in combination with cisplatin followed by chest radiotherapy for patients with stage III non-small-cell lung cancer. Author(s): Medicine Branch, Division of Clinical Sciences, National Cancer Institute (NCI)/National Naval Medical Center, NNMC, Bethesda, Maryland, USA. Source: Breathnach, O S Kasturi, V Kaye, F Herscher, L Georgiadis, M S Edison, M Schuler, B S Pizzella, P Steinberg, S M O'Neil, K Johnson, Bruce E Am-J-Clin-Oncol. 2002 June; 25(3): 269-73 0277-3732

·

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer. Author(s): Department of Internal Medicine, Korea University, College of Medicine, Seoul, Korea. Source: Kim, Y H Kim, J S Choi, Y H In, K H Park, H S Hong, D S Jeong, T J Lee, Y Y Nam, E Lee, S N Lee, K S Kim, H K Int-J-Clin-Oncol. 2002 April; 7(2): 114-9 1341-9625

·

Phase II study of docetaxel and gemcitabine combination chemotherapy in nonsmall-cell lung cancer patients failing previous chemotherapy. Author(s): Chest Department, Taipei Veterans General Hospital, and School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC. Source: Chen, Y M Perng, R P Lin, W C Wu, H W Tsai, C M Whang Peng, J Am-J-ClinOncol. 2002 October; 25(5): 509-12 0277-3732

·

Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. Author(s): Department of Clinical and Biological Sciences, University of Torino, Turin. [email protected] Source: Scagliotti, G V De Marinis, F Rinaldi, M Crino, L Gridelli, C Ricci, S Matano, E Boni, C Marangolo, M Failla, G Altavilla, G Adamo, V Ceribelli, A Clerici, M Di Costanzo, F Frontini, L Tonato, M J-Clin-Oncol. 2002 November 1; 20(21): 4285-91 0732183X

·

Platinum drugs in the treatment of non-small-cell lung cancer. Author(s): AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.

156 Lung Cancer

Source: Cosaert, J Quoix, E Br-J-Cancer. 2002 October 7; 87(8): 825-33 0007-0920 ·

Randomised phase III trial of irinotecan combined with cisplatin for advanced nonsmall-cell lung cancer. Author(s): Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan. [email protected] Source: Negoro, S Masuda, N Takada, Y Sugiura, T Kudoh, S Katakami, N Ariyoshi, Y Ohashi, Y Niitani, H Fukuoka, M Br-J-Cancer. 2003 February 10; 88(3): 335-41 0007-0920

·

Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. Author(s): University of Chicago Medical Center and Cancer and Leukemia Group B, Chicago, IL, USA. [email protected] Source: Vokes, E E Herndon, J E 2nd Crawford, J Leopold, K A Perry, M C Miller, A A Green, M R J-Clin-Oncol. 2002 October 15; 20(20): 4191-8 0732-183X

·

Real-time polymerase chain reaction monitoring of epithelial cell adhesion moleculeinduced T-cell stimulation in patients with lung cancer and healthy individuals using LightCycler technology. Author(s): Division of Oncology, Department of Internal Medicine, University Hospital Zurich, Ramistrasse 100, CH-8091 Zurich, Switzerland. [email protected] Source: TroJanuary, A Urosevic, M Dummer, R Nestle, F O Stahel, R A J-Immunother. 2002 May-June; 25(3): 264-8 1524-9557

·

Recombinant human interleukin-3 administered concomitantly with chemotherapy in patients with relapsed small cell lung cancer. Author(s): Department of Pulmonology, University Hospital, Free University of Amsterdam, The Netherlands. Source: Biesma, B van Kralingen, K W van Leen, R W Koster, M C Postmus, P E J-ExpTher-Oncol. 2002 Jan-February; 2(1): 47-52 1359-4117

·

Risk factors for lung cancer among Canadian women who have never smoked. Author(s): Centre for Chronic Disease Prevention and Control, Population and Public Health Brance, Health Canada, Ottawa, Ont. Source: Hu, J Mao, Y Dryer, D White, K Cancer-Detect-Prevolume 2002; 26(2): 129-38 0361-090X

·

Salvage chemotherapy with the gemcitabine/docetaxel combination in non-small cell lung cancer: an overview of recent phase II studies. Author(s): Department of Medicine, Medical Oncology Unit, Helena-Venizelou Hospital, Athens, Greece. [email protected] Source: Kosmas, C Tsavaris, N Kalofonos, H P Med-Sci-Monit. 2002 June; 8(6): PI58-63 1234-1010

·

Second-line chemotherapy with irinotecan and vinorelbine in stage IIIB and IV nonsmall-cell lung cancer: a phase II study. Author(s): Department of Oncology, Clinica Universitaria de Navarra, University of Navarra, Spain. Source: Gonzalez Cao, M Aramendia, J M Salgado, E Aristu, J Martinez Monje, R Algarra, S M Ordonez, J M Brugarolas, A Am-J-Clin-Oncol. 2002 October; 25(5): 480-4 0277-3732

Nutrition 157

·

Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. Author(s): Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. Source: Herbst, R S Maddox, A M Rothenberg, M L Small, E J Rubin, E H Baselga, J Rojo, F Hong, W K Swaisland, H Averbuch, S D Ochs, J LoRusso, P M J-Clin-Oncol. 2002 September 15; 20(18): 3815-25 0732-183X

·

Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents. Author(s): Department of Internal Medicine, Aichi Cancer Center Hospital, Nagoya 4648681, Japan. [email protected] Source: Hida, T Kozaki, K Ito, H Miyaishi, O Tatematsu, Y Suzuki, T Matsuo, K Sugiura, T Ogawa, M Takahashi, T Takahashi, T Clin-Cancer-Res. 2002 July; 8(7): 2443-7 10780432

·

Slow metabolism and long half life of methadone in a patient with lung cancer and cirrhosis. Author(s): Pharmacie, Hopital Paul-Guiraud, 54, avenue de la Republique, 94806 Villejuif Cedex. [email protected] Source: Beauverie, P Furlan, V Edel, Y A Ann-Med-Interne-(Paris). 2001 November; 152 Suppl 7: 50-2 0003-410X

·

The case for the introduction of new chemotherapy agents in the treatment of advanced non small cell lung cancer in the wake of the findings of The National Institute of Clinical Excellence (NICE). Author(s): Lung Unit, The Royal Marsden Hospital, Sutton, Surrey, UK. Source: Waters, J S O'Brien, M E Br-J-Cancer. 2002 August 27; 87(5): 481-90 0007-0920

·

The role of carotenoids on the risk of lung cancer. Author(s): Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Source: Epstein, K R Semin-Oncol. 2003 February; 30(1): 86-93 0093-7754

·

Tumor lysis syndrome in extensive-stage small-cell lung cancer. Author(s): Department of Radiation Oncology, MS 200, Hahnemann University Hospital, Broad and Vine Street, Philadelphia, PA 19102, USA. Source: Beriwal, S Singh, S Garcia Young, J A Am-J-Clin-Oncol. 2002 October; 25(5): 4745 0277-3732

·

Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer. Author(s): Grupo Oncologico Cooperativo del Sur (G.O.C.S.), Republica Argentina. Source: Perez, Juan E Machiavelli, Mario R Romero, Alberto O Romero Acuna, Luis A Dominguez, Maria E Fasce, Hebe Flores Acosta, Luis Marrone, Nora Romero Acuna, Juan M Langhi, Mario J Amato, Sonia Bologna, Fabrina Ortiz, Eduardo H Leone, Bernardo A Lacava, Juan A Vallejo, Carlos T Am-J-Clin-Oncol. 2002 August; 25(4): 383-7 0277-3732

·

Vinorelbine in the treatment of non-small cell lung cancer. Author(s): Divisione di Oncologia Medica, Azienda Ospedaliera S.G.Moscati, Avellino, Italy. [email protected] Source: Gridelli, C De Vivo, R Curr-Med-Chem. 2002 April; 9(8): 879-91 0929-8673

158 Lung Cancer

·

ZD1839 (Iressa) in non-small cell lung cancer. Author(s): Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. [email protected] Source: Herbst, R S Kies, M S Oncologist. 2002; 7 Suppl 4: 9-15 1083-7159

·

ZD1839 (Iressa): for more than just non-small cell lung cancer. Author(s): Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom. [email protected] Source: Ranson, M Oncologist. 2002; 7 Suppl 4: 16-24 1083-7159

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

A case-control study of lung cancer in Polish women. Author(s): Epidemiology Unit, Centre of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow, Poland. [email protected] Source: Rachtan, J Neoplasma. 2002; 49(2): 75-80 0028-2685

·

A cohort study of dietary carotenoids and lung cancer risk in women (Canada). Author(s): Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA. [email protected] Source: Rohan, T E Jain, M Howe, G R Miller, A B Cancer-Causes-Control. 2002 April; 13(3): 231-7 0957-5243

·

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer. Author(s): Southampton Health Technology Assessments Centre, Wessex Institute for Health Research and Development, University of Southampton, UK. Source: Clegg, A Scott, D A Sidhu, M Hewitson, P Waugh, N Health-Technol-Assess. 2001; 5(32): 1-195 1366-5278

·

Aberrant promoter methylation in Chinese patients with non-small cell lung cancer: patterns in primary tumors and potential diagnostic application in bronchoalevolar lavage. Author(s): University Department of Medicine, Queen Mary Hospital, Hong Kong. Source: Chan, E C Lam, S Y Tsang, K W Lam, B Ho, J C Fu, K H Lam, W K Kwong, Y L Clin-Cancer-Res. 2002 December; 8(12): 3741-6 1078-0432

·

Angiogenesis inhibitors in lung cancer. Author(s): Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 432, Houston 77030, USA. [email protected] Source: Kim, Edward S Herbst, Roy S Curr-Oncol-Repage 2002 July; 4(4): 325-33 15233790

·

Apoptosis of human highly metastatic lung cancer cell line 95-D induced by acutiaporberine, a novel bisalkaloid derived from Thalictrum acutifolium. Source: Chen, Q. Peng, W. Qi, S. Xu, A. Planta-med. Stuttgart : Georg Thieme Verlag,. June 2002. volume 68 (6) page 550-553. 0032-0943

Nutrition 159

·

Bradykinin antagonist dimer, CU201, inhibits the growth of human lung cancer cell lines in vitro and in vivo and produces synergistic growth inhibition in combination with other antitumor agents. Author(s): Lung Cancer Program of the University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver 80262, USA. [email protected] Source: Chan, D C Gera, L Stewart, J M Helfrich, B Zhao, T L Feng, W Y Chan, K K Covey, J M Bunn, P A Jr Clin-Cancer-Res. 2002 May; 8(5): 1280-7 1078-0432

·

Chemoprevention strategies for non-small cell lung cancer. Author(s): Netherlands Cancer Institute, Amsterdam, The Netherlands. [email protected] Source: van Zandwijk, Nico Hirsch, Fred R Curr-Opin-Oncol. 2002 March; 14(2): 185-90 1040-8746

·

Chemotherapy for small cell lung cancer. Author(s): Departments of Thoracic Oncology and Hematology/Oncology, Vanderbilt University, Nashville, TN 37232, USA. Source: Sandler, A B Semin-Oncol. 2003 February; 30(1): 9-25 0093-7754

·

Chemotherapy of non-small cell lung cancer in elderly patients. Author(s): Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy. [email protected] Source: Gridelli, C Maione, P Colantuoni, G Rossi, A Curr-Med-Chem. 2002 August; 9(16): 1487-95 0929-8673

·

Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Author(s): University of Minnesota Cancer Center, Minneapolis, MN 55455, USA. [email protected] Source: Hecht, Stephen S Lancet-Oncol. 2002 August; 3(8): 461-9 1470-2045

·

Comparison of unidimensional and bidimensional measurements in metastatic nonsmall cell lung cancer. Author(s): Department of Oncology, Clinica Universitaria de Navarra, Avenida de Pio XII, 36, 31008 Pamplona, Spain. [email protected] Source: Cortes, J Rodriguez, J Diaz Gonzalez, J A Garzon, C Gurpide, A Arbea, L Gil Bazo, I Navarro, V Cambeiro, M Nicolas, A I Martin Algarra, S Garcia Foncillas, J Calvo, E Br-J-Cancer. 2002 July 15; 87(2): 158-60 0007-0920

·

Concurrent administration of Docetaxel and Stealth liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection. Author(s): Tumour and Angiogenesis Research Group, PO Box 12, Democritus University of Thrace, Alexandroupolis 68100, Greece. [email protected] Source: Koukourakis, M I Romanidis, K Froudarakis, M Kyrgias, G Koukourakis, G V Retalis, G Bahlitzanakis, N Br-J-Cancer. 2002 August 12; 87(4): 385-92 0007-0920

·

Cost-effectiveness of chemotherapy for nonsmall-cell lung cancer. Author(s): Cancer Care Ontario, Toronto, Canada. Source: Dranitsaris, G Cottrell, W Evans, W K Curr-Opin-Oncol. 2002 July; 14(4): 375-83 1040-8746

·

Current role of irinotecan in the treatment of non-small-cell lung cancer. Author(s): Division of Medical Oncology, University of Colorado Health Sciences Center, Denver 80262, USA. [email protected]

160 Lung Cancer

Source: Kelly, K Oncology-(Huntingt). 2002 September; 16(9): 1153-62, 1165; discussion 1165-6 passim 0890-9091 ·

Dietary habits and lung cancer risk among Polish women. Author(s): Epidemiology Unit, Centre of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow, Poland. [email protected] Source: Rachtan, J Acta-Oncol. 2002; 41(4): 389-94 0284-186X

·

Docetaxel followed by gemcitabine in the treatment of advanced non-small cell lung cancer: a phase I study. Author(s): Department of Medical Oncology, Pierantoni Hospital, Forli, Italy. Source: Frassineti, Giovanni Luca Ibrahim, Toni Zoli, Wainer Monti, Manuela Ricotti, Luca Nanni, Oriana Amadori, Dino Tumori. 2002 Mar-April; 88(2): 99-103 0300-8916

·

Docetaxel in combination with platinums (cisplatin or carboplatin) in advanced and metastatic non-small cell lung cancer. Author(s): Lung and Thoracic Cancer Program, University of Pittsburgh Cancer Institute, PA. Source: Belani, Chandra P Semin-Oncol. 2002 June; 29(3 Suppl 12): 4-9 0093-7754

·

Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer. Author(s): First Department of Internal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. [email protected] Source: Yamada, M Kudoh, S Fukuda, H Nakagawa, K Yamamoto, N Nishimura, Y Negoro, S Takeda, K Tanaka, M Fukuoka, M Br-J-Cancer. 2002 July 29; 87(3): 258-63 0007-0920

·

Early results of a randomized phase III trial of platinum-containing doublets versus a nonplatinum doublet in the treatment of advanced non-small cell lung cancer: European Organization for Research and Treatment of Cancer 08975. Author(s): Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. Source: Giaccone, Giuseppe Semin-Oncol. 2002 June; 29(3 Suppl 9): 47-9 0093-7754

·

Epidemiology, etiology, and prevention of lung cancer. Author(s): Department of Medicine, University of California San Francisco at Fresno, University Medical Center, Fresno, California, USA. [email protected] Source: Bilello, Kathryn Smith Murin, Susan Matthay, Richard A Clin-Chest-Med. 2002 March; 23(1): 1-25 0272-5231

·

Exisulind in combination with docetaxel inhibits growth and metastasis of human lung cancer and prolongs survival in athymic nude rats with orthotopic lung tumors. Author(s): University of Colorado Cancer Center, Department of Medicine, Preventive Medicine and Biostatistics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Source: Chan, Daniel C Earle, Keith A Zhao, Tom L M Helfrich, Barbara Zeng, Chan Baron, Anna Whitehead, Clark M Piazza, Gary Pamukcu, Rifat Thompson, W Joseph Alila, Hector Nelson, Peter Bunn, Paul A Jr Clin-Cancer-Res. 2002 March; 8(3): 904-12 1078-0432

·

Familial cancer aggregation and the risk of lung cancer. Author(s): Department of Epidemiology, Public Health School, University of Sao Paulo, Sao Paulo, Brazil. [email protected]

Nutrition 161

Source: Wunsch Filho, V Boffetta, P Colin, D Moncau, J E Sao-Paulo-Med-J. 2002 March 7; 120(2): 38-44 1516-3180 ·

GEM 231, a second-generation antisense agent complementary to protein kinase A RIalpha subunit, potentiates antitumor activity of irinotecan in human colon, pancreas, prostate and lung cancer xenografts. Author(s): Hybridon, Inc., Cambridge, MA 02139, USA. [email protected] Source: Agrawal, S Kandimalla, E R Yu, D Ball, R Lombardi, G Lucas, T Dexter, D L Hollister, B A Chen, S F Int-J-Oncol. 2002 July; 21(1): 65-72 1019-6439

·

Identification of a novel synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9dien-28-oate, that potently induces caspase-mediated apoptosis in human lung cancer cells. Author(s): Department of Thoracic/Head and Neck Medical Oncology, Box 432, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Source: Kim, K B Lotan, R Yue, P Sporn, M B Suh, N Gribble, G W Honda, T Wu, G S Hong, W K Sun, S Y Mol-Cancer-Ther. 2002 January; 1(3): 177-84 1535-7163

·

Incorporation of pemetrexed (Alimta) into the treatment of non-small cell lung cancer (thoracic tumors). Author(s): Lung Cancer Program and Department of Medicine, University of Colorado Cancer Center and University of Colorado Health Sciences Center, Denver, CO 80262, USA. Source: Bunn, Paul A Jr Semin-Oncol. 2002 June; 29(3 Suppl 9): 17-22 0093-7754

·

Insulin-like growth factor-I inhibits cell growth in the a549 non-small lung cancer cell line. Author(s): Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia. Source: Kodama, Y Baxter, R C Martin, J L Am-J-Respir-Cell-Mol-Biol. 2002 September; 27(3): 336-44 1044-1549

·

Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer. Author(s): Center for Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-5671, USA. Source: Wu, H G Choy, H Oncology-(Huntingt). 2002 September; 16(9 Suppl 9): 13-8 0890-9091

·

Irinotecan in the treatment of small cell lung cancer. Author(s): Department of Respiratory Disease, Otemae Hospital, 1-5-34 Otemae, Chuoku, Osaka, Osaka, 540-0008, Japan. Source: Masuda, N Fukuoka, M Expert-Rev-Anticancer-Ther. 2001 August; 1(2): 187-95 1473-7140

·

Irinotecan plus cisplatin in small-cell lung cancer. Author(s): Division of Medical Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-5536, USA. [email protected] Source: Sandler, A Oncology-(Huntingt). 2002 September; 16(9 Suppl 9): 39-43 0890-9091

·

Irinotecan therapy for small-cell lung cancer. Author(s): Vanderbilt University, Medical Center, Nashville, Tennessee 37232, USA. Source: Sandler, A Oncology-(Huntingt). 2002 April; 16(4): 419-25, 428, 433; discussion 433-4, 437-8 0890-9091

162 Lung Cancer

·

Long-term follow-up of patients treated with paclitaxel/carboplatin-based chemotherapy for advanced non-small-cell lung cancer: sequential phase II trials of the Minnie Pearl Cancer Research Network. Author(s): Sarah Cannon Cancer Center and Tennessee Oncology, PLLC, Nashville, TN 37203, USA. Source: Hainsworth, John D Gray, James R Morrissey, Lisa H Kalman, Leonard A Hon, Jeremy K Greco, F Anthony J-Clin-Oncol. 2002 July 1; 20(13): 2937-42 0732-183X

·

Lung cancer prevention with (-)-epigallocatechin gallate using monitoring by heterogeneous nuclear ribonucleoprotein B1. Author(s): Saitama Cancer Center, Ina, Kitaadachi-gun 362-0806, Japan. Source: Fujimoto, Nobukazu Sueoka, Naoko Sueoka, Eisaburo Okabe, Sachiko Suganuma, Masami Harada, Mine Fujiki, Hirota Int-J-Oncol. 2002 June; 20(6): 1233-9 1019-6439

·

Mechanism of vinorelbine-induced radiosensitization of human small cell lung cancer cells. Author(s): Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan. Source: Fukuoka, Kazuya Arioka, Hitoshi Iwamoto, Yasuo Fukumoto, Hisao Kurokawa, Hirokazu Ishida, Tomoyuki Tomonari, Akira Suzuki, Toshihiro Usuda, Jitsuo Kanzawa, Fumihiko Kimura, Hiroshi Saijo, Nagahiro Nishio, Kazuto Cancer-ChemotherPharmacol. 2002 May; 49(5): 385-90 0344-5704

·

New treatment approaches for lung cancer and impact on survival. Author(s): Oncology Department, Hospital Universitario, Madrid, Spain. Source: Cortes Funes, Hernan Semin-Oncol. 2002 June; 29(3 Suppl 8): 26-9 0093-7754

·

Paclitaxel and carboplatin plus megestrol acetate in the treatment of advanced nonsmall cell lung cancer. Author(s): Department of Medicine, Faculty of Medicine, Chiang Mai University, Thailand. Source: Thongprasert, Sumitra Cheewakriangkrai, Rattiya Euathrongchit, Juntima Thaikla, Kanittha J-Med-Assoc-Thai. 2002 April; 85(4): 424-32 0125-2208

·

Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-smallcell lung cancer: a phase III randomized trial. Author(s): Second Medical Oncology Department, Hygeia Hospital, Athens, Greece. [email protected] Source: Kosmidis, P Mylonakis, N Nicolaides, C Kalophonos, C Samantas, E Boukovinas, J Fountzilas, G Skarlos, D Economopoulos, T Tsavdaridis, D Papakostas, P Bacoyiannis, C Dimopoulos, M J-Clin-Oncol. 2002 September 1; 20(17): 3578-85 0732183X

·

Pemetrexed as a single agent in the therapy of advanced lung cancer. Author(s): Department of Pulmonary Diseases, Vrije Universiteit, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. Source: Postmus, Pieter E Bunn, Paul A Jr Semin-Oncol. 2002 April; 29(2 Suppl 5): 17-22 0093-7754

·

Pemetrexed combination therapy in the treatment of non-small cell lung cancer. Author(s): Medical Oncology Service, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. Source: Rosell, Rafael Crino, Lucio Semin-Oncol. 2002 April; 29(2 Suppl 5): 23-9 00937754

Nutrition 163

·

Pemetrexed in the treatment of non-small cell lung cancer. Author(s): University of Toronto and the Princess Margaret Hospital, Toronto, ON, Canada. Source: Shepherd, F A Semin-Oncol. 2002 December; 29(6 Suppl 18): 43-8 0093-7754

·

Perspectives and opportunities: Docetaxel in the current and future treatment of nonsmall cell lung cancer. Author(s): Department of Medicine, Medical University of South Carolina, Charleston 29425, USA. Source: Green, Mark R Semin-Oncol. 2002 June; 29(3 Suppl 12): 17-21 0093-7754

·

Phase I/II study of gemcitabine plus vinorelbine in non-small cell lung cancer. Author(s): Medical Oncology Department, Hospital Central de Asturias, Oviedo, Spain. [email protected] Source: Esteban, E Fra, J Corral, N Valle, M Carrasco, J Sala, M Puerta, J Estrada, E Palacio, I Vieitez, J M Buesa, J M Lacave, A J Invest-New-Drugs. 2002 February; 20(1): 73-82 0167-6997

·

Phase II and pharmacologic study of weekly oral paclitaxel plus cyclosporine in patients with advanced non-small-cell lung cancer. Author(s): Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Source: Kruijtzer, C M Schellens, J H Mezger, J Scheulen, M E Keilholz, U Beijnen, J H Rosing, H Mathot, R A Marcus, S van Tinteren, H Baas, P J-Clin-Oncol. 2002 December 1; 20(23): 4508-16 0732-183X

·

Phase II neoadjuvant trial of paclitaxel by 96-hour continuous infusion (CIVI) in combination with cisplatin followed by chest radiotherapy for patients with stage III non-small-cell lung cancer. Author(s): Medicine Branch, Division of Clinical Sciences, National Cancer Institute (NCI)/National Naval Medical Center, NNMC, Bethesda, Maryland, USA. Source: Breathnach, O S Kasturi, V Kaye, F Herscher, L Georgiadis, M S Edison, M Schuler, B S Pizzella, P Steinberg, S M O'Neil, K Johnson, Bruce E Am-J-Clin-Oncol. 2002 June; 25(3): 269-73 0277-3732

·

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer. Author(s): Department of Internal Medicine, Korea University, College of Medicine, Seoul, Korea. Source: Kim, Y H Kim, J S Choi, Y H In, K H Park, H S Hong, D S Jeong, T J Lee, Y Y Nam, E Lee, S N Lee, K S Kim, H K Int-J-Clin-Oncol. 2002 April; 7(2): 114-9 1341-9625

·

Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. Author(s): Department of Clinical and Biological Sciences, University of Torino, Turin. [email protected] Source: Scagliotti, G V De Marinis, F Rinaldi, M Crino, L Gridelli, C Ricci, S Matano, E Boni, C Marangolo, M Failla, G Altavilla, G Adamo, V Ceribelli, A Clerici, M Di Costanzo, F Frontini, L Tonato, M J-Clin-Oncol. 2002 November 1; 20(21): 4285-91 0732183X

·

Platinum drugs in the treatment of non-small-cell lung cancer. Author(s): AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. Source: Cosaert, J Quoix, E Br-J-Cancer. 2002 October 7; 87(8): 825-33 0007-0920

164 Lung Cancer

·

Randomised phase III trial of irinotecan combined with cisplatin for advanced nonsmall-cell lung cancer. Author(s): Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan. [email protected] Source: Negoro, S Masuda, N Takada, Y Sugiura, T Kudoh, S Katakami, N Ariyoshi, Y Ohashi, Y Niitani, H Fukuoka, M Br-J-Cancer. 2003 February 10; 88(3): 335-41 0007-0920

·

Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. Author(s): University of Chicago Medical Center and Cancer and Leukemia Group B, Chicago, IL, USA. [email protected] Source: Vokes, E E Herndon, J E 2nd Crawford, J Leopold, K A Perry, M C Miller, A A Green, M R J-Clin-Oncol. 2002 October 15; 20(20): 4191-8 0732-183X

·

Real-time polymerase chain reaction monitoring of epithelial cell adhesion moleculeinduced T-cell stimulation in patients with lung cancer and healthy individuals using LightCycler technology. Author(s): Division of Oncology, Department of Internal Medicine, University Hospital Zurich, Ramistrasse 100, CH-8091 Zurich, Switzerland. [email protected] Source: TroJanuary, A Urosevic, M Dummer, R Nestle, F O Stahel, R A J-Immunother. 2002 May-June; 25(3): 264-8 1524-9557

·

Recombinant human interleukin-3 administered concomitantly with chemotherapy in patients with relapsed small cell lung cancer. Author(s): Department of Pulmonology, University Hospital, Free University of Amsterdam, The Netherlands. Source: Biesma, B van Kralingen, K W van Leen, R W Koster, M C Postmus, P E J-ExpTher-Oncol. 2002 Jan-February; 2(1): 47-52 1359-4117

·

Risk factors for lung cancer among Canadian women who have never smoked. Author(s): Centre for Chronic Disease Prevention and Control, Population and Public Health Brance, Health Canada, Ottawa, Ont. Source: Hu, J Mao, Y Dryer, D White, K Cancer-Detect-Prevolume 2002; 26(2): 129-38 0361-090X

·

Salvage chemotherapy with the gemcitabine/docetaxel combination in non-small cell lung cancer: an overview of recent phase II studies. Author(s): Department of Medicine, Medical Oncology Unit, Helena-Venizelou Hospital, Athens, Greece. [email protected] Source: Kosmas, C Tsavaris, N Kalofonos, H P Med-Sci-Monit. 2002 June; 8(6): PI58-63 1234-1010

·

Second-line chemotherapy with irinotecan and vinorelbine in stage IIIB and IV nonsmall-cell lung cancer: a phase II study. Author(s): Department of Oncology, Clinica Universitaria de Navarra, University of Navarra, Spain. Source: Gonzalez Cao, M Aramendia, J M Salgado, E Aristu, J Martinez Monje, R Algarra, S M Ordonez, J M Brugarolas, A Am-J-Clin-Oncol. 2002 October; 25(5): 480-4 0277-3732

·

Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. Author(s): Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Nutrition 165

Source: Herbst, R S Maddox, A M Rothenberg, M L Small, E J Rubin, E H Baselga, J Rojo, F Hong, W K Swaisland, H Averbuch, S D Ochs, J LoRusso, P M J-Clin-Oncol. 2002 September 15; 20(18): 3815-25 0732-183X ·

Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents. Author(s): Department of Internal Medicine, Aichi Cancer Center Hospital, Nagoya 4648681, Japan. [email protected] Source: Hida, T Kozaki, K Ito, H Miyaishi, O Tatematsu, Y Suzuki, T Matsuo, K Sugiura, T Ogawa, M Takahashi, T Takahashi, T Clin-Cancer-Res. 2002 July; 8(7): 2443-7 10780432

·

Slow metabolism and long half life of methadone in a patient with lung cancer and cirrhosis. Author(s): Pharmacie, Hopital Paul-Guiraud, 54, avenue de la Republique, 94806 Villejuif Cedex. [email protected] Source: Beauverie, P Furlan, V Edel, Y A Ann-Med-Interne-(Paris). 2001 November; 152 Suppl 7: 50-2 0003-410X

·

The case for the introduction of new chemotherapy agents in the treatment of advanced non small cell lung cancer in the wake of the findings of The National Institute of Clinical Excellence (NICE). Author(s): Lung Unit, The Royal Marsden Hospital, Sutton, Surrey, UK. Source: Waters, J S O'Brien, M E Br-J-Cancer. 2002 August 27; 87(5): 481-90 0007-0920

·

The role of carotenoids on the risk of lung cancer. Author(s): Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Source: Epstein, K R Semin-Oncol. 2003 February; 30(1): 86-93 0093-7754

·

Tumor lysis syndrome in extensive-stage small-cell lung cancer. Author(s): Department of Radiation Oncology, MS 200, Hahnemann University Hospital, Broad and Vine Street, Philadelphia, PA 19102, USA. Source: Beriwal, S Singh, S Garcia Young, J A Am-J-Clin-Oncol. 2002 October; 25(5): 4745 0277-3732

·

Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer. Author(s): Grupo Oncologico Cooperativo del Sur (G.O.C.S.), Republica Argentina. Source: Perez, Juan E Machiavelli, Mario R Romero, Alberto O Romero Acuna, Luis A Dominguez, Maria E Fasce, Hebe Flores Acosta, Luis Marrone, Nora Romero Acuna, Juan M Langhi, Mario J Amato, Sonia Bologna, Fabrina Ortiz, Eduardo H Leone, Bernardo A Lacava, Juan A Vallejo, Carlos T Am-J-Clin-Oncol. 2002 August; 25(4): 383-7 0277-3732

·

Vinorelbine in the treatment of non-small cell lung cancer. Author(s): Divisione di Oncologia Medica, Azienda Ospedaliera S.G.Moscati, Avellino, Italy. [email protected] Source: Gridelli, C De Vivo, R Curr-Med-Chem. 2002 April; 9(8): 879-91 0929-8673

·

ZD1839 (Iressa) in non-small cell lung cancer. Author(s): Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. [email protected] Source: Herbst, R S Kies, M S Oncologist. 2002; 7 Suppl 4: 9-15 1083-7159

166 Lung Cancer

·

ZD1839 (Iressa): for more than just non-small cell lung cancer. Author(s): Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom. [email protected] Source: Ranson, M Oncologist. 2002; 7 Suppl 4: 16-24 1083-7159

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

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

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

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

·

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

·

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

·

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

·

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

·

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

·

WebMDÒHealth: http://my.webmd.com/nutrition

·

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

Nutrition 167

The following is a specific Web list relating to lung 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 Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Provitamin A Source: Integrative Medicine Communications; www.drkoop.com Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com

·

Minerals Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Quercetin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10053,00.html Selenium Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Selenium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10055,00.html

168 Lung Cancer

·

Food and Diet Arugula Source: Healthnotes, Inc.; www.healthnotes.com Asparagus Source: Healthnotes, Inc.; www.healthnotes.com Beets Source: Healthnotes, Inc.; www.healthnotes.com Bok Choy Source: Healthnotes, Inc.; www.healthnotes.com Broccoli Source: Healthnotes, Inc.; www.healthnotes.com Carrots Source: Healthnotes, Inc.; www.healthnotes.com Chicory Source: Healthnotes, Inc.; www.healthnotes.com Collards Source: Healthnotes, Inc.; www.healthnotes.com Dandelion Greens Source: Healthnotes, Inc.; www.healthnotes.com Endive Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: Healthnotes, Inc.; www.healthnotes.com Kohlrabi Source: Healthnotes, Inc.; www.healthnotes.com Mustard Greens Source: Healthnotes, Inc.; www.healthnotes.com Spinach Source: Healthnotes, Inc.; www.healthnotes.com Summer Squash Source: Healthnotes, Inc.; www.healthnotes.com Sweet Peppers Source: Healthnotes, Inc.; www.healthnotes.com Sweet Potatoes Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition 169

Tomatoes Source: Healthnotes, Inc.; www.healthnotes.com Turnips Source: Healthnotes, Inc.; www.healthnotes.com Winter Squash Source: Healthnotes, Inc.; www.healthnotes.com Yams Source: Healthnotes, Inc.; www.healthnotes.com

171

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

“The guard dies, it does not surrender!” progress in the management of small-cell lung cancer? Author(s): Johnson DH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 15; 20(24): 4618-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488404&dopt=Abstract

·

18F-fluorodeoxyglucose positron emission tomography in small-cell lung cancer. Author(s): Zhao DS, Valdivia AY, Li Y, Blaufox MD. Source: Semin Nucl Med. 2002 October; 32(4): 272-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524651&dopt=Abstract

·

A dose escalation study of docetaxel and oxaliplatin combination in patients with metastatic breast and non-small cell lung cancer.

172 Lung Cancer

Author(s): Kouroussis C, Agelaki S, Mavroudis D, Kakolyris S, Androulakis N, Kalbakis K, Souglakos J, Mallas K, Bozionelou V, Pallis A, Adamtziki H, Georgoulias V. Source: Anticancer Res. 2003 January-February; 23(1B): 785-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680184&dopt=Abstract ·

A little to a lot or a lot to a little? An analysis of pneumonitis risk from dose-volume histogram parameters of the lung in patients with lung cancer treated with 3-D conformal radiotherapy. Author(s): Willner J, Jost A, Baier K, Flentje M. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 2003 August; 179(8): 548-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509954&dopt=Abstract

·

A multicenter phase II study of docetaxel and carboplatin combination as front-line treatment in advanced non-small cell lung cancer. Author(s): Giannakakis T, Kakolyris S, Theodoropoulos E, Kouroussis C, Michailakis E, Papadouris S, Tsitoura M, Kalbakis K, Souglakos J, Agelaki S, Vardakis N, Georgoulias V. Source: Anticancer Res. 2002 November-December; 22(6B): 3743-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552987&dopt=Abstract

·

A multicenter phase II study of the efficacy and safety of docetaxel plus cisplatin in Asian chemonaive patients with metastatic or locally advanced non-small cell lung cancer. Author(s): Ho JC, Tan EH, Leong SS, Wang CH, Sun Y, Li R, Wahid MI, Jusuf A, Liao M, Guan Z, Handoyo P, Huang JS, Chan V, Luna G, Tsang KW, Lam WK; Asian-Pacific Collaborative Group. Source: Respiratory Medicine. 2003 July; 97(7): 796-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854629&dopt=Abstract

·

A phase I study of carboplatin and docetaxel for advanced non-small cell lung cancer using the continual reassessment method. Author(s): Kasahara K, Myo S, Iwasa K, Kimura H, Shirasaki H, Yasuda U, Shibata K, Shintani H, Nishi K, Fujimura M, Nakao S. Source: Japanese Journal of Clinical Oncology. 2002 December; 32(12): 512-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578899&dopt=Abstract

·

A phase I trial of weekly docetaxel and cisplatinum combined to concurrent hyperfractionated radiotherapy for non-small cell lung cancer and squamous cell carcinoma of head and neck. Author(s): Varveris H, Mazonakis M, Vlachaki M, Kachris S, Lyraraki E, Zoras O, Maris T, Froudarakis M, Velegrakis J, Perysinakis C, Damilakis J, Samonis G. Source: Oncol Rep. 2003 January-February; 10(1): 185-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469168&dopt=Abstract

Alternative Medicine 173

·

A phase II study of bryostatin-1 and paclitaxel in patients with advanced non-small cell lung cancer. Author(s): Winegarden JD, Mauer AM, Gajewski TF, Hoffman PC, Krauss S, Rudin CM, Vokes EE. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581572&dopt=Abstract

·

A phase II study of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer. Author(s): Mackay HJ, O'Brien M, Hill S, Lees SM, Thatcher N, Smith IE, Dunlop DJ. Source: Clin Oncol (R Coll Radiol). 2003 June; 15(4): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846495&dopt=Abstract

·

A phase II study of non-platinum based chemotherapy with paclitaxel and vinorelbine in non-small cell lung cancer. Author(s): Ginopoulos P, Kontomanolis E, Kardamakis D, Sougleri M, Rathosis S, Karana A, Christias H, Mandellos G. Source: Lung Cancer (Amsterdam, Netherlands). 2002 November; 38(2): 199-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399133&dopt=Abstract

·

A phase II study of vinorelbine, mitomycin C and cisplatin chemotherapy for advanced non-small cell lung cancer. Author(s): Kwon MR, Jeong TY, Yuh YJ, Kim SR. Source: Korean J Intern Med. 2002 December; 17(4): 240-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647638&dopt=Abstract

·

A phase II study of weekly gemcitabine and paclitaxel in patients with previously untreated stage IIIb and IV non-small cell lung cancer. Author(s): Bhatia S, Hanna N, Ansari R, Pletcher W, Einhorn L, Ng E, Sandler A. Source: Lung Cancer (Amsterdam, Netherlands). 2002 October; 38(1): 73-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367796&dopt=Abstract

·

A phase II trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis. Author(s): Downey RJ, Ng KK, Kris MG, Bains MS, Miller VA, Heelan R, Bilsky M, Ginsberg R, Rusch VW. Source: Lung Cancer (Amsterdam, Netherlands). 2002 November; 38(2): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399132&dopt=Abstract

·

A phase II trial of vinorelbine plus gemcitabine in previously untreated inoperable (stage IIIb/IV) non-small-cell lung cancer patients aged 80 or older. Author(s): Chen YM, Perng RP, Chen MC, Tsai CM, Ming-Liu J, Whang-Peng J.

174 Lung Cancer

Source: Lung Cancer (Amsterdam, Netherlands). 2003 May; 40(2): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711125&dopt=Abstract ·

A phase III randomized evaluation of amifostine in stage IIIA/IIIB non-small cell lung cancer patients receiving concurrent carboplatin, paclitaxel, and radiation therapy followed by gemcitabine and cisplatin intensification: preliminary findings. Author(s): Senzer N. Source: Seminars in Oncology. 2002 December; 29(6 Suppl 19): 38-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577242&dopt=Abstract

·

A randomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer (JCOG 9209). Author(s): Nagai K, Tsuchiya R, Mori T, Tada H, Ichinose Y, Koike T, Kato H; Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 February; 125(2): 25460. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579093&dopt=Abstract

·

A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-smallcell lung cancer. Author(s): Massarelli E, Andre F, Liu DD, Lee JJ, Wolf M, Fandi A, Ochs J, Le Chevalier T, Fossella F, Herbst RS. Source: Lung Cancer (Amsterdam, Netherlands). 2003 January; 39(1): 55-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499095&dopt=Abstract

·

Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancer. Author(s): Schellens JH, Planting AS, van Zandwijk N, Ma J, Maliepaard M, van der Burg ME, de Boer-Dennert M, Brouwer E, van der Gaast A, van den Bent MJ, Verweij J. Source: British Journal of Cancer. 2003 March 24; 88(6): 814-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644815&dopt=Abstract

·

Alpha-1-acid glycoprotein as an independent predictor for treatment effects and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel. Author(s): Bruno R, Olivares R, Berille J, Chaikin P, Vivier N, Hammershaimb L, Rhodes GR, Rigas JR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 March; 9(3): 1077-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631610&dopt=Abstract

·

An advance in small-cell lung cancer treatment--more or less. Author(s): Laskin J, Sandler A, Johnson DH.

Alternative Medicine 175

Source: Journal of the National Cancer Institute. 2003 August 6; 95(15): 1099-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902431&dopt=Abstract ·

Antiproliferative and chemopreventive effects of adlay seed on lung cancer in vitro and in vivo. Author(s): Chang HC, Huang YC, Hung WC. Source: Journal of Agricultural and Food Chemistry. 2003 June 4; 51(12): 3656-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769541&dopt=Abstract

·

Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by anti-microtubule agents in human lung cancers. Author(s): Masuda A, Maeno K, Nakagawa T, Saito H, Takahashi T. Source: American Journal of Pathology. 2003 September; 163(3): 1109-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937152&dopt=Abstract

·

Bcl-2 and bax expression in advanced non-small cell lung cancer: lack of correlation with chemotherapy response or survival in patients treated with docetaxel plus vinorelbine. Author(s): Krug LM, Miller VA, Filippa DA, Venkatraman E, Ng KK, Kris MG. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581565&dopt=Abstract

·

Beta-carotene and lung cancer: a lesson for future chemoprevention investigations? Author(s): Greenwald P. Source: Journal of the National Cancer Institute. 2003 January 1; 95(1): E1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509411&dopt=Abstract

·

Breathlessness clinics within specialist palliative care settings can improve the quality of life and functional capacity of patients with lung cancer. Author(s): Hately J, Laurence V, Scott A, Baker R, Thomas P. Source: Palliative Medicine. 2003 July; 17(5): 410-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882259&dopt=Abstract

·

Camptothecin and taxane regimens for small-cell lung cancer. Author(s): Kwong MS, Bleickardt E, Murren JR. Source: Oncology (Huntingt). 2002 September; 16(9 Suppl 9): 33-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375799&dopt=Abstract

·

Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells. Author(s): Shibakura M, Niiya K, Kiguchi T, Nakata Y, Tanimoto M.

176 Lung Cancer

Source: Acta Medica Okayama. 2002 October; 56(5): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530505&dopt=Abstract ·

Camptothecins and lung cancer: improved delivery systems by aerosol. Author(s): Koshkina NV, Waldrep JC, Knight V. Source: Current Cancer Drug Targets. 2003 August; 3(4): 251-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871056&dopt=Abstract

·

Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsyproven stage IIIA N2 non-small cell lung cancer. an EORTC phase II study (EORTC 08958). Author(s): O'Brien ME, Splinter T, Smit EF, Biesma B, Krzakowski M, Tjan-Heijnen VC, Van Bochove A, Stigt J, Smid-Geirnaerdt MJ, Debruyne C, Legrand C, Giaccone G; EORTC Lung Cancer Group. Source: European Journal of Cancer (Oxford, England : 1990). 2003 July; 39(10): 1416-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826045&dopt=Abstract

·

Carboplatin plus vinorelbine with concomitant radiation therapy in advanced nonsmall cell lung cancer: a phase I study. Author(s): Hoffman PC, Cohen EE, Masters GA, Haraf DJ, Mauer AM, Rudin CM, Krauss SA, Huo D, Vokes EE. Source: Lung Cancer (Amsterdam, Netherlands). 2002 October; 38(1): 65-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367795&dopt=Abstract

·

Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer. Author(s): Altorki NK, Keresztes RS, Port JL, Libby DM, Korst RJ, Flieder DB, Ferrara CA, Yankelevitz DF, Subbaramaiah K, Pasmantier MW, Dannenberg AJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 July 15; 21(14): 2645-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860939&dopt=Abstract

·

Chemotherapy for elderly patients with advanced non-small-cell lung cancer. Author(s): Bunn PA Jr, Lilenbaum R. Source: Journal of the National Cancer Institute. 2003 March 5; 95(5): 341-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618492&dopt=Abstract

·

Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. Author(s): Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferrau F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators.

Alternative Medicine 177

Source: Journal of the National Cancer Institute. 2003 March 5; 95(5): 362-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618501&dopt=Abstract ·

Chemotherapy for small cell lung cancer in patients over 80 years old. Author(s): Ueda H, Kuwahara M, Sakada T, Motohiro A. Source: Anticancer Res. 2002 November-December; 22(6B): 3629-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552967&dopt=Abstract

·

Chemotherapy for small cell lung cancer. Author(s): Sandler AB. Source: Seminars in Oncology. 2003 February; 30(1): 9-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635086&dopt=Abstract

·

Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. Author(s): Sundstrom S, Bremnes RM, Kaasa S, Aasebo U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 15; 20(24): 4665-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488411&dopt=Abstract

·

Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. Author(s): Alberola V, Camps C, Provencio M, Isla D, Rosell R, Vadell C, Bover I, RuizCasado A, Azagra P, Jimenez U, Gonzalez-Larriba JL, Diz P, Cardenal F, Artal A, Carrato A, Morales S, Sanchez JJ, de las Penas R, Felip E, Lopez-Vivanco G; Spanish Lung Cancer Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3207-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947054&dopt=Abstract

·

Cisplatin plus vinorelbine as induction chemotherapy followed by surgery in the treatment of stage IIIB non-small cell lung cancer. Final results of a multicenter phase II study. Author(s): Cigolari S, Curcio C, Maiorino A, Sessa R, Cioffi A, Massimo M. Source: Anticancer Res. 2003 March-April; 23(2C): 1803-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820462&dopt=Abstract

·

Cisplatin-etoposide alternating with topotecan in patients with extensive stage small cell lung cancer (SCLC). A multicenter phase II study. Author(s): Mavroudis D, Veslemes M, Kouroussis Ch, Tzanakis N, Ferdoutsis E,

178 Lung Cancer

Toumbis M, Ziotopoulos P, Agelidou M, Tselepatiotis E, Kalbakis K, Souglakos J, Magkanas E, Samonis G, Georgoulias V; Hellenic Oncology Research Group. Source: Lung Cancer (Amsterdam, Netherlands). 2002 October; 38(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367794&dopt=Abstract ·

Combination chemotherapy with gemcitabine and vinorelbine in the treatment of patients with relapsed or refractory small cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network. Author(s): Hainsworth JD, Burris HA 3rd, Erland JB, Baker M, Scullin DC Jr, Shaffer DW, Greco FA; Minnie Pearl Cancer Research Network. Source: Cancer Investigation. 2003 April; 21(2): 193-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743984&dopt=Abstract

·

Combination second-line chemotherapy with gemcitabine and docetaxel for recurrent non-small-cell lung cancer after platinum-containing chemotherapy: a phase I/II trial. Author(s): Niho S, Kubota K, Goto K, Ohmatsu H, Matsumoto T, Kakinuma R, Nishiwaki Y. Source: Cancer Chemotherapy and Pharmacology. 2003 July; 52(1): 19-24. Epub 2003 April 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712259&dopt=Abstract

·

Comment on “A pilot trial of G3139, a bcl-2 antisense oligonucleotide, and paclitaxel in patients with chemorefractory small-cell lung cancer”, by C. M. Rudin et al. (Ann Oncol 2002; 13: 539-545). Author(s): Gautschi O, Zangemeister-Wittke U, Stahel RA. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 January; 14(1): 170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488311&dopt=Abstract

·

Comparing whole body 18F-2-deoxyglucose positron emission tomography and technetium-99m methylene diophosphate bone scan to detect bone metastases in patients with non-small cell lung cancer. Author(s): Hsia TC, Shen YY, Yen RF, Kao CH, Changlai SP. Source: Neoplasma. 2002; 49(4): 267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382027&dopt=Abstract

·

Concomitant weekly docetaxel, cisplatin and radiation therapy in locally advanced non-small cell lung cancer: a dose finding study. Author(s): Mudad R, Ramsey M, Kovitz K, Curiel TJ, Hartz R, Nedzi LL, Weiner RS, Zakris EL. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581570&dopt=Abstract

Alternative Medicine 179

·

Concurrent two-dimensional radiotherapy and weekly docetaxel in the treatment of stage III non-small cell lung cancer: a good local response but no good survival due to radiation pneumonitis. Author(s): Onishi H, Kuriyama K, Yamaguchi M, Komiyama T, Tanaka S, Araki T, Nishikawa K, Ishihara H. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660011&dopt=Abstract

·

Conservation of the class I beta-tubulin gene in human populations and lack of mutations in lung cancers and paclitaxel-resistant ovarian cancers. Author(s): Sale S, Sung R, Shen P, Yu K, Wang Y, Duran GE, Kim JH, Fojo T, Oefner PJ, Sikic BI. Source: Molecular Cancer Therapeutics. 2002 January; 1(3): 215-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467216&dopt=Abstract

·

Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-smallcell lung cancer: phase II Southwest Oncology Group Study S9504. Author(s): Gandara DR, Chansky K, Albain KS, Leigh BR, Gaspar LE, Lara PN Jr, Burris H, Gumerlock P, Kuebler JP, Bearden JD 3rd, Crowley J, Livingston R; Southwest Oncology Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 May 15; 21(10): 2004-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743155&dopt=Abstract

·

Current role of irinotecan in the treatment of non-small-cell lung cancer. Author(s): Kelly K. Source: Oncology (Huntingt). 2002 September; 16(9): 1153-62, 1165; Discussion 1165-6 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380945&dopt=Abstract

·

DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer. Author(s): Hansen LT, Lundin C, Helleday T, Poulsen HS, Sorensen CS, Petersen LN, Spang-Thomsen M. Source: Lung Cancer (Amsterdam, Netherlands). 2003 May; 40(2): 157-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711116&dopt=Abstract

·

Do age and comorbidity impact treatment allocation and outcomes in limited stage small-cell lung cancer? a community-based population analysis. Author(s): Ludbrook JJ, Truong PT, MacNeil MV, Lesperance M, Webber A, Joe H, Martins H, Lim J.

180 Lung Cancer

Source: International Journal of Radiation Oncology, Biology, Physics. 2003 April 1; 55(5): 1321-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654444&dopt=Abstract ·

Docetaxel as neoadjuvant therapy for radically treatable stage III non-small-cell lung cancer: a multinational randomised phase III study. Author(s): Mattson KV, Abratt RP, ten Velde G, Krofta K. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 January; 14(1): 116-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488303&dopt=Abstract

·

Docetaxel as second-line chemotherapy for advanced non-small cell lung cancer. Author(s): Thongprasert S, Cheewakriangkrai R, Napapan S. Source: J Med Assoc Thai. 2002 December; 85(12): 1296-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678167&dopt=Abstract

·

Docetaxel in non-small cell lung cancer: a review. Author(s): Davies AM, Lara PN Jr, Mack PC, Gandara DR. Source: Expert Opinion on Pharmacotherapy. 2003 April; 4(4): 553-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667118&dopt=Abstract

·

Dose-dense therapy with a novel irinotecan regimen for small-cell lung cancer. Author(s): Johnson FM, Kurie JM, Peeples BO, Pisters KM, Fossella FV, Papadimitrakopoulou VA, Blumenschein GR, Komaki R, Glisson BS. Source: Oncology (Huntingt). 2003 July; 17(7 Suppl 7): 17-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886869&dopt=Abstract

·

Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer. Author(s): Choi NC, Fischman AJ, Niemierko A, Ryu JS, Lynch T, Wain J, Wright C, Fidias P, Mathisen D. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 November 15; 54(4): 1024-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419428&dopt=Abstract

·

Dramatic effect of ZD1839 ('Iressa') in a patient with advanced non-small-cell lung cancer and poor performance status. Author(s): Fujiwara K, Kiura K, Ueoka H, Tabata M, Hamasaki S, Tanimoto M. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660009&dopt=Abstract

Alternative Medicine 181

·

Drugs for preventing lung cancer in healthy people. Author(s): Caraballoso M, Sacristan M, Serra C, Bonfill X. Source: Cochrane Database Syst Rev. 2003; (2): Cd002141. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804424&dopt=Abstract

·

Early change in patient-reported health during lung cancer chemotherapy predicts clinical outcomes beyond those predicted by baseline report: results from Eastern Cooperative Oncology Group Study 5592. Author(s): Eton DT, Fairclough DL, Cella D, Yount SE, Bonomi P, Johnson DH; Eastern Cooperative Oncology Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 April 15; 21(8): 1536-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697878&dopt=Abstract

·

Early tandem high-dose ifosfamide, carboplatin, etoposide therapy with stem cell rescue for small-cell lung cancer: brief report on the results of a phase-I/II trial. Author(s): Oelmann E, Thomas M, Serve H, Kienast J, Zuhlsdorf M, Mohr M, Klinke F, Dolken G, Macha H, Schmidt EW, Berdel WE. Source: Oncology. 2002; 63(3): 248-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381904&dopt=Abstract

·

Economic evaluation of antibiotic prophylaxis in small-cell lung cancer patients receiving chemotherapy: an EORTC double-blind placebo-controlled phase III study (08923). Author(s): Tjan-Heijnen VC, Caleo S, Postmus PE, Ardizzoni A, Burghouts JT, Buccholz E, Biesma B, Gorlia T, Crott R, Giaccone G, Debruyne C, Manegold C; European Organisation for Research Treatment of Cancer-Lung Cancer Group and Health Economics Unit. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 248-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562652&dopt=Abstract

·

Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small-cell lung cancer. Author(s): Antonadou D, Throuvalas N, Petridis A, Bolanos N, Sagriotis A, Synodinou M. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 October 1; 57(2): 402-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957251&dopt=Abstract

·

Effects of radiotherapy and chemotherapy on lung function in patients with nonsmall-cell lung cancer. Author(s): Gopal R, Starkschall G, Tucker SL, Cox JD, Liao Z, Hanus M, Kelly JF, Stevens CW, Komaki R.

182 Lung Cancer

Source: International Journal of Radiation Oncology, Biology, Physics. 2003 May 1; 56(1): 114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694829&dopt=Abstract ·

Efficacy of modified regimen with attenuated doses of paclitaxel plus carboplatin combination chemotherapy in elderly and/or weak patients with advanced non-small cell lung cancer. Author(s): Choi IS, Kim BS, Park SR, Lee SY, Kim do Y, Kim JH, Lee SH, Kim TY, Heo DS, Bang YJ, Kim NK. Source: Lung Cancer (Amsterdam, Netherlands). 2003 January; 39(1): 99-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499101&dopt=Abstract

·

End-of-life care in patients with lung cancer. Author(s): Griffin JP, Nelson JE, Koch KA, Niell HB, Ackerman TF, Thompson M, Cole FH Jr; American College of Chest Physicians. Source: Chest. 2003 January; 123(1 Suppl): 312S-331S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527587&dopt=Abstract

·

Epiphora induced by intermittent docetaxel (taxotere) in patients with non-small cell lung cancer. Author(s): Spell DW, Estephan FF, Lin JT, Jones DV Jr. Source: Cancer Investigation. 2003; 21(4): 550-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14533445&dopt=Abstract

·

Fatal pulmonary fibrosis associated with induction chemotherapy with carboplatin and vinorelbine followed by CHART radiotherapy for locally advanced non-small cell lung cancer. Author(s): Kirkbride P, Hatton M, Lorigan P, Joyce P, Fisher P. Source: Clin Oncol (R Coll Radiol). 2002 October; 14(5): 361-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555874&dopt=Abstract

·

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer. Author(s): Watanabe R, Takiguchi Y, Moriya T, Oda S, Kurosu K, Tanabe N, Tatsumi K, Nagao K, Kuriyama T. Source: British Journal of Cancer. 2003 January 13; 88(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556954&dopt=Abstract

·

Fractionated administration of irinotecan and cisplatin for treatment of extensivedisease small-cell lung cancer: a phase II study. Author(s): Takigawa N, Fujiwara K, Ueoka H, Kiura K, Tabata M, Hiraki A, Shibayama T, Segawa Y, Kamei H, Hiraki S, Tanimoto M, Harada M.

Alternative Medicine 183

Source: Anticancer Res. 2003 January-February; 23(1B): 557-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680145&dopt=Abstract ·

Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from nonsmall-cell lung cancer. Author(s): Cortes J, Rodriguez J, Aramendia JM, Salgado E, Gurpide A, Garcia-Foncillas J, Aristu JJ, Claver A, Bosch A, Lopez-Picazo JM, Martin-Algarra S, Brugarolas A, Calvo E. Source: Oncology. 2003; 64(1): 28-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457029&dopt=Abstract

·

Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET). Author(s): Neuhouser ML, Patterson RE, Thornquist MD, Omenn GS, King IB, Goodman GE. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 April; 12(4): 350-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692110&dopt=Abstract

·

Gemcitabine and docetaxel every 2 weeks in advanced non-small cell lung cancer: a phase II study of the Gruppo Oncologico Italia Meridionale. Author(s): Galetta D, Gebbia V, Giotta F, Durini E, Romito S, Borsellino N, Cazzato C, Pezzella G, Colucci G. Source: Lung Cancer (Amsterdam, Netherlands). 2002 October; 38(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367797&dopt=Abstract

·

Gemcitabine and vinorelbine followed by docetaxel in patients with advanced nonsmall-cell lung cancer: a multi-institutional phase II trial of nonplatinum sequential triplet combination chemotherapy (JMTO LC00-02). Author(s): Hosoe S, Komuta K, Shibata K, Harada H, Iwamoto Y, Ohsaki Y, Morioka T, Origasa H, Fukushima M, Furuse K, Kawahara M. Source: British Journal of Cancer. 2003 February 10; 88(3): 342-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569374&dopt=Abstract

·

Gemcitabine pharmacokinetics and interaction with paclitaxel in patients with advanced non-small-cell lung cancer. Author(s): Shord SS, Faucette SR, Gillenwater HH, Pescatore SL, Hawke RL, Socinski MA, Lindley C. Source: Cancer Chemotherapy and Pharmacology. 2003 April; 51(4): 328-36. Epub 2003 March 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721761&dopt=Abstract

184 Lung Cancer

·

Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. Author(s): Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 15; 21(16): 3025-34. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837810&dopt=Abstract

·

Gemcitabine, cisplatin and vinorelbine as induction chemotherapy followed by radical therapy in stage III non-small-cell lung cancer: a multicentre study of galicianlung-cancer-group. Author(s): Leon L, Cueva-Banuelos JF, Huidobro G, Firvida JL, Amenedo M, Lazaro M, Romero C, Estevez SV, Baron FJ, Grande C, Garcia Mata J, Gonzalez A, Castellanos J, Gomez A, Caeiro M, Rodriguez MR, Casal J; Galician Lung Cancer Group. Source: Lung Cancer (Amsterdam, Netherlands). 2003 May; 40(2): 215-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711124&dopt=Abstract

·

GL331 inhibits HIF-1alpha expression in a lung cancer model. Author(s): Chang H, Shyu KG, Lee CC, Tsai SC, Wang BW, Hsien Lee Y, Lin S. Source: Biochemical and Biophysical Research Communications. 2003 February 28; 302(1): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593853&dopt=Abstract

·

GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbinecisplatin with vinorelbine-ifosfamide-cisplatin in metastatic non-small-cell lung cancer patients. Author(s): Souquet PJ, Tan EH, Rodrigues Pereira J, Van Klaveren R, Price A, Gatzemeier U, Jaworski M, Burillon JP, Aubert D. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 December; 13(12): 1853-61. Erratum In: Ann Oncol. 2003 February; 14(2): 347. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453852&dopt=Abstract

·

In regard to hyperfractionation for non-small-cell lung cancer: fire, ready, aim! Author(s): Beitler JJ. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 April 1; 55(5): 1460; Author Reply 1460-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654462&dopt=Abstract

·

In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM. Author(s): Dehdashti F, Mintun MA, Lewis JS, Bradley J, Govindan R, Laforest R, Welch MJ, Siegel BA.

Alternative Medicine 185

Source: European Journal of Nuclear Medicine and Molecular Imaging. 2003 June; 30(6): 844-50. Epub 2003 April 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692685&dopt=Abstract ·

Influence of cisplatin-use, age, performance status and duration of chemotherapy on symptom control in advanced non-small cell lung cancer: detailed symptom analysis of a randomised study comparing cisplatin-vindesine to gemcitabine. Author(s): Vansteenkiste J, Vandebroek J, Nackaerts K, Dooms C, Galdermans D, Bosquee L, Delobbe A, Deschepper K, Van Kerckhoven W, Vandeurzen K, Deman R, D'Odemont JP, Siemons L, Van den Brande P, Dams N; Leuven Lung Cancer Group. Source: Lung Cancer (Amsterdam, Netherlands). 2003 May; 40(2): 191-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711121&dopt=Abstract

·

Inhibition of phosphatidylinositol 3-kinase-Akt signaling blocks growth, promotes apoptosis, and enhances sensitivity of small cell lung cancer cells to chemotherapy. Author(s): Krystal GW, Sulanke G, Litz J. Source: Molecular Cancer Therapeutics. 2002 September; 1(11): 913-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481412&dopt=Abstract

·

Intraoperative radioguided sentinel lymph node biopsy in non-small cell lung cancer. Author(s): Melfi FM, Chella A, Menconi GF, Givigliano F, Boni G, Mariani G, Sbragia P, Angeletti CA. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 February; 23(2): 214-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559345&dopt=Abstract

·

Invasive aspergillosis mimicking stage IIIA non-small-cell lung cancer on FDG positron emission tomography. Author(s): Wilkinson MD, Fulham MJ, McCaughan BC, Constable CJ. Source: Clinical Nuclear Medicine. 2003 March; 28(3): 234-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592137&dopt=Abstract

·

Irinotecan and carboplatin in metastatic or recurrent non-small-cell lung cancer. Author(s): Govindan R, Read W, Faust J, Mc Leod H. Source: Oncology (Huntingt). 2003 July; 17(7 Suppl 7): 27-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886871&dopt=Abstract

·

Irinotecan and vinorelbine in patients with non-small cell lung cancer previously treated with platinum-based chemotherapy. A phase II study of the Hellenic Cooperative Oncology Group. Author(s): Pectasides D, Fountzilas G, Rigopoulos A, Bountouroglou NG, Koutras A, Glotsos J, Onyenadum A, Makatsoris T, Kalofonos HP.

186 Lung Cancer

Source: Anticancer Res. 2002 November-December; 22(6B): 3501-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552946&dopt=Abstract ·

Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer. Author(s): Wu HG, Choy H. Source: Oncology (Huntingt). 2002 September; 16(9 Suppl 9): 13-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375796&dopt=Abstract

·

Irinotecan plus cisplatin in small-cell lung cancer. Author(s): Sandler A. Source: Oncology (Huntingt). 2002 September; 16(9 Suppl 9): 39-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375800&dopt=Abstract

·

Irinotecan, cisplatin/carboplatin, and COX-2 inhibition in small-cell lung cancer. Author(s): Natale RB. Source: Oncology (Huntingt). 2003 July; 17(7 Suppl 7): 22-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886870&dopt=Abstract

·

Is cisplatin still the best platinum compound in non-small-cell lung cancer? Author(s): Soria JC, Le Chevalier T. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 October; 13(10): 1515-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377638&dopt=Abstract

·

Limited stage small cell lung cancer: treatment and therapy. Author(s): Turrisi AT 3rd. Source: Curr Treat Options Oncol. 2003 February; 4(1): 61-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525280&dopt=Abstract

·

Low-dose weekly paclitaxel as second-line treatment for advanced non-small cell lung cancer: a phase II study. Author(s): Juan O, Albert A, Ordono F, Casany R, Caranana V, Campos JM, Alberola V. Source: Japanese Journal of Clinical Oncology. 2002 November; 32(11): 449-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499416&dopt=Abstract

·

Lung cancer. Practice organization. Author(s): Alberts WM, Bepler G, Hazelton T, Ruckdeschel JC, Williams JH Jr; American College of Chest Physicians. Source: Chest. 2003 January; 123(1 Suppl): 332S-337S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527588&dopt=Abstract

Alternative Medicine 187

·

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial. Author(s): Betticher DC, Hsu Schmitz SF, Totsch M, Hansen E, Joss C, von Briel C, Schmid RA, Pless M, Habicht J, Roth AD, Spiliopoulos A, Stahel R, Weder W, Stupp R, Egli F, Furrer M, Honegger H, Wernli M, Cerny T, Ris HB. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 May 1; 21(9): 1752-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721251&dopt=Abstract

·

Mediastinal lymph node involvement in non-small cell lung cancer: evaluation with 99mTc-tetrofosmin SPECT and comparison with CT. Author(s): Schillaci O, Spanu A, Scopinaro F, Monteleone F, Solinas ME, Volpino P, Pirina P, Marongiu P, Cangemi V, Madeddu G. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 August; 44(8): 1219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902410&dopt=Abstract

·

Mediastinal lymph node involvement in potentially resectable lung cancer: comparison of CT, positron emission tomography, and endoscopic ultrasonography with and without fine-needle aspiration. Author(s): Fritscher-Ravens A, Bohuslavizki KH, Brandt L, Bobrowski C, Lund C, Knofel WT, Pforte A. Source: Chest. 2003 February; 123(2): 442-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576364&dopt=Abstract

·

Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET. Author(s): Hoekstra CJ, Hoekstra OS, Stroobants SG, Vansteenkiste J, Nuyts J, Smit EF, Boers M, Twisk JW, Lammertsma AA. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2002 October; 43(10): 1304-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368367&dopt=Abstract

·

Mitochondrial damage prior to apoptosis in furanonaphthoquinone treated lung cancer cells. Author(s): Simamura E, Hirai K, Shimada H, Pan J, Koyama J. Source: Cancer Detection and Prevention. 2003; 27(1): 5-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600411&dopt=Abstract

·

Modification of lung cancer susceptibility by green tea extract as measured by the comet assay. Author(s): Zhang H, Spitz MR, Tomlinson GE, Schabath MB, Minna JD, Wu X.

188 Lung Cancer

Source: Cancer Detection and Prevention. 2002; 26(6): 411-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507225&dopt=Abstract ·

Molecular markers and targeted therapy with novel agents: prospects in the treatment of non-small cell lung cancer. Author(s): Rosell R, Fossella F, Milas L; Spanish Lung Cancer Group. Source: Lung Cancer (Amsterdam, Netherlands). 2002 December; 38 Suppl 4: 43-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480194&dopt=Abstract

·

Multicenter, randomized trial for stage IIIB or IV non-small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation. Author(s): Belani CP, Barstis J, Perry MC, La Rocca RV, Nattam SR, Rinaldi D, Clark R, Mills GM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 1; 21(15): 2933-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885812&dopt=Abstract

·

Neoadjuvant radiotherapy concurrent with weekly paclitaxel and carboplatin and followed by surgery in locally advanced non-small-cell lung cancer. Author(s): Kuten A, Anacak Y, Abdah-Bortnyak R, Chetver L, Zen Al Deen I, Daoud K, Nijem R, Billan S, Best L. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 April; 26(2): 184-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714893&dopt=Abstract

·

Non-platinum gemcitabine combinations in non-small cell lung cancer. Author(s): Marx G, Harper P. Source: Lung Cancer (Amsterdam, Netherlands). 2002 November; 38 Suppl 2: S51-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431830&dopt=Abstract

·

Outpatient intensive chemotherapy for small cell lung cancer: five years experience of modified 'ICE' ifosfamide carboplatin and etoposide. Author(s): Hand S, Baker J, Smith AP, Macbeth FR. Source: Clin Oncol (R Coll Radiol). 2002 October; 14(5): 367-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555875&dopt=Abstract

·

P21 response to DNA damage induced by genistein and etoposide in human lung cancer cells. Author(s): Ding H, Duan W, Zhu WG, Ju R, Srinivasan K, Otterson GA, Villalona-Calero MA.

Alternative Medicine 189

Source: Biochemical and Biophysical Research Communications. 2003 June 13; 305(4): 950-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767922&dopt=Abstract ·

p53 status and its in vitro relationship to radiosensitivity and chemosensitivity in lung cancer. Author(s): Bergqvist M, Brattstrom D, Gullbo J, Hesselius P, Brodin O, Wagenius G. Source: Anticancer Res. 2003 March-April; 23(2B): 1207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820372&dopt=Abstract

·

Paclitaxel (taxol) and taxoid derivates for lung cancer treatment: potential for aerosol delivery. Author(s): Gautam A, Koshkina N. Source: Current Cancer Drug Targets. 2003 August; 3(4): 287-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871059&dopt=Abstract

·

Patterns of failure in patients who had response-assessment by PET after radical radiotherapy for non-small cell lung cancer support the case for more intensive local therapy. Author(s): Mac Manus MP, Hicks R, Jane M, Andrew W, Danny R, Annette H, David BL. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 October 1; 57(2 Suppl): S167. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965403&dopt=Abstract

·

PET scanning in lung cancer: current status and future directions. Author(s): Mac Manus MP, Hicks RJ. Source: Seminars in Surgical Oncology. 2003; 21(3): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508847&dopt=Abstract

·

PG490-mediated sensitization of lung cancer cells to Apo2L/TRAIL-induced apoptosis requires activation of ERK2. Author(s): Frese S, Pirnia F, Miescher D, Krajewski S, Borner MM, Reed JC, Schmid RA. Source: Oncogene. 2003 August 21; 22(35): 5427-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934102&dopt=Abstract

·

Phase I and pharmacokinetic study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer. Author(s): Ichiki M, Gohara R, Fujiki R, Hoashi S, Rikimaru T, Aizawa H. Source: Cancer Chemotherapy and Pharmacology. 2003 July; 52(1): 67-72. Epub 2003 May 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743738&dopt=Abstract

190 Lung Cancer

·

Phase I study of irinotecan and cisplatin with concurrent split-course radiotherapy in limited-disease small-cell lung cancer. Author(s): Oka M, Fukuda M, Kuba M, Ichiki M, Rikimaru T, Soda H, Tsurutani J, Nakamura Y, Kawabata S, Nakatomi K, Narasaki F, Nagashima S, Takatani H, Fukuda M, Kinoshita A, Kohno S. Source: European Journal of Cancer (Oxford, England : 1990). 2002 October; 38(15): 19982004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376204&dopt=Abstract

·

Phase I study of paclitaxel and topotecan for the first-line treatment of extensive-stage small cell lung cancer. Author(s): West W, Birch R, Schnell F, Hainsworth J, Tongol J, Campos L. Source: The Oncologist. 2003; 8(1): 76-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604734&dopt=Abstract

·

Phase I trial of weekly docetaxel in elderly patients with non-small cell lung cancer. Author(s): Inoue A, Kunitoh H, Mori K, Nukiwa T, Fukuoka M, Saijo N. Source: Lung Cancer (Amsterdam, Netherlands). 2002 November; 38(2): 205-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399134&dopt=Abstract

·

Phase I/II investigation of paclitaxel, ifosfamide and carboplatin for advanced nonsmall-cell lung cancer. Author(s): Mauer AM, Ansari RH, Hoffman PC, Krauss SA, Taber D, Tembe SA, Gabrys GT, Cotter T, Schumm LP, Szeto L, Vokes EE. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 May; 14(5): 722-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702526&dopt=Abstract

·

Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer. Author(s): Kiura K, Ueoka H, Segawa Y, Tabata M, Kamei H, Takigawa N, Hiraki S, Watanabe Y, Bessho A, Eguchi K, Okimoto N, Harita S, Takemoto M, Hiraki Y, Harada M, Tanimoto M; Okayama Lung Cancer Study Group. Source: British Journal of Cancer. 2003 September 1; 89(5): 795-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942107&dopt=Abstract

·

Phase I/II study of escalating doses of nedaplatin in combination with irinotecan for advanced non-small-cell lung cancer. Author(s): Oshita F, Yamada K, Kato Y, Ikehara M, Noda K, Tanaka G, Nomura I, Suzuki R, Saito H. Source: Cancer Chemotherapy and Pharmacology. 2003 July; 52(1): 73-8. Epub 2003 May 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750839&dopt=Abstract

Alternative Medicine 191

·

Phase I/II study of paclitaxel, gemcitabine and vinorelbine as first-line chemotherapy of non-small-cell lung cancer. Author(s): Lorusso V, Crucitta E, Panza N, Silvestris N, Guida M, Carpagnano F, Mancarella S, Sambiasi D, De Lena M. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 December; 13(12): 1862-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453853&dopt=Abstract

·

Phase I/II trial of gemcitabine plus cisplatin and etoposide in patients with small-cell lung cancer. Author(s): De Marinis F, Migliorino MR, Paoluzzi L, Portalone L, Ariganello O, Cortesi E, Gamucci T, Gasperoni S, Cipri A, Martelli O, Nelli F; Foundation for Oncological Research. Source: Lung Cancer (Amsterdam, Netherlands). 2003 March; 39(3): 331-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609572&dopt=Abstract

·

Phase I/II trial of vinorelbine and divided-dose carboplatin in advanced non-small cell lung cancer. Author(s): Masters GA, Hahn EA, Shevrin DH, Kies MS. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581577&dopt=Abstract

·

Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507. Author(s): Sekine I, Nishiwaki Y, Kakinuma R, Kubota K, Hojo F, Matsumoto T, Ohmatsu H, Goto K, Kodama T, Eguchi K, Shinkai T, Tamura T, Ohe Y, Kunitoh H, Yoshimura K, Saijo N. Source: British Journal of Cancer. 2003 March 24; 88(6): 808-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644814&dopt=Abstract

·

Phase II and pharmacologic study of weekly oral paclitaxel plus cyclosporine in patients with advanced non-small-cell lung cancer. Author(s): Kruijtzer CM, Schellens JH, Mezger J, Scheulen ME, Keilholz U, Beijnen JH, Rosing H, Mathot RA, Marcus S, van Tinteren H, Baas P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 1; 20(23): 4508-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454106&dopt=Abstract

·

Phase II non-randomized study of three different sequences of docetaxel and vinorelbine in patients with advanced non-small cell lung cancer. Author(s): Sanchez JM, Balana C, Font A, Sanchez JJ, Manzano JL, Guillot M, Margeli M, Richardet M, Rosell R.

192 Lung Cancer

Source: Lung Cancer (Amsterdam, Netherlands). 2002 December; 38(3): 309-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445754&dopt=Abstract ·

Phase II study of carboplatin and 1-h intravenous etoposide and paclitaxel in a novel sequence as first-line treatment of patients with small-cell lung cancer. Author(s): Vieitez JM, Valladares M, Gracia M, Gonzalez-Baron M, Martin G, Mel JR, Rodriguez R, Constenla M, Gomez Aldavari JL, Dominguez S, Dorta J, Garcia-Giron C, Lopez R, Sevilla I, Esteban E, Anton LM, Pelaez I, Lopez E, Lacave AJ. Source: Lung Cancer (Amsterdam, Netherlands). 2003 January; 39(1): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499098&dopt=Abstract

·

Phase II study of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with stage IIIb and IV non-small-cell lung cancer. Author(s): Fujita A, Ohkubo T, Hoshino H, Takabatake H, Tagaki S, Sekine K, Abe S. Source: British Journal of Cancer. 2003 September 15; 89(6): 1008-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966417&dopt=Abstract

·

Phase II study of docetaxel and gemcitabine combination chemotherapy in nonsmall-cell lung cancer patients failing previous chemotherapy. Author(s): Chen YM, Perng RP, Lin WC, Wu HW, Tsai CM, Whang-Peng J. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 October; 25(5): 509-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393994&dopt=Abstract

·

Phase II study of docetaxel and ifosfamide combination chemotherapy in non-smallcell lung cancer patients failing previous chemotherapy with or without paclitaxel. Author(s): Chen YM, Shih JF, Lee CS, Chen MC, Lin WC, Tsai CM, Perng RP. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 209-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581575&dopt=Abstract

·

Phase II study of irinotecan and carboplatin for advanced non-small cell lung cancer. Author(s): Takeda K, Takifuji N, Uejima H, Yoshimura N, Terakawa K, Negoro S. Source: Lung Cancer (Amsterdam, Netherlands). 2002 December; 38(3): 303-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445753&dopt=Abstract

·

Phase II study of irinotecan and carboplatin in patients with the refractory or relapsed small cell lung cancer. Author(s): Hirose T, Horichi N, Ohmori T, Ogura K, Hosaka T, Ando K, Ishida H, Noguchi H, Adachi M. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 333-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781433&dopt=Abstract

Alternative Medicine 193

·

Phase II study of irinotecan and ifosfamide in patients with advanced non-small cell lung cancer. Author(s): Ichiki M, Rikimaru T, Gohara R, Koga T, Kawayama T, Matunami M, Oshita Y, Kamimura T, Aizawa H. Source: Oncology. 2003; 64(4): 306-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759525&dopt=Abstract

·

Phase II study of neoadjuvant chemotherapy in patients with surgically-proven, unresectable stage III non-small cell lung cancer. Author(s): Grossi F, Pennucci MC, Serrano J, Frola C, Mereu C, Scolaro T, Ratto GB, Tixi L, Ardizzoni A. Source: Anticancer Res. 2002 November-December; 22(6B): 3519-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552949&dopt=Abstract

·

Phase II study of paclitaxel (Genaxol) and cisplatin combination in treating Chinese patients with advanced non-small cell lung cancer (NSCLC). Author(s): Chen CH, Chang WC, Lin MC, Hsu JW, Chao TY, Tsao TC. Source: Lung Cancer (Amsterdam, Netherlands). 2002 October; 38(1): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367799&dopt=Abstract

·

Phase II study of Taxol combined With ifosfamide and carboplatin in the treatment of stage IIIb-IV non-small-cell lung cancer. Author(s): Zaniboni A, Ardizzoni A, De Marinis F, Portalone L, Boni C, Meriggi F, Cafferata MA, Ariganello O, Torri V, Neumaier CE, Rosso R. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 February; 26(1): 84-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576930&dopt=Abstract

·

Phase II study of three-dimensional conformal radiotherapy and concurrent mitomycin-C, vinblastine, and cisplatin chemotherapy for Stage III locally advanced, unresectable, non-small-cell lung cancer. Author(s): Lee SW, Choi EK, Lee JS, Lee SD, Suh C, Kim SW, Kim WS, Ahn SD, Yi BY, Kim JH, Noh YJ, Kim SS, Koh Y, Kim DS, Kim WD. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 July 15; 56(4): 996-1004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829135&dopt=Abstract

·

Phase II study with vinorelbine and cisplatin in advanced non-small cell lung cancer after failure of previous chemotherapy. Author(s): Chen YM, Lee CS, Lin WC, Tsai CM, Perng RP. Source: J Chin Med Assoc. 2003 April; 66(4): 241-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854877&dopt=Abstract

194 Lung Cancer

·

Phase II trial of paclitaxel, ifosfamide, and carboplatin in extensive-stage small cell lung cancer. Author(s): Socinski MA, Neubauer MA, Olivares J, Ketchel S, Tynan M, Moore M, Lee JH, Davis K, Schell M, Garfield D. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660013&dopt=Abstract

·

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Author(s): Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, Berthet P, Breau JL, Lianes P, Nicholson M, Ardizzoni A, Chemaissani A, Bogaerts J, Gallant G. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 October; 13(10): 1539-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377641&dopt=Abstract

·

Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. Author(s): Scagliotti GV, De Marinis F, Rinaldi M, Crino L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, Altavilla G, Adamo V, Ceribelli A, Clerici M, Di Costanzo F, Frontini L, Tonato M; Italian Lung Cancer Project. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 November 1; 20(21): 4285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409326&dopt=Abstract

·

Pilot trial of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib plus carboplatin and paclitaxel in patients with stage IIIB or IV non-small-cell lung cancer. Author(s): Miller VA, Johnson DH, Krug LM, Pizzo B, Tyson L, Perez W, Krozely P, Sandler A, Carbone D, Heelan RT, Kris MG, Smith R, Ochs J. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 1; 21(11): 2094-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775734&dopt=Abstract

·

Platinum drugs in the treatment of non-small-cell lung cancer. Author(s): Cosaert J, Quoix E. Source: British Journal of Cancer. 2002 October 7; 87(8): 825-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373594&dopt=Abstract

·

Platinum-based, leukocyte-depleting chemotherapy does not alter induced sputum markers of neutrophilic inflammation in COPD patients with unresectable non-small cell lung cancer. Author(s): Beeh KM, Beier J, Ernst M, Kornmann O, Buhl R.

Alternative Medicine 195

Source: Respiration; International Review of Thoracic Diseases. 2003 March-April; 70(2): 166-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740514&dopt=Abstract ·

Positron emission tomography (PET) and combined imaging modalities for staging lung cancer. Author(s): Scott WJ. Source: The Surgical Clinics of North America. 2002 June; 82(3): 477-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371581&dopt=Abstract

·

Positron emission tomography in lung cancer. Author(s): Shon IH, O'doherty MJ, Maisey MN. Source: Semin Nucl Med. 2002 October; 32(4): 240-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524650&dopt=Abstract

·

Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. Author(s): Weber WA, Petersen V, Schmidt B, Tyndale-Hines L, Link T, Peschel C, Schwaiger M. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 July 15; 21(14): 2651-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860940&dopt=Abstract

·

Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. Author(s): Mac Manus MP, Hicks RJ, Matthews JP, McKenzie A, Rischin D, Salminen EK, Ball DL. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 April 1; 21(7): 1285-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663716&dopt=Abstract

·

Potential for reduced toxicity and dose escalation in the treatment of inoperable nonsmall-cell lung cancer: a comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation. Author(s): Grills IS, Yan D, Martinez AA, Vicini FA, Wong JW, Kestin LL. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 November 1; 57(3): 875-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529795&dopt=Abstract

·

Potentiation of the effect of paclitaxel and carboplatin by antioxidant mixture on human lung cancer h520 cells. Author(s): Pathak AK, Singh N, Khanna N, Reddy VG, Prasad KN, Kochupillai V.

196 Lung Cancer

Source: Journal of the American College of Nutrition. 2002 October; 21(5): 416-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356783&dopt=Abstract ·

Predicting chemotherapy response to paclitaxel-based therapy in advanced nonsmall-cell lung cancer with P-glycoprotein expression. Author(s): Yeh JJ, Hsu WH, Wang JJ, Ho ST, Kao A. Source: Respiration; International Review of Thoracic Diseases. 2003 January-February; 70(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584388&dopt=Abstract

·

Preliminary results of radiotherapy with or without weekly paclitaxel in locally advanced non-small cell lung cancer. Author(s): Cuneyt Ulutin H, Pak Y. Source: Journal of Cancer Research and Clinical Oncology. 2003 January; 129(1): 52-6. Epub 2003 January 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618901&dopt=Abstract

·

Pretreatment clinical prognostic factors in patients with stage IV non-small cell lung cancer (NSCLC) treated with chemotherapy. Author(s): Jeremic B, Milicic B, Dagovic A, Aleksandrovic J, Nikolic N. Source: Journal of Cancer Research and Clinical Oncology. 2003 February; 129(2): 114-22. Epub 2003 March 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669236&dopt=Abstract

·

Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer. Author(s): Laack E, Kohler A, Kugler C, Dierlamm T, Knuffmann C, Vohwinkel G, Niestroy A, Dahlmann N, Peters A, Berger J, Fiedler W, Hossfeld DK. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 October; 13(10): 1550-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377642&dopt=Abstract

·

Prevention of lung cancer: summary of published evidence. Author(s): Kelley MJ, McCrory DC. Source: Chest. 2003 January; 123(1 Suppl): 50S-59S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527564&dopt=Abstract

·

Preventive effect of Kampo medicine (Hangeshashin-to) against irinotecan-induced diarrhea in advanced non-small-cell lung cancer. Author(s): Mori K, Kondo T, Kamiyama Y, Kano Y, Tominaga K.

Alternative Medicine 197

Source: Cancer Chemotherapy and Pharmacology. 2003 May; 51(5): 403-6. Epub 2003 April 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687289&dopt=Abstract ·

Prognostic factors in Greek patients with small cell lung cancer (SCLC). A Hellenic Cooperative Oncology Group study. Author(s): Christodolou C, Pavlidis N, Samantas E, Fountzilas G, Kouvatseas G, Pagdatoglou K, Palamidas F, Nikolaidis C, Angelidou M, Kalofonos HP, Kosmidis P, Skarlos DV. Source: Anticancer Res. 2002 November-December; 22(6B): 3749-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552988&dopt=Abstract

·

Prolonged administration of infusional cisplatin and oral etoposide in advanced nonsmall cell lung cancer. Author(s): Jazieh AR, Kyasa MJ, Muirhead MJ. Source: Anti-Cancer Drugs. 2002 September; 13(8): 815-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394265&dopt=Abstract

·

Prospective use of serial questionnaires to evaluate the therapeutic efficacy of 18Ffluorodeoxyglucose (FDG) positron emission tomography (PET) in suspected lung cancer. Author(s): Herder GJ, Van Tinteren H, Comans EF, Hoekstra OS, Teule GJ, Postmus PE, Joshi U, Smit EF. Source: Thorax. 2003 January; 58(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511720&dopt=Abstract

·

Pulmonary function following high-dose radiotherapy of non-small-cell lung cancer. Author(s): De Jaeger K, Seppenwoolde Y, Boersma LJ, Muller SH, Baas P, Belderbos JS, Lebesque JV. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 April 1; 55(5): 1331-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654445&dopt=Abstract

·

Radiation-induced apoptosis in human non-small-cell lung cancer cell lines is secondary to cell-cycle progression beyond the G2-phase checkpoint. Author(s): Stuschke M, Sak A, Wurm R, Sinn B, Wolf G, Stuben G, Budach V. Source: International Journal of Radiation Biology. 2002 September; 78(9): 807-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428922&dopt=Abstract

·

Randomised phase III trial of irinotecan combined with cisplatin for advanced nonsmall-cell lung cancer. Author(s): Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West.

198 Lung Cancer

Source: British Journal of Cancer. 2003 February 10; 88(3): 335-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569373&dopt=Abstract ·

Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small-cell lung cancer. Author(s): Leong SS, Tan EH, Fong KW, Wilder-Smith E, Ong YK, Tai BC, Chew L, Lim SH, Wee J, Lee KM, Foo KF, Ang P, Ang PT. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 May 1; 21(9): 1767-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721253&dopt=Abstract

·

Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. Author(s): Vokes EE, Herndon JE 2nd, Crawford J, Leopold KA, Perry MC, Miller AA, Green MR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 October 15; 20(20): 4191-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377962&dopt=Abstract

·

Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer (JCOG9902-DI). Author(s): Sekine I, Nishiwaki Y, Noda K, Kudoh S, Fukuoka M, Mori K, Negoro S, Yokoyama A, Matsui K, Ohsaki Y, Nakano T, Saijo N; Japan Clinical Oncology Group (JCOG) Lung Cancer Study Group. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 May; 14(5): 709-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702524&dopt=Abstract

·

Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. Author(s): Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Source: Journal of the National Cancer Institute. 2003 August 6; 95(15): 1118-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902441&dopt=Abstract

·

Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell Lung cancer. Author(s): Scagliotti GV, Fossati R, Torri V, Crino L, Giaccone G, Silvano G, Martelli M, Clerici M, Cognetti F, Tonato M; Adjuvant Lung Project Italy/European Organisation for Research Treatment of Cancer-Lung Cancer Cooperative Group Investigators. Source: Journal of the National Cancer Institute. 2003 October 1; 95(19): 1453-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519751&dopt=Abstract

Alternative Medicine 199

·

Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. Author(s): Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 15; 21(16): 3016-24. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837811&dopt=Abstract

·

Recombinant human interleukin-3 administered concomitantly with chemotherapy in patients with relapsed small cell lung cancer. Author(s): Biesma B, van Kralingen KW, van Leen RW, Koster MC, Postmus PE. Source: Journal of Experimental Therapeutics & Oncology. 2002 January-February; 2(1): 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415620&dopt=Abstract

·

Response to cisplatin-etoposide treatment and survival in patients with small-cell lung cancer in North Lebanon. Author(s): Kalaajieh WK. Source: Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre. 2003 April-June; 12(2): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634468&dopt=Abstract

·

Role of mycobacterium w as adjuvant treatment of lung cancer (non-small cell lung cancer). Author(s): Sur PK, Dastidar AG. Source: J Indian Med Assoc. 2003 February; 101(2): 118, 120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841498&dopt=Abstract

·

Safety and pharmacokinetic effects of TNP-470, an angiogenesis inhibitor, combined with paclitaxel in patients with solid tumors: evidence for activity in non-small-cell lung cancer. Author(s): Herbst RS, Madden TL, Tran HT, Blumenschein GR Jr, Meyers CA, Seabrooke LF, Khuri FR, Puduvalli VK, Allgood V, Fritsche HA Jr, Hinton L, Newman RA, Crane EA, Fossella FV, Dordal M, Goodin T, Hong WK. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 November 15; 20(22): 4440-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431966&dopt=Abstract

·

Screening for early lung cancer with low-dose spiral computed tomography. Author(s): Diederich S. Source: Lancet. 2003 August 23; 362(9384): 588-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944053&dopt=Abstract

200 Lung Cancer

·

Second-line chemotherapy with irinotecan and vinorelbine in stage IIIB and IV nonsmall-cell lung cancer: a phase II study. Author(s): Gonzalez Cao M, Aramendia JM, Salgado E, Aristu J, Martinez Monje R, Algarra SM, Ordonez JM, Brugarolas A. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 October; 25(5): 480-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393989&dopt=Abstract

·

Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial. Author(s): Reid ME, Duffield-Lillico AJ, Garland L, Turnbull BW, Clark LC, Marshall JR. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433704&dopt=Abstract

·

Sensitivity of non-small-cell lung cancer cell lines established from patients treated with prolonged infusions of Paclitaxel. Author(s): Fujishita T, Loda M, Turner RE, Gentler M, Kashii T, Breathnach OS, Johnson BE. Source: Oncology. 2003; 64(4): 399-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759538&dopt=Abstract

·

Sequential administration of cisplatin-etoposide followed by topotecan in patients with extensive stage small cell lung cancer. A multicenter phase II study. Author(s): Mavroudis D, Pavlakou G, Blazoyiannakis G, Veslemes M, Apostolopoulou F, Kouroussis Ch, Kakolyris S, Agelaki S, Androulakis N, Vardakis N, Magkanas E, Samonis G, Georgoulias V. Source: Lung Cancer (Amsterdam, Netherlands). 2003 January; 39(1): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499097&dopt=Abstract

·

Sequential high-dose chemotherapy with autologous stem cell support in patients with limited-stage small cell lung cancer. Author(s): Ziske C, Gorschluter M, Mey U, Offergeld R, Glasmacher A, Schmidt-Wolf IG. Source: Anticancer Res. 2002 November-December; 22(6B): 3723-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552983&dopt=Abstract

·

Staging of non-small-cell lung cancer and application of FDG-PET. A cost modeling approach. Author(s): Verboom P, Herder GJ, Hoekstra OS, Smit EF, van den Bergh JH, van Velthoven PC, Grijseels EW.

Alternative Medicine 201

Source: International Journal of Technology Assessment in Health Care. 2002 Summer; 18(3): 576-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391950&dopt=Abstract ·

Staging tools for nonsmall cell lung cancer. Author(s): Zawin M. Source: Respir Care Clin N Am. 2003 March; 9(1): 77-118, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820713&dopt=Abstract

·

Supportive care in patients with advanced non-small-cell lung cancer. Author(s): Di Maio M, Perrone F, Gallo C, Iaffaioli RV, Manzione L, Piantedosi FV, Cigolari S, Illiano A, Barbera S, Robbiati SF, Piazza E, Ianniello GP, Frontini L, Veltri E, Castiglione F, Rosetti F, De Maio E, Maione P, Gridelli C, Rossi A, Barletta E, Barzelloni ML, Signoriello G, Bilancia D, Dinota A, Rosati G, Germano D, Lamberti A, Pontillo V, Brancacio L, Crispino C, Esposito M, Battiloro C, Tufano G, Cioffi A, Guardasole V, Angelini V, Guidetti G, Barbera S, Renda F, Romano F, Volpintesta A, Robbiati SF, Sannicolo M, Filipazzi V, Esani G, Gambaro A, Ferrario S, Tinessa V, Caprio MG, Zonato S, Cabiddu M, Raina A, Veltri E, D'Aprile M, Pistillucci G, Porcile G, Ostellino O, Vinante O, Azzarello G, Gebbia V, Borsellino N, Testa A, Gasparini G, Morabito A, Gattuso D, Romito S, Carrozza F, Fava S, Calcagno A, Grimi E, Bertetto O, Ciuffreda L, Parello G, Maiorino L, Santoro A, Santoro M, Failla G, Aiello RA, Bearz A, Sorio R, Scalone S, Clerici M, Bollina R, Belloni P, Sacco C, Sibau A, Adamo V, Altavilla G, Scimone A, Spatafora M, Bellia V, Hopps MR, Monfardini S, Favaretto A, Stefani M, Corradini GM, Pavia G, Scagliotti G, Novello S, Selvaggi G, Tonato M, Darwish S, Michetti G, Belometti MO, Labianca R, Quadri A, De Marinis F, Migliorino MR, Martelli O, Colucci G, Galetta D, Giotta F, Isa L, Candido P, Rossi N, Calandriello A, Ferrau F, Malaponte E, Barni S, Cazzaniga M, Gebbia N, Valerio MR, Belli M, Colantuoni G, Capuano MA, Angiolillo M, Sollitto F, Ardizzoia A, Luporini G, Locatelli MC, Pari F, Aitini E, Pedicini T, Febbraro A, Zollo C, Di Costanzo F, Bartolucci R, Gasperoni S, Gaion F, Palazzolo G, Galligioni E, Caffo O, Cortesi E, D'Auria G, Curcio C, Vasta M, Bumma C, Celano A, Bretti S, Nettis G, Anselmo A, Mattioli R, Nistico C, Aschelter A, Foa P. Source: British Journal of Cancer. 2003 September 15; 89(6): 1013-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966418&dopt=Abstract

·

Taxanes for advanced non-small cell lung cancer. Author(s): Ramalingam S, Belani CP. Source: Expert Opinion on Pharmacotherapy. 2002 December; 3(12): 1693-709. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472367&dopt=Abstract

·

Taxanes in the treatment of advanced (stage III and IV) non-small cell lung cancer (NSCLC): recent developments. Author(s): Simon GR, Bunn PA Jr. Source: Cancer Investigation. 2003; 21(1): 87-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643013&dopt=Abstract

202 Lung Cancer

·

The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. Author(s): Sasaki J, Ramesh R, Chada S, Gomyo Y, Roth JA, Mukhopadhyay T. Source: Molecular Cancer Therapeutics. 2002 November; 1(13): 1201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479701&dopt=Abstract

·

The clinical usefulness of post-treatment FDG-PET for prediction of prognosis in lung cancer patients treated with radiation therapy. Author(s): Nakayama Y, Kitamoto Y, Ishikawa H, Saitoh J, Sakurai H, Akimoto T, Hasegawa M, Nakano T. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 October 1; 57(2 Suppl): S410-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965801&dopt=Abstract

·

The global role of irinotecan in the treatment of lung cancer: 2003 update. Author(s): Langer CJ. Source: Oncology (Huntingt). 2003 July; 17(7 Suppl 7): 30-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886872&dopt=Abstract

·

The outcome of combined-modality therapy for stage III non-small-cell lung cancer in the elderly. Author(s): Schild SE, Stella PJ, Geyer SM, Bonner JA, McGinnis WL, Mailliard JA, Brindle J, Jatoi A, Jett JR; North Central Cancer Treatment Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3201-6. Epub 2003 July 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874270&dopt=Abstract

·

The protective effect of the Mediterranean diet on lung cancer. Author(s): Fortes C, Forastiere F, Farchi S, Mallone S, Trequattrinni T, Anatra F, Schmid G, Perucci CA. Source: Nutrition and Cancer. 2003; 46(1): 30-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925301&dopt=Abstract

·

The role of carotenoids on the risk of lung cancer. Author(s): Epstein KR. Source: Seminars in Oncology. 2003 February; 30(1): 86-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635093&dopt=Abstract

·

The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer. Author(s): Hansen LT, Lundin C, Spang-Thomsen M, Petersen LN, Helleday T.

Alternative Medicine 203

Source: International Journal of Cancer. Journal International Du Cancer. 2003 July 1; 105(4): 472-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712436&dopt=Abstract ·

The therapeutic effects of the radiotherapy plus TCM treatment observed in senile non-parvicellular lung cancer patients at the late stage. Author(s): Lan X, Jiang Y. Source: J Tradit Chin Med. 2003 March; 23(1): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747193&dopt=Abstract

·

The value of [18F]fluoro-2-deoxy-D-glucose positron emission tomography in the selection of patients with stage IIIA-N2 non-small cell lung cancer for combined modality treatment. Author(s): Hoekstra CJ, Stroobants SG, Hoekstra OS, Vansteenkiste J, Biesma B, Schramel FJ, van Zandwijk N, van Tinteren H, Smit EF. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 151-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581567&dopt=Abstract

·

Thermoradiotherapy for local control of chest wall invasion in patients with advanced non-small cell lung cancer. Author(s): Sakao S, Takiguchi Y, Nemoto K, Tatsumi K, Tanabe N, Kurosu K, Ooiwa T, Shirasawa H, Kuriyama T. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2002 December; 7(6): 343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494249&dopt=Abstract

·

Three-week schedule of irinotecan and cisplatin in advanced non-small cell lung cancer: a multicentre phase II study. Author(s): Cardenal F, Domine M, Massuti B, Carrato A, Felip E, Garrido P, Juan O, Artal A, Barneto I, Lopez-Vivanco G, Balcells M, Rosell R. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581574&dopt=Abstract

·

Tissue diagnosis of suspected lung cancer: selecting between bronchoscopy, transthoracic needle aspiration, and resectional biopsy. Author(s): Yung RC. Source: Respir Care Clin N Am. 2003 March; 9(1): 51-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820712&dopt=Abstract

·

Topoisomerase inhibitor-induced apoptosis accompanied by down-regulation of Bcl2 in human lung cancer cells. Author(s): Oizumi S, Isobe H, Ogura S, Ishida T, Yamazaki K, Nishimura M, Kawakami Y, Dosaka-Akita H.

204 Lung Cancer

Source: Anticancer Res. 2002 November-December; 22(6C): 4029-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553028&dopt=Abstract ·

Traditional Chinese medicine Astragalus reverses predominance of Th2 cytokines and their up-stream transcript factors in lung cancer patients. Author(s): Wei H, Sun R, Xiao W, Feng J, Zhen C, Xu X, Tian Z. Source: Oncol Rep. 2003 September-October; 10(5): 1507-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883732&dopt=Abstract

·

Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer. Author(s): Rosell R, Scagliotti G, Danenberg KD, Lord RV, Bepler G, Novello S, Cooc J, Crino L, Sanchez JJ, Taron M, Boni C, De Marinis F, Tonato M, Marangolo M, Gozzelino F, Di Costanzo F, Rinaldi M, Salonga D, Stephens C. Source: Oncogene. 2003 June 5; 22(23): 3548-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789263&dopt=Abstract

·

Triplet chemotherapy with vinorelbine, gemcitabine, and cisplatin for advanced nonsmall cell lung cancer: a phase II study. Author(s): Niho S, Kubota K, Goto K, Ohmatsu H, Matsumoto T, Kakinuma R, Nishiwaki Y. Source: British Journal of Cancer. 2002 December 2; 87(12): 1360-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454762&dopt=Abstract

·

Use of temozolomide with other cytotoxic chemotherapy in the treatment of patients with recurrent brain metastases from lung cancer. Author(s): Ebert BL, Niemierko E, Shaffer K, Salgia R. Source: The Oncologist. 2003; 8(1): 69-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604733&dopt=Abstract

·

Usefulness of chest single photon emission computed tomography with technetium99m methoxyisobutylisonitrile to predict taxol based chemotherapy response in advanced non-small cell lung cancer. Author(s): Shih CM, Hsu WH, Huang WT, Wang JJ, Ho ST, Kao A. Source: Cancer Letters. 2003 September 10; 199(1): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963129&dopt=Abstract

·

Using technetium-99m tetrofosmin chest imaging to predict taxol-based chemotherapy response in non-small cell lung cancer but not related to lung resistance protein expression. Author(s): Shih CM, Shiau YC, Wang JJ, Ho ST, Kao A.

Alternative Medicine 205

Source: Lung. 2003; 181(2): 103-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953149&dopt=Abstract ·

Value of accelerated multimodality therapy in stage IIIA and IIIB non-small cell lung cancer. Author(s): DeCamp MM, Rice TW, Adelstein DJ, Chidel MA, Rybicki LA, Murthy SC, Blackstone EH. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 July; 126(1): 17-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878935&dopt=Abstract

·

Value of FDG-PET in the management of non-small cell lung cancer. Author(s): Stroobants S, Verschakelen J, Vansteenkiste J. Source: European Journal of Radiology. 2003 January; 45(1): 49-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499064&dopt=Abstract

·

Value of whole-body FDG PET in management of lung cancer. Author(s): Higashi K, Matsunari I, Ueda Y, Ikeda R, Guo J, Oguchi M, Tonami H, Yamamoto I. Source: Ann Nucl Med. 2003 February; 17(1): 1-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691125&dopt=Abstract

·

Vinorelbine and carboplatin in inoperable non-small cell lung cancer: a monoinstitutional phase II study. Author(s): Cremonesi M, Mandala M, Cazzaniga M, Rezzani C, Gambera M, Barni S. Source: Oncology. 2003; 64(2): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566905&dopt=Abstract

·

Vinorelbine: a review of its use in elderly patients with advanced non-small cell lung cancer. Author(s): Curran MP, Plosker GL. Source: Drugs & Aging. 2002; 19(9): 695-721. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381238&dopt=Abstract

·

Weekly low-dose docetaxel in advanced non-small cell lung cancer previously treated with two chemotherapy regimens. Author(s): Petrioli R, Pozzessere D, Messinese S, Sabatino M, Ceciarini F, Marsili S, Correale P, Fiaschi AI, Voltolini L, Gotti G, Francini G. Source: Lung Cancer (Amsterdam, Netherlands). 2003 January; 39(1): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499099&dopt=Abstract

·

Weekly paclitaxel for advanced non-small cell lung cancer patients not suitable for platinum-based therapy.

206 Lung Cancer

Author(s): Juan O, Albert A, Villarroya T, Sanchez R, Casan R, Caranana V, Campos JM, Alberola V. Source: Neoplasma. 2003; 50(3): 204-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937854&dopt=Abstract ·

Weekly paclitaxel in the treatment of metastatic and/or recurrent non-small cell lung cancer. Author(s): Alberola V, Cortesi E, Juan O. Source: Critical Reviews in Oncology/Hematology. 2002 December 27; 44 Suppl: S31-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505597&dopt=Abstract

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

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

·

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

·

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

The following is a specific Web list relating to lung 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 Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com

Alternative Medicine 207

Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Emphysema Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com ·

Alternative Therapy Nutrition Source: Integrative Medicine Communications; www.drkoop.com Reflexology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,730,00.html

·

Herbs and Supplements Asian Ginseng Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

208 Lung Cancer

B-carotene Source: Integrative Medicine Communications; www.drkoop.com Beta-carotene Source: Healthnotes, Inc.; www.healthnotes.com Beta-carotene Alternative names: b-carotene, Trans-beta Carotene; Provitamin A, Betacarotenum Source: Integrative Medicine Communications; www.drkoop.com Beta-carotene Source: Prima Communications, Inc.www.personalhealthzone.com Beta-carotene Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10103,00.html Betacarotenum Source: Integrative Medicine Communications; www.drkoop.com Camellia Sinensis Source: Integrative Medicine Communications; www.drkoop.com Carotenoids Source: Healthnotes, Inc.; www.healthnotes.com Carotenoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Flavonoids Source: Healthnotes, Inc.; www.healthnotes.com Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 209

Ginseng Source: Prima Communications, Inc.www.personalhealthzone.com Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Green Tea Alternative names: Camellia sinensis Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Prima Communications, Inc.www.personalhealthzone.com Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thuja Plicata Alternative names: Western Red Cedar Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Trans-beta-carotene 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.

211

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

Dissertations on Lung 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 lung 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: ·

4hpr-x Radiation Mechanisms of Interactions in Non-small Cell Lung Cancer (nsclc) Cells in Vitro by Nasca, Melita Maria; Phd from The Univ. of Texas H.s.c. at Houston Grad. Sch. of Biomed. Sci., 2002, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3046065

·

An Epidemiological Investigation of the Roles of Dietary Antioxidant Nutrients, Fruits and Vegetables, and Residential Radon Exposure in the Etiology of Lung Cancer by Wright, Margaret Elaine; Phd from Yale University, 2003, 106 pages http://wwwlib.umi.com/dissertations/fullcit/3084386

·

Bcl-2 Proteins in Human Lung Cancer: Molecular Heterogeneity and Prognostic Value by Huang, Chris Ing-yi; Phd from Harvard University, 2002, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3051190

·

Effect of Cigarette Tar Yield and Mentholation on the Occurrence of Lung Cancer by Brooks, Daniel Rinzberg; Scd from Boston University, 2002, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3043278

212 Lung Cancer

·

Gelsolin Expression and Non-small Cell Lung Cancer by Yang, Jun; , Phd from State University of New York at Buffalo, 2002, 223 pages http://wwwlib.umi.com/dissertations/fullcit/3052559

·

Gene Expression Analysis of Human Non-small Cell Lung Cancer Subtypes, Adenocarcinoma and Squamous Cell Carcinoma, and Mouse Lung Epithelial Cell Lines: Implications in Lung Tumorigenesis by Silvers, Amy Lynn; Phd from Medical College of Ohio at Toledo, 2002, 270 pages http://wwwlib.umi.com/dissertations/fullcit/3062769

·

Geographic Concentrations of Lung Cancer Mortality in Texas and Their Relationships to Environmental and Socioeconomic Conditions by Zhou, Xinnong; Phd from Texas State University - San Marcos, 2000, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3025226

·

Investigation of the Mechanisms Responsible for Decreased Cyclin D2 in Non-smallcell Lung Cancer Cell Lines by Wu, Ding; Msbs from Medical College of Ohio at Toledo, 2002, 67 pages http://wwwlib.umi.com/dissertations/fullcit/1407774

·

Isolation and Characterization of Organ Specific Neoantigen from the Urine of Lung Cancer Patients by Fink, Aaron; Phd from Mcgill University (canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK60944

·

Lung Cancer, Radon Daughter Exposure, and Smoking a Nested Case-control Study Within a Cohort of Uranium Mine Workers by L'abbé Kristan A; Phd from University of Toronto (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL46389

·

Lung Cancer: Epidemiological and Clinical Studies with Special Reference to Surgical Treatment (sweden) by Myrdal, Gunnar; Phd from Uppsala Universitet (sweden), 2003, 90 pages http://wwwlib.umi.com/dissertations/fullcit/f148657

·

Perceived Control As a Determinant of Preventive Action for Heart Disease and Lung Cancer by Allison, Kenneth R; Phd from University of Toronto (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39646

·

Radiosensitivity in Lung Cancer with Focus Onp53 by Bergqvist, Michael; Phd from Uppsala Universitet (sweden), 2002, 59 pages http://wwwlib.umi.com/dissertations/fullcit/f738897

·

Regulation of Lung Cancer Cell Growth and Differentiation by Notch Signaling by Sriuranpong, Virote; Phd from The Johns Hopkins University, 2002, 119 pages http://wwwlib.umi.com/dissertations/fullcit/3028334

·

Reliability and Validity of Proxy Reported Information in a Case-control Study of Lung Cancer by Pron, Gaylene E; Phd from University of Toronto (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39766

·

Restriction Landmark Genomic Scanning to Identify Novel Methylated and Amplified Dna Sequences in Human Lung Cancer by Dai, Zunyan; Phd from The Ohio State University, 2002, 167 pages http://wwwlib.umi.com/dissertations/fullcit/3081908

·

The Chemoprevention of Lung Cancer Using Nonsteroidal Anti-inflammatory Drugs (nsaids) by Elliott, Christopher S.; Phd from The Ohio State University, 2003, 127 pages http://wwwlib.umi.com/dissertations/fullcit/3088847

Dissertations 213

·

The Incidence of Lung Cancer among Schizophrenic Males Versus Nonschizophrenic Males by Breen, Mary Julie, Edd from United States International University, 1981, 100 pages http://wwwlib.umi.com/dissertations/fullcit/8117016

·

The Longitudinal Effects of Cancer Treatment on Sexuality in Individuals with Lung Cancer by Shell, Judith Ann; Phd from Michigan State University, 2002, 110 pages http://wwwlib.umi.com/dissertations/fullcit/3064308

·

The Relationship of Information Preferences, Family Functioning, Learned Resourcefulness, and Quality of Life among Patients with Lung Cancer by Hinds, Cora; Edd from University of Toronto (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL46318

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.

215

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

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

Carboplatin and Etoposide With or Without Thalidomide in Treating Patients With Limited-Stage or Extensive-Stage Small Cell Lung Cancer Condition(s): extensive stage small cell lung cancer; limited stage small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): London Lung Cancer Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as carboplatin and etoposide use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. It is not yet known if combination chemotherapy is more effective with or without thalidomide in treating small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combining carboplatin and etoposide with or without thalidomide in treating patients who have limited- or extensive-stage small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061919

8

These are listed at www.ClinicalTrials.gov.

216 Lung Cancer

·

Carboplatin, Paclitaxel, and Radiation Therapy With or Without Thalidomide in Treating Patients With Stage III Non-small Cell Lung Cancer Condition(s): adenocarcinoma of the lung; adenosquamous cell lung cancer; bronchoalveolar cell lung cancer; large cell lung cancer; Non-small cell lung cancer; squamous cell lung 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. Thalidomide may stop the growth of non-small cell lung cancer by stopping blood flow to the tumor. It is not yet known if combination chemotherapy plus radiation therapy is more effective with or without thalidomide. PURPOSE: Randomized phase III trial to compare the effectiveness of carboplatin, paclitaxel, and radiation therapy with or without thalidomide in treating patients who have newly diagnosed stage III non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004859

·

Combination Chemotherapy in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer Condition(s): Non-small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as gemcitabine, carboplatin, and paclitaxel 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 which chemotherapy regimen is more effective in treating non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating patients who have stage IIIB, stage IV, or recurrent non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054392

·

Combination Chemotherapy Plus Thalidomide in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer Condition(s): Non-small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI)

Clinical Trials 217

Purpose - Excerpt: RATIONALE: Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining thalidomide with chemotherapy may kill more tumor cells and be an effective treatment for stage IIIB or stage IV non-small cell lung cancer. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus thalidomide in treating patients who have stage IIIB or stage IV nonsmall cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025285 ·

Gefitinib in Treating Patients With Non-Small Cell Lung Cancer That Has Been Surgically Removed Condition(s): Non-small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute of Canada; National Cancer Institute (NCI); Eastern Cooperative Oncology Group; Southwest Oncology Group Purpose - Excerpt: RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of the tumor. It is not yet known if gefitinib is effective in delaying the recurrence of non-small cell lung cancer. PURPOSE: Randomized phase III trial to study the effectiveness of gefitinib in treating patients who have undergone surgery for stage IB, stage II, or stage IIIA non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049543

·

Inhaled Doxorubicin in Treating Patients With Primary Lung Cancer or Lung Metastases Condition(s): lung metastases; Non-small cell lung cancer; Small Cell Lung Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of inhaled doxorubicin in treating patients who have primary lung cancer or lung metastases. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004930

218 Lung Cancer

·

Isotretinoin With or Without Vitamin E for Prevention of Lung Cancer Condition(s): Non-small cell lung cancer; Small Cell Lung Cancer; Drug Toxicity Study Status: This study is currently recruiting patients. Sponsor(s): University of Colorado Cancer Center Purpose - Excerpt: RATIONALE: Isotretinoin may prevent the development of cancer cells. PURPOSE: Randomized double-blinded phase II trial to study the effectiveness of isotretinoin with or without vitamin E for chemoprevention of cancer in persons at high risk of developing lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002586

·

Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer Condition(s): acute leukemia; atypical chronic myeloid leukemia; Melanoma; myelodysplastic and myeloproliferative disease; Non-small cell lung cancer; ovarian epithelial cancer Study Status: This study is currently recruiting patients. Sponsor(s): Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have ovarian epithelial cancer, melanoma, acute myeloid leukemia, myelodysplastic syndrome, or non-small cell lung cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039091

·

Radiation Therapy Combined With Paclitaxel and Carboplatin in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer Condition(s): Non-small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI) 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 more than one drug and giving them with specialized radiation therapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy combined with paclitaxel and carboplatin in treating patients who have stage I, stage II, or stage III non-small cell lung cancer. Phase(s): Phase I; Phase II

Clinical Trials 219

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023673 ·

Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer in Complete Remission Condition(s): limited stage small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): Institut Gustave Roussy; EORTC Radiotherapy Cooperative Group; EORTC Lung Cancer Cooperative Group Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells and prevent the spread of cancer to the brain. It is not yet known if standard-dose radiation therapy is more effective than high-dose radiation therapy in preventing the spread of limited-stage small cell lung cancer cells to the brain. PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of radiation therapy in treating patients who have limited-stage small cell lung cancer in complete remission. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005062

·

Radiation Therapy to Prevent Brain Metastases in Patients With Previously Treated Extensive-Stage Small Cell Lung Cancer Condition(s): extensive stage small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Cooperative Group

Radiotherapy

Cooperative

Group;

EORTC

Lung

Cancer

Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiation therapy to the brain may be effective in preventing brain metastases. It is not yet known if radiation therapy is effective following chemotherapy in preventing brain metastases. PURPOSE: Randomized phase III trial to determine the effectiveness of radiation therapy in preventing brain metastases in patients who have received chemotherapy for extensive-stage small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016211 ·

TLK286 and Docetaxel in Treating Patients With Stage IIIB or Stage IV PlatinumResistant Non-Small Cell Lung Cancer Condition(s): Non-small cell lung cancer Study Status: This study is currently recruiting patients.

220 Lung Cancer

Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as TLK286 and docetaxel, use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of combining TLK286 with docetaxel in treating patients who have stage IIIB or stage IV non-small cell lung cancer that is resistant to platinum chemotherapy (such as carboplatin or cisplatin). Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068705 ·

ZD6474 and Docetaxel in Treating Patients With Locally Advanced or Metastatic NonSmall Cell Lung Cancer Condition(s): Non-small cell lung cancer 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. ZD6474 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Randomized phase II trial to compare the effectiveness of different regimens of ZD6474 combined with docetaxel in treating patients who have locally advanced or metastatic non-small cell lung cancer that is refractory to platinum-based chemotherapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054093

·

Zileuton in Preventing Lung Cancer in Patients With Bronchial Dysplasia Condition(s): Hypopharyngeal Cancer; Laryngeal Cancer; lip and oral cavity cancer; Lung Cancer; Nasopharyngeal Cancer; Oropharyngeal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Barbara Ann Karmanos Cancer Institute; 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 zileuton may be an effective way to prevent lung cancer in patients who have bronchial dysplasia. PURPOSE: Randomized phase II trial to study the effectiveness of zileuton in preventing lung cancer in patients who have bronchial dysplasia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056004

Clinical Trials 221

·

Chemotherapy and Radiation Therapy With or Without Epoetin alfa in Treating Patients With Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer Condition(s): stage IIIA non-small cell lung cancer; squamous cell lung cancer; bronchoalveolar cell lung cancer; stage IIIB non-small cell lung cancer; adenocarcinoma of the lung; large cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Comprehensive Cancer Center of Wake Forest University 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. Epoetin alfa may stimulate red blood cell production and prevent or treat anemia in patients who are undergoing radiation therapy and chemotherapy. It is not yet known if chemotherapy combined with radiation therapy is more effective with or without epoetin alfa in treating non-small cell lung cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of chemotherapy combined with radiation therapy with or without epoetin alfa in treating patients who have stage IIIA or stage IIIB non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028938

·

Chemotherapy Followed by Surgery or Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer Condition(s): squamous cell lung cancer; large cell lung cancer; stage IIIA non-small cell lung cancer; adenocarcinoma of the lung; adenosquamous cell lung cancer; bronchoalveolar cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Lung 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. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed during surgery. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether chemotherapy followed by surgery with or without radiation therapy is more effective than chemotherapy followed by radiation therapy alone in treating non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by surgery with or without radiation therapy to that of chemotherapy followed by radiation therapy alone in treating patients who have stage III non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002623

222 Lung Cancer

·

Chemotherapy Plus Radiation Therapy in Treating Patients With Stage I, Stage II, or Stage III Non-small Cell Lung Cancer That Cannot Be Surgically Removed Condition(s): stage I non-small cell lung cancer; stage II non-small cell lung cancer; stage III non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Lung 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. Radiation therapy used high-energy x-rays to damage tumor cells. It is not yet know whether chemotherapy followed by radiation therapy is more effective than chemotherapy given with radiation therapy for non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of chemotherapy and radiation therapy in treating patients who have unresectable stage I, stage II, or stage III non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003803

·

Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer Condition(s): stage IIIA non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Arthur G. James Cancer Hospital & Richard J. Solove Research Institute 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. Drugs such as gadolinium texaphyrin may make the tumor cells more sensitive to radiation therapy. Combining chemotherapy, radiation therapy, and surgery may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining carboplatin and paclitaxel, radiation therapy with gadolinium texaphyrin, and surgery in treating patients who have stage IIIA non-small cell lung cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005065

·

Combination Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery Condition(s): stage IIIA non-small cell lung cancer; stage II non-small cell lung cancer; stage IIIB non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Baptist Hospital of Miami

Clinical Trials 223

Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Specialized radiation therapy delivers a high dose of radiation directly to the tumor which may kill more tumor cells and cause less damage to normal tissue. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and specialized high-dose radiation therapy in treating patients who have stage II or stage III non-small cell lung cancer that cannot be removed by surgery. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004253 ·

Combination Chemotherapy Plus Radiation Therapy Followed by Surgery in Treating Patients With Stage IIIB Non-Small Cell Lung Cancer Condition(s): stage IIIB non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Lung 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. 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 combining chemotherapy and radiation therapy before surgery in treating patients who have stage IIIB non-small cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021112

·

Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer Condition(s): stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Robert H. Lurie Cancer Center 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 and radiation therapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients who have stage III non-small cell lung cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004093

224 Lung Cancer

·

Combination Chemotherapy With or Without Erlotinib in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer Condition(s): stage IV non-small cell lung cancer; stage IIIB non-small cell lung cancer; recurrent non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Genentech Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for cancer growth. Combining combination chemotherapy with erlotinib may kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without erlotinib in treating nonsmall cell lung cancer. PURPOSE: Randomized double-blinded phase III trial to determine the effectiveness of combining carboplatin and paclitaxel with or without erlotinib in treating patients who have stage IIIB or stage IV non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029016

·

Combination Chemotherapy With or Without Filgrastim in Treating Patients With Previously Untreated Extensive-Stage Small Cell Lung Cancer Condition(s): extensive stage small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); North Central Cancer Treatment Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without filgrastim in treating patients who have extensive-stage small cell lung cancer that has not been previously treated. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028925

·

Combination Chemotherapy With or Without Tirapazamine in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer Condition(s): stage IV non-small cell lung cancer; squamous cell lung cancer; stage IIIB non-small cell lung cancer; recurrent non-small cell lung cancer; adenocarcinoma of the lung; large cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Southwest Oncology Group

Clinical Trials 225

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 which combination chemotherapy regimen is more effective for non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of carboplatin plus paclitaxel with or without tirapazamine in treating patients who have stage IIIB or stage IV non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006484 ·

Comparison of Two Combination Chemotherapy Regimens in Treating Non-small Cell Lung Cancer Condition(s): Non-small cell lung 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 tumor cells. It is not yet known which combination chemotherapy regimen is more effective for treating non-small cell lung cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have non-small cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006004

·

Detection of Early Metastases in Patients With Stage I Non-small Cell Lung Cancer Condition(s): stage I non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Cancer and Leukemia Group B Purpose - Excerpt: RATIONALE: Detecting very early metastases in bone marrow and/or lymph nodes may help doctors plan better treatment for non-small cell lung cancer. PURPOSE: Clinical trial to detect the presence of metastatic cancer in patients with stage I non-small cell lung cancer that has not been previously treated. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003006

·

Docetaxel and Cisplatin in Treating Patients With Untreated Stage IIIA Non-small Cell Lung Cancer Condition(s): stage IIIA non-small cell lung cancer

226 Lung Cancer

Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Lung 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 drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of docetaxel and cisplatin in treating patients who have untreated stage IIIA non-small cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005868 ·

Docetaxel With or Without Exisulind in Treating Patients With Non-Small Cell Lung Cancer Condition(s): Non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Cell Pathways 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 if docetaxel is more effective with or without exisulind in treating non-small cell lung cancer. PURPOSE: Randomized phase III trial to study the effectiveness of docetaxel with or without exisulind in treating patients who have advanced non-small cell lung cancer that has not responded to previous treatment. PROTOCOL OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to performance status (0 vs 1 vs 2) and extent of disease (locally advanced vs metastatic). Patients are randomized to one of two treatment arms. Arm I: Patients receive oral exisulind twice daily beginning on days -3 and continuing through day 21. Patients receive docetaxel IV over 1 hour on day 0. Arm II: Patients receive oral placebo twice daily beginning on day -3 and continuing through day 21. Patients receive docetaxel as in arm I. For subsequent courses, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 30 days. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036322

·

Donepezil and Vitamin E to Prevent Side Effects Caused By Radiation Therapy to the Head in Patients Receiving Treatment for Small Cell Lung Cancer Condition(s): extensive stage small cell lung cancer; limited stage small cell lung cancer; Depression; Delirium; Recurrent Small Cell Lung Cancer; radiation toxicity; psychosocial effects/treatment; Quality of Life Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); North Central Cancer Treatment Group

Clinical Trials 227

Purpose - Excerpt: RATIONALE: Donepezil and vitamin E may be able to decrease side effects caused by radiation therapy given to prevent brain metastases in patients with small cell lung cancer. It is not yet known if donepezil and vitamin E are effective in preventing side effects caused by radiation therapy to the head. PURPOSE: Randomized phase III trial to determine the effectiveness of donepezil and vitamin E in preventing side effects caused by radiation therapy given to prevent brain metastases in patients who have small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006349 ·

Gemcitabine Plus Supportive Care in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Condition(s): stage IIIA non-small cell lung cancer; stage IV non-small cell lung cancer; stage IIIB non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Christie Hospital N.H.S. Trust Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Treatment plus supportive care may improve quality of life in patients undergoing cancer treatment. PURPOSE: Randomized phase II/III trial to compare the effect of different gemcitabine regimens plus supportive care on quality of life in patients who have locally advanced or metastatic non-small cell lung cancer. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022009

·

INS316 Compared With Saline for Sputum Collection in Diagnosing Lung Cancer Condition(s): Small Cell Lung Cancer; Non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Jonsson Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: INS316 may produce a better sputum sample for laboratory analysis and may provide a less invasive method of diagnosing lung cancer. PURPOSE: Randomized diagnostic trial to compare the effectiveness of INS316 with that of saline for sputum collection in diagnosing lung cancer in patients suspected of having lung cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033527

228 Lung Cancer

·

Lometrexol Plus Folic Acid in Treating Patients With Stage IIIB or Stage IV NonSmall Cell Lung Cancer Condition(s): stage IV non-small cell lung cancer; adenosquamous cell lung cancer; squamous cell lung cancer; stage IIIB non-small cell lung cancer; recurrent non-small cell lung cancer; adenocarcinoma of the lung; large cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Tularik Purpose - Excerpt: RATIONALE: Lometrexol may stop or slow the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Folic acid may be effective in preventing or lessening the side effects of lometrexol. Combining lometrexol with folic acid may be an effective treatment for non-small cell lung cancer. PURPOSE: Phase II trial to study the effectiveness of combining lometrexol with folic acid in treating patients who have stage IIIB or stage IV non-small cell lung cancer that has been previously treated. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033722

·

Megestrol in Treating Patients Who Are Undergoing Radiation Therapy for Lung Cancer Condition(s): limited stage small cell lung cancer; Anorexia; stage IIIA non-small cell lung cancer; stage II non-small cell lung cancer; Cachexia; stage IIIB non-small cell lung cancer; stage I non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Comprehensive Cancer Center of Wake Forest University Purpose - Excerpt: RATIONALE: Megestrol helps improve appetite. It is not yet known if megestrol is effective in limiting weight loss in patients who are undergoing radiation therapy. PURPOSE: Randomized phase III trial to determine the effectiveness of megestrol in limiting weight loss in patients who are undergoing radiation therapy for lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031785

·

Monoclonal Antibody Therapy Plus BCG in Treating Patients With Limited-Stage Small Cell Lung Cancer Condition(s): limited stage small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Lung Cancer Cooperative Group Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal

Clinical Trials 229

cells. BCG may activate the immune system to kill tumor cells. Combining monoclonal antibody therapy with BCG may kill more tumor cells. It is not yet known if monoclonal antibody therapy plus BCG is an effective treatment for limited-stage small cell lung cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of monoclonal antibody therapy plus BCG in treating patients who have limited-stage small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006352 ·

Nitrocamptothecin in Treating Patients With Advanced Small Cell Lung Cancer Condition(s): extensive stage small cell lung cancer; Recurrent Small Cell Lung Cancer Study Status: This study is no longer recruiting patients. Sponsor(s): European Organization for Research and Treatment of Cancer 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 nitrocamptothecin in treating patients who have advanced small cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006082

·

Oltipraz in the Prevention of Lung Cancer in People Who Smoke Condition(s): Small Cell Lung Cancer; prevention of lung cancer; Non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Robert H. Lurie Cancer Center Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. PURPOSE: Randomized phase I trial to study the effectiveness of oltipraz in preventing lung cancer in people who smoke. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006457

·

Paclitaxel and Carboplatin Chemotherapy Compared With Standard Chemotherapy in Treating Patients With Stage III or Stage IV Non-small Cell Lung Cancer That Cannot Be Removed During Surgery Condition(s): stage IIIA non-small cell lung cancer; stage IV non-small cell lung cancer; stage IIIB non-small cell lung cancer Study Status: This study is no longer recruiting patients.

230 Lung Cancer

Sponsor(s): Christie Hospital N.H.S. Trust 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 whether paclitaxel and carboplatin is more effective than standard chemotherapy for advanced non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of paclitaxel and carboplatin chemotherapy with that of standard chemotherapy in treating patients who have stage III or stage IV non-small cell lung cancer that cannot be removed during surgery. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004887 ·

Paclitaxel and Carboplatin With or Without BMS-275291 in Treating Patients With Advanced or Metastatic Non-small Cell Lung Cancer Condition(s): stage IV non-small cell lung cancer; stage IIIB non-small cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): 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. It is not yet known whether giving paclitaxel and carboplatin with BMS-275291 is more effective than giving paclitaxel and carboplatin alone for non-small cell lung cancer. PURPOSE: Randomized phase II/III trial to compare the effectiveness of paclitaxel and carboplatin with or without BMS-275291 in treating patients who have advanced or metastatic non-small cell lung cancer. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006229

·

Paclitaxel in Treating Patients With Lung Cancer Condition(s): stage IIIB non-small cell lung cancer; recurrent non-small cell lung cancer; stage IV non-small cell lung cancer; adenocarcinoma of the lung Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Lung 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. PURPOSE: Phase II trial to study the effectiveness of paclitaxel in treating patients who have unresectable stage IIIB, stage IV or recurrent lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002972

Clinical Trials 231

·

Photodynamic Therapy With HPPH in Treating Patients With Early Stage Lung Cancer Condition(s): squamous cell lung cancer; stage 0 non-small cell lung cancer; adenocarcinoma of the lung; large cell lung cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Roswell Park Cancer Institute Purpose - Excerpt: RATIONALE: Photodynamic therapy uses light and drugs that make tumor cells more sensitive to light to kill tumor cells. Photosensitizing drugs such as HPPH are absorbed by tumor cells and, when exposed to light, become active and kill the tumor cells. PURPOSE: Phase I trial to study the effectiveness of photodynamic therapy with HPPH in treating patients who have early stage lung cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025571

·

Topotecan and Paclitaxel in Treating Patients With Recurrent or Refractory Small Cell Lung Cancer Condition(s): Recurrent Small Cell Lung Cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); North Central Cancer Treatment Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of topotecan and paclitaxel in treating patients who have recurrent or refractory small cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003281

·

Celecoxib and Docetaxel in Treating Patients With Advanced Non-Small Cell Lung Cancer Condition(s): stage IIIA non-small cell lung cancer; stage IV non-small cell lung cancer; stage IIIB non-small cell lung cancer; recurrent non-small cell lung cancer Study Status: This study is suspended. Sponsor(s): Barbara Ann Karmanos Cancer Institute Purpose - Excerpt: RATIONALE: Celecoxib may slow the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with celecoxib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining celecoxib and docetaxel in treating patients who have advanced non-small cell lung cancer that has been previously treated with platinum -based chemotherapy. Phase(s): Phase II

232 Lung Cancer

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030420 ·

Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer Condition(s): squamous cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer; stage IIIA non-small cell lung cancer; large cell lung cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Southwest Oncology Group; Eastern Cooperative Oncology Group; Cancer and Leukemia Group B; North Central Cancer Treatment Group; National Cancer Institute of Canada; Radiation Therapy Oncology Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known if chemotherapy plus radiation therapy is more effective with or without surgery for lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin and etoposide plus radiation therapy with or without surgery in treating patients with stage IIIA non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002550

·

Combination Chemotherapy and Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer Condition(s): limited stage small cell lung cancer Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); North Central Cancer Treatment Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy before, during, and after radiation therapy in treating patients who have limited-stage small cell lung cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006012

·

Combination Chemotherapy Plus Fluoxetine in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer Condition(s): Anxiety Disorder; Depression; Fatigue; Non-small cell lung cancer

Clinical Trials 233

Study Status: This study is suspended. 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. Combining more than one chemotherapy drug may kill more cancer cells. An antidepressant such as fluoxetine may improve the quality of life in patients undergoing chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus fluoxetine in treating patients who have advanced or recurrent non-small cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005850 ·

Depsipeptide to Treat Lung Cancer Condition(s): Lung cancer; Lung Neoplasm Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will evaluate the ability of Depsipeptide to shrink or stop the growth of tumors in lung cancer patients. This drug has shrunk tumors in various other kinds of cancers in laboratory and animal studies. Patients with lung cancer who wish to participate in this study will be screened with various tests to determine their eligibility. These include an electrocardiogram (EKG), blood tests, imaging tests (X-rays and scans), lung function tests, and a tumor biopsy. The biopsy-a procedure in which a small sample of tumor is removed-is done in one of two ways, depending on the location of the tumor: 1. The back of the throat is sprayed with a numbing medicine and a bronchoscope (a long flexible tube) is passed down the throat into the lungs to remove the tissue. This procedure is done in the operating room. Or, 2. The skin on the chest is numbed and a thin needle is inserted through the chest to the tumor, where a sample of tissue is taken. This procedure is done in the diagnostic radiology department. Study participants will undergo two 21-day treatment cycles of Depsipeptide. The drug will given in two four-hour infusions-on days one and seven of each cycle-through a catheter (long, thin plastic tube) placed in a vein in the arm or neck or under the collarbone. For each infusion, the patient will be admitted to the hospital for 24 hours. Biopsies will be repeated on day eight of both cycles. Blood samples will be taken several times during the treatment period to evaluate blood levels of the drug and its effects on the body. EKGs will also be done periodically to monitor the heart. Participants have a follow-up evaluation about two weeks after the end of treatment to determine the response to the drug. Tests will include scans of the chest, abdomen, pelvis and brain. Patients whose tumor has shrunk will be offered additional Depsipeptide cycles. This study may provide information that will lead to more effective treatments for lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005656

234 Lung Cancer

·

Docetaxel With or Without Infliximab in Treating Weight Loss, Loss of Appetite, and Fatigue in Patients with Advanced Non-Small Cell Lung Cancer Condition(s): Anorexia; Cachexia; Fatigue; Non-small cell lung cancer; Quality of Life Study Status: This study is suspended. Sponsor(s): North Central Cancer Treatment 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. Infliximab may improve cancer-related weight loss, lack of appetite, and fatigue. It is not yet known whether docetaxel is more effective with or without infliximab in preventing weight loss and fatigue in patients with advanced cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of docetaxel with or without infliximab in preventing weight loss, loss of appetite, and fatigue in patients who have advanced non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040885

·

Phenylbutyrate Plus Azacitidine in Treating Patients With Acute Myeloid Leukemia, Myelodysplasia, Non-Hodgkin's Lymphoma, Multiple Myeloma, Non-small Cell Lung Cancer, or Prostate Cancer Condition(s): Lung Cancer; Leukemia; Lymphoma; Prostate Cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of phenylbutyrate plus azacitidine in treating patients who have acute myeloid leukemia, myelodysplasia, non-Hodgkin's lymphoma, multiple myeloma, nonsmall cell lung cancer, or prostate cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006019

·

Trastuzumab in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer That Overexpresses HER2 Condition(s): stage IV non-small cell lung cancer; stage IIIB non-small cell lung cancer; recurrent non-small cell lung cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Cancer and Leukemia Group B Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase II trial to study the effectiveness of trastuzumab in treating

Clinical Trials 235

patients who have stage IIIB or stage IV non-small cell lung cancer that overexpresses HER2. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004883 ·

Vaccine Therapy and Sargramostim in Treating Patients With Non-small Cell Lung Cancer Condition(s): stage IIIA non-small cell lung cancer; stage IV non-small cell lung cancer; stage II non-small cell lung cancer; bronchoalveolar cell lung cancer; stage IIIB nonsmall cell lung cancer; adenocarcinoma of the lung; large cell lung cancer; stage I nonsmall cell lung cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. PURPOSE: Phase I trial to study the effectiveness of vaccine therapy and sargramostim in treating patients who have non-small cell lung cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005630

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 “lung 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/

236 Lung Cancer

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

237

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

Patents on Lung Cancer By performing a patent search focusing on lung 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.

238 Lung Cancer

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

Antisense oligonucleotides for IL-8 and IL-8 receptor Inventor(s): Pietrzkowski; Zbigniew (Santa Ana, CA), Olbina; Gordana (Huntington Beach, CA), Cieslak; Dariusz (Santa Ana, CA) Assignee(s): ICN Pharmaceuticals, Inc. (Costa Mesa, CA) Patent Number: 5,849,903 Date filed: February 5, 1997 Abstract: Oligonucleotides are provided which are effective in inhibiting the growth, metastasis and/or angiogenesis of tumors, including particularly melanoma and/or lung cancer. Methods are also provided for use of these oligonucleotides in the treatment of diseases. Excerpt(s): The field of the invention is oligonucleotide therapeutics, and more particularly the use of oligonucleotides to modulate the expression of IL-8 and/or IL-8 Receptor to control growth, metastasis and/or angiogenesis in tumors. Interleukin-8 (IL8, neutrophil activating protein-1, or NAP-1) is a member of C-X-C chemokine family of related cytokines having broad involvement in inflammatory responses, tissue injury, growth regulation and cellular adhesion. Cerretti, D. P., et al., Molecular Characterization of Receptors for Human Interleukin-8, GRO/Melanoma GrowthStimulatory Activity and Neutrophil Activating Peptide-2, Molecular Immunology, 30(4), 359-367 (1993); and Koch, A. E., et al., In situ expression of cytokines and cellular adhesion molecules in the skin of patients with systemic sclerosis, Pathobiology, 61(5-6), 239-46 (1993). A review of the C-X-C family is given in Streiker, R. M., et al., Role of C-XC Chemokines As Regulators Of Angiogenesis In Lung Cancer, J. of Leukocyte Biology, 57, 752-762 (1995). IL-8 has also been shown to have a potent stimulatory effect on angiogenesis. See, e.g., Koch, A. E., Interleukin-8 as a Macrophage-Derived Mediator of Angiogenesis, Science, 258, 1798-1800 (1992). It is known that IL-8 is produced by a variety of normal human somatic cells including monocytes/macrophages, dermal fibroblasts, vascular endothelial cells, keratinocytes, and mesangeal cells. Yasumoto, K., et al., Tumor Necrosis Factor Alpha and Interferon Gamma Synergistically Induce Interleukin 8 Production in a Human Gastric Cancer Cell Line Though Acting Concurrently on AP-1 and NF-kB-like Binding Sites of the Interleukin 8 Gene, J. of Biological Chemistry, 267(31), 22506-11 (1992). Apparently, such cells produce IL-8 only when stressed, and not under conditions of normal growth and homeostasis,. Factors which induce IL-8 production include inflammation, IL-1, TNF, LPS and thrombin. Web site: http://www.delphion.com/details?pn=US05849903__

·

Breath test for detection of lung cancer Inventor(s): Phillips; Michael (1 Horizon Rd., Fort Lee, NJ 07024) Assignee(s): none reported Patent Number: 6,312,390 Date filed: October 1, 1999 Abstract: Carcinogenesis is accompanied by increased production of oxygen free radicals (OFRs) which degrade membranes by lipid peroxidation. The process evolves

Patents 239

volatile organic compounds (VOCs), principally alkanes, which are excreted in the breath. VOCs in alveolar breath provided sensitive and specific markers of lung cancer. Breath VOC analysis is a non-invasive test which may potentially detect lung cancer at an early stage and reduce the high mortality of the disease. Excerpt(s): The invention relates to methods of detecting and diagnosing lung cancers in mammals. Primary carcinoma of the lung is the leading cause of cancer death in the United States. Every year, more than 100,000 males and 50,000 females develop lung cancer, and most of them die within twelve months. There is a clinical need for a screening test which can detect lung cancer in its earliest stages because prompt treatment of localized disease improves the 5-year survival rate to 30% in males and 50% in females. However, most cases are not detected until local or metastatic growth causes symptoms, and prospective screening with frequent radiography and sputum cytology has not improved the survival rate in smoking males aged 45 years or older. Since early detection of lung cancer can potentially reduce mortality, researchers have investigated alternative diagnostic technologies such as breath testing. The rationale of a breath test for lung cancer is based upon three observations: first, carcinogenesis is accompanied by increased production of oxygen free radicals (OFRs), second, OFRs degrade cell membranes by lipid peroxidation, evolving alkanes such as ethane and pentane, and third, these alkanes are volatile organic compounds (VOCs) which are excreted in the breath. Web site: http://www.delphion.com/details?pn=US06312390__ ·

Cancer treatment with Go 6976 Inventor(s): Lu; Zhimin (10172 Black Mountain Rd., Apt. 103, San Diego, CA 92126), Wang; Keming (79 East Ximei Street, Apt. 303, Suzhou, CN) Assignee(s): none reported Patent Number: 6,303,646 Date filed: August 9, 1999 Abstract: A chemotheraputic cancer treatment in which Go6976 or one of its derivatives is administered to a mammal for the treatment of the cancer. The Go6976 or its derivative is directed to PKC.alpha. activity. Experiments have shown Go6976 to be effective for the treatment of breast cancer, leukemia, lung cancer, bone cancer and skin cancer. These treatments may be accomplished utilizing Go6976 or its derivatives alone or in combination with other prior art chemotherapy agents or in combination with radiation therapy. In a preferred embodiment Go6976 is used for the treatment of cancer as a preventative drug by preventing cancer cell formation. Excerpt(s): This invention relates to cancer treatments and especially to cancer treatments directed to protein kinase C.alpha. enzyme. Researchers have recognized that a family of enzymes known as protein kinase C enzymes is associated with a large number of cancers. This family includes at least eleven isoenzymes. A particular member of this family is identified as the protein kinase C alpha enzyme, abbreviated: PKC.alpha. Researches have reported increases in PKC.alpha. activity in human breast tumors (NG et al., Science. 283:2085-2089) and significant increases in PKC.alpha. expression in prostate cancers (Cornford et al., Am. J. Pathol. 154: 137-144). Researchers have reported that PKC.alpha. is required for the metastasis of human melanoma (Dennis et al., Cancer Lett. 128:65-70) and that PKC.alpha. is related to the progression of brain tumors (Shen et al., Mol. Pharmacol. 55:396-402). There is general agreement

240 Lung Cancer

among many cancer researchers that some of the most dangerous cancers can be treated with chemotheraputic agents or specially designed oligonuclotides targeted to PKC.alpha. Web site: http://www.delphion.com/details?pn=US06303646__ ·

Compounds and methods for therapy and diagnosis of lung cancer Inventor(s): Fanger; Gary R. (Mill Creek, WA), Hosken; Nancy A. (Seattle, WA), Bangur; Chaitanya S. (Seattle, WA), Wang; Tongtong (Medina, WA), Fan; Liqun (Bellevue, WA), Kalos; Michael D. (Seattle, WA) Assignee(s): Corixa Corporation (Seattle, WA) Patent Number: 6,518,256 Date filed: April 4, 2000 Abstract: Compounds and methods for the treatment and diagnosis of lung cancer are provided. The inventive compounds include polypeptides containing at least a portion of a lung tumor protein. Vaccines and pharmaceutical compositions for immunotherapy of lung cancer comprising such polypeptides, or DNA molecules encoding such polypeptides, are also provided, together with DNA molecules for preparing the inventive polypeptides. Excerpt(s): The present invention relates generally to therapy and diagnoses of cancer, such as lung cancer. The invention is more specifically related to polypeptides comprising at least a portion of a lung tumor protein, and to polynucleotides encoding such polypeptidies. Such polypeptides and polynucleotides may be used in vaccines and pharmaceutical compositions for prevention and treatment of lung cancer, and for the diagnosis and monitoring of such cancers. Lung cancer is the primary cause of cancer death among both men and women in the U.S., with an estimated 172,000 new cases being reported in 1994. The five-year survival rate among all lung cancer patients, regardless of the stage of disease at diagnosis, is only 13%. This contrasts with a fiveyear survival rate of 46% among cases detected while the disease is still localized. However, only 16% of lung cancers are discovered before the disease has spread. Early detection is difficult since clinical symptoms are often not seen until the disease has reached an advanced stage. Currently, diagnosis is aided by the use of chest x-rays, analysis of the type of cells contained in sputum and fiberoptic examination of the bronchial passages. Treatment regimens are determined by the type and stage of the cancer, and include surgery, radiation therapy and/or chemotherapy. In spite of considerable research into therapies for the disease, lung cancer remains difficult to treat. Web site: http://www.delphion.com/details?pn=US06518256__

·

Control of CD44 gene expression for therapeutic use Inventor(s): Pietrzkowski; Zbigniew (Santa Ana, CA), Ruzdijic; Sabera (Santa Ana, CA), Cieslak; Dariusz (Santa Ana, CA) Assignee(s): ICN Pharmaceuticals, Inc. (Costa Mesa, CA) Patent Number: 5,990,299 Date filed: August 14, 1995

Patents 241

Abstract: Neoplastic cells which over-express CD44, including especially non-small cell lung cancer and melanoma cancer cells, are treated with antisense oligonucleotides to control CD44 expression. Test results show that the claimed oligonucleotides significantly decreases cell growth in a CD44 sequence specific manner of lung cancer or melanoma cells, or both, but are largely non-toxic to normal cells. Examples of dosing in a clinical setting are provided. Excerpt(s): The present invention relates to the field of cancer therapy, and more particularly to the use of antisense oligonucleotides to control the expression of CD44. Within a single cell CD44 may be expressed as two or more variants, presumably depending on the changing needs of the cell. The polymorphic diversity of the variants is generated by alternative splicing of the CD44 mRNA, which occurs when the various coding sequences (exons) of CD44 genes are transcribed (expressed) in different combinations. Protein products of splice variants (isoforms) of CD44 vary widely in size (from 110 kDa to more than 250 kDa) and in function. The extracellular domain of CD44 protein is known to involve cell-cell adhesion and the binding of extracellular matrix components including hyaluronic acid, fibronectin and collagen, while the intracellular domain of CD44 has been associated with ankyrin cytoskeletal proteins critical for CD44-dependent cellular mobility. CD44 has also been found to function in hematopoiesis and in lymphocyte infiltration into general circulation (4, 5, 6). The various functions of CD44 are intriguing because they can be used to explain similar behaviors between activated lymphocytes and metastasizing tumor cells. Both types of cells have relatively high expression of CD44, and both show invasive behavior, cell migration involving reversible adhesive contacts, accumulation and expansion in lymphoid tissue, and release into general circulation (6). The association with lymphoid tissue is especially interesting in that both lymphocytes and metastasizing tumor cells use CD44 variants to bind a specific ligand residing either in the extracellular matrix of the lymph nodes or on the surface of dendritic or other cells of the lymphoid tissue. Moreover, following growth and differentiation in the lymph nodes, both lymphocytes and tumor cells are synchronously released into the efferent lymphatic vessels in the general circulation. The release process requires a complex series of interactions between the lymphocytes and tumor cells, the extracellular matrix component and surrounding cells, and probably involves adhesion receptors, proteolytic enzymes, growth factors and growth factor receptors. These processes may be dependent upon clipping of the CD44 molecules, and specificity in the process may be mediated by tissue-specific ligands interacting with CD44 isoforms. Expression of CD44 in malignant cells is therefore an important factor in primary tumor growth, local invasiveness and metastatic proclivity (7,8,9). The CD44 gene locus in human genome is on chromosome 11p13 (10). Recently, most of the genomic structure of the human CD44 gene has been established (11). Over a length of about 60 kilobases (kb), at least 20 exons are distributed. Ten of these encode sequences for the standard form of CD44 (exons 1-5 and 16-20). Between exons 5 and 16, at least ten further exons are localized, which are subjected to alternative splicing (exons 6-15). In humans as in other species, the CD44 gene codes a variety of alternatively spliced proteins having different sizes and functions. Several CD44 isoforms have been purified and characterized to date, including an 89-90 kDa glycoprotein referred to as the "standard" or "hematopoietic" isoform (CD44s), and 180 kDa or more glycoproteins referred to as "epithelial" or variant isoforms (CD44v). Isolation and characterization of cDNA clones encoding the standard and epithelial isoforms have shown that the protein sequences are identical except that the epithelial isoforms contain additional sequences of 134 or more amino acids arising from at least ten exons (v1-v10 ) which code for extra-cellular domain, and the epithelial isoforms are more heavily glycosylated (12, 29). While it is now recognized that the

242 Lung Cancer

CD44 standard form plays a key role in the control of cell migration, the precise functions of the alternatively spliced CD44 variants, which predominate in most cell types are unknown. Web site: http://www.delphion.com/details?pn=US05990299__ ·

Cytolytic bradykinin antagonists Inventor(s): Whalley; Eric T. (Golden, CO), Gera; Lajos (Denver, CO), Chan; Daniel C. (Denver, CO), Stewart; John M. (Denver, CO) Assignee(s): University of Colorado (Boulder, CO), Cortech, Inc. (Denver, CO) Patent Number: 5,849,863 Date filed: September 8, 1995 Abstract: The present invention provides bradykinin antagonists effective to inhibit cancer cell growth. Also provided are methods of inhibiting lung cancer cell growth by administering a therapeutically effective amount of a dimerized bradykinin antagonist. Excerpt(s): Bradykinin (BK) is a potent inflammatory peptide whose generation in tissues and body fluids elicits many physiological responses including vasodilation, smooth muscle spasm, edema, as well as pain and hyperalgesia (Burch et al., "Molecular Biology and Pharmacology of Bradykinin Receptors", Landes Comp. (1993); Burch, edited: "Bradykinin Antagonists", Dekker (1991)). There is increasing evidence that BK and related kinins contribute to the inflammatory response in acute and chronic diseases including allergic reactions, arthritis, asthma, sepsis, viral rhinitis, and inflammatory bowel disease. Recently BK was implied to be involved as an autocrine in the pathogenesis of human lung cancer (Bunn et al., Proc Natl. Acad.Sci. USA 87:2162-2166 (1990); Bunn et al., Cancer Research 52:24-31 (1992)). BK has been shown to be the most potent peptide stimulant of intracellular Ca.sup.++ release in the highest fraction of human lung cancer cell lines (Bunn et al., Cancer Research 52:24-31 (1992)). The design and synthesis of specific, potent and stable bradykinin antagonists (BKA) has long been considered a desirable goal in medicinal chemistry. In the past few years, efforts have been directed towards the development of potent BK antagonists as a means for the chemoprevention and therapeutic treatment of human lung cancers. Lung cancer is the second most common and the most lethal cancer in the United States. A large fraction of lung cancers (all small cell lung cancers (SCLC), some adenocarcinomas and a few squamous carcinomas) have a neuroendocrine phenotype (Becker et al., "The Endocrine Lung in Health & Disease", Saunders (1984)). These cancers and their premalignant precursors utilize a neuropeptide autocrine/paracrine growth factor pathway, i.e., they produce a variety of neuropeptides, express cell surface receptors for these peptides, and show autocrine stimulation by these peptides. Over the years, a number of specific and potent neuropeptide antagonists (including bradykinin, bombesin, cholecystokinin and many others) and anti-peptide antibodies were developed and used in an attempt to inhibit the growth of the lung cancer cells which expressed receptors for these specific neuropeptides (Bunn et al., Cancer Research 54:3602-3610 (1994)). However, this approach failed to inhibit a majority of lung cancer cells because of the heterogeneity of neuropeptide receptor expression among the lung cancer cells. It has been shown that broad spectrum substance P derivatives inhibited the growth of several lung cancer cell lines. However, very high concentrations (>40.mu.M) of these compounds were required, presumably because this interference occurs at the downstream level of the signal pathway (Bunn et al., Cancer Research 54:3602-3610 (1994)). It is thus desirable to provide neuropeptide antagonists with improved potency and specificity.

Patents 243

Web site: http://www.delphion.com/details?pn=US05849863__ ·

Detecting cancerous conditions by assaying for telomerase activity Inventor(s): West; Michael D. (Boston, MA), Kim; Nam Woo (San Jose, CA), Weinrich; Scott L. (Redwood City, CA), Wright; Woodring E. (Dallas, TX), Harley; Calvin B. (Palo Alto, CA), Shay; Jerry W. (Dallas, TX) Assignee(s): The University of Texas Systems (Austin, TX), Geron Corporation and Board of Regents (Menlo Park, CA) Patent Number: 6,391,554 Date filed: November 23, 1999 Abstract: Methods and kits are provided for diagnosis of specific cancerous conditions. The invention features a method for diagnosis of a condition in a patient associated with an elevated level of telomerase activity within a cell. The method involves determining the presence or amount of telomerase within the cells in the patient, e.g. by the use of the polymerase chain reaction. In one embodiment of the invention, the condition associated with elevated telomerase activity is chosen from prostate cancer, breast cancer, colon cancer, renal cancer, ovarian/cervical cancer, lung cancer, and leukemia. The invention allows cancer to be detected even in tissues and cells which are not positive by pathology. Excerpt(s): This invention relates to methods for diagnosis of cellular senescence and immortalization. The following is a general description of art relevant to the present invention. None is admitted to be prior art to the invention. Michael D. West et al., entitled "Therapy and Diagnosis of Conditions Related to Telomere Length and/or Telomerase Activity," U.S. application Ser. No. 08/151,477, filed Nov. 12, 1993, and PCT WO 93/04546 filed Nov. 25, 1993, both hereby incorporated by reference, generally describe art which relates to cellular senescence, and theories or hypotheses which explain such aging and the mechanisms by which cells escape senescence and immortalize. West et al. discusses the use of telomerase activity detection for diagnosis of various cancerous conditions. Web site: http://www.delphion.com/details?pn=US06391554__

·

Dihalocephalomannine and methods of use therefor Inventor(s): Pandey; Ramesh C. (Highland Park, NJ), Yankov; Luben K. (Edison, NJ) Assignee(s): Xechem International, Inc. (New Brunswick, NJ) Patent Number: 5,840,748 Date filed: December 13, 1995 Abstract: Provided are antineoplastic derivatives by a process of selective halogenation of side chains of unsaturated taxanes; more particularly, the process involves the use of halogens, particularly bromine, which is easily added to the side chain double bond of cephalomannine, leaving paclitaxel unchanged, and wherein diastereomeric mixtures of 2", 3"-dibromocephalomannine display high activity against: Leukemia cell line HL-60 (TB); Non-Small Cell Lung Cancer line NCI-H522; Colon Cancer cell lines COLO 205 and HT 29; CNS Cancer cell lines SF-539 and SNB-75; Ovarian Cancer Cell line OVCAR-

244 Lung Cancer

3; Renal Cancer cell line RXF-393; and Breast Cancer cell lines MCF7, MDA-MB231/ATCC, HS 578T, MDA-MB-435 and MDA-N. Excerpt(s): This invention relates to halogenated cephalomannine, especially 2", 3"dibromocephalomannine, its preparation, methods of its use as an effective antitumor agent and as an alternative to paclitaxel in bioactivity testing. Cephalomannine is a natural product which can be found in the bark of the pacific yew tree Taxus brevifolia, and such other yew species as T. baccata, T. cuspidata, as well as T. yannanensis and other plant materials including T. hicksii, T. densiformis, T. gem, T. wardii, T. cuspidata, T. capitata, T. brownii and T. dark green spreader. It can also be found in Cephalotaxus species, such as, for example, Cephalotaxus mannii as well as cultured plant cells and fungi. Cephalomannine is most often present with its well known and structurally similar analog, paclitaxel, the structures of both which are shown in FIGS. 1 and 2. Paclitaxel has been approved by the Food and Drug Administration for treatment of ovarian cancer and breast cancer. At present it is undergoing clinical trials for treatment of various other cancers. Web site: http://www.delphion.com/details?pn=US05840748__ ·

Epithelial protein and DNA thereof for use in early cancer detection Inventor(s): Tockman; Melvin S. (Baltimore, MD), Mulshine; James L. (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC), The Johns Hopkins University (Baltimore, MD) Patent Number: 6,251,586 Date filed: October 2, 1996 Abstract: The present invention is a purified and isolated epithelial protein, peptide and variants thereof whose increased presence in an epithelial cell is indicative of precancer. One epithelial protein which is an early detection marked for lung cancer was purified from two human lung cancer cell lines, NCI-H720 and NCI-H157. Using a six-step procedure, the epithelial protein was purified using a Western blot detection system under both non-reducing and reducing conditions. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C.sub.18 HPLC and analytic C.sub.4 HPLC. After an approximately 25,000 fold purification the immunostaining protein was >90% pure as judged by coomassie blue staining after reducing SDS-PAGE. The primary epithelial protein share some sequence homology with the heterogeneous nuclear ribonucleoprotein (hnRNP) A2. A minor co-purifying epithelial protein shares some sequence homology with the splice variant hnRNP-B1. Molecular analysis of primary normal bronchial epithelial cell cultures demonstrated a low level the epithelial protein expression, consistent with immunohistochemical staining of clinical samples, and an increased level of expression in most lung cancer cells. The epithelial protein is a marker of epithelial transformation in lung, breast, bone, ovary, prostate, kidney, melanoma and myeloma and may be casual in the process of carcinogenesis. Methods are provided for monitoring the expression of the epithelial protein, peptides and variants using molecular and immunological techniques as a screen for precancer and cancer in mammals. A method of computerized diagnoses of cancer and precancer is provided which detects levels of hnRNP messenger RNA. Excerpt(s): The present invention relates to the area of cancer diagnostics and therapeutics. More specifically, the invention relates to the isolation and purification of an early cancer detection marker protein of epithelial cells and the cloning of the DNA

Patents 245

sequence encoding the protein. The invention further relates to the protein and DNA sequence for detecting and diagnosing individuals predisposed to cancer. The present inventin relates to a computerized method for generating a discriminant function predictive of cancer. The present invention also relates to therapeutic intervention to, regulate the expression of the gene product. Lung cancer is the most frequent cause of cancer death of both males and females in the United States, accounting for one in three cancer deaths.sup.(1). In the last thirty years, cancer-related survival of this disease has improved only minimally. Successful treatment of this disease by surgical resection and drug chemotherapy is strongly dependent on identification of early-stage tumors. A conceptually attractive early detection approach is to establish the presence of a cancer by evaluation of shed bronchial epithelial cells. In the late 1960's Saccomanno et al. proposed the use of sputum cytology to evaluate cytomorphologic changes in the exfoliated bronchial epithelium as a technique to enhance the early detection of lung cancer.sup.(2). However, clinical trials using combination chest X-ray and sputum cytology have not shown any decrease in cancer-related mortality.sup.(3). In 1988, Tockman et al. reported a sensitive method for early lung cancer detection by immunostaining cells contained within sputum samples with two lung cancerassociated monoclonal antibodies.sup.(4). The basis for this approach was to identify early pre-neoplastic changes in cells shed from bronchial epithelium. The antibodies used in that study were mouse monoclonal IgG's designated 703D4, disclosed in U.S. Pat. No. 4,569,788, and 624H12. In an analysis of the contribution of the individual monoclonal antibodies to early detection of lung cancer, 703D4 alone identified 20 of the 21 detected true positive cases (4; U.S. Ser. No. 08/152,881 which issues to U.S. Pat. No. 5,455,159 on Oct. 3, 1995). 624H12 has been shown to detect an oncofetal antigen which is the Lewis.sup.x -related portion of a cell-surface glycoprotein (Mulshine/Magnani). The antigen for 703D4 was unknown. Web site: http://www.delphion.com/details?pn=US06251586__ ·

Gene therapy for solid tumors using adenoviral vectors comprising suicide genes and cytokine genes Inventor(s): Chen; Shu-Hsia (Houston, TX), Woo; Savio L. C. (Houston, TX) Assignee(s): Baylor College of Medicine (Houston, TX) Patent Number: 6,066,624 Date filed: February 15, 1996 Abstract: The present invention provides a novel method of treating localized solid tumors and papillomas in an individual, as well as metastatic carcinomas. The method comprises delivering a suicide gene, by way of a recombinant adenoviral vector or other DNA transport system, into the tumor, papilloma or wart of an individual. Subsequently, a prodrug, such as the drug gaciclovir.TM., is administered to the individual. Additionally, the present invention provides a method for treating solid tumors, papillomas, warts and metastatic carcinomas, said method comprising introducing both a suicide gene and one or more cytokine genes into the tumor, papilloma or wart of an individual, and subsequently administering a prodrug to the individual. The methods of the present invention may be used to treat several different types of cancers and papillomas, including colon carcinoma, prostate cancer, breast cancer, lung cancer, melanoma, hepatoma, brain lymphoma and head and neck cancer. Excerpt(s): The present invention relates generally to the field of gene therapy. More particularly, the present invention relates to a novel gene therapy method of treating

246 Lung Cancer

solid tumors, papillomas and warts using an adenoviral vector, a combination of adenoviral vectors, other viral vectors, and non-viral DNA transporter systems. Direct introduction of therapeutic genes into malignant cells in vivo can provide an effective treatment of localized tumors. Several novel treatment modalities have recently been attempted. For example, one treatment involves the delivery of normal tumor suppressor genes and/or inhibitors of activated oncogenes into tumor cells. A second treatment involves the enhancement of immunogeneity of tumor cells in vivo by the introduction of cytokine genes. A third treatment involves the introduction of genes that encode enzymes capable of conferring to the tumor cells sensitivity to chemotherapeutic agents. The herpes simplex virus-thymidine kinase (HSV-TK) gene can specifically convert a nucleoside analog (ganciclovir) into a toxic intermediate and cause death in dividing cells. It has recently been reported by Culver et al. (Science 256:1550-1552, 1992) that after delivery of the HSV-TK gene by retroviral transduction, subsequent ganciclovir treatment effectively caused brain tumor regression in laboratory animals. An attractive feature of this treatment modality for localized tumors is the so called "bystander" effect. In the "by-stander" effect, the HSV-TK expressing tumor cells prevent the growth of adjacent non-transduced tumor cells in the presence of ganciclovir. Thus, not every tumor cell has to express HSV-TK for effective cancer treatment. The HSV-TK retrovirus used by Culver et al., however, was limited by low viral titer. Thus, effective treatment of brain tumors necessitated the inoculation into animals of virus-producing cells rather than the viral isolate itself. Additionally, in previous experiments with synergeneic rats treated with a retrovirus and ganciclovir, the tumors were necrotic and were invaded by macrophages and lymphocytes. In Example 1, below, athymic mice were used and the tumor cells were destoyed without apparent involvement of the cellular immune response. The prior art remains deficient in the lack of an efficient gene therapy technique for the treatment of solid tumors. Web site: http://www.delphion.com/details?pn=US06066624__ ·

Hybridomas for lung cancer marker and monoclonal antibodies thereof Inventor(s): Bollon; Arthur P. (Dallas, TX), Torczynski; Richard M. (Farmers Branch, TX) Assignee(s): Cytoclonal Pharmaceutics, Inc. (Dallas, TX) Patent Number: 6,117,981 Date filed: June 3, 1999 Abstract: Hybridomas secreting monoclonal antibodies specific for an epitope found in the amino acids of LCGA associated with non-small cell lung carcinoma protein have been found. The monoclonal antibodies produced by these hybridomas can be used in in vivo and in vitro clinical diagnosis of non-small cell lung carcinoma and ovarian carcinoma and as target selective carriers for various anti-tumor agents and radioimaging agents. Excerpt(s): Lung cancer is the most common form of cancer in the world. Typical diagnosis of lung cancer combines x-ray with sputum cytology. Unfortunately, by the time a patient seeks medical attention for their symptoms, the cancer is at such an advanced state it is usually incurable. Consequently, research has been focused on early detection of tumor markers before the cancer becomes clinically apparent and while the cancer is still localized and amenable to therapy. The World Health Organization has classified lung cancer into four major histological or morphological types: (1) squamous cell carcinoma, (2) adenocarcinoma, (3) large cell carcinoma, and (4) small cell lung carcinoma. (World Health Organization. 1982. "The World Health Organization

Patents 247

Histological Typing of Lung Tumors," Am J Clin Pathol 77:123-136). However, there is a great deal of tumor heterogeneity even within the various subtypes, and it is not uncommon for lung cancer to have features of more than one morphological subtype. The term "non-small cell lung carcinoma" (NSCLS) has been used to distinguish squamous carcinomas, adenocarcinomas, and large cell carcinomas from small cell lung carcinomas. Particular interest has been given to the identification of antigens associated with lung cancer. These antigens have been used in screening, diagnosis, clinical management, and potential treatment of lung cancer. For example, carcinoembryonic antigen (CEA) has been used as a tumor marker of cancer including lung cancer. (Nutini, et al. 1990. "Serum NSE, CEA, CT, CA 15-3 levels in human lung cancer," Int J Biol Markers 5:198-202). Squamous cell carcinoma antigen (SCC) is another established serum marker. (Margolis, et al. 1994. "Serum tumor markers in non-small cell lung cancer," Cancer 73:605-609.). Other serum antigens for lung cancer include antigens recognized by monoclonal antibodies (MAb) 5E8, 5C7, and 1F10, the combination of which distinguishes between patients with lung cancer from those without. (Schepart, et al. 1988. "Monoclonal antibody-mediated detection of lung cancer antigens in serum," Am Rev Respir Dis 138:1434-8). Serum CA 125, initially described as an ovarian cancerassociated antigen, has been investigated for its use as a prognostic factor in NSCLC. (Diez, et al. 1994. "Prognostic significance of serum CA 125 antigen assay in patients with non-small cell lung cancer," Cancer 73:136876). Other tumor markers studied for utilization in multiple biomarker assays for lung cancer include carbohydrate antigen CA19-9, neuron specific enolase (NSE), tissue polypeptide antigen (TPA), alpha fetoprotein (AFP), HCG beta subunit, and LDH. (Mizushima, et al. 1990. "Clinical significance of the number of positive tumor markers in assisting the diagnosis of lung cancer with multiple tumor marker assay," Oncology 47:43-48; Lombardi, et al. 1990. "Clinical significance of a multiple biomarker assay in patients with lung cancer," Chest 97:639-644; and Buccheri, et al. 1986. "Clinical value of a multiple biomarker assay in patients with bronchogenic carcinoma," Cancer 57:2389-2396). Web site: http://www.delphion.com/details?pn=US06117981__ ·

Inhibiting the growth p53 deficient tumor cells by administering the p53 gene Inventor(s): Mukhopadhyay; Tapas (Houston, TX), Roth; Jack A. (Houston, TX), Tainsky; Michael A. (Houston, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX) Patent Number: 6,017,524 Date filed: October 13, 1992 Abstract: Disclosed are methods and compositions for the selective manipulation of gene expression through the preparation of retroviral expression vectors for expressing antisense sequences, such as K-ras oncogene antisense sequences, or sequences encoding a desired product, such as wild type p53 sequences. Preferred retroviral vectors of the present invention incorporate the.beta.-actin promoter in a reverse orientation with respect to retroviral transcription. Preferred antisense RNA constructs of the present invention employ the use of antisense intron DNA corresponding to distinct intron regions of the gene whose expression is targeted for down-regulation. In an exemplary embodiment, a human lung cancer cell line (NCI-H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a genomic segment of K-ras in antisense orientation. Translation of the mutated K-ras mRNA was specifically inhibited, whereas expression of H-ras and N-ras

248 Lung Cancer

was unchanged. A three-fold growth inhibition occurred in H460a cells when expression of the mutated ras p21 protein was down-regulated by antisense RNA and cells remained viable. The growth of H460a tumors in nu/nu mice was substantially reduced by expressed K-ras antisense RNA. Excerpt(s): The present invention relates to methods and nucleic acid vector compositions for modifying gene expressing, involving the preparation and use of improved retroviral vectors which encode antisense RNA molecules or, alternatively, transcriptionally active RNAs that encode selected proteins. The retroviral constructs of the present invention may be employed for introducing desired gene expression units into selected target cells, such as into tumor cells within individuals afflicted with cancer. It is now well established that a variety of diseases, ranging from certain cancers to various genetic defects, are caused, at least in part, by genetic abnormalities that result in either the over expression of one or more genes, or the expression of an abnormal or mutant gene or genes. For example, many forms of cancer in man are now known to be the result of, at least indirectly, the expression of "oncogenes". Oncogenes are genetically altered genes whose altered expression product somehow disrupts normal cellular function or control (Spandidos, et al., 1989). Most oncogenes studied to date have been found to be "activated" as the result of a mutation, often a point mutation, in the coding region of a normal cellular gene or of a "protooncogene", that results in amino acid substitutions in the protein expression product. This altered expression product, in turn, exhibits an abnormal biological function that somehow takes part in the neoplastic process (Travali, et al., 1990). The underlying mutations can arise by various means, such as by chemical mutagenesis or ionizing radiation. Web site: http://www.delphion.com/details?pn=US06017524__ ·

MAP-2 as a determinant of metastatic potential Inventor(s): White; Wain (Winston-Salem, NC), Setaluri; Vijayasaradhi (Winston-Salem, NC), Fang; Dong (Winston-Salem, NC) Assignee(s): Wake Forest University Health Sciences (Winston-Salem, NC) Patent Number: 6,613,534 Date filed: March 20, 2001 Abstract: The invention relates to detection of MAP-2 (microtubule associated protein-2) as a marker to determine the metastatic potential of a tumor, including tumors derived from the neural crest such as melanomas, gliomas, Schwanomas, chromocytomas and small cell lung cancer. In one aspect, the invention comprises a method for determining the metastatic potential of a tumor sample, wherein decreased levels of MAP-2 expression in a test sample relative to controls indicates that the sample has increased metastatic potential as compared to the control. In another aspect, the invention comprises a method to prevent tumor progression in metastatic melanoma by increasing levels of MAP-2 protein in cells. Excerpt(s): The invention relates to methods for the detection, diagnosis, prognosis and treatment of cancer. Specifically, the invention describes the detection of microtubule associated protein--2 (MAP-2) in tumor cells, and the use of MAP-2 as an indicator of metastatic potential. The invention also describes the use of MAP-2 to prevent nonmetastatic primary tumors from progressing to later stage disease. Publications referred to throughout the text of this document are incorporated by reference in their entireties in order to more fully describe the state of the art as known to those skilled therein as of

Patents 249

the date of the invention described and claimed herein. Cancer is the second leading cause of death in the United States after heart disease (Boring et al., CA Cancer J. Clin., 43:7 (1993)). Cancer is characterized by the growth of abnormal (neoplastic) cells which develop from normal tissue. In cancer, cells acquire the ability to override normal constraints on the cell and proliferate under conditions in which normal cells would not grow. Among the most potent cancer causing agents (carcinogens) are ultraviolet and ionizing forms of radiation. Thus, cancer is a typically a disease of malfunctioning cellular genes (or unwanted viral expression) which leads to unchecked growth of tissue. It is generally accepted that multiple mutations must occur to cause cancer, and that cells must progress through several steps in the transformation from normal cells to an early-stage tumor and finally, to invasive and metastatic disease. Web site: http://www.delphion.com/details?pn=US06613534__ ·

Method and apparatus for inducing sputum samples for diagnostic evaluation Inventor(s): Van Brunt; Nicholas P. (White Bear Lake, MN), Gagne; Donald J. (St. Paul, MN) Assignee(s): Advanced Respiratory, Inc. (St. Paul, MN) Patent Number: 6,379,316 Date filed: August 31, 1999 Abstract: An apparatus for inducing sputum samples for diagnosing pulmonary disorders, especially as it relates to detection of early stages of lung cancer. The apparatus is comprised of a pneumatic chest compression vest, a pneumatic pressure generator, and a mouthpiece connected to a nebulizer. Sputum samples are induced by applying an oscillating force to the chest via the pneumatic chest compression vest and pressure generator, while simultaneously providing an aerosolized solution (such as normal or hypertonic saline) via the nebulizer while the patient is standing. The sample is subsequently evaluated to ascertain a patient's risk of or the presence of a pulmonary disorder such as lung cancer. Excerpt(s): This application is related to "Chest Compression Vest with Front Panel Bib" and "Chest Compression Vest with Connecting Belt", which were filed on the same day and also assigned to American Biosystems. The present invention relates to an apparatus and method for inducing sputum samples from a patient. In particular, the present invention relates to obtaining high quality sputum samples for diagnosing pulmonary disorders, especially lung cancer. Lung cancer has a survival rate of only 14% and is the leading cause of cancer death in the United States. The poor prognosis for lung cancer is related to both the lack of effective early detection methods, and the inability to precisely locate the diseased area of the lung to be treated. However, improved imaging techniques now allow much better tumor location capabilities, once detected, to allow specific treatment even at very early stages. Web site: http://www.delphion.com/details?pn=US06379316__

250 Lung Cancer

·

Method and reagent for treatment of lung cancer and other malignancies caused by the deregulation of L-MYC gene expression Inventor(s): Draper; Kenneth G. (Boulder, CO), Thompson; James D. (Boulder, CO) Assignee(s): Ribozyme Pharmaceuticals, Inc. (Boulder, CO) Patent Number: 6,492,512 Date filed: August 26, 1992 Abstract: An enzymatic RNA molecule which cleaves mRNA associated with development or maintenance of lung cancer. Excerpt(s): This invention relates to methods for inhibition of growth of transformed cells, and inhibition of progression to a transformed phenotype in pre-neoplastic cells. Transformation is a cumulative process whereby normal control of cell growth and differentiation is interrupted, usually through the accumulation of mutations affecting the expression of genes that regulate cell growth and differentiation. Scanlon WO91/18625, WO91/18624, and WO91/18913 describes a ribozyme effective to cleave oncogene RNA from the H-ras gene. This ribozyme is said to inhibit H-ras expression in response to exogenous stimuli. Reddy WO92/00080 describes use of ribozymes as therapeutic agents for leukemias, such as CML by targeting specific portions of the BCRABL gene transcript. Web site: http://www.delphion.com/details?pn=US06492512__

·

Method and system for re-screening nodules in radiological images using multiresolution processing, neural network, and image processing Inventor(s): Lin; Jyh-Shyan (Derwood, MD), Lure; Yuan-Ming F (Rockville, MD), Yeh; Hwa-Young M (Potomac, MD) Assignee(s): Caelum Research Corporation (Rockville, MD) Patent Number: 6,125,194 Date filed: February 4, 1998 Abstract: An automated detection method and system improve the diagnostic procedures of radiological images containing abnormalities, such as lung cancer nodules. The detection method and system use a multi-resolution approach to enable the efficient detection of nodules of different sizes, and to further enable the use of a single nodule phantom for correlation and matching in order to detect all or most nodule sizes. The detection method and system use spherical parameters to characterize the nodules, thus enabling a more accurate detection of non-conspicuous nodules. A robust pixel threshold generation technique is applied in order to increase the sensitivity of the system. In addition, the detection method and system increase the sensitivity of true nodule detection by analyzing only the negative cases, and by recommending further re-assessment only of cases determined by the detection method and system to be positive. The detection method and system use multiple classifiers including back propagation neural network, data fusion, decision based pruned neural network, and convolution neural network architecture to generate the classification score for the classification of lung nodules. Such multiple neural network architectures enable the learning of subtle characteristics of nodules to differentiate the nodules from the corresponding anatomic background. A final decision making then selects a portion of films with highly suspicious nodules for further reviewing.

Patents 251

Excerpt(s): The present invention relates to methods and systems for the digital processing of radiological images, and it more specifically relates to an automated method and system for the re-screening and detection of abnormalities, such as lung nodules in radiological chest images using multi-resolution processing, digital image processing and artificial neural networks. Lung cancer is the leading type of cancer in both men and women worldwide. Early detection and treatment of localized lung cancer at a potentially curable stage can significantly increase the patients' survival rate. Studies have shown that approximately 68% of retrospectively detected lung cancers were detected by one reader and approximately 82% were detected with an additional reader as a "second-reader". A long-term lung cancer screening program conducted at the Mayo Clinic found that 90% of peripheral lung cancers were visible in small sizes in retrospect, in earlier radiographs. Among the common detection techniques, such as chest X-ray, analysis of the types of cells in sputum specimens, and fiber optic examination of bronchial passages, chest radiography remains the most effective and widely used method. Although skilled pulmonary radiologist can achieve a high degree of accuracy in diagnosis, problems remain in the detection of the lung nodules in chest radiography due to errors that cannot be corrected by current methods of training even with a high level of clinical skill and experience. Web site: http://www.delphion.com/details?pn=US06125194__ ·

Method of inhibiting cancer growth Inventor(s): McNamara; Thomas F. (Box 44, Port Jefferson, NY 11777), Simon; Sanford (71 Cedar St., Stony Brook, NY 11790), Ramamurthy; Nungavaram S. (10 Lynam Ct., Smithtown, NY 11787), Golub; Lorne M. (29 Whitney Gate, Smithtown, NY 11787), Block; Norman L. (19000 SW. 72nd Ave., Miami, FL 33156), Selzer; Marie G. (6035 Bayview Dr., Fort Lauderdale, FL 33308), Lokeshwar; Balakrishna L. (12615 SW. 112 Ct., Miami, FL 33176), Lee; Hsi-Ming (20 Allyson Pl., Setauket, NY 11733) Assignee(s): none reported Patent Number: 6,100,248 Date filed: January 15, 1998 Abstract: The invention is a method of inhibiting cancer growth, by inhibiting cellular proliferation, invasiveness, or metastasis, or by inducing cytotoxicity against cancer in mammals. The method employs 6-demethyl-6-deoxy-4-de(dimethylamino)tetracycline (CMT-3) and other functionally related chemically modified, preferably nonantibacterial, tetracycline compounds to inhibit cancer growth. The method is particularly effective to inhibit the establishment, growth, and metastasis of solid tumors, such as tumors derived from colon cancer cells, breast cancer cells, melanoma cells, prostatic carcinoma cells, or lung cancer cells. Excerpt(s): The invention relates to methods of reducing cancer growth in biological systems. More specifically, the invention relates to the inhibition of solid tumor invasiveness and metastasis in mammals. Cancer, in all of its myriad manifestations, remains a devastating scourge upon mankind. While progress in preventing and treating cancer has been made, including particular success against Hodgkin's lymphoma and certain other forms, many types of cancer remain substantially impervious to prevailing treatment protocols. Typically, cancer is treated by chemotherapy, in which highly toxic chemicals are given to the patient, or by radiotherapy, in which toxic doses of radiation are directed at the patient. While commonly effective to kill huge numbers of cancer cells, these "cytotoxic" treatments

252 Lung Cancer

also kill extraordinary numbers of healthy cells, causing the patient to experience acute debilitating symptoms including nausea, diarrhea, hypersensitivity to light, hair loss, etc. The side effects of these cytotoxic compounds limits the frequency and dosage at which they can be administered. Such disabling side effects can be mitigated to some degree by using compounds that selectively target cycling cells, i.e., interfering with DNA replication or other growth processes in cells that are actively reproducing. Since cancer cells are characterized by their extraordinary ability to proliferate, such protocols preferentially kill a larger proportion of cancer cells in comparison to healthy cells, but cytotoxicity and ancillary sickness remains a problem. Other more recent developments include efforts to develop monoclonal antibodies specific for oncogenes or HLA specificities, to identify cancer cells with great precision. However, these procedures are very expensive and extremely procedurally elaborate, yet still fail to produce the desired efficacy. Indeed, such procedures have been reported to be effective in only a small subpopulation of treated patients. Web site: http://www.delphion.com/details?pn=US06100248__ ·

Methods for analyzing PRLTS DNA Inventor(s): Nakamura; Yusuke (Kanagawa, JP), Fujiwara; Yoshiyuki (Tokyo, JP) Assignee(s): Eisai Co., Ltd. (Tokyo, JP), Cancer Institute (Tokyo, JP) Patent Number: 5,935,786 Date filed: May 6, 1997 Abstract: A gene is provided which is present in the deletion region of a chromosome common in lung cancer, hepatocellular carcinoma and colorectal cancer and encodes a novel protein, a protein encoded by the gene (PRLTS protein), and a method of discriminating tumor cells. Excerpt(s): The present invention relates to PRLTS proteins, DNAs encoding the proteins and methods of discriminating tumor cells in which use is made of the DNAs. The present invention is usefully applied in the fields of medical science and pharmaceuticals. There has long been a conception that mutations in cellular proteins play an important role in carcinogenesis. The progress of genetic engineering achieved in recent years has made it possible to analyze the amplification of the DNA encoding a specified protein and gene mutations in tumor cells, thereby rapidly advancing cancer research. The analysis and identification of genes (oncogenes) encoding proteins believed as participating in the malignant alteration of cells and the abnormal proliferation of tumor cells have been promoted, so that the identification of such genes number in the tens. On the other hand, counteracting genes (tumor suppressor genes) are highlighted in recent years. Tumor suppressor genes hitherto discovered include the Rb gene capable of suppressing retinoblastoma ›Friend, S. H., et al., Proc. Natl. Acad. Sci. USA., 84, 9095 (1987)!, the p53 gene capable of suppressing colorectal cancer ›Lane, D. P., et al., Nature, 278, 261 (1979)!, the APC gene capable of suppressing colorectal cancer ›Kenneth, W. K., et al., Science, 253, 661 (1991)! and the WTI gene capable of suppressing Wilms' tumor ›Call, K. M., et al., Cell, 60, 509 (1990)!. With respect to the p53 gene, cases are known in which germ-line mutations in the gene are inherited ›"LiFraumeni syndrome" (Makin, D., et al., Science, 250, 1233 (1990); and Srivastava, S., et al., Nature, 348, 747 (1990))!. It is gradually becoming apparent that defects in not only a single gene but also in multiple genes participate in the progression of the malignant phenotype of cancer, and it is believed that there will be further discovered a large number of unidentified oncogenes and tumor suppressor genes. Their discovery and

Patents 253

elucidation are anticipated by not only research and clinical experts but also people worldwide. Web site: http://www.delphion.com/details?pn=US05935786__ ·

Methods for the early diagnosis of ovarian, breast and lung cancer Inventor(s): O'Brien; Timothy J. (Little Rock, AR) Assignee(s): The Board of Trustees of the University of Arkansas (Little Rock, AR) Patent Number: 6,316,213 Date filed: January 27, 2000 Abstract: The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. The detected proteases are themselves specifically overexpressed in certain cancers, and their presence may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment. Excerpt(s): Generally, the present invention relates to the fields of molecular biology and medicine. More specifically, the present invention is in the field of ovarian and other cancer diagnosis. To date, ovarian cancer remains the number one killer of women with gynecologic malignant hyperplasia. Approximately 75% of women diagnosed with such cancers are already at an advanced stage (III and IV) of the disease at their initial diagnosis. During the past 20 years, neither diagnosis nor five year survival rates have greatly improved for these patients. This is substantially due to the high percentage of high-stage initial detections of the disease. Therefore, the challenge remains to develop new markers that improve early diagnosis and thereby reduce the percentage of highstage initial diagnoses. Extracellular proteases have already been implicated in the growth, spread and metastatic progression of many cancers, due to the ability of malignant cells not only to grow in situ, but to dissociate from the primary tumor and to invade new surfaces. The ability to disengage from one tissue and re-engage the surface of another tissue is what provides for the morbidity and mortality associated with this disease. Therefore, extracellular proteases may be good candidates for markers of neoplastic development. Web site: http://www.delphion.com/details?pn=US06316213__

·

Optical projection imaging system and method for automatically detecting cells having nuclear and cytoplasmic densitometric features associated with disease Inventor(s): Nelson; Alan C. (1509 56th Ave. Ct. NW., Gig Harbor, WA 98335) Assignee(s): none reported Patent Number: 6,519,355 Date filed: January 22, 2002 Abstract: A system and method for rapidly detecting cells of interest using multidimensional, highly quantitative, nuclear and cytoplasmic densitometric features (NDFs and CDFs) includes a flow optical tomography (FOT) instrument capable of generating various optical projection images (or shadowgrams) containing accurate density information from a cell, a computer and software to analyze and reconstruct the projection images into a multi-dimensional data set, and automated feature collection

254 Lung Cancer

and object classifiers. The system and method are particularly useful in the early detection of cancers such as lung cancer using a bronchial specimen from sputum or cheek scrapings and cervical/ovarian cancer using a cervical scraping, and the system can be used to detect rare cells in specimens including blood. Excerpt(s): The present invention relates to projection imaging systems in general and cell classification, and more particularly, to high throughput flow based automated systems using projection imaging, such as flow optical tomography (FOT), for detecting abnormal and malignant cells and for detecting rare cells based on highly quantative measurements of nuclear and cytoplasmic densitometric features (NDFs and CDFs) associated with disease. The most common method of diagnosing cancer in patients is by obtaining a sample of the suspect tissue and examining it under a microscope for the presence of obviously malignant cells. While this process is relatively easy when the anatomic location of the suspect tissue is known, it is not so easy when there is no readily identifiable tumor or pre-cancerous lesion. For example, to detect the presence of lung cancer from a sputum sample requires one or more relatively rare cancer cells to be present in the sample. Therefore, patients having lung cancer may not be diagnosed properly if the sample does not perceptively and accurately reflect the conditions of the lung. One example of a microscope-based system and method for detecting diagnostic cells and cells having malignancy-associated changes is disclosed in Palcic et al., U.S. Pat. No. 6,026,174. The Palcic et al. system includes an automated classifier having a conventional microscope, camera, image digitizer, a computer system for controlling and interfacing these components, a primary classifier for initial cell classification, and a secondary classifier for subsequent cell classification. The method utilizes the automated classifier to automatically detect diagnostic cells and cells having malignancy-associated changes. However, the quality of the diagnostic result is limited by the use of a conventional microscope, which does not permit accurate measurement of stain densities. The method of Palcic et al. does not address the use of molecular probes. Web site: http://www.delphion.com/details?pn=US06519355__ ·

Pharmaceutical compositions, methods, and kits for treatment and diagnosis of lung cancer Inventor(s): Manyak; Michael J. (Chevy Chase, MD), Patierno; Steven R. (Falls Church, VA) Assignee(s): George Washington University (Washington, DC) Patent Number: 6,509,316 Date filed: December 9, 1997 Abstract: The present invention relates to pharmaceutical compositions, methods and kits that provide for the early diagnosis and treatment of lung cancer. More particularly, the present invention relates to pharmaceutical compositions containing uteroglobin for preventing or inhibiting metastasis of lung tumor cells and methods of using the same to prevent or inhibit metastasis of lung tumor cells. The present invention also relates to methods and kits for early diagnosis of metastatic lung cancer by assaying for uteroglobin and comparing the results against control cells. The present invention also relates to methods and kits for detection of metastatic lung cancer by assaying for the presence of an aberrant form of uteroglobin. Excerpt(s): The present invention relates to pharmaceutical compositions, methods and kits that provide for the early diagnosis and treatment of lung cancer. More particularly,

Patents 255

the present invention relates to pharmaceutical compositions containing uteroglobin for treating or inhibiting metastasis of lung epithelial tumor cells and methods of using the same to treat or inhibit metastasis of lung epithelial tumor cells. The present invention also relates to methods and kits for early diagnosis of metastatic lung cancer by assaying for uteroglobin and comparing the results against control cells. Cancers develop from uncontrolled multiplication of cells. All cancers are life threatening, and lung cancer remains the major cause of cancer death among both males and females. There are four types of lung cancer found in humans: squamous, adeno, small cell, and large cell. Each tumor expresses specific differentiation features or surface phenotype determinants, all of which distinguish these cells form normal cells. The development of monoclonal antibody diagnostic techniques has greatly enhanced the production of reagents capable of differentiating normal cells from cancer cells and differentiating between cancer cell types. However, none of these markers have been able to provide information concerning when a tumor cell or cells will become metastatic. Web site: http://www.delphion.com/details?pn=US06509316__ ·

Proteins for cancer cell specific induction of apoptosis and method for isolation thereof Inventor(s): Tsai; David (2500 Townsgate Rd. Unit C, Westlake Village, CA 91361), Yu; Jenny (2500 Townsgate Rd. Unit C, Westlake Village, CA 91361) Assignee(s): none reported Patent Number: 5,994,298 Date filed: September 8, 1998 Abstract: The present invention provides the methods to isolate the proteins specifically induced apoptosis (programmed cell death) in prostate cancer cells (LNCAP), leukemia cells (HL-60), and breast cancer cells (MCF-70), but without effect in normal human lung fibroblast cells (CCD 39 Lu). P-1 has no effect on breast cancer cells. Five proteins have been isolated from the conditioned media of culture cells: (1) Apogen P-1: the proteins (Apogen P-1a, Apogen P-1b and Apogen P-1c) isolated from the conditioned medium of XC cells are able to induce apoptosis in prostate cancer cells (LNCAP) without effect in normal human lung fibroblast (CCD 39 Lu), colon cancer (T84), breast cancer (MCF-7) and leukemia (HL-60) cells. (2) Apogen P-2: the protein isolated from the conditioned medium of C3H10T1/2 cells is able to induce apoptosis in prostate cancer cells (LNCAP) and breast cancer (MCF-7) without effect in normal human lung fibroblast (CCD 39 Lu) and colon cancer (T84) cells. (3) Apogen L: the protein isolated from the conditioned medium of XC cells is able to induce apoptosis in leukemia cells (HL-60), and breast cancer (MCF-7) without effect in normal human lung fibroblast (CCD 39 Lu), colon cancer (T84) and prostate cancer (LNCAP) cells. The isolated protein Apogen P-2 is at least in part comprised of bovine fetuin. When properly prepared, fetuin is able to induce apoptosis in leukemia cells (HL-60), prostate cancer (LNCaP and PC-3) cells, colon cancer (Colo 205) cells, breast cancer (MCF-7) cells, and lung cancer (Calu-1) cells. The invention may lead to the discovery of a novel class of anticancer drug that aims at prostate cancer, breast cancer, leukemia and other cancers by inducing apoptosis in cancer cells without affecting normal cells. Excerpt(s): Human beings have had a long battle against cancer. Because the disease is so widespread, manifests itself in so many different ways and is so relentless, the potential market for effective cancer therapies is enormous. It is estimated that 10 million people in the U.S. either have or have had cancer. The National Cancer Institute

256 Lung Cancer

(NCI) projects that in 1995, some 1.2 million new cases of cancer will be diagnosed in the United States, and that 538,000 people will die of the disease. Cancer is currently treated, with a low degree of success, with combinations of surgery, chemotherapy and radiation. The reason of the low degrees of success in cancer chemotherapy is as the following: Current chemotherapeutic approaches target rapidly dividing tumor cells. This approach is ineffective when the cancer is dormant or growing slowly. Such treatments also affect other, noncancerous cells that divide rapidly, causing harmful side effects. Only in the last several years has a new approach emerged in the battle against cancer. This approach is based on the newly discovered biological phenomenon called "Apoptosis". Apoptosis is also called "programmed cell death" or "cell suicide". (Krammer, et al., "Apoptosis in the APO-1 System", Apoptosis: The molecular Basis of Cell Death, pp. 87-99 Cold Spring Harbor Laboratory Press, 1991). In contrast to the cell death caused by cell injury, apoptosis is an active process of gene-directed, cellular selfdestruction and that it serves a biologically meaningful function. (Kerr, J. F. R and J. Searle J. Pathol. 107:41, 1971). One of the examples of the biologically meaningful functions of apoptosis is the morphogenesis of embryo. (Michaelson, J. Biol. Rev. 62:115, 1987). Just like the sculpturing of a sculpture, which needs the addition as well as removal of clay, the organ formation (Morphogenesis) of an embryo relies on cell growth (addition of clay) as well as cell death (removal of clay). As a matter of fact, apoptosis plays a key role in the human body from the early stages of embryonic development through to the inevitable decline associated with old age. (Wyllie, A. H. Int. Rev. Cytol. 68:251, 1980). The normal function of the immune, gastrointestinal and hematopoietic system relies on the normal function of apoptosis. When the normal function of apoptosis goes awry, the cause or the result can be one of a number of diseases, including: cancer, viral infections, auto-immune disease/allergies, neurodegeneration or cardiovascular diseases. Because of the versatility of apoptosis involved in human diseases, apoptosis is becoming a prominent buzzword in the pharmaceutical research field. Huge amounts of time and money are being spent in an attempt to understand how it works, how it can be encouraged or Inhibited and what this means for practical medicine. A handful of companies have been formed with the prime direction of turning work in this nascent field into marketable pharmaceutical products. The emergence of a core of innovative young companies combined with the tentative steps being taken by established industrial players are certain to make apoptosis research one of the fastest-growing and most promising areas of medical study of the 1990s. The idea that cancer may be caused by insufficient apoptosis merged only recently (Cope, F. O and Wille, J. j, "Apoptosis": The Molecular Basis of Cell Death, Cold Spring Harbor Laboratory Press, p. 61, 1991). This idea however, opens a door for a new concept in cancer therapy--Cancer cells may be killed by encouraging apoptosis. Apoptosis modulation, based on the processes present in normal development, is a potential mechanism for controlling the growth of tumor cells. Restoring apoptosis in tumor cells is an attractive approach because, at least in theory, it would teach the cells to commit suicide. Nevertheless, since the objective of cancer treatment is to kill cancer cells without killing the host, although apoptosis may open a new door for cancer therapy by inducing apoptosis in tumor cells, the success of this treatment is still dependent on the availability of drugs that can selectively induce apoptosis in tumor cells without affecting normal cells. In this patent application, we described the methods for the Isolation of proteins that specifically induce apoptosis in cancer cells without effect in normal cells. These proteins may present a new class of anticancer drugs that induce apoptosis in cancer cells which may offer a breakthrough in cancer therapy. Web site: http://www.delphion.com/details?pn=US05994298__

Patents 257

·

Purified compositions of 10-propargyl-10-deazaaminopterin and methods of using same in the treatment of tumors Inventor(s): Sirotnak; Francis M. (New York, NY), Piper; James R. (Birmingham, AL), DeGraw; Joseph I. (Missoula, MT), Colwell; William T. (Menlo Park, CA) Assignee(s): Southern Research Institute (Birmingham, AL), SRI International (Menlo Park, CA), Sloan-Kettering Institute for Cancer Research (New York, NY) Patent Number: 6,028,071 Date filed: March 8, 1999 Abstract: Highly purified 10-propargyl-10-deazaaminopterin (10-propargyl-10dAM) compositions tested in xenograft models for their efficacy against human tumors are shown to be far superior to methotrexate ("MTX") and are even superior to the newer clinical candidate edatrexate ("EDX"). Moreover, 10-propragyl-10dAM showed a surprising ability to cure tumors such that there was no evidence of tumor growth several weeks after the cessation of therapy. Thus, highly purified compositions containing 10-propargyl-10dAM can be used to treat human tumors, particularly human mammary tumors and human lung cancer. Excerpt(s): This application relates to a purified composition of the compound 10propargyl-10-deazaaminopterin and to methods of using this compound in the treatment of tumors. Surprisingly, however, more highly purified 10-propargyl-10dAM compositions when tested in a xenograft model for their efficacy against human tumors have now been shown to be far superior to methotrexate ("MTX") and are even superior to edatrexate ("ETX"), a more recent clinical candidate. Moreover, 10-propargyl-10dAM showed a surprising ability to cure tumors such that there was no evidence of tumor growth several weeks after the cessation of therapy. Thus, a first aspect of the present invention is a highly purified composition containing 10-propargyl-10dAM. This composition can be used in accordance with the invention to treat tumors, particularly human mammary tumors and human lung cancer. This application relates to "highly purified" 10-propargyl-10dAM. As used in the specification and claims hereof, compositions which are "highly purified" contain 10-propargyl-10dAM substantially free of other folic acid derivatives particularly 10-deazaaminopterin, which can interfere with the antitumor activity of the 10-propargyl-10dAM. A composition within the scope of the invention may include carriers or excipients for formulating the 10-propargyl10dAM into a suitable dosage unit form for therapeutic use. Web site: http://www.delphion.com/details?pn=US06028071__

·

Reagents and methods useful for detecting diseases of the lung Inventor(s): Roberts-Rapp; Lisa (Gurnee, IL), Klass; Michael R. (Libertyville, IL), Hodges; Steven C. (Buffalo Grove, IL), Stroupe; Steven D. (Libertyville, IL), Russell; John C. (Kenosha, WI), Friedman; Paula N. (Deerfield, IL), Cohen; Maurice (Highland Park, IL), Kratochvil; Jon D. (Kenosha, WI), Gordon; Julian (Lake Bluff, IL) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,939,265 Date filed: November 5, 1997 Abstract: A set of contiguous and partially overlapping RNA sequences and polypeptides encoded thereby, designated as LU103 and transcribed from lung tissue is

258 Lung Cancer

described. A fully sequenced clone representing the longest continuous sequence of LU103 is also disclosed. These sequences are useful for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, or determining the predisposition of an individual to diseases and conditions of the lung such as lung cancer. Excerpt(s): The invention relates generally to detecting diseases of the lung. More particularly, the invention relates to reagents such as polynucleotide sequences and the polypeptide sequences encoded thereby, as well as methods which utilize these sequences. The polynucleotide and polypeptide sequences are useful for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, or determining predisposition to diseases or conditions of the lung such as lung cancer. Lung cancer is the second most common cancer for both men and women in the United States, with an estimated 178,100 newly diagnosed during 1997 (American Cancer Society statistics). It also is the most common cause of cancer death for both sexes, with over 160,000 lung cancer related deaths expected in 1997. Lung cancer is a major health problem in other areas of the world, with approximately 135,000 new cases occurring each year in the European Union, and its incidence rapidly increasing in Central and Eastern Europe. See, Genesis Report, February 1995 and T. Reynolds, J. Natl. Cancer Inst. 87: 1348-1349 (1995). Early stage lung cancer can be detected by chest radiograph and the sputum cytological examination; however, these procedures do not have sufficient sensitivity for routine use as screening tests for asymptomatic individuals. Potential technical problems which can limit the sensitivity of chest radiograph include suboptimal technique, insufficient exposure, and positioning and cooperation of the patient. T. G. Tape et al., Ann. Intern. Med. 104: 663-670 (1986). Moreover, radiologists often disagree on interpretations of chest radiographs; over 40% of these disagreements are significant or potentially significant, with false-negative interpretations being the cause of most errors. P. G. Herman et al., Chest 68: 278-282 (1975). Inconclusive results require additional follow-up testing for clarification. T. G. Tape et al., supra. Sputum cytology is even less sensitive than chest radiography in detecting early lung cancer; of 160 lung cancer cases, radiography alone detected 123 cases (77%) while cytological examination alone detected 67 cases (42%). The National Cancer Institute "Early Lung Cancer Detection: Summary and Conclusion," Am. Rev. Resp. Dis. 130: 565-567 (1984). Factors affecting the ability of sputum cytological examination to diagnose lung cancer include the ability of the patient to produce sufficient sputum, the size of the tumor, the proximity of the tumor to major airways, the histologic type of the tumor, and the experience and training of the cytopathologist. R. J. Ginsberg et al. In: Cancer: Principles and Practice of Oncology, Fourth Edition, V. T. DeVita, S. Hellman, S. A. Rosenburg, pp. 673-723, Philadelphia, Pa.: J. B. Lippincott Co. (1993). Web site: http://www.delphion.com/details?pn=US05939265__ ·

System and method for detection of a biological condition Inventor(s): Berry; Michael J. (Carmel, CA) Assignee(s): Quadrivium, L.L.C. (Phoenix, AZ) Patent Number: 6,363,772 Date filed: December 10, 1999 Abstract: A system and method that allows for early detection of biological conditions, such as a disease, through analysis of appropriate gaseous samples. The system and method are particularly amenable to the early screening for diseases, such as lung cancer, through the detection of specific biomarkers when present in exhaled breath

Patents 259

from an individual. A preferred system implements a CO overtone laser that generates radiation and directs it through a photoacoustic cell. The absorption of the radiation is detected acoustically, and the absorption characteristics are utilized in determining the presence of a specific biological condition. Excerpt(s): The present invention relates generally to the detection of volatile organic compounds that serve as biomarkers for a biological condition, such as a disease, and particularly to a noninvasive system and method for determining the presence of such condition in an individual or substance through analysis of a gaseous sample from the individual or substance. Early detection of disease in an individual is often important to successful treatment of that disease. A variety of techniques are used to test for specific diseases either before or after symptoms occur. For example, blood samples and urine samples are routinely taken for analysis and detection of abnormalities indicative of disease. Many of these techniques are invasive or uncomfortable for the patient. One potential noninvasive technique for determining the presence of a variety of diseases in the body of an individual is breath analysis. There are over three hundred distinct chemical compounds that may be detected in human expired breath, and each of these distinct chemical compounds has its own absorption spectrum. Studies have shown that specific alterations or changes in this expired air are indicative of specific diseases. This is true for some diseases because of the direct compositional relationship between constituents carried in the blood stream and constituents excreted into the alveolar spaces of the lungs. In any event, the changes or alterations in the constituents of an individual's breath can be detected to determine whether the individual has a particular biological condition, such as a disease or metabolic disorder. Web site: http://www.delphion.com/details?pn=US06363772__ ·

Use of betulinic acid derivatives for inhibiting cancer growth Inventor(s): Ramadoss; Sunder (Delhi, IN), Siddiqui; Mohammad Jamshed Ahmed (Ghaziabad, IN), Khanna; Achla B. (Delhi, IN), Jaggi; Manu (Haryana, IN) Assignee(s): Dabur Research Foundation (Ghaziabad, IN) Patent Number: 6,214,814 Date filed: February 17, 1999 Abstract: The invention relates to the use of betulinic acid and its derivatives for the inhibition and/or prevention or cancer growth. The invention also relates to novel betulinic acid derivatives useful for the inhibition of tumor/cancer cells and a process for the preparation of the derivatives. The invention also relates to the antileukemic, and anti-lymphoma activity of the betulinic acid derivatives, and the use of the derivatives for the treatment of prostate, ovarian and lung cancer. Excerpt(s): The invention relates to the use of betulinic acid and its derivatives for the inhibition and/or prevention or cancer growth. The invention also relates to novel betulinic acid derivatives useful for the inhibition of tumor/cancer cells and a process for the preparation of the derivatives. The invention also relates to the antileukemic, and anti-lymphoma activity of the betulinic acid derivatives, and the use of the derivatives for the treatment of prostate, ovarian and lung cancer. Under the auspices of a National Cooperative Natural Product Drug Discovery Group supported by the National Cancer Institute, the potential antitumor activity of approximately 2500 extracts derived from globally collected plants was evaluated in a panel of enzyme based assays and in a battery of cultured human tumor cell lines. One such extract, prepared from the stem

260 Lung Cancer

bark of Ziziphus mauritiana Lam. (Rhamnaceae), displayed selective cytotoxicity against cultured human melanoma cells (Nature Medicine, Vo. 1 (10), 1995, WO 96/29068). As a result of bioactivity guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma-specific cytotoxic agent. In follow-up studies conducted with a thymic mice carrying human melanomas, tumor growth was completely inhibited without toxicity. As judged by a variety of cellular responses, antitumor activity was mediated by the induction of apoptosis. A number of triterpenoids, including betulinic acid, have several known medical applications, including use as anticancer drugs. Anderson et al., in WO 95/04526, have discussed the derivatives of triterpenoids which have been used in cancer therapy, including their activity against polyamines which are required by cells to grow at an optimal rate. Some of these triterpenoids have been found to interfere with enzymatic synthesis of polyamines required for optimal cell growth, and thus inhibit the growth of cancer cells, particularly by inhibiting ornithine decarboxylase (Yasukawa, K. et al., Oncology 48: 7276, 1991), The anti-cancer activity of betulinic acid and some derivatives has been demonstrated using mouse sarcoma 180 cells implanted subcutaneously in nude mice (JP 87,301,580). Choi et al have shown that betulinic acid 3-monoacetate, and betulinic acid methyl ester exhibit ED.sub.50 values of 10.5 and 6.8.mu.g/ml, respectively, against p388 lymphocytic leukemia cells (Choi, Y-H et al., Planta Medical vol. XLVII, pages 511513, 1988). Web site: http://www.delphion.com/details?pn=US06214814__

Patent Applications on Lung 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 lung cancer: ·

21910, a novel human membrane-associated guanylate kinase and uses thereof Inventor(s): Kapeller-Libermann, Rosana; (Chestnut Hill, MA), Hunter, John Joseph; (Somerville, MA) Correspondence: LAHIVE & COCKFIELD; 28 STATE STREET; BOSTON; MA; 02109; US Patent Application Number: 20030108934 Date filed: October 22, 2002 Abstract: The invention provides isolated nucleic acid molecules, designated MAGK nucleic acid molecules, which encode novel guanylate kinase related molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing MAGK nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a MAGK gene has been introduced or disrupted. The invention still further provides isolated MAGK proteins, fusion proteins, antigenic peptides and anti-MAGK antibodies. Treatment and diagnostic methods for cellular growth or proliferation diseases or disorders, e.g., cancer, including, but not limited to colon cancer and lung cancer, utilizing compositions of the invention, are also provided.

10

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

Patents 261

Excerpt(s): This application claims the benefit of prior-filed provisional patent application Serial No. 60/205,447, filed May 19, 2000, entitled "21910, A Novel Human Membrane-Associated Guanylate Kinase and Uses Thereof". The entire content of the above-referenced application is incorporated herein by this reference. Guanylate kinases are essential enzymes in nucleotide metabolism pathways catalyzing the ATPdependent phosphorylation of either GMP to GDP or dGMP to dGDP. Guanyate kinase molecules also function in the recovery of cGMP (cGMP.fwdarw.GMP.fwdarw.GDP.fwdarw.GTP.fwdarw.cGMP) thereby serving to regulate the supply of guanine nucleotides to signal transduction pathway components (Brady et al. (1996) J. Biol. Chem. 271(28):16734-40; Kumar, et al. (2000) Eur. J. Biochem. 267(2):606). Guanylate kinases are essential to a wide range of cellular processes including but not limited to nucleotide metabolic processes (e.g., supplying the building blocks for nucleic acids), phototransduction processes (e.g., regulating the opening and/or closing of cGMP gated-channels), cellular growth and proliferation, and signaling pathways (Fitzgibbon, et al (1996) FEBS Letters 385:185-188). Membranebound forms of guanylate kinase molecules have also been discovered. Members of the membrane-associated guanylate kinase family interact with the cytoskeleton of the cell and regulate cell proliferation, signaling pathways, and intercellular junctions. (Kim, et al. (1996) Genomics 31(2):223). These molecules participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane and cluster ion channels, receptors, adhesion molecules and cytosolic signaling proteins at synapses, cellular junctions, and polarized membrane domains (Fannin and Anderson (1999) Curr. Opin. Cell Biol. 11(4):432; Dobrosotskaya, et al. (1997) J. Biol. Chem. 272(50):31589). In addition, membrane-associated guanylate kinases have recently been found to have a transcriptional regulatory function (Hsueh, et al. (2000) Nature 404(6775):298). Typically, these molecules contain multiple protein-protein interaction motifs including a PDZ domain in the N-terminal portion of the protein, followed by a SH3 domain, followed by a guanylate kinase domain at the C-terminus (Dobrosotskaya, et al., supra). Membrane-associated guanylate kinases have been found to be localized to tight junctions in epithelial cell membranes and more notably in neuronal cells (Wu, et al. (2000) Proc. Natl Acad. Sci. USA 97(8):4233); Hsuesh, supra). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

2-Methoxyestradiol-induced apoptosis in cancer cells Inventor(s): Mukhopadhyay, Tapas; (Houston, TX), Roth, Jack A.; (Houston, TX) Correspondence: Steven L. Highlander, Esq.; FULBRIGHT & JAWORSKI L.L.P.; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20030099614 Date filed: June 25, 2002 Abstract: The present invention details methods for the treatment of cancer. In particular, it concerns the induction of apoptosis of cancer cells following treatment with methoxyestradiol. 2-methoxyestradiol (2-MeOE.sub.2) increase wild-type p53 levels in a human non-small lung cancer cell lines associated with accumulation of cyclin dependent kinase inhibitor p21WAF1/CIP1. Significant apoptotic cell death occurred after the drug treatment. Thus, 2-MeOE.sub.2 facilitates induction of p53-mediated apoptosis. Excerpt(s): The present invention relates generally to the field of cancer therapy. More particularly, it concerns the use of methoxyestradiol to stimulate p53 expression in

262 Lung Cancer

tumor cells, thereby inducing programmed cell death. Normal tissue homeostasis is achieved by an intricate balance between the rate of cell proliferation and the rate of cell death. Disruption of this balance is thought to be a major deleterious event in the development of cancer. The inhibition of apoptosis (programmed cell death) has been linked to this disruptive event. The effects of such defects are catastrophic, causing over half a million deaths per annum in the United States alone. The p53 gene is well recognized as a tumor suppressor gene (Montenarh, 1992). There is now considerable evidence linking mutations of p53 in the oncogenesis of many human cancers. There are numerous reports demonstrating that the growth of, for example, colon, glioblastoma, breast cancer, osteosarcoma and lung tumor cells can be suppressed by the expression of wild-type p53. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Angiotensin-(1-7) and angiotensin-(1-7) agonists for inhibition of cancer cell growth Inventor(s): Tallant, E. Ann; (Lewisville, NC), Gallagher, Patricia E.; (Lewisville, NC), Ferrario, Carlos M.; (Winston-Salem, NC) Correspondence: Cynthia B. Rothschild, Esq.; Kilpatrick Stockton LLP; 1001 West Fourth Street; Winston-Salem; NC; 27101-2400; US Patent Application Number: 20030203834 Date filed: February 27, 2003 Abstract: The present invention describes the use of angiotensin-(1-7) peptide as an anticancer therapeutic. Thus, in one embodiment, the present invention comprises a composition to inhibit the growth of cancer cells in an individual comprising a pharmaceutically effective amount of an agonist for the angiotensin-(1-7) receptor to inhibit cancer cell growth or proliferation. Application of a pharmaceutically effective amount of angiotensin-(1-7) or angiotensin-(1-7) receptor agonist is associated with an increase in the expression of genes involved in tumor suppression, apoptosis, and/or cell cycle inhibition, and a decrease the expression of known oncogenes, protein kinases, and/or cell cycle progression genes. Cancers treated using the methods and compositions described herein include cancers having an angiotensin-(1-7) receptor, including, but not limited to, breast and lung cancer. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/359,847, filed Feb. 27, 2002. The disclosure of U.S. Provisional Application Serial No. 60/359,847 is incorporated herein by reference in its entirety. The present invention relates to compositions and methods for the treatment and prevention of cancer. More specifically, the present invention relates to the use of angiotensin-(1-7) or other agonists for the angiotensin-(l1-7) receptor as anticancer therapeutics. Angiotensin-(1-7) [Ang-(17)] is an endogenous peptide hormone which is normally present in the circulation at concentrations similar to angiotensin II (Ang II) and is primarily derived from angiotensin I (Ang I) by tissue peptidases, including neprilysin, thimet oligopeptidase and prolyl endopeptidase (Ferrario, C. M. et al., Hypertension, 1997, 30:535-541) and by angiotensin converting enzyme (ACE) 2 from angiotensin II (Ang II) (Vickers, C., et al., J. Biol. Chem., 2002, 277:14836-14843). In addition, Ang-(1-7) is a substrate for ACE (Chappell, M. C. et al. Hypertension, 1998, 31:362-367). ACE catalyzes the conversion of angiotensin I (Ang I) to the biologically active peptide angiotensin II [Ang II]. Treatment of patients or animals with ACE inhibitors results in a significant elevation in the circulating and tissue levels of Ang II, as well as the N-terminal heptapeptide fragment of Ang II, angiotensin-(1-7) (Campbell, M. C. et al., Hypertension, 1993, 22:513-522;

Patents 263

Kohara, K. et al., Hypertension, 1991, 17:131-138; Lawrence, A. C. et al., J. Hypertens., 1990, 8:715-724; and Luque, M. et al., J. Hypertens., 1996, 14:799-805). It has been suggested that ACE inhibition not only elevates Ang-(1-7) by increasing Ang I, the substrate for Ang-(1-7) production, but also by preventing Ang-(1-7) conversion to the inactive fragment Ang-(1-5). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Aziridinyl quinone antitumor agents based on indoles and cyclopent[b]indoles Inventor(s): Skibo, Edward B.; (Mesa, AZ), Xing, Chengguo; (Somerville, MA) Correspondence: FENNEMORE CRAIG; 3003 NORTH CENTRAL AVENUE; SUITE 2600; PHOENIX; AZ; 85012; US Patent Application Number: 20030139609 Date filed: September 10, 2002 Abstract: A large number of aziridinyl quinones represented by Series 1-9 were studied with respect to their DT-diaphorase substrate activity, DNA reductive alkylation, cytostatic/cytotoxic activity, and in vivo activity. As a result generalizations have been made with respect with respect to the following: DT-diaphorase substrate design, DTdiaphorase-cytotoxicity QSAR, and DNA reductive alkylating agent design. A saturating relationship exists between the substrate specificity for human recombinant DT-diaphorase and the cytotoxicity in the human H460 non-small-cell lung cancer cell line. The interpretation of this relationship is that reductive activation is no longer rate limiting for substrates with high DT-diaphorase substrate specificities. High DTdiaphorase substrate specificity is not desirable in the indole and cylopent[b]indole systems because of the result is the loss of cancer selectivity along with increased toxicity. We conclude that aziridinyl quinones of this type should possess a substrate specificity (VMAX/KM )<10.times.10-4 s-1 for DT-diaphorase in order not to be too toxic or nonselective. While some DNA alkylation was required for cytostatic and cytotoxic activity by Series 1-9, too much alkylation results in loss of cancer selectivity as well as increased in vivo toxicity. Indeed, the most lethal compounds are the indole systems with a leaving group in the 3a-position (like the antitumor agent EO-9). We conclude that relatively poor DNA alkylating agents (according to our assay) show the lowest toxicity with the highest antitumor activity. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/318,846 filed Sep. 10, 2001. The present invention relates generally to the field of chemotherapy and more particularly to the isolation, elucidation of novel antineoplastic agents based on indoles and cyclopent[b]indoles. The PBIs were developed in this laboratory and found to possess cytotoxicity with minimal antitumor activity. {Skibo, E. B., The Discovery of the Pyrrolo[1,2-a]benzimidazole Antitumor Agents--The Design of Selective Antitumor Agents, Curr. Med. Chem., 1996, 2, 900-931; Skibo, E. B., Pyrrolobenzimidazoles in Cancer Treatment, Exper. Opin. Ther. Patents, 1998, 8, 673-701} The indoloquinone EO9 was considered to be a promising antitumor agent, {Hendriks, H. R., Pizao, P. E., Berger, D. P., Kooistra, K. L., Bibby, M. C., Boven, E., Dreef-van der Meulen, H. C., Henrar, H. H., Fiebig, H. H., Double, J. A., Hornstra, H. W., Pinedo, H. M., Workman, P., and Schwartsmann, G., EO9: A Novel Bioreductive Alkylating Indoloquinone With Prefential Solid Tumour Activity and Lack of Bone Marrow Toxicity in Preclinical Models, Eur. J. Cancer, 1993, 29A, 8997-906; Maliepaard, M., Wolfs, A., Groot, S. E., de Mol, N. J., and Janssen, L. H. M., Indoloquinone EO9: DNA Interstrand Cross-linking Upon Reduction by DT-Diaphorase or Xanthine

264 Lung Cancer

Oxidase, Br.J. Cancer, 1995, 71, 836-839}but Phase I clinical trials revealed short plasma half-lives as well as toxicity. {Schellens, J. H. M., Planting, A. S. T., Vanacker, B. A. C., Loos, W. J., Deboerdennert, M., Vanderburg, M. E. L., Koier, I., Krediet, R. T., Stoter, G., and Verweij, J., Phase-I and Pharmacological Study of the Novel Indoloquinone Bioreductive Alkylating Cytotoxic Drug E09, J. Nat. Cancer Inst., 1994, 86, 906-912; Aamdal, S., Lund, B., Koier, I., Houten, M., Wanders, J., and Verweij, J., Phase I trial with Weekly EO9, a Novel Bioreductive Alkylating Indoloquinone, by the EORTC Early Clinical Study Group (ECSG), Cancer Chemother. Pharmacol, 2000, 45, 85-88; Loadman, P. M., Phillips, R. M., Lim, L. E., and Bibby, M. C., Pharmacological Properties of a New Aziridinylbenzoquinone, RH1 (2,5-diaziridinyl-3-(Hydroxymethyl)-6-methyl-1,4benzoquinone), in Mice, Biochem Pharmaco, 2000, 59, 831-837.} The cyclopent[b]indoles, reported in the past year, {Xing, C. G., Wu, P., Skibo, E. B., and Dorr, R. T., Design of cancer-specific antitumor agents based on aziridlinylcyclopent[b]indoloquinones, J. Med. Chem., 2000, 43, 457-466 } possess promising antitumor activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Cell-based detection and differentiation of lung cancer Inventor(s): Pressman, Norman J.; (Glencoe, IL), Hirsch, Kenneth S.; (Redwood City, CA), Hirsch, Adrian; (Redwood City, CA) Correspondence: FOLEY AND LARDNER; SUITE 500; 3000 K STREET NW; WASHINGTON; DC; 20007; US Patent Application Number: 20030104499 Date filed: March 12, 2002 Abstract: The present invention provides a method for detecting and differentiating disease states with high sensitivity and specificity. The method allows for a determination of whether a cell-based sample contains abnormal cells and, for certain diseases, is capable of determining the histologic type of disease present. The method detects changes in the level and pattern of expression of the molecular markers in the cell-based sample. Panel selection and validation procedures are also provided. Excerpt(s): The present invention relates to early detection of a general disease state in a patient. The present invention also relates to discrimination (differentiation) between specific disease states in their early stages. Early detection of a specific disease state can greatly improve a patient's chance for survival by permitting early diagnosis and early treatment while the disease is still localized and its pathologic effects limited anatomically and physiologically. Two key evaluative measures of any test or disease detection method are its sensitivity (Sensitivity=True Positives/(True Positives+False Negatives) and specificity (Specificity=True Negatives/(False Positives+True Negatives), which measure how well the test performs to accurately detect all affected individuals without exception, and without falsely including individuals who do not have the target disease. Historically, many diagnostic tests have been criticized due to poor sensitivity and specificity. Sensitivity is a measure of a test's ability to detect correctly the target disease in an individual being tested. A test having poor sensitivity produces a high rate of false negatives, i.e., individuals who have the disease but are falsely identified as being free of that particular disease. The potential danger of a false negative is that the diseased individual will remain undiagnosed and untreated for some period of time, during which the disease may progress to a later stage wherein treatments, if any, may be less effective. An example of a test that has low sensitivity is a protein-based blood test for HIV. This type of test exhibits poor sensitivity because it

Patents 265

fails to detect the presence of the virus until the disease is well established and the virus has invaded the bloodstream in substantial numbers. In contrast, an example of a test that has high sensitivity is viral-load detection using the polymerase chain reaction (PCR). High sensitivity is achieved because this type of test can detect very small quantities of the virus (see Lewis, D. R. et al. "Molecular Diagnostics: The Genomic Bridge Between Old and New Medicine: A White Paper on the Diagnostic Technology and Services Industry" Thomas Weisel Partners, Jun. 13, 2001). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

COMPOSITION, FORMULATIONS & METHOD FOR PREVENTION & TREATMENT OF DISEASES AND CONDITIONS ASSOCIATED WITH BRONCHOCONSTRICTION, ALLERGY(IES) & INFLAMMATION Inventor(s): NYCE, JONATHAN W.; (PRINCETON, NJ) Correspondence: VIVIANA AMZEL, PH.D.; EpiGenesis Pharmaceuticals, Inc.; 7 Clarke Drive; Cranbury; NJ; 05812; US Patent Application Number: 20030087845 Date filed: June 9, 1998 Abstract: A pharmaceutical composition effective for preventing and alleviating bronchoconstriction, allergy(ies) and/or inflammation comprises a surfactant and a nucleic acid comprising an oligonucleotide anti-sense to an adenosine A1, A2a, A2b or A3 receptor gene, mRNA, flanking regions or regions bridging the intro/exon borders, analogues which bind thymidine but have low adenosine content or exhibit lower or no adenosine receptor agonist activity, combinations thereof, physiologically acceptable salts thereof or mixtures thereof, and optionally a carrier and other agents such as therapeutic agents and formulation products known in the art. The composition is formulated for administration by a multiplicity of routes for the prevention or alleviation of diseases and conditions associated with breathing difficulties, impeded and obstructed airways, bronchoconstriction, allergy and/or inflammation. Among the appplications of this technology are the prevention and treatment of diseases and conditions such as asthma, kidney damage or failure, ARDS, pulmonary vasoconstriction, inflammation, allergies, impeded respiration, respiratory distress syndrome, pain, cystic fibrosis, pulmonary hypertension, pulmonary vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), and cancers such as leukemias, lymphomas, carcinomas, and the like, e.g. colon cancer, breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, kidney cancer, melanoma, hepatic, lung, breast, and prostate metastases, etc., to counter the renal damage and failure associated with ischemic conditions and the administration of certain drugs and radio active diagnostic and therapeutic agents, as well as a joint therapy with the administration of adenosine and adenosine-like agents in the treatment of arrhythmias such as SVT and in cardiovascular function tests (stress tests). The present agent(s) is (are) also suitable for administration before, during and after other treatments, including radiation, chemotherapy, antibody therapy, phototherapy and cancer, and other types of surgery. Alternatively, the present agent may be effectively administered preventatively, prophylactically or therapeutically, and in conjunction with other therapies, or by itself for conditions without known therapies or as a substitute for therapies that have significant negative side effects. Excerpt(s): This invention relates to compositions and formulations of oligonucleotides and surfactants, which are highly effective for the prevention and treatment of diseases

266 Lung Cancer

and conditions associated with difficult breathing, bronchoconstriction, impeded airways, allergy(ies) and inflammation of the lungs. Adenosine A.sub.1-mediated diseases and conditions, such as asthma and Acute Respiratory Distress Syndrome (ARDS), among others, are common diseases in industrialized countries, and in the United States alone account for extremely high health care costs. These diseases or conditions have recently been increasing at an alarming rate, both in terms of prevalence and mortality. Occupational asthma is predicted to be the preeminent occupational lung disease in the next decade. In many of these, the underlying causes remain poorly understood. Adenosine, a natural nucleoside, may constitute an important natural mediator of bronchial asthma and ARDS. The potential role of adenosine in these diseases or conditions is supported by experimental findings that, for example and in contrast to normal individuals, asthmatics respond to aerosolized adenosine with marked bronchoconstriction. Similarly, asthmatic rabbits produced using the dust mite allergic rabbit model of human asthma also were shown to respond to aerosolized adenosine with marked bronchoconstriction, while non-asthmatic rabbits showed no response. Recent work using this model system has suggested that adenosine-mediated bronchoconstriction in asthma is mediated through the stimulation of the adenosine A.sub.1 receptor. Other experimental data suggest the possibility that adenosine receptors may also be involved in allergic and inflammatory responses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

COMPOSITIONS AND METHODS FOR THERAPY AND DIAGNOSIS OF LUNG CANCER Inventor(s): WANG, TONGTONG; (MEDINA, WA), BANGUR, CHAITANYA S.; (SEATTLE, WA) Correspondence: SEED INTELLECTUAL PROPERTY LAW GROUP PLLC; 701 FIFTH AVE; SUITE 6300; SEATTLE; WA; 98104-7092; US Patent Application Number: 20030125245 Date filed: December 30, 1999 Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as lung cancer, are disclosed. Compositions may comprise one or more lung tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a lung tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as lung cancer. Diagnostic methods based on detecting a lung tumor protein, or mRNA encoding such a protein, in a sample are also provided. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. ______, filed Dec. 17, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09/419,356, filed Oct. 15, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09/346,492, filed Jun. 30, 1999. The present invention relates generally to therapy and diagnosis of cancer, such as lung cancer. The invention is more specifically related to polypeptides comprising at least a portion of a lung tumor protein, and to polynucleotides encoding such polypeptides. Such polypeptides and polynucleotides may be used in vaccines and pharmaceutical compositions for prevention and treatment of lung cancer, and for the diagnosis and monitoring of such cancers. Cancer is a significant health problem throughout the world. Although advances have been made in detection and therapy of cancer, no vaccine or other

Patents 267

universally successful method for prevention or treatment is currently available. Current therapies, which are generally based on a combination of chemotherapy or surgery and radiation, continue to prove inadequate in many patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compositions and methods relating to lung specific genes and proteins Inventor(s): Chen, Sei-Yu; (Foster City, CA), Recipon, Herve E.; (San Francisco, CA), Sun, Yongming; (San Jose, CA), Liu, Chenghua; (San Jose, CA), Turner, Leah R.; (Sunnyvale, CA) Correspondence: LICATLA & TYRRELL P.C.; 66 E. MAIN STREET; MARLTON; NJ; 08053; US Patent Application Number: 20030068624 Date filed: October 26, 2001 Abstract: The present invention relates to newly identified nucleic acids and polypeptides present in normal and neoplastic lung cells, including fragments, variants and derivatives of the nucleic acids and polypeptides. The present invention also relates to antibodies to the polypeptides of the invention, as well as agonists and antagonists of the polypeptides of the invention. The invention also relates to compositions comprising the nucleic acids, polypeptides, antibodies, variants, derivatives, agonists and antagonists of the invention and methods for the use of these compositions. These uses include identifying, diagnosing, monitoring, staging, imaging and treating lung cancer and non-cancerous disease states in lung, identifying lung tissue, monitoring and identifying and/or designing agonists and antagonists of polypeptides of the invention. The uses also include gene therapy, production of transgenic animals and cells, and production of engineered lung tissue for treatment and research. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Application Serial No. 60/243,461 filed Oct. 26, 2000, U.S. Provisional Application No. 60/252,055, filed Nov. 20, 2000, and U.S. Provisional Application No. 60/252,496, filed Nov. 22, 2000, which are herein incorporated by reference in their entireties. The present invention relates to newly identified nucleic acid molecules and polypeptides present in normal and neoplastic lung cells, including fragments, variants and derivatives of the nucleic acids and polypeptides. The present invention also relates to antibodies to the polypeptides of the invention, as well as agonists and antagonists of the polypeptides of the invention. The invention also relates to compositions comprising the nucleic acids, polypeptides, antibodies, variants, derivatives, agonists and antagonists of the invention and methods for the use of these compositions. These uses include identifying, diagnosing, monitoring, staging, imaging and treating lung cancer and non-cancerous disease states in lung, identifying lung tissue and monitoring and identifying and/or designing agonists and antagonists of polypeptides of the invention. The uses also include gene therapy, production of transgenic animals and cells, and production of engineered lung tissue for treatment and research. Throughout the last hundred years, the incidence of lung cancer has steadily increased, so much so that now in many countries, it is the most common cancer. In fact, lung cancer is the second most prevalent type of cancer for both men and women in the United States and is the most common cause of cancer death in both sexes. Lung cancer deaths have increased ten-fold in both men and women since 1930, primarily due to an increase in cigarette smoking, but also due to an increased exposure to arsenic, asbestos, chromates, chloromethyl ethers, nickel, polycyclic aromatic hydrocarbons and other agents. See Scott, Lung Cancer: A

268 Lung Cancer

Guide to Diagnosis and Treatment, Addicus Books (2000) and Alberg et al., in Kane et al. (eds.) Biology of Lung Cancer, pp.11-52, Marcel Dekker, Inc. (1998). Lung cancer may result from a primary tumor originating in the lung or a secondary tumor which has spread from another organ such as the bowel or breast. Although there are over a dozen types of lung cancer, over 90% fall into two categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). See Scott, supra. About 20-25% of all lung cancers are characterized as SCLC, while 70-80% are diagnosed as NSCLC. Id. A rare type of lung cancer is mesothelioma, which is generally caused by exposure to asbestos, and which affects the pleura of the lung. Lung cancer is usually diagnosed or screened for by chest x-ray, CAT scans, PET scans, or by sputum cytology. A diagnosis of lung cancer is usually confirmed by biopsy of the tissue. Id. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

COMPOUNDS AND METHODS FOR THERAPY AND DIAGOSIS OF LUNG CANCER Inventor(s): WANG, TONGTONG; (MEDINA, WA) Correspondence: JANE E.R. POTTER; SEED INTELLECTUAL PROPERTY LAW GROUP PLLC; 701 FIFTDSH AVENUE; SUITE 6300; SEATTLE; WA; 98104-7092; US Patent Application Number: 20030119763 Date filed: December 17, 1999 Abstract: Compounds and methods for the treatment and diagnosis of lung cancer are provided. The inventive compounds include polypeptides containing at least a portion of a lung tumor protein. Vaccines and pharmaceutical compositions for immunotherapy of lung cancer comprising such polypeptides, or DNA molecules encoding such polypeptides, are also provided, together with DNA molecules for preparing the inventive polypeptides. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/285,479, filed Apr. 2, 1999, which claims priority from PCT Application No. PCT/US99/05798, filed Mar. 17, 1999, which claims priority from U.S. patent application Ser. No. 09/221,107, filed Dec. 22, 1998, which is a continuation-in-part of U.S. patent application Ser. No. 09/123,912, filed Jul. 27, 1998, which is a continuationin-part of U.S. patent application Ser. No. 09/040,802, filed Mar. 18, 1998. The present invention relates generally to therapy and diagnosis of cancer, such as lung cancer. The invention is more specifically related to polypeptides comprising at least a portion of a lung tumor protein, and to polynucleotides encoding such polypeptides. Such polypeptides and polynucleotides may be used in vaccines and pharmaceutical compositions for prevention and treatment of lung cancer, and for the diagnosis and monitoring of such cancers. Lung cancer is the primary cause of cancer death among both men and women in the U.S., with an estimated 172,000 new cases being reported in 1994. The five-year survival rate among all lung cancer patients, regardless of the stage of disease at diagnosis, is only 13%. This contrasts with a five-year survival rate of 46% among cases detected while the disease is still localized. However, only 16% of lung cancers are discovered before the disease has spread. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 269

·

Crystal form of N-(4-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamid- e Inventor(s): Faasch, Holger; (Hochheim, DE), Hedtmann, Udo; (Frankfurt, DE), Westenfelder, Uwe; (Frankfurt, DE), Paulus, Erich; (Eppstein, DE) Correspondence: FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER; LLP; 1300 I STREET, NW; WASHINGTON; DC; 20005; US Patent Application Number: 20030166945 Date filed: November 25, 2002 Abstract: The invention relates to a crystal modification of the compound of the formula I 1and the processes for the preparation of and use that crystal modifications 1. The invention is used for treating acute immunological episodes, such as sepsis, allergies, graft-versus-host and host-versus-graft-reactions, autoimmune diseases, in particular rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, atopic dermatitis, asthma, urticaria, rhinitis, uveitis, type II diabetes, liver fibrosis, cystic fibrosis, colitis, cancers, such as lung cancer, leukemia, ovarian cancer, sarcomas, Kaposi's sarcoma, meningioma, intestinal cancer, lymphatic cancer, brain tumors, breast cancer, pancreatic cancer, prostate cancer, or skin cancer. Excerpt(s): This case claims benefit under 35 U.S.C.sctn.119 of German priority document 19734438.0 filed on Aug. 8, 1997. This document, as well as German priority document 19756093.8, filed Dec. 17, 1997, are hereby incorporated by reference. The compound of formula I crystallizes in the first crystal modification in the space group P2.sub.1/c with 8 molecules in the unit cell. Molecules of the compound of formula I are present as dimers which originate from the individual molecules by formation of a -C.dbd.O. HN hydrogen bridge bond (2.938.ANG.), the two molecular levels being virtually perpendicular to one another (91.2.degree.). The two molecules have very different conformations. The angles made by the five- and six-membered rings with the central carbonyl group are 5.4.degree. and 2.1.degree. and 23.4.degree. and 23.1.degree., respectively. The latter twist creates the steric preconditions permitting the hydrogen bridge bond between the two molecules. Lines of strong intensity: 16.70; 18.90; 23.00; 23.65; and 29.05 degrees. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

·

Fucosyl gm1-klh conjugate vaccine against small cell lung cancer Inventor(s): Ragupathi, Govindaswami; (New York, NY), Livingston, Philip O; (New York, NY) Correspondence: John P White; Cooper & Dunham LLP; 1185 Avenue of the Americas; New York; NY; 10036; US Patent Application Number: 20030171261 Date filed: March 24, 2000 Abstract: This invention provides for a composition comprising a fucosyl GM1 ganglioside or an oligosaccharide thereof conjugated to an immunogenic protein, an adjuvant, the amounts thereof being effective to stimulate or enhance antibody production in a subject, and a pharmaceutically acceptable carrier. This invention also provides a method of stimulating antibody production in a subject which comprises administering to the subject an effective amount of the above-described composition to stimulate antibody production. This invention also provides a method of enhancing

270 Lung Cancer

antibody production in a subject which comprises administering to the subject an effective amount of the above-described composition to enhance antibody production. This invention also provides a method of preventing cancer in a subject which comprises administering to the subject an amount of the above-described composition effective to prevent cancer. This invention also provides a method of treating cancer in a subject which comprises administering to the subject an amount of the above-described composition effective to treat cancer. Excerpt(s): This application is claims the benefit of U.S. Provisional Application No. 60/059,664, filed Sep. 25, 1997, the contents of which is hereby incorporated by reference. Throughout this application, various publications are referenced by author and date or by Arabic numbers. Full citations for these publications may be found listed alphabetically at the end of the third set of experiments and at the end of the fourth set of experiments immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. Lung cancer remains the leading cause of cancer death in the United States, with 160,100 deaths estimated for 1998 (Landis, S. H. et al., 1998). In the United States, lung cancer remains the leading cause of cancer death in men, and has surpassed breast cancer as the leading cause of cancer death in women. Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancer cases, and is the fifth leading cause of death from cancer (Wingo, P., et al., 1995). Distant metastases are present in more than two-thirds of patients with SCLC at diagnosis (Inhde, D. C., 1995), and in the absence of treatment, tumor progression is rapid, with a median survival of only 2 to 4 months. SCLC, however, is very responsive to chemotherapy, with over 80% of patients with limited stage disease (LD) and >60% of patients with extensive stage disease (ED) achieving a major response to treatment. Despite these results, relapses are common, and most patients die within two years of their diagnosis. For patients who have achieved a major response, after completion of chemotherapy with or without radiation therapy, standard treatment is observation alone. The median survival of patients with LD is 14-20 months, and those with ED is 812 months. Over the past decade, no additional therapy has been shown to improve overall survival, and standard therapy is observation alone for patients who have achieved a major response after 4 to 6 cycles of chemotherapy. Because of these modest results, new approaches to adjuvant therapy are needed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Genes expressed in lung cancer Inventor(s): Turner, Christopher M.; (Stanford, CA), Lasek, Amy K. W.; (Oakland, CA), Shyjan, Andrew W.; (San Carlos, CA) Correspondence: LEGAL DEPARTMENT; INCYTE GENOMICS, INC.; 3160 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20030175704 Date filed: October 4, 2001 Abstract: The present invention relates to a combination comprising a plurality of cDNAs which are differentially expressed in respiratory disorders and which may be used in their entirety or in part to diagnose, to stage, to treat, or to monitor the treatment of a subject with a respiratory disorder including lung cancer, chronic obstructive pulmonary disease, emphysema, and asthma.

Patents 271

Excerpt(s): The present invention relates to a combination comprising a plurality of cDNAs which are differentially expressed in lung cancer and which may be used entirely or in part to diagnose, to stage, to treat, or to monitor the progression or treatment of respiratory disorders such as lung cancer, chronic obstructive pulmonary disease, emphysema, and asthma. Array technology can provide a simple way to explore the expression of a single polymorphic gene or the expression profile of a large number of related or unrelated genes. When the expression of a single gene is examined, arrays are employed to detect the expression of a specific gene or its variants. When an expression profile is examined, arrays provide a platform for examining which genes are tissue specific, carrying out housekeeping functions, parts of a signaling cascade, or specifically related to a particular genetic predisposition, condition, disease, or disorder. The potential application of gene expression profiling is particularly relevant to improving diagnosis, prognosis, and treatment of respiratory disorders. For example, the levels at which particular sequences are expressed in lung cancer may be compared with the levels and sequences expressed in lung tissue that is normal or affected by other diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Genetically modified cells expressing a TGFbeta inhibitor, the cells being lung cancer cells Inventor(s): Fakhrai, Habib; (La Jolla, CA) Correspondence: KNOBBE MARTENS OLSON & BEAR LLP; 2040 MAIN STREET; FOURTEENTH FLOOR; IRVINE; CA; 92614; US Patent Application Number: 20030147867 Date filed: September 16, 2002 Abstract: The present invention relates to compositions comprising a therapeutically effective amount of genetically modified cells containing a genetic construct expressing a TGF.beta. inhibitor effective to reduce expression of TGF.beta., where the genetically modified cells are non-small cell lung cancer (NSCLC) cells or small cell lung cancer (SCLC) cells, and related methods. Excerpt(s): This application is a continuation of international application number PCT/US01/10339, and claims the benefit of priority of international application number PCT/US01/10339, having international filing date of Mar. 30, 2001, designating the United States of America and published in English, which claims the benefit of priority of U.S. provisional patent application No. 60/193,497, filed Mar. 31, 2000; both of which are hereby expressly incorporated by reference in their entireties. The present invention relates to compositions comprising a therapeutically effective amount of genetically modified cells containing a genetic construct expressing a TGF.beta. inhibitor effective to reduce expression of TGF.beta., where the genetically modified cells are non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) cells, and related methods. Lung cancer remains the most prevalent cancer in the western world, accounting for 30% of all cancer-related deaths (Ramanathan and Belani, 1997). The current prognosis for patients with lung cancer is poor. The overall cure rate is estimated as low as 13%. Approximately 180,000 new cases of lung cancer are expected in the United States in 1999. The majority of these patients will die of their disease with 160,000 deaths from lung cancer expected nation-wide in 1999. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

272 Lung Cancer

·

Human PEN11B-related gene variant associated with lung cancers Inventor(s): Dai, Ken-Shwo; (Hsinchu, TW) Correspondence: Ladas & Parry; 26 West 61st Street; New York; NY; 10023; US Patent Application Number: 20030190620 Date filed: March 20, 2002 Abstract: The invention relates to a novel human PEN11B-related gene variant, and to the use of the nucleic acid of the gene variant in diagnosing diseases, in particular, lung cancer, e.g. small cell lung cancer. Excerpt(s): The invention relates to the nucleic acid of a novel human PEN11B-related gene variant, and the uses of the same in diagnosing diseases associated with the deficiency of PEN11B gene, in particular, lung cancers, e.g. small cell lung cancer (SCLC). Lung cancer is one of the major causers of cancer-related deaths in the world. There are two primary types of lung cancers: small cell lung cancer and non-small cell lung cancer (NSCLC) (Carney, (1992a) Curr. Opin. Oncol. 4:292-8). Small cell lung cancer accounts for approximately 25% of lung cancer and spreads aggressively (Smyth et al. (1986) Q J Med. 61: 969-76; Carney, (1992b) Lancet 339: 843-6). Non-small cell lung cancer represents the majority (about 75%) of lung cancer and is further divided into three main subtypes: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma (Ihde and Minna, (1991) Cancer 15: 105-54). In recent years, much progress has been made toward understanding the molecular and cellular biology of lung cancers. Many important contributions have been made by the identification of several key genetic factors associated with lung cancers. However, the treatments of lung cancers still mainly depend on surgery, chemotherapy, and radiotherapy. This is because the molecular mechanisms underlying the pathogenesis of lung cancers remain largely unclear. A recent hypothesis suggested that lung cancer is caused by genetic mutations of at least 10 to 20 genes (Sethi, (1997) BMJ. 314: 652-655). Therefore, future strategies for the prevention and treatment of lung cancers will be focused on the elucidation of these genetic substrates, in particular, the genes localized on chromosome 11p15.5, a region shown to be associated with the development of lung cancer (Kondo et al. (1996) Oncogene 12:1365-8; O'Briant and Bepler, (1997) Genes Chromosomes Cancer 18:111-4; Sanchez-Cespedes et al. (1997) Clin Cancer Res 3: 1229-35; Bepler et al. (1998) Cancer Detect Prev 22:14-9; Pitterle et al. (1999) Mamm Genome 10:916-22; Xu et al. (2001) Cancer Res 61:7943-9). A human PEN11B gene was mapped on this region (GenBank Accession No. AF020089), suggesting that PEN11B gene may have a role in the tumorigenic process of lung cancer. Therefore, the discovery of gene variants of PEN11B may be important targets for diagnostic markers of lung cancers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

·

Intra-bronchial device that provides a medicant intra-bronchially to the patient Inventor(s): Wang, John H.; (Sammamish, WA), Springmeyer, Steven Chase; (Bellevue, WA), Gonzalez, Hugo X.; (Woodinville, WA), Shea, Richard O.; (Kenmore, WA), DeVore, Lauri J.; (Seattle, WA) Correspondence: GRAYBEAL, JACKSON, HALEY LLP; 155 - 108TH AVENUE NE; SUITE 350; BELLEVUE; WA; 98004-5901; US Patent Application Number: 20030154988 Date filed: June 21, 2002

Patents 273

Abstract: An intra-bronchial device provides a medicant intra-bronchially. The medicant may be used for controlling biological interaction of an intra-bronchial obstruction device with the patient, to treat a disease or condition of the lungs such as pneumonia or lung cancer, or to treat a systemic disease or condition. The medicant is provided by associating a medicant with the intra-bronchial device, either before, at the time of placement, or after placement. The medicant may overlie at least a portion of the intrabronchial device, be absorbed into at least a portion of the intra-bronchial device, or be carried in a chamber. The intra-bronchial device may further include an absorptive member, and the medicant is absorbed by the absorptive member. Excerpt(s): This application is a continuation-in-part of and claims priority based on an application entitled "INTRA-BRONCHIAL OBSTRUCTING DEVICE THAT CONTROLS BIOLOGICAL INTERACTION WITH THE PATIENT" filed Feb. 21, 2002, application Ser. No. 10/081,712. The present invention is generally directed to a device, system, and method that provides a medicant intra-bronchially to a patient by an intrabronchial device placed in an air passageway. The present invention is more particularly directed to an intra-bronchial device that provides a medicant that controls biological interaction of the device with the patient, or that provides a medicant intra-bronchially that treats diseases and conditions of the patient, particularly those associated with the lungs such as pneumonia and lung cancer. An aspect of the invention is directed toward treating Chronic Obstructive Pulmonary Disease (COPD), which has become a major cause of morbidity and mortality in the United States over the last three decades. COPD is characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema. The airflow obstruction in COPD is due largely to structural abnormalities in the smaller airways. Important causes are inflammation, fibrosis, goblet cell metaplasia, and smooth muscle hypertrophy in terminal bronchioles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Lactone formulations and method of use Inventor(s): Terrero, David; (Ensanche Quisquella, DO) Correspondence: PATREA L. PABST; HOLLAND & KNIGHT LLP; SUITE 2000, ONE ATLANTIC CENTER; 1201 WEST PEACHTREE STREET, N.E.; ATLANTA; GA; 303093400; US Patent Application Number: 20030069393 Date filed: June 12, 2002 Abstract: Compounds of Formulae Ia and Ic having a lactone structure and an methylene group at the alpha-position of the lactone structure and methods for using and making the compounds have been disclosed. The lactone compounds can be reacted with an neucleaphilic agent to open the lactone ring to a compound of Formula Ib. The lactone of Formula Ia and its functional derivatives have been isolated from Securidaca virgata. These compounds are referred to as LMSV-6 or Securolide.TM. The purified compounds have demonstrated activity in assays for anti-bacterial and anti-fungal activities, and for treating proliferation disorders such as cancer. Based on the in vitro assays, the lactones are useful for treating proliferation disorders including, for example, breast cancer, colon cancer, rectal cancer, stomach cancer, pancreatic cancer, lung cancer, liver cancer, ovarian cancer, esophageal cancer, and leukemia. They are also effective for treatment of bacterial and fungal infections, including treatment of peptic ulcer disease, gingivitis and periodontitis. The lactone and its derivatives has the following chemical structure: 1wherein R.sub.1-R.sub.9 and Y.sub.1-Y.sub.3 taken independently are

274 Lung Cancer

preferably a hydrogen atom, a halogen atom, a hydroxyl group, or any other organic groups or groupings which optionally include a heteroatom such as oxygen, sulfur, or nitrogen groupings in linear, branched, or cyclic structural formats; Z and X are independently and preferably a heteroatom such as oxygen, sulfur, or nitrogen groupings in linear, branched, or cyclic structural formats; and Z' may a hydrogen atom, a halogen atom, a hydroxyl group, or any other organic groups or groupings which optionally include a heteroatom such as oxygen, sulfur, or nitrogen groupings in linear, branched, or cyclic structural formats. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/297,875 filed Jun. 13, 2001. The present inventions are generally in the fields of pharmaceutically active lactones, their pharmaceutical formulations, and method of use thereof, and methods for the synthetic preparation of chemically functionalized lactones useful therefor as anticancer and antiinfective agents. Despite the development of many different compounds which are useful in the treatment of infection, cancer, and other disorders, there remains a need for the development of new compounds which may be effective at lower dosages, more selective, having fewer side effects or capable of treating diseases or disorders where resistance to the known compounds has developed. Chemotherapeutic agents are used for the treatment of infections, cancer, abnormal proliferation disorders (endometriosis, restenosis, psoriasis), and other disorders. Most chemotherapeutic agents have side effects due to lack of specificity. For example, cancer is one of the leading causes of death. One of the primary modes of treating cancer, chemotherapy, is used specifically to limit cell growth and replication. Most chemotherapy agents also affect neoplastic and rapid proliferating cells of normal tissues (e.g., bone marrow, hair follicles, etc.), which results in several negative side effects including hair loss, nausea, vomiting, and suppression of bone marrow function. Moreover, effectiveness of these agents frequently diminishes over time due to the development of resistance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Method and apparatus to determine bone mineral density utilizing a flat panel detector Inventor(s): Unger, Christopher D.; (Delafield, WI), Eberhard, Jeffrey W.; (Albany, NY), Thomas, Carson; (Brookfield, WI), Avinash, Gopal; (New Berlin, WI), Zhao, Jianguo; (Niskayuna, NY) Correspondence: MCANDREWS HELD & MALLOY, LTD; 500 WEST MADISON STREET; SUITE 3400; CHICAGO; IL; 60661 Patent Application Number: 20030194120 Date filed: April 12, 2002 Abstract: A method and apparatus for using a flat panel detector to determine bone mineral density are provided. The apparatus includes a dual energy X-ray emitter, a flat panel detector for receiving X-rays sent from the X-ray emitter, and may optionally include an image corrector, adapted to emit corrected image information. The apparatus also includes a basis material decomposer that includes a calibration database, the decomposer being adapted to create a bone image and a soft tissue image. The apparatus further includes a bone mineral density calculator that is adapted to compute bone mineral density from the first image, and a display for displaying at least the computed bone mineral density. A method for using a flat panel detector to detect multiple disease states is also provided. The method includes emitting X-rays from a

Patents 275

dual energy X-ray source through an area of a patient's body sought to be imaged and receiving X-rays with a flat panel detector. The method also includes generating multiple images, using dual energy X-ray absorptiometry, to detect for a first disease state and a second disease state and analyzing the images for the first and second disease states. The first disease state includes lung cancer, breast cancer, pneumonia, chronic obstructive pulmonary disease, tuberculosis, bone fracture or an abnormally sized or shaped organ and the second disease state comprises osteoporosis. Excerpt(s): Certain embodiments of the present invention relate to the detection of osteoporosis and more particularly relates to the detection of bone mineral density using a flat panel detector. Osteoporosis is a disease of the skeleton in which the amount of calcium present in the bones slowly decreases to the point where the bones become brittle and prone to fracture. In other words, the bone loses density. Osteoporosis is diagnosed when bone density has decreased to the point where fractures occur even under mild stress, also referred to as the fracture threshold. In the United States alone, ten million people have osteoporosis and eighteen million more have low bone mass (80% of whom are women), a condition which indicates an increased risk of developing osteoporosis. Osteoporosis is responsible for one-and-one-half million fractures annually. As a result, statistics indicate that one of every two women over age fifty will have an osteoporosis-related fracture in their lifetime. As a reference, a woman's risk of an osteoporosis-related fracture is equal to her combined risk of acquiring breast, uterine and ovarian cancer. The most common sites of fractures are the hip, spine, wrist and ribs. Perhaps the most devastating of these fractures is the hip fracture. On average, 24% of hip fractures in patients 50 and over lead to death within one year. Osteoporotic fractures such as these cost an estimated $18 billion annually. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Method for using thymosin beta-10 for gene therapy of solid malignant tumors Inventor(s): Lee, Je-Ho; (Seoul, KR), Kim, Seung-Hoon; (Seoul, KR) Correspondence: GATES & COOPER LLP; HOWARD HUGHES CENTER; 6701 CENTER DRIVE WEST, SUITE 1050; LOS ANGELES; CA; 90045; US Patent Application Number: 20030099617 Date filed: August 30, 2002 Abstract: A method for using thymosin.beta.-10 for cancer treatment by expressing thymosin.beta.-10 in solid malignant tumor cells. More precisely, the present invention relates to a cancer treatment method wherein thymosin.beta.-10 is expressed in solid malignant tumor cells by infecting adenovirus including thymosin.beta.-10. The gene therapy for cancer using thymosin.beta.-10 of the present invention is very effective for the treatment of ovarian cancer, cervical cancer, stomach cancer and lung cancer. Excerpt(s): This application claims the benefit of priority to Korean Patent Application No. 2001-63524, filed Oct. 10, 2001, the entire contents of which are incorporated herein by reference. The present invention relates to a method for using thymosin.beta.-10 for cancer treatment by expressing thymosin.beta.-10 in solid malignant tumor cells. More precisely, the present invention relates to a cancer treatment method wherein thymosin.beta.-10 is expressed in solid malignant tumor cells by infecting adenovirus including thymosin.beta.-10. The gene therapy for cancer using thymosin.beta.-10 of the present invention is very effective for the treatment of ovarian cancer, cervical cancer, stomach cancer and lung cancer. Gene therapy is a kind of treatment for genetic diseases

276 Lung Cancer

and cancers caused by aberration of genes, whose mechanism is to introduce diseaserelated genes directly to patients in order to normalize the cell function by expressing those genes inside cells. Gene therapy is very effective not only for the treatment of diseases, but also for prevention of many diseases and even more reinforcing the treatment since the therapy can bestow new function on human body by introducing a specific gene. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Method of isolating extract from the euphorbaciae obesa plant and methods for using the same Inventor(s): Donato, Nicholas J.; (Sugarland, TX), McMurray, John S.; (Houston, TX), Sample, David C.; (Porter, TX), Donato, Nicholas D.; (San Marcos, CA), Perez, Margot; (Houston, TX), Newman, Robert A.; (Sugarland, TX) Correspondence: FOLEY & LARDNER; P.O. BOX 80278; SAN DIEGO; CA; 92138-0278; US Patent Application Number: 20030118677 Date filed: December 12, 2001 Abstract: The present invention is directed to a process of isolating an extract from a Euphorbaciae obesa (EO) plant by: preparing a sample of said plant comprising removal of the latex material; dissolving said sample with first solvent to form a solution; seperating said solution into a liquid and a pulp fraction; and purifying said pulp fraction. The isolated EO extract induces apoptosis and inhibits growth of a cancerous cell. Thus, the present invention is also directed to a method for inducing apoptosis and growth inhibition of a cancerous cell by contacting the cell with an effective amount of the EO extract by the process of the invention. Preferably, the extract is administered both to the tumor directly and intravenously. The preferred lines of cancerous cells are melanoma, non-small cell lung cancer, prostate cancer, breast carcinoma, ovarian cancer, lymphoma and leukemia cells. Excerpt(s): This invention generally relates to compounds for treating cancer that are derived from plants and, in particular, the isolation and use of an extract from a Euphorbaciae obesa plant having anti-tumor effects on a variety of cancerous cells. Plants and marine organisms provide a rich source of compounds that have been investigated and exploited for a variety of medicinal and biological applications. The Euphorbiaceae family is one of the largest families of plants with about 300 genera and 7,500 species, mostly monoecious herbs, shrubs and trees, sometimes succulent and cactus-like, that are further frequently characterized by a milky sap or latex material. Members of the Euphorbiaceae family have been investigated as providing potential treatments for cancers, tumors and warts. Active components found in members of this plant family may be common to several genera or species of the family or may be limited to a particular genus or species. Certain Euphorbiaceae species have been shown to synthesize phorbol ester and diterpene diester compounds having therapeutic effects on certain cancers. For instance, the isolation and characterization of antileukemic properties from Euphorbia esula L and Croton tiglium L. have been reported. S. M. Kupchan et al., Science 191: 571-572 (1976). The fractionation of an active extract led to the characterization of the antileukemic component from Euphorbia esula L as a diterpene diester. Fractionation of croton oil led to the characterization of the active component known as a phorbol diester, phorbol 12-tiglate 13-decanoate.

Patents 277

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

Methods and compositions for the diagnosis and treatment of cellular proliferation disorders using 20750 Inventor(s): Williamson, Mark; (Saugus, MA) Correspondence: Steven A. Bossone; Millennium Pharmaceuticals, Inc.; 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20030108937 Date filed: October 30, 2002 Abstract: The present invention provides methods and compositions for the diagnosis and treatment of cellular proliferation disorders, e.g., cancer, including, but not limited to colon, breast, and lung cancer. The invention further provides methods for identifying a compound capable of treating a cellular proliferation disorder. The invention also provides methods for identifying a compound capable of modulating a cellular proliferation disorder. In addition, the invention provides a method for treating a subject having a cellular proliferation disorder characterized by aberrant 20750 polypeptide activity or aberrant 20750 nucleic acid expression. Excerpt(s): This application claims priority to U.S. provisional application number 60/335,006, filed Oct. 31, 2001, the entire contents of which are herein incorporated by reference. Cancer is the second leading cause of death in the United States, after heart disease (Boring, et al., (1993) CA Cancer J. Clin. 43:7). Cancer is characterized primarily by an increase in the number of abnormal, or neoplastic, cells derived from a normal tissue which proliferate to form a tumor mass, the invasion of adjacent tissues by these neoplastic tumor cells, and the generation of malignant cells which spread via the blood or lymphatic system to regional lymph nodes and to distant sites. The latter progression to malignancy is referred to as metastasis. Colorectal cancer is among the most common cancers affecting the western world. An estimated 129,400 new cases of colorectal cancer occurred in the United States in 1999 (Rudy, et al. (2000) Am Fam Physician 61(6):175970, 1773-4). By the age of 70 years, at least 50% of the Western population will develop some form of colorectal tumor, including early benign polyps and invasive adenocarcinomas. It is estimated that approximately 10% of the benign polypoid lesions will progress to invasive carcinoma (Fahy et al. (1998) Surg Oncol 7(3-4):115-23). Colorectal cancer arises from a precursor lesion, the adenomatous polyp, which forms in a field of epithelial cell hyperproliferation and crypt dysplasia. Progression from this precursor lesion to colorectal cancer is a multistep process (Winawer (1999) Am J Med 106(1A):3S-6S). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

·

Methods and compositions for the treatment and diagnosis of cellular proliferation disorders using 54394 Inventor(s): Williamson, Mark; (Saugus, MA) Correspondence: Steven A. Bossone; Millennium Pharmaceuticals, Inc.; 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20030113776 Date filed: October 30, 2002

278 Lung Cancer

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of cellular proliferation disorders, including, but not limited to, breast cancer, ovarian cancer, lung cancer, and colon cancer. The invention further provides methods for identifying a compound capable of treating a cellular proliferation disorders disorder or modulating cellular proliferation. The invention also provides a method for modulating cellular proliferation, e.g., modulating cellular proliferation in a subject. In addition, the invention provides a method for treating a subject having a cellular proliferation disorder characterized by aberrant 54394 polypeptide activity or aberrant 54394 nucleic acid expression. Excerpt(s): This application claims priority to U.S. provisional application No. 60/335,076, filed Oct. 31, 2001, the entire contents of which are incorporated herein by reference. Colorectal cancer is the fourth most common cancer worldwide and the second most common cause of cancer deaths. Within the United States alone, there will be over 150,000 new cases and 55,000 deaths this year. In fact, it is postulated that 50% of the Western population will develop a colorectal tumor by the age of 70, with 10% of these tumors progressing to malignancy. Despite advances in therapeutic treatment, the prognosis remains poor, with only a five-year survival rate around 45%. Although the progression of the disease has been well characterized (areas of dysplasia within the colon develop into polyps, which eventually have the potential to become adenocarcinomas; adenocarcinomas become invasive and metastasize to various regions of the body, predominately the liver), diagnosis is primarily made during later stages of the disease. Lung cancer is among the most common cancers in the Western world. In the United States, there were approximately 170,000 new cases of lung cancer in 1999. Since the mid-1990s, about 150,000 Americans have died each year from this disease. Lung cancer is the leading category of cancer death in men, and--since the late 1980s--it has surpassed breast cancer as the leading category of cancer death in women. Findings from the U.S. National Cancer Institute (NCI) indicate that the upward trend in cancerrelated death is due to the rapidly increasing rate of lung cancer mortality. Statistical projections suggest that lung cancer mortality in this decade will continue to rise to a rate of over 50 deaths per year per 100,000 population in America. Current lung cancer prevention programs are not expected to influence lung cancer death rates until after the year 2000. There is a close relationship between the number of lung cancer cases and lung cancer deaths in America. This is because of the low 5-year survival rate for this disease. Although lung cancer survival rates have improved over the last 40 years, the percentage (approximately 13%) continues to be low in comparison to other cancers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Methods of treating cancer using an FPT inhibitor and antineoplastic Inventor(s): Meyers, Michael L.; (Hastings-on-Hudson, NY), Zaknoen, Sara L.; (Hoboken, NJ), Baum, Charles; (Westfield, NJ), Cutler, David L.; (Moorestown, NJ) Correspondence: SCHERING-PLOUGH CORPORATION; PATENT DEPARTMENT (K6-1, 1990); 2000 GALLOPING HILL ROAD; KENILWORTH; NJ; 07033-0530; US Patent Application Number: 20030185831 Date filed: November 25, 2002 Abstract: Disclosed is a method of treating cancer in a patient in need of such treatment comprising administering a therapeutically effective amount of an FPT inhibitor and therapeutically effective amounts of one or more antineoplastic agents. Methods of

Patents 279

treating non small cell lung cancer, CML, AML, non-Hodgkin's lymphoma and multiple myeloma are disclosed. Excerpt(s): This application claims the benefit of Provisional Application Serial No. 60/334411 filed on Nov. 30, 2001. WO 98/54966 published Dec. 10, 1998 discloses methods of treating cancer by administering at least two therapeutic agents selected from a group consisting of a compound which is an antineoplastic agent and a compound which is an inhibitor of prenyl-protein transferase (e.g., a farnesyl protein transferase inhibitor). Farnesyl Protein Transferase (FPT) Inhibitors are known in the art, see for example U.S. Pat. No. 5,874,442 issued Feb. 23, 1999. Methods of treating proliferative diseases (e.g., cancers) by administering an FPT inhibitor in conjunction with an antineoplastic agent and/or radiation therapy are also known, see for example U.S. Pat. No. 6,096,757 issued Aug. 1, 2000. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Nitric oxide synthase gene diagnostic polymorphisms Inventor(s): Moskowitz, David W.; (St. Louis, MO) Correspondence: SENNIGER POWERS LEAVITT AND ROEDEL; ONE METROPOLITAN SQUARE; 16TH FLOOR; ST LOUIS; MO; 63102; US Patent Application Number: 20030170674 Date filed: October 10, 2002 Abstract: Disclosed is a method for determining a genetic predisposition to hypertension, end stage renal disease due to hypertension, non-insulin dependent diabetes mellitus, end stage renal disease due to non-insulin dependent diabetes mellitus, breast cancer, lung cancer or prostate cancer by detecting the presence or absence of single nucleotide polymorphisms in the nitric oxide synthase gene. Also disclosed are kits for detecting the presence or absence of the single nucleotide polymorphisms, methods for the treatment and/or prophylaxis of diseases, conditions, or disorders associated with the single nucleotide polymorphisms. Excerpt(s): This application claims the benefit of U.S. provisional application serial No. 60/177,775, filed Jan. 24, 2000 and U.S. provisional application serial No. 60/220,662 filed Jul. 25, 2000 both of which are herein incorporated by reference in their entirety. This invention relates to detection of an individual's genetic predisposition for a disease, condition or disorder based on the presence or absence of single nucleotide polymorphisms (SNPs). During the course of evolution, spontaneous mutations appear in the genomes of organisms. It has been estimated that variations in genomic DNA sequences are created continuously at a rate of about 100 new single base changes per individual (Kondrashow, J. Theor. Biol., 175:583-594, 1995; Crow, Exp. Clin. Immunogenet., 12:121-128, 1995) These changes in the progenitor nucleotide sequences may confer an evolutionary advantage, in which case the frequency of the mutation will likely increase, an evolutionary disadvantage in which case the frequency of the mutation is likely to decrease, or the mutation will be neutral. In certain cases the mutation may be lethal in which case the mutation is not passed on to the next generation and so is quickly eliminated from the population. In many cases, an equilibrium is established between the progenitor and mutant sequences so that both are present in the population. The presence of both forms of the sequence results in genetic variation or polymorphism. Over time, a significant number of mutations can

280 Lung Cancer

accumulate within a population such that considerable polymorphism can exist between individuals within the population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Patient data mining for lung cancer screening Inventor(s): Sandilya, Sathyakama; (Cranbury, NJ), Rao, R. Bharat; (Berwyn, PA) Correspondence: Siemens Corporation; Intellectual Property Department; 186 Wood Avenue South; Iselin; NJ; 08830; US Patent Application Number: 20030120133 Date filed: November 4, 2002 Abstract: A system and method for lung cancer screening is provided. The system includes a database including structured patient information for a patient population and a domain knowledge base including information about lung cancer; an individual patient record; and a processor for analyzing the patient record with data from the database to determine if a patient has indications of lung cancer. The method includes the steps of inputting patient-specific data into a patient record; performing at least one lung cancer screening procedure on a patient, wherein at least one result from the at least one procedure is inputted into the patient record in a structured format; and analyzing the patient record with a domain knowledge base to determine if the patient has indications of lung cancer. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/335,542, filed on Nov. 2, 2001, which is incorporated by reference herein in its entirety. The present invention relates to medical information processing systems, and, more particularly to a computerized system and method for screening patients for lung cancer, monitoring nodule detection in patients and managing patients exhibiting lung cancer indications. In the United States, lung cancer is the second most common cause of cancer and the leading cause of cancer deaths for both men and women. Survival from lung cancer is dependent on the stage of the cancer. The stage is determined by the size and location of nodules (e.g., tumors), the presence of cancer in the surrounding lymph nodes, and the spread of cancer to distant sites. When lung cancer is treated in its earliest stage, the cure rate approaches 70% or greater. Therefore, early detection is crucial for increasing the survival rates for patient with lung cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

·

Prediction of cancer by detection of ATM mutations Inventor(s): Yahalom, Joachim; (New York, NY), Gilad, Shlomit; (Gedera, IL) 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-

Patents 281

Hodgkin's lymphoma. This method includes the steps of detecting a mutation in 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 ·

Process for affecting neurologic progression Inventor(s): Miller, Richard A.; (Portola Valley, CA) Correspondence: VINIT G. KATHARDEKAR; PHARMACYCLICS, INC.; 995 E. ARQUES AVENUE; SUNNYVALE; CA; 94085; US Patent Application Number: 20030130252 Date filed: December 12, 2002

282 Lung Cancer

Abstract: The present invention relates to use of a compound of Formula I: 1for improving neurologic functions in patients afflicted with systemic lung cancer that has metastasized to the brain (brain metastases). Excerpt(s): The present application claims priority from U.S. Provisional Patent Application No. 60/339,650, filed Dec. 13, 2001, and U.S. Provisional Patent Application No. 60/346,584, filed Jan. 7, 2002, the contents of which are incorporated herein by reference in their entirety. The present invention relates to use of a compound of Formula I for improving neurologic functions in patients afflicted with systemic lung cancer that has metastasized to the brain (brain metastases). Brain metastases are known to be a secondary manifestation of some forms of systemic cancer, including breast cancer, lung cancer, pancreatic cancer, skin cancer, and prostrate cancer. The effect of radiation therapy in the treatment of brain metastases has been studied over the years. One such study was reported by Chao et al., Cancer, pp. 682-89 (1954). A number of factors have been reported to influence the degree of response to irradiation. Those factors include primary site and extent of metastases, status of primary site, neurologic status, and general functional status. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Proton-transfer-reaction/ion-mobility-spectrometer and method of using the same Inventor(s): Kanik, Isik; (Monrovia, CA), Beegle, Luther W.; (Pasadena, CA) Correspondence: Daniel L. Dawes; MYERS, DAWES & ANDRAS LLP; Ste 1150; 19900 MacArthur Blvd; Irvine; CA; 92612; US Patent Application Number: 20030116705 Date filed: October 30, 2002 Abstract: A high-pressure hollow cathode ionizer is combined with an ion-mobilityspectrometer (IMS) for the detection of trace amounts of organic compounds in gas. The ionizer uses H.sub.30+, ions which do not react with air to ionize the organic compounds and the organic compounds are soft ionized. The ionized organic compounds are detected in the IMS at levels of parts per billion and identified using calibrated reference tables. Applications include but are not limited to the fields of: (1) medicine as a breath analyzer for detection of lung cancer, diabetes, liver cirrhosis, (2) law enforcement in drug interdiction and explosives detection, (3) food monitoring and control, (4) environmental monitoring and (5) space applications Excerpt(s): The present application is related to U.S. Provisional Patent Application serial No. 60/334,437, filed on Nov. 30, 2001, which is incorporated herein by reference and to which priority is claimed pursuant to 35 USC 119. The invention relates to the field of ionizers combined with ion-mobility spectrometers (IMS) for the detection of trace amounts of organic compounds in gas and methods of using the same. Miniature mass spectrometry is a powerful in-situ tool for identifying a wide variety of chemical compounds. For applications that cover many disciplines such as planetary exploration, residual gas analysis, and environmental applications, there is a need for an in-situ analytical separation device or chemical sensor which is rugged, light weight, low power, small, fast, and requires minute quantities of sample for analysis. These requirements are also applicable for the detection of certain organics in the medical sciences (analyzing human breath to detect compounds associated with certain deadly diseases such as lung cancer and cirrhosis of the liver), for a chemical sensor for use on

Patents 283

the battlefield (chemical warfare agents), law enforcement (drug interdiction and explosives detection), and food monitoring and control. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Reagents and methods useful for detecting diseases of the lung Inventor(s): Friedman, Paula N.; (Deerfield, IL), Gordon, Julian; (Lake Bluff, IL), Cohen, Maurice; (Highland Park, IL), Hodges, Steven C.; (Buffalo Grove, IL), Klass, Michael R.; (Libertyville, IL), Kratchvil, Jon D.; (Kenosha, WI), Russell, John C.; (Pleasant Prairie, WI), Billing-Medel, Patricia A.; (Gurnee, IL), Granados, Edward N.; (Vernon Hills, IL), Stroupe, Stephen D.; (Libertyville, IL), Colpitts, Tracey L.; (Round Lake, IL), RobertsRapp, Lisa; (Gurnee, IL) Correspondence: STEVEN F. WEINSTOCK; ABBOTT LABORATORIES; 100 ABBOTT PARK ROAD; DEPT. 377/AP6A; ABBOTT PARK; IL; 60064-6008; US Patent Application Number: 20030165909 Date filed: July 10, 2002 Abstract: A set of contiguous and partially overlapping cDNA sequences and polypeptides encoded thereby, designated as LS170 and transcribed from lung tissue, is described. These sequences are useful for the detecting, diagnosing, staging, monitoring, prognosticating, in vivo imaging, preventing or treating, or determining the predisposition of an individual to diseases and conditions of the lung, such as lung cancer. Also provided are antibodies which specifically bind to a LS170-encoded polypeptide or protein, and agonists or inhibitors which prevent action of tissue-specific LS170 polypeptides, which molecules are useful for the therapeutic treatment of lung diseases, tumors or metastases. Excerpt(s): This application is related to U.S. provisional patent application serial No. 60/049,183, filed Jun. 11, 1997, from which priority is claimed pursuant to 35 U.S.C.sctn.119(e)(1) and which is incorporated herein by reference in its entirety. The invention relates generally to detecting diseases of the lung. Furthermore, the invention also relates to reagents and methods for detecting diseases of the lung. More particularly, the present invention relates to reagents such as polynucleotide sequences and the polypeptide sequences encoded thereby, as well as methods which utilize these sequences. The polynucleotide and polypeptide sequences are useful for detecting, diagnosing, staging, monitoring, prognosticating, in vivo imaging, preventing or treating, or determining predisposition to diseases or conditions of the lung, such as lung cancer. Lung cancer is the second most common cancer for both men and women in the United States, with an estimated 171,500 newly diagnosed during 1998 (American Cancer Society statistics). It also is the most common cause of cancer death for both sexes, with over 160,000 lung cancer related deaths expected in 1998. Lung cancer is a major health problem in other areas of the world, with approximately 135,000 new cases occurring each year in the European Union, and its incidence rapidly increasing in Central and Eastern Europe. See, Genesis Report, February 1995 and T. Reynolds, J. Natl. Cancer Inst. 87: 1348-1349 (1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

284 Lung Cancer

·

Therapeutical treatments Inventor(s): Vetvicka, Vaclav; (Louisville, KY), Yvin, Jean-Claude; (Saint-Malo, FR) Correspondence: JOHN S. PRATT, ESQ; KILPATRICK STOCKTON, LLP; 1100 PEACHTREE STREET; SUITE 2800; ATLANTA; GA; 30309; US Patent Application Number: 20030119780 Date filed: November 30, 2001 Abstract: Therapeutical method comprising administration to a patient of an effective amount of especially soluble laminarin for the treatment of tumors and more generally of cancers of the group comprising breast cancer, lung cancer, oesophagus cancer, stomach cancer, intestine and colon cancers, and for the treatment of viral, bacterial and fungal diseases as well as diseases related to immunostimulant deficiencies of human beings and warm-blood animals. Excerpt(s): The invention relates to therapeutical treatments. More particularly it relates to therapeutical treatments based on the immunostimulant antitumoral and cytokine synthesis-inducing and -accelerating activities of laminarin, especially of soluble laminarin, a well known glucan, which activities were surprisingly and unexpectedly discovered by the Applicants in the course of extensive and thorough studies and searches and on which are founded the hereafter disclosed and claimed applications and uses. The therapeutical treatments in question are intended to treat cancers, viral, bacterial and fungal diseases as well as diseases related to immunostimulant deficiencies of human beings and warm-blood animals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

·

Transmembrane protein differentially expressed in prostate and lung tumors Inventor(s): Spancake, Kimberly M.; (Mountain View, CA), Rickert, Paula K.; (Pacifica, CA), Lal, Preeti G.; (Santa Clara, CA), Ison, Craig H.; (San Jose, CA) Correspondence: INCYTE GENOMICS, INC.; 3160 PORTER DRIVE; PALO ALTO; CA; 94304; US Patent Application Number: 20030064397 Date filed: July 24, 2002 Abstract: The invention provides a cDNA which encodes a transmembrane protein differentially expressed in prostate and lung cancer. It also provides for the use of the cDNA, fragments, complements, and variants thereof and of the encoded protein, portions thereof and antibodies thereto for diagnosis and treatment of cancer, in particular, prostate or lung cancers. The invention additionally provides expression vectors and host cells for the production of the protein and a transgenic model system. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/963,896 filed Sep. 26, 2001, which is a divisional application of U.S. Ser. No. 09/397,558, filed Sep. 16, 1999, which is a divisional application of U.S. Ser. No. 09/083,521, filed May 22, 1998, which issued on Apr. 11, 2000 as U.S. Pat. No. 6,048,970, all entitled PROSTATE GROWTH-ASSOCIATED MEMBRANE PROTEINS, and of U.S. Ser. No. 09/802,520, filed Mar. 9, 2001, entitled STEAP-RELATED PROTEIN, all of which applications and patents are incorporated by reference herein. This invention relates to a transmembrane protein, its encoding cDNA, and an antibody which specifically binds the protein and to their use to diagnose, to stage, to treat, or to monitor the progression or treatment of

Patents 285

cancer, in particular, lung or prostate cancer. Cancers and malignant tumors are characterized by continuous cell proliferation and cell death and are related causally to both genetics and the environment. Genes whose expression are associated with cancer are of potentially great importance as cancer markers in the early diagnosis and prognosis of various cancers, as well as potential targets in cancer treatment. 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 lung 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 “lung 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 lung cancer. You can also use this procedure to view pending patent applications concerning lung 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.

287

CHAPTER 7. BOOKS ON LUNG CANCER Overview This chapter provides bibliographic book references relating to lung cancer. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on lung 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 “lung 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 lung cancer: ·

Atlas of Prostatic Diseases Source: New York, NY: Parthenon Publishing Group. 1997. 96 p. Contact: Available from Parthenon Publishing. One Blue Hill Plaza, P.O. Box 1564, Pearl River, NY 10963. (800) 735-4744 or (914) 735-9363. Fax (914) 725-1385. PRICE: $85.00. ISBN: 1850705852. Summary: This atlas brings together text and illustrations to tell the story of the prostate gland and the diseases to which it is prone. The author notes that treatment options at present are ever-changing and often ephemeral. As a consequence, this volume concentrates on the causes and pathology of prostatic disorders, together with the methods available for their diagnosis, rather than on their management and treatment. The first section of the book presents a literary review of the major diseases of the prostate, beginning with the anatomy and embryology of the prostate, and concluding with the diagnostic tests currently available for assessment of the prostate gland. The

288 Lung Cancer

second section of the atlas contains 109 photomicrographs and diagrammatic illustrations that convey the important concepts related to prostatic diseases. The author reminds readers that two common disorders, benign prostatic hyperplasia (BPH) and prostatitis, frequently result in considerable impairment of the quality of life; a third, prostate cancer, is now second only to lung cancer as a cause of cancer death in men. The author hopes that this atlas will provide an accessible format to make more health care providers knowledgeable about the various prostatic diseases. A subject index concludes the volume. 48 references. (AA-M). ·

Strategies to control tobacco use in the United States: A blueprint for public health action in the 1990's Source: Bethesda, MD: National Cancer Institute, U.S. Department of Health and Human Services. 1991. 307 pp. Contact: Available from Publications Office, National Cancer Institute, Building 31, Room 10A03, 9000 Rockville Pike, Bethesda, MD 20832-2580. Telephone: (301) 435-3848 / fax: (301) 402-0894h / Web site: http://www.nci.nih.gov/. Available at no charge. Summary: This volume provides a summary of what has been learned over nearly 40 years of the public health effort against smoking, from the early trial-and-error health information campaigns of the 1960's to the National Cancer Institute's science-based ASSIST project (the American Stop Smoking Intervention Study for Cancer Prevention), which began in the fall of 1991. It presents an historical accounting of these efforts as well as the reason why comprehensive smoking control strategies are now needed to address the smoker's total environment and reduce smoking prevalence significantly over the next decade. Chapters cover the scientific rationale for comprehensive, community-based, smoking control strategies, evolution of smoking control strategies, smoking prevalence and lung cancer death rates, approaches directed to the individual and to the social environment, and interdependence and synergy among smoking control activities.

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

100 Questions & Answers About Lung Cancer by Karen Parles, Joan H. Schiller (2002); ISBN: 0763720569; http://www.amazon.com/exec/obidos/ASIN/0763720569/icongroupinterna

·

21st Century Complete Medical Guide to Lung Cancer and Mesothelioma Authoritative Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment Options by PM Medical Health News; ISBN: 1592480063; http://www.amazon.com/exec/obidos/ASIN/1592480063/icongroupinterna

Books

289

·

A Colour Atlas of Endoscopic Diagnosis in Early Stage Lung Cancer by Harubumi Kato, et al; ISBN: 0723416877; http://www.amazon.com/exec/obidos/ASIN/0723416877/icongroupinterna

·

A Colour Atlas of Sputum Cytology: The Early Diagnosis of Lung Cancer by Gordon Canti MB Bs Lond MRCS Eng LRCP Lond FRCPath; ISBN: 0723409161; http://www.amazon.com/exec/obidos/ASIN/0723409161/icongroupinterna

·

A Patient Guide to COPD & Lung Cancer by Tim Peters; ISBN: 1879874032; http://www.amazon.com/exec/obidos/ASIN/1879874032/icongroupinterna

·

Abstracts : II World Conference on Lung Cancer, Copenhagen, Denmark, June 9-13, 1980; ISBN: 9021912430; http://www.amazon.com/exec/obidos/ASIN/9021912430/icongroupinterna

·

American Cancer Society Atlas of Clinical Oncology: Lung Cancer (Book with CDROM) by Robert J. Ginsberg MD, Robert J. Ginsberg; ISBN: 1550090992; http://www.amazon.com/exec/obidos/ASIN/1550090992/icongroupinterna

·

Atlas of Early Lung Cancer by National Cancer Institute; ISBN: 0896400786; http://www.amazon.com/exec/obidos/ASIN/0896400786/icongroupinterna

·

Atlas of Lung Cancer by Raymond, Md. Yesner; ISBN: 0397516460; http://www.amazon.com/exec/obidos/ASIN/0397516460/icongroupinterna

·

Atlas of Lung Cancer and Other Chest Tumors by Dame Margaret Turner-Warwick, et al (1991); ISBN: 0397448384; http://www.amazon.com/exec/obidos/ASIN/0397448384/icongroupinterna

·

Basic and Clinical Concepts of Lung Cancer (Cancer Treatment and Research Series) by Heine H. Hansen (Editor) (1990); ISBN: 0792301536; http://www.amazon.com/exec/obidos/ASIN/0792301536/icongroupinterna

·

Biology and Management of Lung Cancer by F. Anthony Greco (Editor) (1983); ISBN: 0898385547; http://www.amazon.com/exec/obidos/ASIN/0898385547/icongroupinterna

·

Biology of Lung Cancer (Lung Biology in Health & Disease) by Madeleine A. Kane (Editor), Paul A., Jr. Bunn (Editor) (1998); ISBN: 0824701321; http://www.amazon.com/exec/obidos/ASIN/0824701321/icongroupinterna

·

Biology of Lung Cancer: Diagnosis and Treatment (Lung Biology in Health and Disease, Vol 37) by Steven T. Rosen, James L. Mulshine; ISBN: 0824776429; http://www.amazon.com/exec/obidos/ASIN/0824776429/icongroupinterna

·

Bird keeping as a source of lung cancer and other human diseases : a need for higher hygienic standards by Peter A. J. Holst; ISBN: 3540535551; http://www.amazon.com/exec/obidos/ASIN/3540535551/icongroupinterna

·

Bone metastases in lung cancer : a clinical study in 200 consecutive patients with bronchogenic carcinoma and its therapeutic implications for small cell carcinoma by Heine H²i Hansen; ISBN: 8716019016; http://www.amazon.com/exec/obidos/ASIN/8716019016/icongroupinterna

·

Clinical and Biological Basis of Lung Cancer Prevention by Y. Martinet (Editor), et al (1998); ISBN: 3764357789; http://www.amazon.com/exec/obidos/ASIN/3764357789/icongroupinterna

290 Lung Cancer

·

Clinical and Experimental Pathology of Lung Cancer (Developments in Oncology) by J.G. McVie (Editor) (2002); ISBN: 0898387647; http://www.amazon.com/exec/obidos/ASIN/0898387647/icongroupinterna

·

Clinical Experiences with Platinum and Etoposide Therapy in Lung Cancer by H. Niitani (Editor), et al (1992); ISBN: 380555639X; http://www.amazon.com/exec/obidos/ASIN/380555639X/icongroupinterna

·

Color Atlas of Endoscopic Diagnosis in Early Stage Lung Cancer by Takeshi, M.D. Horai, et al; ISBN: 0815149824; http://www.amazon.com/exec/obidos/ASIN/0815149824/icongroupinterna

·

Contemporary Issues in Lung Cancer: A Nursing Perspective (Jones and Bartlett Series in Oncology) by Marilyn Haas (Editor); ISBN: 0763719145; http://www.amazon.com/exec/obidos/ASIN/0763719145/icongroupinterna

·

Controversies in Lung Cancer: A Multidisciplinary Approach (Bco Basic and Clinical Oncology) by Benjamin Movsas (Editor), et al (2001); ISBN: 0824702743; http://www.amazon.com/exec/obidos/ASIN/0824702743/icongroupinterna

·

Current topics in lung cancer; ISBN: 3540543015; http://www.amazon.com/exec/obidos/ASIN/3540543015/icongroupinterna

·

Current Topics in Lung Cancer (Monographs/European School of Oncology) by P.A. Bunn; ISBN: 0387543015; http://www.amazon.com/exec/obidos/ASIN/0387543015/icongroupinterna

·

Diagnosis and Treatment of Lung Cancer: An Evidence-Based Guide for the Practicing Clinician by Frank C., Md. Detterbeck (Editor), et al; ISBN: 0721691927; http://www.amazon.com/exec/obidos/ASIN/0721691927/icongroupinterna

·

Drugs of Tomorrow 2001: Lung Cancer [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3NY; http://www.amazon.com/exec/obidos/ASIN/B00008R3NY/icongroupinterna

·

EORTC Symposium on Progress and Perspectives in Lung Cancer Treatment, Brussels, Belgium, May 3-5, 1979; ISBN: 0080259294; http://www.amazon.com/exec/obidos/ASIN/0080259294/icongroupinterna

·

Epidemiology of Lung Cancer by Jonathan M. Samet (1994); ISBN: 0824788532; http://www.amazon.com/exec/obidos/ASIN/0824788532/icongroupinterna

·

European Multicentre Case-control Study of Lung Cancer in Non-smokers: Detailed Results on Exposure to Environmental Tobacco Smoke (IARC Technical Report: 33) by Paolo Boffetta (1998); ISBN: 9283224051; http://www.amazon.com/exec/obidos/ASIN/9283224051/icongroupinterna

·

Health Effects of Passive Smoking: Assessment of Lung Cancer in Adults and Respiratory Disorders in Children (Pb90261652) (1997); ISBN: 9992093714; http://www.amazon.com/exec/obidos/ASIN/9992093714/icongroupinterna

·

Iaslc Textbook of Prevention and Early Detection of Lung Cancer by Fred R. Hirsch (2003); ISBN: 1841843016; http://www.amazon.com/exec/obidos/ASIN/1841843016/icongroupinterna

·

Ifosfamide in the Treatment of Lung Cancer: Satellite Symposium of the 19th German Cancer Congress, Frankfurt/Main, February 28, 1988 (Contributions to Oncology, Vol 35) by D. K. Hossfeld (Editor), Germany) Deutscher Krebskongress 1988 Frankfurt Am Main (Editor) (1990); ISBN: 3805551991; http://www.amazon.com/exec/obidos/ASIN/3805551991/icongroupinterna

Books

291

·

Indoor Radon and Lung Cancer: Reality or Myth?: Twenty-Ninth Hanford Symposium on Health and the Environment by Fredrick T. Cross (Editor); ISBN: 0935470697; http://www.amazon.com/exec/obidos/ASIN/0935470697/icongroupinterna

·

Jaagsiekte Sheep Retrovirus and Lung Cancer by H. Fan (Editor); ISBN: 3540440968; http://www.amazon.com/exec/obidos/ASIN/3540440968/icongroupinterna

·

Living With Lung Cancer by Barbara G. Cox, Robert E. Lee (Contributor); ISBN: 0937404195; http://www.amazon.com/exec/obidos/ASIN/0937404195/icongroupinterna

·

Living with Lung Cancer: A Guide for Patients and Their Families by Barbara G. Cox, et al; ISBN: 0937404535; http://www.amazon.com/exec/obidos/ASIN/0937404535/icongroupinterna

·

Living Your Life With Lung Cancer by Frank Fossella, et al; ISBN: 1891483110; http://www.amazon.com/exec/obidos/ASIN/1891483110/icongroupinterna

·

Lung Cancer by Chris Williams (1992); ISBN: 0192614185; http://www.amazon.com/exec/obidos/ASIN/0192614185/icongroupinterna

·

Lung Cancer by Desmond N. Carney (Editor) (1995); ISBN: 0340567597; http://www.amazon.com/exec/obidos/ASIN/0340567597/icongroupinterna

·

Lung Cancer by Frank V., Md. Fossella (Editor), et al; ISBN: 0387955070; http://www.amazon.com/exec/obidos/ASIN/0387955070/icongroupinterna

·

Lung Cancer by G. Pontifex; ISBN: 0444902244; http://www.amazon.com/exec/obidos/ASIN/0444902244/icongroupinterna

·

Lung Cancer by Bruce E. Johnson (Editor), David H. Johnson (Editor); ISBN: 0471012858; http://www.amazon.com/exec/obidos/ASIN/0471012858/icongroupinterna

·

Lung Cancer by Turrisi, et al (2000); ISBN: 1901865428; http://www.amazon.com/exec/obidos/ASIN/1901865428/icongroupinterna

·

Lung cancer; ISBN: 9024723949; http://www.amazon.com/exec/obidos/ASIN/9024723949/icongroupinterna

·

Lung Cancer - Novel Therapeutics with Potential to Drive Market Success [DOWNLOAD: PDF] by Drug and Market Development Publishing (Author); ISBN: B00005Y27Q; http://www.amazon.com/exec/obidos/ASIN/B00005Y27Q/icongroupinterna

·

Lung Cancer (International Trends in General Thoracic Surgery, Vol 1) by Norman C. Delarue, et al; ISBN: 0721613497; http://www.amazon.com/exec/obidos/ASIN/0721613497/icongroupinterna

·

Lung Cancer (Recent Results in Cancer Research, Vol. 92) by William Duncan (Editor); ISBN: 0387131167; http://www.amazon.com/exec/obidos/ASIN/0387131167/icongroupinterna

·

Lung cancer : clinical diagnosis and treatment; ISBN: 0808909983; http://www.amazon.com/exec/obidos/ASIN/0808909983/icongroupinterna

·

Lung cancer : natural history, prognosis, and therapy; ISBN: 0123750504; http://www.amazon.com/exec/obidos/ASIN/0123750504/icongroupinterna

292 Lung Cancer

·

Lung Cancer : New Medical Therapies by Lisa Henderson; ISBN: 1930624018; http://www.amazon.com/exec/obidos/ASIN/1930624018/icongroupinterna

·

Lung cancer : progress in therapeutic research; ISBN: 0890042233; http://www.amazon.com/exec/obidos/ASIN/0890042233/icongroupinterna

·

Lung cancer : textbook for general practitioners; ISBN: 3540530754; http://www.amazon.com/exec/obidos/ASIN/3540530754/icongroupinterna

·

Lung Cancer 1982 by S. Ishikawa; ISBN: 0444902384; http://www.amazon.com/exec/obidos/ASIN/0444902384/icongroupinterna

·

Lung Cancer Chronicles by John A. Meyer (1990); ISBN: 0813514932; http://www.amazon.com/exec/obidos/ASIN/0813514932/icongroupinterna

·

Lung cancer diagnosis; ISBN: 0896400735; http://www.amazon.com/exec/obidos/ASIN/0896400735/icongroupinterna

·

Lung Cancer Differentiation: Implications for Diagnosis and Treatment (Lung Biology in Health and Disease, Vol 58) by Samuel D. Bernal, Paul J. Hesketh (Editor); ISBN: 0824786386; http://www.amazon.com/exec/obidos/ASIN/0824786386/icongroupinterna

·

Lung Cancer Handbook by Dela Cruz Kato.; ISBN: 3718653303; http://www.amazon.com/exec/obidos/ASIN/3718653303/icongroupinterna

·

Lung Cancer Risk from Indoor Exposures to Radon Daughters (Icrp Publication, 50) by International Commission of Radiological (Editor); ISBN: 008035579X; http://www.amazon.com/exec/obidos/ASIN/008035579X/icongroupinterna

·

Lung Cancer Therapy Annual by Heine H. Hansen, Paul A. Bunn (1901); ISBN: 1841841153; http://www.amazon.com/exec/obidos/ASIN/1841841153/icongroupinterna

·

Lung Cancer Therapy Annual 2000 by Heine H. Hansen, Paul A. Bunn (2001); ISBN: 1853179000; http://www.amazon.com/exec/obidos/ASIN/1853179000/icongroupinterna

·

Lung Cancer Therapy Annual 3 by Heine Hansen, et al (2004); ISBN: 1841843024; http://www.amazon.com/exec/obidos/ASIN/1841843024/icongroupinterna

·

Lung Cancer: A Comprehensive Treatise by Jacob D. Bitran; ISBN: 0808918761; http://www.amazon.com/exec/obidos/ASIN/0808918761/icongroupinterna

·

Lung Cancer: A Guide to Diagnosis and Treatment by Walter J. Scott M.D. (2001); ISBN: 1886039437; http://www.amazon.com/exec/obidos/ASIN/1886039437/icongroupinterna

·

Lung Cancer: A Practical Guide to Management by Fergus R. Macbeth, William Steward; ISBN: 3718658607; http://www.amazon.com/exec/obidos/ASIN/3718658607/icongroupinterna

·

Lung Cancer: Advances in Basic and Clinical Research (Cancer Treatment and Research, Vol 72) by Heine H. Hansen (Editor) (1995); ISBN: 0792328353; http://www.amazon.com/exec/obidos/ASIN/0792328353/icongroupinterna

·

Lung Cancer: Advances in Research and Treatment (Contemporary Issues in Oncology, Vol 3) by Joseph Aisner (Editor) (1985); ISBN: 0443082510; http://www.amazon.com/exec/obidos/ASIN/0443082510/icongroupinterna

Books

293

·

Lung Cancer: Basic and Clinical Aspects (Cancer Treatment and Research) by Heine H. Hansen (Editor) (1986); ISBN: 0898387639; http://www.amazon.com/exec/obidos/ASIN/0898387639/icongroupinterna

·

Lung Cancer: Causes and Prevention by International Lung Cancer Update Conference (1984); ISBN: 0895731355; http://www.amazon.com/exec/obidos/ASIN/0895731355/icongroupinterna

·

Lung Cancer: Clinical Diagnosis and Treatment by Marc J. Straus (Editor); ISBN: 0808914871; http://www.amazon.com/exec/obidos/ASIN/0808914871/icongroupinterna

·

Lung Cancer: Current Status and Prospects for the Future (Annual Clinical Conference on Cancer, No 28) by Clifton F. Mountain (1987); ISBN: 0292746520; http://www.amazon.com/exec/obidos/ASIN/0292746520/icongroupinterna

·

Lung Cancer: Diagnostic Procedures and Therapeutic Management With Special Reference to Radiotherapy (Medical Radiology) by C.W. Scarantino (Editor) (1985); ISBN: 0387131760; http://www.amazon.com/exec/obidos/ASIN/0387131760/icongroupinterna

·

Lung Cancer: Handbook of Evaluation and Management by Christine Marie A. Dela Cruz, Harubumi Kato (1992); ISBN: 3718652943; http://www.amazon.com/exec/obidos/ASIN/3718652943/icongroupinterna

·

Lung Cancer: Making Sense of Diagnosis, Treatment, and Options by Lorraine Johnston (2001); ISBN: 0596500025; http://www.amazon.com/exec/obidos/ASIN/0596500025/icongroupinterna

·

Lung Cancer: Molecular Pathology Methods and Reviews (Methods in Molecular Medicine, 74-75) by Barbara, Phd. Driscoll (Editor), Robert Hopkins Miller (2002); ISBN: 0896039854; http://www.amazon.com/exec/obidos/ASIN/0896039854/icongroupinterna

·

Lung Cancer: Perspectives of Medical Science and Holistic Healing by Chris K.H. Teo (2001); ISBN: 9839948954; http://www.amazon.com/exec/obidos/ASIN/9839948954/icongroupinterna

·

Lung Cancer: Principles and Practice by Harvey I. Md. Pass (Editor), et al; ISBN: 0781717914; http://www.amazon.com/exec/obidos/ASIN/0781717914/icongroupinterna

·

Lung Cancer: Textbook for General Practitioners (Europe Against Cancer: European Commission Series for General practitionerS) by Heine H. Hansen (Editor); ISBN: 0387530754; http://www.amazon.com/exec/obidos/ASIN/0387530754/icongroupinterna

·

Lung Cancer: The Art of Detection by Conventional Radiography by Alfred Szamosi, et al (1995); ISBN: 9163029804; http://www.amazon.com/exec/obidos/ASIN/9163029804/icongroupinterna

·

Lung Cancer: The Evolution of Concepts by John G. Gruhn, Steven T. Rosen; ISBN: 0938607170; http://www.amazon.com/exec/obidos/ASIN/0938607170/icongroupinterna

·

Lung Cancer: The Facts (Oxford Medical Publications) by Chris Williams (1995); ISBN: 0192622501; http://www.amazon.com/exec/obidos/ASIN/0192622501/icongroupinterna

294 Lung Cancer

·

Management of Lung Cancer by John F. Smyth (Editor); ISBN: 0713144300; http://www.amazon.com/exec/obidos/ASIN/0713144300/icongroupinterna

·

Management of Small Cell Lung Cancer by Heine H. Hansen, Paul E.G. Kristjansen (Editor); ISBN: 0444812172; http://www.amazon.com/exec/obidos/ASIN/0444812172/icongroupinterna

·

Morphogenesis of Lung Cancer by Yukio, M.D. Shimosato, et al (1982); ISBN: 0849365260; http://www.amazon.com/exec/obidos/ASIN/0849365260/icongroupinterna

·

Multimodality Treatment of Lung Cancer by Arthur T. Skarin (Editor); ISBN: 0824702360; http://www.amazon.com/exec/obidos/ASIN/0824702360/icongroupinterna

·

Myths & Facts about Lung Cancer by John C. Ruckdeschel (1999); ISBN: 1891483048; http://www.amazon.com/exec/obidos/ASIN/1891483048/icongroupinterna

·

Myths & Facts About Lung Cancer: What You Need to Know by John Ruckdeschel, John C. Ruckdeschel (2002); ISBN: 1891483153; http://www.amazon.com/exec/obidos/ASIN/1891483153/icongroupinterna

·

New Hope: Avoiding Lung Cancer [DOWNLOAD: ADOBE READER] by Noel L. Griese (2003); ISBN: B0000T7XYM; http://www.amazon.com/exec/obidos/ASIN/B0000T7XYM/icongroupinterna

·

New Perspectives in Lung Cancer by N. Thatcher (Editor), S. Spiro (Editor) (1994); ISBN: 0727907867; http://www.amazon.com/exec/obidos/ASIN/0727907867/icongroupinterna

·

Novel Therapies in Lung Cancer Management: An Update on the Role of Topotecan: Based on Proceedings from the 9th World Conference on Lung Cancer, Tokyo, September 2Ooo (Supplement Issue: Oncology 2001, 1) by J. H. Schiller (Editor) (2001); ISBN: 3805572999; http://www.amazon.com/exec/obidos/ASIN/3805572999/icongroupinterna

·

Paramalignant syndromes in lung cancer by Gerald Anderson; ISBN: 0433006102; http://www.amazon.com/exec/obidos/ASIN/0433006102/icongroupinterna

·

Particle Overload in the Rat Lung and Lung Cancer: Implications for Human Risk Assessment: Proceedings of a Conference Held at the Massachusetts Institute of Technology on March 29 and 30, 1995 by Joe L. Mauderly (Editor), Robert J. McCunney (Editor) (1996); ISBN: 1560325437; http://www.amazon.com/exec/obidos/ASIN/1560325437/icongroupinterna

·

Peptide Hormones in Lung Cancer (Recent Results in Cancer Research, Vol 99) by K. Havemann, et al (1985); ISBN: 038715504X; http://www.amazon.com/exec/obidos/ASIN/038715504X/icongroupinterna

·

Perspectives in lung cancer : proceedings of the Frederick E. Jones Memorial Symposium in Thoracic Surgery, Columbus, Ohio, October 7-8, 1976; ISBN: 3805526490; http://www.amazon.com/exec/obidos/ASIN/3805526490/icongroupinterna

·

Pocket Guide to Lung Cancer by Marilyn Haas (2003); ISBN: 0763724211; http://www.amazon.com/exec/obidos/ASIN/0763724211/icongroupinterna

·

Progress and Perspectives in the Treatment of Lung Cancer by Paul Van Houtte (Editor), et al; ISBN: 3540625488; http://www.amazon.com/exec/obidos/ASIN/3540625488/icongroupinterna

Books

295

·

Respiratory Health Effects of Passive Smoking: Lung Cancer & Other Disorders (1993); ISBN: 1568067380; http://www.amazon.com/exec/obidos/ASIN/1568067380/icongroupinterna

·

Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders by United States; ISBN: 0160415969; http://www.amazon.com/exec/obidos/ASIN/0160415969/icongroupinterna

·

Scientists discover. foreign paperbacks linked to lung cancer! by Phillip Edmonds; ISBN: 0869320203; http://www.amazon.com/exec/obidos/ASIN/0869320203/icongroupinterna

·

Slide Atlas of Lung Cancer and Tumours of the Heart and Mediastinum (Slide Atlas of Diagnostic Oncology) by Arthur T. Skarin MD; ISBN: 1563750325; http://www.amazon.com/exec/obidos/ASIN/1563750325/icongroupinterna

·

Small Cell Lung Cancer by M. Marangolo, G. Fiorentini (Editor); ISBN: 0080366317; http://www.amazon.com/exec/obidos/ASIN/0080366317/icongroupinterna

·

Small cell lung cancer; ISBN: 080891345X; http://www.amazon.com/exec/obidos/ASIN/080891345X/icongroupinterna

·

Small Cell Lung Cancer (Recent Results in Cancer Research, Vol 97) by S. Seeber (Editor); ISBN: 038713798X; http://www.amazon.com/exec/obidos/ASIN/038713798X/icongroupinterna

·

Survival As a Response Criterion for Small-Cell Lung Cancer (Onkologie, 32) by P. Drings (Editor) (2000); ISBN: 3805570880; http://www.amazon.com/exec/obidos/ASIN/3805570880/icongroupinterna

·

Taxanes in Lung Cancer Therapy by David H. Johnson (Editor), Jean Klastersky (Editor); ISBN: 0824798929; http://www.amazon.com/exec/obidos/ASIN/0824798929/icongroupinterna

·

Textbook of Lung Cancer by Heine H. Hansen (Editor) (2000); ISBN: 1853177083; http://www.amazon.com/exec/obidos/ASIN/1853177083/icongroupinterna

·

The Biology and Molecular Genetics of Lung Cancer (Medical Intelligence Unit) by Adi F. Gazdar, David P. Carbone (1994); ISBN: 1570590087; http://www.amazon.com/exec/obidos/ASIN/1570590087/icongroupinterna

·

The Lung Cancer Manual by The Alliance for Lung Cancer Advocacy Support and Education, et al; ISBN: 0967915406; http://www.amazon.com/exec/obidos/ASIN/0967915406/icongroupinterna

·

The Official Patient's Sourcebook on Non-Small Cell Lung Cancer: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597834806; http://www.amazon.com/exec/obidos/ASIN/0597834806/icongroupinterna

·

The Official Patient's Sourcebook on Small Cell Lung Cancer: Directory for the Internet Age by James N., Md. Parker (Editor), et al (2002); ISBN: 0597834946; http://www.amazon.com/exec/obidos/ASIN/0597834946/icongroupinterna

·

Treatment Modalities in Lung Cancer (Antibiotics and Chemotherapy, Vol 41) by R. Arriagada, t Le Chevalier (Editor) (1988); ISBN: 3805547757; http://www.amazon.com/exec/obidos/ASIN/3805547757/icongroupinterna

296 Lung Cancer

·

Updates in Advances in Lung Cancer (Progress in Respiratory Research, Vol 29) by J. H. Schiller (Editor) (1997); ISBN: 3805565577; http://www.amazon.com/exec/obidos/ASIN/3805565577/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 “lung 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 ·

A doctor looks at smoking and lung cancer. Author: Shryock, Harold.; Year: 1965; [Mountain View, Calif., Pacific Press Pub. Assn., c1960]

·

A study on neoplastic cells in sputum as a contribution to the diagnosis of primary lung cancer, by H. H. Wandall. Author: Wandall, Hans Heugh.; Year: 1965; Copenhagen, Nyt nordisk forlag, A. Busck, 1944

·

Aetiology of lung cancer; a morphological, epidemiological, and experimental analysis. Author: Kreyberg, Leiv,; Year: 1969; Oslo, Universitetsforlaget [c1969]

·

An analysis of the cigarette and lung cancer theory. Author: MacDonald, Ian.; Year: 1959; [Washington? 1957]

·

Cigarette smoking and lung cancer. Author: New York (State) Bureau of Cancer Control.; Year: 1950; [Albany] c1959

·

Cytologic diagnosis of lung cancer, by Seymour M. Farber [and others]. Author: Farber, Seymour M.; Year: 1944; Springfield, Ill., C. C. Thomas [c1950]

·

Environmental and personal factors in lung cancer and bronchitis mortality in Northern Ireland, 1960-1962: a report Author: Wicken, A. J.; Year: 1979; London: Tobacco Research Council, 1966

·

Experimental lung cancer; carcinogenesis and bioassays. International symposium held at the Battelle Seattle Research Center, Seattle, WA, USA, June 23-26, 1974. Edited by Eberhard Karbe and James F. Park. Author: Karbe, Eberhard.; Year: 1963; New York, Springer-Verlag, 1974; ISBN: 0387069968

·

Lung cancer and cigarette smoking. Author: Castillo, Juan J.; Year: 1965; New York, Carlton [c1965]

·

Lung cancer. Author: Farber, Seymour M.; Year: 1972; Springfield, Ill., Thomas [c1954]

·

Lung cancer: surgery and survival. Author: Borrie, John.; Year: 1961; New York, Appleton-Century-Crofts [c1965]

·

Mediastinal obstruction in lung cancer. Author: Howard, Norman.; Year: 1961; Edinburgh, Livingstone, 1967

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

Books

297

·

Moments of decision in lung cancer; a self testing and self instructional unit. Author: American College of Radiology. Commission on Radiation Therapy. Committee on Education.; Year: 1957; [Chicago, c1971]

·

Observations concerning the blood volume, red cells and erythropoiesis in patients with lung cancer; a pre- and postoperative study. Author: Kyllönen, Kaarlo Eino Johannes,; Year: 1967; Helsinki, 1961

·

Rationale and methods of early detection in lung cancer. Author: Veeze, P.; Year: 1968; Assen, Van Gorcum, 1968

·

Selected references on the etiology of lung cancer, specifically in relation to inhalants. Author: American Cancer Society. Medical and Scientific Library.; Year: 1972; New York, 1953

·

Smoking and its effects, with special reference to lung cancer. Author: Russ, Sidney,; Year: 1957; [London] Hutchinson [1955]

·

Smoking and lung cancer. Author: Lees, Thomas Watson.; Year: 1960; [Edinburgh] 1959

·

Smoking and lung cancer; the conflict of opinion. Author: Tobacco Manufacturers' Standing Committee.; Year: 1959; London, 1957

·

Smoking, lung cancer and you. Author: McCurdy, Robert Nigel Charles.; Year: 1972; London, Linden Press, 1958

·

The question of smoking and lung cancer. Author: Greene, Harry Sylvestre Nutting,; Year: 1957; [Washington? 1957?]

·

Tobacco smoke and lung cancer. Author: Cook, James Wilfred,; Year: 1968; London, 1961

Chapters on Lung Cancer In order to find chapters that specifically relate to lung cancer, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and lung cancer using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes 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 “lung cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on lung cancer: ·

Respiratory Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 154-172. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Respiratory disorders are common and may significantly affect dental treatment, especially general anesthesia. Respiratory diseases are often also a contraindication to opioids, benzodiazepines and other respiratory depressants. This chapter on respiratory disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include upper respiratory tract viral infections, sinusitis, lower respiratory tract infections, pulmonary

298 Lung Cancer

tuberculosis, Legionnaire's disease (legionellosis), lung abscess, bronchiectasis, cystic fibrosis, chronic obstructive airways diseases, asthma, bronchogenic carcinoma (lung cancer), occupational lung disease, sarcoidosis, postoperative respiratory complications (including aspiration of gastric contents), obstructive sleep apnea syndrome, and respiratory distress syndromes (RDS). For each disease, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 figure. 5 tables. 51 references. ·

Laryngeal Cancer Source: in Jafek, B.W.; Stark, A.K., eds. ENT Secrets: Questions You Will Be Asked On Rounds, In the Clinic, In the OR, On Exams. Philadelphia, PA: Hanley and Belfus. 1996. p. 208-213. Contact: Available from Hanley and Belfus. Medical Publishers, 210 South 13th Street, Philadelphia, PA 19107. (800) 962-1892 or (215) 546-7293; Fax (215) 790-9330; http://www.hanleyandbelfus.com. PRICE: $35.95 plus shipping and handling. ISBN: 1560531592. Summary: This chapter on laryngeal cancer is from a book that utilizes a question and answer format to review details of the specialty of otorhinolaryngology (ear, nose and throat, or ENT). Topics discussed include the incidence of laryngeal cancer, different types of laryngeal cancer, risk factors that predispose one to laryngeal carcinoma (the most important of which are smoking and alcohol abuse), anatomic divisions of the larynx and the types of cancer in each, barriers that exist in the larynx, staging of laryngeal cancer, diagnostic tests, symptoms of laryngeal cancer, implications of a 'fixed' or nonworking vocal cord, Reinke's space, injuries to the recurrent nerve or superior laryngeal nerve to the larynx, survival rates for laryngeal cancer, treatment options, relationship between laryngeal and lung cancers, patient criteria for performing a horizontal supraglottic laryngectomy, pyriform sinus cancer and its significance to the larynx, patterns of endolaryngeal lymphatic drainage, and controversies in the treatment of laryngeal cancer. The chapter focuses on helping readers acquire the vocabulary required to discuss laryngeal cancer. 2 figures. 1 table. 8 references.

·

Vegetarian Diets Source: in American Diabetes Association. Diabetes A to Z: What You Need to Know About Diabetes, Simply Put. 4th ed. Alexandria, VA: American Diabetes Association. 2000. p. 176-179. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $12.95 for members; $14.95 for nonmembers; plus shipping and handling. ISBN: 1580400353. Summary: This chapter provides people who have diabetes with information on vegetarian diets. This type of diet is based on plant foods, including fruits, vegetables, grains, legumes, nuts, and seeds. A vegetarian diet can be a healthy choice for people with diabetes because vegetarians are less likely to be overweight; to have high cholesterol levels or high blood pressure; and are less likely to get heart disease, blood vessel damage, colon or lung cancer, or osteoporosis. People who are vegetarians get enough protein from high protein grains, legumes, nuts, and seeds. Types of vegetarians include vegan, lacto-vegetarian, ovo-vegetarian, lacto-ovo-vegetarian, and semivegetarian. The chapter explains what each type of vegetarian eats and offers tips for trying a vegetarian diet. 1 figure.

299

CHAPTER 8. MULTIMEDIA ON LUNG CANCER Overview In this chapter, we show you how to keep current on multimedia sources of information on lung 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 lung cancer is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “lung 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 “lung cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on lung cancer: ·

Steven's Message Contact: YouthWave, 3450 Sacramento St Ste 351, San Francisco, CA, 94118, (415) 6479283. Summary: This videorecording is a message from Steven Murrell, a young man who contracted HIV through an unsafe heterosexual contact. He urges all adolescents to practice safer sexual behavior, and expresses deep regrets that he did not. A series of snapshots show him before and after he became HIV-positive. His wish was that this video would be similar to that made by Yul Brynner before his death from lung cancer caused by cigarette smoking. The video ends with the dates of Steven's birth and his death.

300 Lung Cancer

Bibliography: Multimedia on Lung 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 lung 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 lung cancer: ·

An Orientation to chronic obstructive pulmonary disease and lung cancer [slide] Source: American Lung Association, American Thoracic Society; produced by EmersonBraxton & Co., Inc; Year: 1983; Format: Slide; [New York, N.Y.]: The Association, c1983

·

Current role of chemotherapy in inoperable lung cancer [slide] Source: RSNA; Year: 1986; Format: Slide; [Chicago, Ill.]: RSNA, c1986

·

Current role of radiotherapy in inoperable lung cancer [videorecording] Source: Radiological Society of North America; Year: 1985; Format: Videorecording; [Chicago, Ill.]: The Society, [1985]

·

Current therapy in lung cancer and the nursing implications [sound recording] Source: Roswell Park Memorial Institute; Year: 1977; Format: Sound recording; [Buffalo]: Communications in Learning, 1977

·

Hyperalimentation as adjunctive treatment for the patient with lung cancer [videorecording] Source: University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute; produced by MDA-TV; Year: 1977; Format: Videorecording; Houston: The Center, 1977

·

Investigational chemotherapy for lung cancer [slide] Source: RSNA; Year: 1986; Format: Slide; [Chicago, Ill.]: RSNA, c1986

·

Lung cancer: an epidemic [videorecording]. Part 1 Source: U. S. Army Medical Dept.; produced by Academy of Health Sciences; Year: 1973; Format: Videorecording; Fort Sam Houston, Tex.: The Academy, [1973]

·

Lung cancer: chemotherapy, radiation therapy & prognosis [videorecording]. Part 6 Source: U. S. Army Medical Dept.; produced by Academy of Health Sciences; Year: 1973; Format: Videorecording; Fort Sam Houston, Tex.: The Academy, [1973]

·

Lung cancer: extrapulmonary manifestations [videorecording]. Part 4 Source: U. S. Army Medical Dept.; produced by Academy of Health Sciences; Year: 1973; Format: Videorecording; Fort Sam Houston, Tex.: The Academy, [1973]

·

Lung cancer: pathological cell types and frequency [videorecording]. Part 2 Source: U. S. Army Medical Dept.; produced by Academy of Health Sciences; Year: 1973; Format: Videorecording; Fort Sam Houston, Tex.: The Academy, [1973]

·

Lung cancer: surgical treatment and prognosis [videorecording]. Part 5 Source: U. S. Army Medical Dept.; produced by Academy of Health Sciences; Year: 1973; Format: Videorecording; Fort Sam Houston, Tex.: The Academy, [1973]

·

Lung cancer [motion picture]: early diagnosis and management Source: American Cancer Society, with assistance and cooperation of The Virginia Mason Hospital; produced by Raring Film; Year: 1969; Format: Motion picture; [New York]: The Society, c1969

·

Lung cancer [videorecording] Source: University of Texas, System Cancer Center, M. D. Anderson Hospital and Tumor Institute; produced by MDA-TV; Year: 1973; Format: Videorecording; Houston: The Center, 1973

Multimedia 301

·

Lung cancer [videorecording] Source: a production of the Office of Health Extension, Public Service, and Research for the University of Alabama, School of Medicine, UAB; Year: 1983; Format: Videorecording; [Birmingham, Ala.]: University of Alabama in Birmingham, the Medical Center, c1983

·

Lung cancer and current therapy [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic and St. Joseph's Hospital; Year: 1985; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1985]

·

Lung cancer staging [electronic resource]: a tutorial Source: Chariot Software Group; Year: 1987; Format: Electronic resource; [San Diego, Calif.?]: UCSD Regents, c1987

·

Multimodal management of stage III A, III B, non small cell lung cancer [sound recording]: ASCO fall conference. Year: 1990; Format: Sound recording; Chicago, IL: Teach'em, [1990]

·

Non-small cell lung cancer [videorecording]: the multimodality approach to treatment: a continuing medical education program Source: from the Albany Medical College, an institution of the Albany Medical Center; Year: 1989; Format: Videorecording; NY, NY, USA: LP Communications, c1989

·

Prognostic factors in lung cancer [slide] Source: RSNA; Year: 1986; Format: Slide; [Chicago, Ill.]: RSNA, c1986

·

Radical surgery for advanced lung cancer [motion picture] Source: produced by Sturgis-Grant Productions, Inc.; by Adrian Lambert; Year: 1954; Format: Motion picture; United States: Sturgis-Grant Productions, [1954]

·

Segmental resection for lung cancer [videorecording] Source: from the Motion Picture Library of the American College of Surgeons; Year: 1986; Format: Videorecording; Danbury, Conn.: American College of Surgeons, Davis & Geck Surgical Film-Video Library, [1986]

·

Small cell lung cancer [videorecording]: current treatment and future directions Source: a continuing medical education activity from Vanderbilt University, School of Medicine, Division of Continuing Medical Education; Year: 1989; Format: Videorecording; New York, NY: LP Communications, c1989

·

Smoking and lung cancer [motion picture]: an authentic case filmed at the Royal Edward Chest Hospital, Montreal: the diagnostic tests, assessment, preparation for removal of a lung from a patient with a long history of cigarette smoking Source: produced by Rob; Year: 1965; Format: Motion picture; Canada: Anderson Associates, [1965]

·

Smoking and lung cancer [videorecording] Source: a Films for the Humanities and Sciences presentation; Year: 1987; Format: Videorecording; [Princeton, NJ]: Films for the Humanities, c1987

·

Survival with inoperable lung cancer [videorecording]: an integration of clinical variables Source: University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute; Year: 1976; Format: Videorecording; Houston: The Institute, 1976

·

Technique of mediastinal lymph node dissection for the staging of non-small cell lung cancer [videorecording] Source: filmed under the direction of Steven M. Keller and James L. Weese; Year: 1988; Format: Videorecording; [Philadelphia, Pa.]: Fox Chase

·

The Histopathology of lung cancer [slide] Source: RSNA; Year: 1986; Format: Slide; [Chicago, Ill.]: RSNA, c1986

·

The Natural history of lung cancer [slide] Source: RSNA; Year: 1986; Format: Slide; [Chicago, Ill.]: RSNA, c1986

302 Lung Cancer

·

Treating lung cancer [videorecording] Source: produced for the Department of Clinical Oncology, University of Sheffield; Sheffield University Television; Year: 1992; Format: Videorecording; Princeton, N.J.: Films for the Humanities, c1992

·

Treatment of lung cancer [slide] Source: Roswell Park Memorial Institute in Buffalo, in cooperation with the Lakes Area Regional Medical Program; Year: 1975; Format: Slide; [Buffalo]: Communications in Learning, 1975

303

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

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

Delay in lung cancer diagnosis doesn't cut survival Source: Reuters Health eLine Date: October 23, 2003

·

Surgery for advanced lung cancer questioned Source: Reuters Health eLine Date: October 22, 2003

304 Lung Cancer

·

Lung cancer soaring among women in France Source: Reuters Health eLine Date: October 22, 2003

·

Lung cancer screening helps smokers kick the habit Source: Reuters Health eLine Date: October 20, 2003

·

Chemo no help after lung cancer surgery Source: Reuters Health eLine Date: October 09, 2003

·

Belief may cause some to reject lung cancer surgery Source: Reuters Health eLine Date: October 06, 2003

·

Lung cancer therapy no less effective in elderly Source: Reuters Health eLine Date: September 17, 2003

·

Low-dose CT offers cost-effective lung cancer test Source: Reuters Health eLine Date: September 03, 2003

·

Age no bar to chemotherapy for lung cancer Source: Reuters Health eLine Date: August 29, 2003

·

Lung cancer trials deemed cost effective Source: Reuters Industry Breifing Date: August 25, 2003

·

Insurance should cover lung cancer trials: study Source: Reuters Health eLine Date: August 25, 2003

·

Aventis says Taxotere helps fight early lung cancer Source: Reuters Industry Breifing Date: August 14, 2003

·

Paclitaxel-based regimen outperforms standard therapy for small-cell lung cancer Source: Reuters Industry Breifing Date: August 07, 2003

·

PET imaging predicts response to chemotherapy for non-small cell lung cancer Source: Reuters Industry Breifing Date: August 01, 2003

·

First-line docetaxel improves survival in advanced non-small cell lung cancer Source: Reuters Industry Breifing Date: July 25, 2003

·

Gefitinib effective in advanced, pretreated non-small-cell lung cancer Source: Reuters Industry Breifing Date: July 08, 2003

·

Gene mutation may predict lung cancer odds: report Source: Reuters Health eLine Date: July 01, 2003

Periodicals and News

·

ImClone gets payment for lung cancer drug progress Source: Reuters Industry Breifing Date: June 26, 2003

·

Cell Therapeutics lung cancer drug on 'fast track' Source: Reuters Industry Breifing Date: June 16, 2003

·

Survival improved with adjuvant chemotherapy in resected early lung cancer Source: Reuters Industry Breifing Date: June 02, 2003

·

Studies offer hope for lung cancer treatment Source: Reuters Health eLine Date: June 02, 2003

·

Genentech, OSI lung cancer drug works best in patients who have never smoked: study Source: Reuters Industry Breifing Date: June 02, 2003

·

Smoking may speed lung cancer patients' death Source: Reuters Health eLine Date: May 23, 2003

·

Electronic device can detect scent of lung cancer Source: Reuters Industry Breifing Date: May 19, 2003

·

'Electronic nose' sniffs out lung cancer: study Source: Reuters Health eLine Date: May 19, 2003

·

AstraZeneca cleared to sell Iressa for lung cancer in Australia Source: Reuters Industry Breifing Date: May 01, 2003

·

NSAID use may protect smokers against lung cancer Source: Reuters Industry Breifing Date: April 22, 2003

·

Nicotine may speed lung cancer growth Source: Reuters Health eLine Date: March 26, 2003

·

Smokers' lung cancer risk varies widely: study Source: Reuters Health eLine Date: March 18, 2003

·

In UK, elderly lung cancer patients get poorer care Source: Reuters Health eLine Date: March 14, 2003

·

Plant compound kills lung cancer cells Source: Reuters Health eLine Date: February 21, 2003

·

Plant product shows promise as anti-lung cancer agent Source: Reuters Industry Breifing Date: February 18, 2003

305

306 Lung Cancer

·

Irradiated, GM-CSF-secreting tumor cells can engender lung cancer immunity Source: Reuters Industry Breifing Date: February 14, 2003

·

Drug co. reports more deaths from lung cancer drug Source: Reuters Health eLine Date: February 06, 2003

·

Vitamin A cousin may help treat lung cancer -study Source: Reuters Health eLine Date: February 05, 2003

·

Medarex, diaDexus in antibody collaboration to target lung cancer Source: Reuters Industry Breifing Date: January 29, 2003

·

New thalidomide trial goes ahead in lung cancer Source: Reuters Health eLine Date: January 28, 2003

·

Genaera cuts enrollment in lung cancer trial short on cash woes Source: Reuters Industry Breifing Date: January 28, 2003

·

Large new thalidomide trial goes ahead in lung cancer Source: Reuters Industry Breifing Date: January 27, 2003

·

Affymetrix, Boston University collaborate on lung cancer test Source: Reuters Industry Breifing Date: January 22, 2003

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

Periodicals and News

307

Market Wire’s home page at http://www.marketwire.com/mw/home, type “lung 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 “lung cancer” (or synonyms). If you know the name of a company that is relevant to lung cancer, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “lung cancer” (or synonyms).

Academic Periodicals covering Lung Cancer Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to lung cancer. In addition to these sources, you can search for articles covering lung cancer that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

309

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 lung cancer. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ 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 lung 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

310 Lung Cancer

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to lung cancer: Docetaxel ·

Systemic - U.S. Brands: Taxotere http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202920.html

Doxorubicin ·

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

Etoposide ·

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

Paclitaxel ·

Systemic - U.S. Brands: Taxol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202682.html

Porfimer ·

Systemic - U.S. Brands: Photofrin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203593.html

Topotecan ·

Systemic - U.S. Brands: Hycamtin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203049.html

Vinorelbine ·

Systemic - U.S. Brands: Navelbine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203542.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 ConsultÔ Mosby’s Drug ConsultÔ 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/.

Researching Medications

311

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to lung cancer by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “lung cancer” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for lung cancer: ·

Iodine I 131 bis(indium-diethylenetriaminep entaac (trade name: bispecific monclonal antibody Pentacea) http://www.rarediseases.org/nord/search/nodd_full?code=1024

·

Ricin (blocked) conjugated murine MCA (n901) http://www.rarediseases.org/nord/search/nodd_full?code=473

·

MN14 monoclonal antibody to carcinoembryonic antig (trade name: CEA-CIDE) http://www.rarediseases.org/nord/search/nodd_full?code=940

312 Lung Cancer

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.

313

APPENDICES

315

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.

316 Lung Cancer

·

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

·

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

·

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

·

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

·

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

·

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

·

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

·

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

·

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

·

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

·

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

·

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

·

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

·

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

·

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

·

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

·

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

·

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

Physician Resources 317

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.

318 Lung Cancer

·

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

·

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “lung 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 98249 943 1109 100 13 100414

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

15

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

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

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

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

Physician Resources 319

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: ·

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

·

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Lung Cancer In the following section, we will discuss databases and references which relate to the Genome Project and lung cancer.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information.

20 Adapted from 21

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

320 Lung Cancer

To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “lung 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 lung cancer: ·

Lung Cancer Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?211980

·

V-MYC Avian Myelocytomatosis Viral Oncogene Homolog 1, Lung CarcinomaDerived; MYCL1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?164850

·

Small Cell Cancer of the Lung Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?182280

·

Integrin, ALPHA-9; ITGA9 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603963

·

Immunoglobulin Superfamily, Member 4; IGSF4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605686

·

Tumor Suppressor Gene on Chromosome 11 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603040

·

Deleted in Lung and Esophageal Cancer 1; DLEC1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604050

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

Physician Resources 321

disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html ·

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

·

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

·

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

·

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html

Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

·

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

·

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

·

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

·

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

·

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

322 Lung Cancer

·

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

·

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

·

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

·

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “lung cancer” (or synonyms) into the search box and click “Go.”

Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. 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. 24

Physician Resources 323

To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “lung 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).

325

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 lung 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 lung 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 lung 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 “lung cancer”:

326 Lung Cancer

·

Guides on lung cancer Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Lung Cancer http://www.nlm.nih.gov/medlineplus/lungcancer.html

·

Other guides Bladder Cancer http://www.nlm.nih.gov/medlineplus/bladdercancer.html Carcinoid Tumors http://www.nlm.nih.gov/medlineplus/carcinoidtumors.html Head and Neck Cancer http://www.nlm.nih.gov/medlineplus/headandneckcancer.html Immune System and Disorders http://www.nlm.nih.gov/medlineplus/immunesystemanddisorders.html Liver Cancer http://www.nlm.nih.gov/medlineplus/livercancer.html Neurofibromatosis http://www.nlm.nih.gov/medlineplus/neurofibromatosis.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html

Within the health topic page dedicated to lung cancer, the following was listed: ·

General/Overview Asbestos Source: Agency for Toxic Substances and Disease Registry http://www.atsdr.cdc.gov/tfacts61.html Public Health Statement for Asbestos Source: Agency for Toxic Substances and Disease Registry http://www.atsdr.cdc.gov/ToxProfiles/phs9004.html Sources of Indoor Air Pollution - Asbestos Source: Environmental Protection Agency http://www.epa.gov/iaq/asbestos.html Tox Town Source: National Library of Medicine http://toxtown.nlm.nih.gov/ TOXNET Databases Source: National Library of Medicine http://toxnet.nlm.nih.gov/

Patient Resources

·

327

Specific Conditions/Aspect Asbestos in Your Home Source: Environmental Protection Agency http://www.epa.gov/asbestos/ashome.html Current Best Practices for Vermiculite Attic Insulation Source: Environmental Protection Agency http://www.epa.gov/asbestos/insulation.html Mesothelioma: Questions and Answers Source: National Cancer Institute http://cis.nci.nih.gov/fact/6_36.htm NIOSH Recommendations for Limiting Potential Exposures of Workers to Asbestos Associated with Vermiculite from Libby, Montana Source: National Institute for Occupational Safety and Health http://www.cdc.gov/niosh/docs/2003-141/ Questions and Answers - Exposure to Asbestos in Sources Other than Insulation Source: Agency for Toxic Substances and Disease Registry http://www.atsdr.cdc.gov/NEWS/asbestosnoins.html Vermiculite Consumer Products Source: Agency for Toxic Substances and Disease Registry http://www.atsdr.cdc.gov/NEWS/vermiculite051603.html

·

Children ABCs of Asbestos in Schools http://www.epa.gov/asbestos/abcsfinal.pdf

·

From the National Institutes of Health Asbestos Exposure: Questions and Answers Source: National Cancer Institute http://cis.nci.nih.gov/fact/3_21.htm

·

Law and Policy National Primary Drinking Water Regulations: Asbestos Source: Environmental Protection Agency, Office of Water http://www.epa.gov/safewater/dwh/c-ioc/asbestos.html

·

Organization American Lung Association http://www.lungusa.org/ Environmental Protection Agency http://www.epa.gov/ National Institute for Occupational Safety and Health http://www.cdc.gov/niosh/homepage.html Occupational Safety and Health Administration http://www.osha.gov/

328 Lung Cancer

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on lung 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: ·

Secondhand smoke: What you can do about secondhand smoke as parents, decision makers, and building occupants Source: Washington, DC: U.S. Environmental Protection Agency. 1993. 4 pp. Contact: Available from Air and Radiation (6203J), U.S. Environmental Protection Agency, Washington, DC 20460. Summary: This brochure gives information on what secondhand smoke is, its ability to cause lung cancer in nonsmokers, its serious health risks to children, other health implications, and how to protect your health against secondhand smoke. Organizations to contact for more information are listed.

·

Health Risk Appraisal: Smoking Source: Columbia, SC: South Carolina Department of Health and Environmental Control. 1992. 2 p. Contact: Available from Materials Library. South Carolina Department of Health and Environmental Control, 2600 Bull Street, Columbia, SC 29201. (803) 737-3941; FAX: (803) 737-3946. PRICE: Single copy free. Mail orders only; material only distributed within the state of South Carolina. Order Number 02027. Summary: This fact sheet discusses the health risks of smoking. The fact sheet documents how cigarette smoke affects the smoker's body; smokers' increased risk for lung cancer, cancers of the mouth, bladder, kidney, pancreas and other organs, heart attack, high blood pressure, and stroke; the benefits of quitting smoking; how to quit smoking; and additional resources to help. The document is provided by the Materials Library, a distribution center for health and environmental educational materials and teaching aids.

Patient Resources

329

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 “lung cancer” (or synonyms). The following was recently posted: ·

Altered fractionation of radical radiation therapy in the management of unresectable non-small cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1999 October 8 (revised online 2002 Sep); 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3599&nbr=2825&a mp;string=lung+AND+cancer

·

Chemotherapy in stage IV (metastatic) non-small cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1996 February 14 (updated online 2002 Jan); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3196&nbr=2422&a mp;string=lung+AND+cancer

·

Diagnosis of lung cancer: the guidelines Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3641&nbr=2867&a mp;string=lung+AND+cancer

·

Guidelines on treatment of stage IIIB non-small cell lung cancer Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3648&nbr=2874&a mp;string=lung+AND+cancer

·

Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3639&nbr=2865&a mp;string=lung+AND+cancer

330 Lung Cancer

·

Lung cancer prevention: the guidelines Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3636&nbr=2862&a mp;string=lung+AND+cancer

·

Lung cancer. Invasive staging: the guidelines Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3643&nbr=2869&a mp;string=lung+AND+cancer

·

Management of lung cancer. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1998 February; 53 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2899&nbr=2125&a mp;string=lung+AND+cancer

·

Postoperative adjuvant radiation therapy in stage II or IIIA completely resected nonsmall cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1997 September 15 (revised online 2002 Sep); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3604&nbr=2830&a mp;string=lung+AND+cancer

·

Prophylactic cranial irradiation in small cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2000 March 22 (updated online 2002 Jul); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3459&nbr=2685&a mp;string=lung+AND+cancer

·

Screening for lung cancer: the guidelines Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3637&nbr=2863&a mp;string=lung+AND+cancer

Patient Resources

·

331

Testing for early lung cancer detection. In: American Cancer Society guidelines for the early detection of cancer Source: American Cancer Society - Disease Specific Society; 2001; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2750&nbr=1976&a mp;string=lung+AND+cancer

·

The noninvasive staging of non-small cell lung cancer: the guidelines Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3642&nbr=2868&a mp;string=lung+AND+cancer

·

The physiologic evaluation of patients with lung cancer being considered for resectional surgery Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3640&nbr=2866&a mp;string=lung+AND+cancer

·

The role of single-agent docetaxel (Taxotere®) as a second-line treatment for advanced non-small-cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2001 January 17; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3195&nbr=2421&a mp;string=lung+AND+cancer

·

The role of thoracic radiotherapy as an adjunct to standard chemotherapy in limitedstage small cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1999 October 8 (updated online 2003 Jan); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3765&nbr=2991&a mp;string=lung+AND+cancer

·

Treatment of early stage non-small cell lung cancer Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3644&nbr=2870&a mp;string=lung+AND+cancer

332 Lung Cancer

·

Treatment of stage II non-small cell lung cancer Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3646&nbr=2872&a mp;string=lung+AND+cancer

·

Treatment of stage IIIA non-small cell lung cancer Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3647&nbr=2873&a mp;string=lung+AND+cancer

·

Unresected stage III non-small cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1997 March 14 (updated online 2003 Jan); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3702&nbr=2928&a mp;string=lung+AND+cancer

·

Use of gemcitabine in non-small cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1998 October 14 (revised 2002 Sep); 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3602&nbr=2828&a mp;string=lung+AND+cancer

·

Use of vinorelbine in non-small cell lung cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1996 August 15 (new information released online August 2001); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3202&nbr=2428&a mp;string=lung+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:

Patient Resources

·

333

Alpha-Tocopherol, Beta Carotene Cancer Prevention Study (ATBC) Summary: Report of a National Cancer Institute (NCI)-sponsored prevention trial conducted in Finland which showed that vitamin E and beta carotene supplements did not prevent lung cancer in a group of male Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2003

·

Asian Americans and Pacific Islanders and Tobacco Summary: Smoking is responsible for 87% of the lung cancer deaths in the United States. In 1993, lung cancer was the leading cause of cancer death 22.3% among Asian Americans and Pacific Islanders. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7487

·

Environmental Tobacco Smoke Summary: Fact sheet discusses the health risk of ETS -- lung cancer, elevated rates of respiratory symptoms and respiratory tract infections in children -- and public policies restricting smoking. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2461

·

Facts About Lung Cancer Summary: Describes lung cancer and its prevention, causes, detection, and treatment. Source: American Lung Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6588

·

FAQ - About Radon Health Risks Summary: Online answers to consumer questions about the adverse health effects of radon -- radon as a carcinogen and the cause of lung cancer. Source: U.S. Environmental Protection Agency http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2984

·

Lung Cancer Glossary of Terms Summary: A comprehensive glossary of lung cancer terminology. Source: Alliance for Lung Cancer Advocacy, Support and Education http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6591

334 Lung Cancer

·

Lung Cancer Support Groups Summary: A state listing of support groups for persons diagnosed with lung cancer and, in some cases, their families. Source: Alliance for Lung Cancer Advocacy, Support and Education http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6136

·

Non-small Cell Lung Cancer (PDQ®): Treatment Summary: This fact sheet details treatment choices by cancer stage for non-small cell lung cancer, a lung cancer type usually associated with prior smoking, passive smoking, or radon exposure. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6140

·

Occupational Lung Disease Summary: Information about a variety of occupational lung and respiratory diseases, including brown lung, silicosis, asbestosis and occupational lung cancer. Source: American Lung Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4171

·

Questions and Answers About Asbestos Exposure Summary: Answers to consumers' questions about asbestos exposure and the health risks, including lung cancer risks, from long- and short term exposure. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2068

·

Small Cell Lung Cancer (PDQ®): Treatment Summary: This fact sheet details treatment choices by cancer stage for small cell lung cancer, a lung cancer type usually found in people who smoke or who used to smoke cigarettes. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6141

·

State/Territory Cancer Data Summary: This page links to State Cancer Burden Data fact sheets, which contain data on lung cancer, colorectal cancer, breast cancer, and prostate cancer, and the National Program of Cancer Registries Source: National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7177

Patient Resources

·

335

What You Need To Know About™ Lung Cancer Summary: Information about some causes and ways to prevent lung cancer, and descriptions of the symptoms, detection, diagnosis, and treatment of this disease. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6137 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 lung 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/

·

WebMDÒHealth: 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 lung cancer. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lung 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 lung cancer. For more information, see

336 Lung Cancer

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 “lung 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 “lung 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 “lung 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 “lung cancer” (or a synonym) into the search box, and click “Submit Query.”

337

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.

338 Lung Cancer

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: ·

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

·

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

·

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

·

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

·

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

·

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

·

California: Gateway Health Library (Sutter Gould Medical Foundation)

·

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

·

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

·

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

·

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

·

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

·

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

·

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

·

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

·

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

·

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

·

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

339

·

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

·

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

·

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

·

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

·

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

·

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

·

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

·

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

·

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

·

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

·

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

·

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

·

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

·

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

·

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

·

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

·

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

·

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

·

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

·

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

340 Lung Cancer

·

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

·

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

·

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

·

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

·

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

·

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

·

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

·

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

·

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

·

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

·

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

·

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

·

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

·

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

·

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

·

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

341

·

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

·

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

·

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

·

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

·

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

·

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

·

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

·

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

·

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

·

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

·

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

·

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

·

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

·

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

·

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

·

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

·

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

·

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

·

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

342 Lung Cancer

·

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

·

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

·

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

·

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

343

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: ·

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

·

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

·

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

·

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

·

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

·

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

·

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

·

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

·

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

·

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

345

LUNG CANCER DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] 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] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many

346 Lung Cancer

immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign 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] 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]

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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the 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

Dictionary 347

intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Distribution: The frequency of different ages or age groups in a given population. The distribution may refer to either how many or what proportion of the group. The population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [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,

348 Lung Cancer

magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a 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] Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [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 Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [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] 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] 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 shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH]

Dictionary 349

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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [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 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] 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]

Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anthelmintic: An agent that is destructive to worms. [EU] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] 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] Antidepressant: A drug used to treat depression. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a

350 Lung Cancer

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] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] 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] 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] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antitumour: Counteracting tumour formation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon nonmultiplying cells. [NIH] Apnea: A transient absence of spontaneous respiration. [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]

Dictionary 351

Aqueous: Having to do with water. [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] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH]

352 Lung Cancer

Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous tumor cells: Cancer cells from an individual's own tumor. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] 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] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [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]

Dictionary 353

Benchmarking: Method of measuring performance against established standards of best practice. [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] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [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 duct: A tube through which bile passes in and out of the liver. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [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] 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,

354 Lung Cancer

pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] 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 transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bombesin: A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [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]

Dictionary 355

Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] 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] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [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] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Bryostatin-1: A drug used for its antitumor activity. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the

356 Lung Cancer

buccal surface of a tooth. [EU] Buccal mucosa: The inner lining of the cheeks and lips. [NIH] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [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] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [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] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] 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 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]

Dictionary 357

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] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [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] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] 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] 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 Death: The termination of the cell's ability to carry out vital functions such as

358 Lung Cancer

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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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] Cellular adhesion: The close adherence (bonding) to adjoining cell surfaces. [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] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] 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]

Dictionary 359

Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [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] 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] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [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] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chromates: Salts of chromic acid containing the CrO(2-)4 radical. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all

360 Lung Cancer

human cells contain 46 chromosomes. [NIH] Chromosome Aberrations: Deviations from the normal number or structure of chromosomes, not necessarily associated with disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [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] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] 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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other

Dictionary 361

Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [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, 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

362 Lung Cancer

lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized 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] Concurrent therapy: A treatment that is given at the same time as another. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH]

Dictionary 363

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] 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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] 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] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU]

364 Lung Cancer

Cranial Irradiation: The exposure of the head to roentgen rays or other forms of radioactivity for therapeutic or preventive purposes. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [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] Croton Oil: Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent mortality. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [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] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they

Dictionary 365

produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to

366 Lung Cancer

meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [NIH] Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diagnostic trial: A research study that evaluates methods of detecting disease. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dicumarol: An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases. [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] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] 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]

Dictionary 367

Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: 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 individual more than usually susceptible to certain diseases. [NIH] Dissection: Cutting up of an organism for study. [NIH] 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] 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]

Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] 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-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Dose-rate: The strength of a treatment given over a period of time. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [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

368 Lung Cancer

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] Duodenum: The first part of the small intestine. [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] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edatrexate: An anticancer drug that belongs to a family of drugs called antimetabolites. [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] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH]

Dictionary 369

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]

Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emetic: An agent that causes vomiting. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] 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 of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [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] 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, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH]

370 Lung Cancer

Endotoxin: Toxin from cell walls of bacteria. [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] 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 Monitoring: The monitoring of the level of toxins, chemical pollutants, microbial contaminants, or other harmful substances in the environment or workplace by measuring the amounts of these toxicants in the bodies of people and animals in that environment, among other methods. It also includes the measurement of environmental exposure. Levels in humans and animals are used as indicators of toxic levels of undesirable chemicals. [NIH] Environmental tobacco smoke: ETS. Smoke that comes from the burning of a tobacco product and smoke that is exhaled by smokers (second-hand smoke). Inhaling ETS is called involuntary or passive smoking. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [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 healthrelated 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] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [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.

Dictionary 371

Also called squamous cell carcinoma. [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] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Epoetin alfa: A colony-stimulating factor that is made in the laboratory. It increases the production of red blood cells. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a

372 Lung Cancer

peripheral sense organ. [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] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exisulind: A drug that is being studied in the treatment and prevention of cancer. It has been shown to cause apoptosis (cell death) in cancerous and precancerous cells by acting through a group of cellular enzymes called cGMP phosphodiesterases. [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] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensive-stage small cell lung cancer: Cancer that has spread outside the lung to other tissues in the chest or to other parts of the body. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] 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 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]

Dictionary 373

Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. [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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The

374 Lung Cancer

condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [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] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [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] Follicles: Shafts through which hair grows. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the

Dictionary 375

outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gadolinium texaphyrin: A substance that makes tumor cells more sensitive to radiation; it can also enhance tumor images using magnetic resonance imaging (MRI). Gadolinium texaphyrin belongs to the family of drugs called metalloporphyrin complexes. [NIH] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]

Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH]

376 Lung Cancer

Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Neoplasms: Tumors or cancer of the gastrointestinal system. [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] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Gene-modified: Cells that have been altered to contain different genetic material than they originally contained. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base

Dictionary 377

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 Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] 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] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [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] 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

378 Lung Cancer

(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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [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. [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] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] 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] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and

Dictionary 379

at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [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] 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] Guanine: One of the four DNA bases. [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] 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] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Halogens: A family of nonmetallic, generally electronegative, elements of group VIIa of the periodic table. They are all multivalent and have oxidation numbers of -1 (the most common), 1, 3, 5, and 7. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or

380 Lung Cancer

regional blood circulation. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatoma: A liver tumor. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH]

Dictionary 381

Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [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] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Hospital Mortality: A vital statistic measuring or recording the rate of death from any cause in hospitalized populations. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic 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] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [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

382 Lung Cancer

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] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperfractionation: A way of giving radiation therapy in smaller-than-usual doses two or three times a day instead of once a day. [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] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] 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] Idiopathic: Describes a disease of unknown cause. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune 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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU]

Dictionary 383

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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease.

384 Lung Cancer

[EU]

Infiltrating cancer: Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called invasive cancer. [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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Inflammatory breast cancer: A type of breast cancer in which the breast looks red and swollen and feels warm. The skin of the breast may also show the pitted appearance called peau d'orange (like the skin of an orange). The redness and warmth occur because the cancer cells block the lymph vessels in the skin. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] 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] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate 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] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as 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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous

Dictionary 385

isotropic layer between adjacent primary walls of cells. [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-3: A multilineage cell growth factor secreted by lymphocytes, epithelial cells, and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Also called multi-CSF, it is considered one of the hematopoietic colony stimulating factors. [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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, 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] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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] Intracellular: Inside a cell. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invasive cancer: Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called infiltrating cancer. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential

386 Lung Cancer

element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Iodine-131: Radioactive isotope of iodine. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [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] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point. [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Isoenzymes: One of various structurally related forms of an enzyme, each having the same mechanism but with differing chemical, physical, or immunological characteristics. [NIH] Isothiocyanates: Organic compounds with the general formula R-NCS. [NIH] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as

Dictionary 387

defined by their number, size, shape, etc. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [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] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large cell carcinomas: A group of lung cancers in which the cells are large and look abnormal when viewed under a microscope. [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] Laryngeal: Having to do with the larynx. [NIH] Laryngectomy: Total or partial excision of the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Legionellosis: Infections with bacteria of the genus Legionella. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [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

388 Lung Cancer

tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] 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] Limited-stage small cell lung cancer: Cancer found in one lung and in nearby lymph nodes. [NIH]

Linear accelerator: An accelerator in which charged particles are accelerated along a straight path either by means of a traveling electromagnetic field or through a series of small gaps between electrodes that are so connected to an alternating voltage supply of high frequency. [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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] 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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobectomy: The removal of a lobe. [NIH] Local therapy: Treatment that affects cells in the tumor and the area close to it. [NIH]

Dictionary 389

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] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Lung metastases: Cancer that has spread from the original (primary) tumor to the lung. [NIH]

Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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]

Lymph node mapping: The use of dyes and radioactive substances to identify lymph nodes that contain tumor cells. [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 Metastasis: Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system. [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] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoepithelioma: A type of cancer that begins in the tissues covering the nasopharynx (the upper part of the throat behind the nose). [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in

390 Lung Cancer

which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant mesothelioma: A rare type of cancer in which malignant cells are found in the sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Marijuana Smoking: Inhaling and exhaling the smoke from Cannabis. [NIH] Marimastat: An anticancer drug that belongs to the family of drugs called angiogenesis inhibitors. Marimastat is a matrix metalloproteinase inhibitor. [NIH] Mass Screening: Organized periodic procedures performed on large groups of people for the purpose of detecting disease. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Mebendazole: A nematocide in humans and animals. It acts by interfering with the carbohydrate metabolism and associated energy production of the parasite. [NIH] Mediastinoscopy: Endoscopic examination, therapy or surgery of the anterior superior mediastinum of the thorax. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH]

Dictionary 391

Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Megestrol Acetate: A drug that belongs to the group of hormones called progestins, used as hormone therapy to block estrogen and to suppress the effects of estrogen and androgens. [NIH]

Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] 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] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [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] Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [NIH] 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

392 Lung Cancer

application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [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] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] 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] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic

Dictionary 393

centimeter (cc) of liquid are the same. [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] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness,

394 Lung Cancer

and air sickness. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] 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 proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [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]

Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]

Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system

Dictionary 395

cell. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nebulizer: A device used to turn liquid into a fine spray. [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] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Nematocide: A chemical used to kill nematodes. [NIH] Neoadjuvant Therapy: Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] 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] Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA), an important marker in the diagnosis of human acute lymphocytic leukemia. EC 3.4.24.11. [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] 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] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the

396 Lung Cancer

dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [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.

Dictionary 397

[NIH]

Nitrocamptothecin: An alkaloid drug belonging to a class of anticancer agents called topoisomerase inhibitors. [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] Node-negative: Cancer that has not spread to the lymph nodes. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] 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] NSAIDs: Nonsteroidal anti-inflammatory drugs. A group of drugs that decrease fever, swelling, pain, and redness. [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 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 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] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [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] 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, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH]

398 Lung Cancer

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] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [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] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] 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] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteolytic: Causing the breakdown of bone. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Otorhinolaryngology: That branch of medicine concerned with medical and surgical treatment of the head and neck, including the ears, nose and throat. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian epithelial cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] 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]

Dictionary 399

Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

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] 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] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [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] 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] 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] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Paraneoplastic syndrome: A group of symptoms that may develop when substances released by some cancer cells disrupt the normal function of surrounding cells and tissue. [NIH]

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]

400 Lung Cancer

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] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [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] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Peau d'orange: A dimpled condition of the skin of the breast, resembling the skin of an orange, sometimes found in inflammatory breast cancer. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of

Dictionary 401

proteins. Peptides are combined to make proteins. [NIH] Perennial: Lasting through the year of for several years. [EU] Performance status: A measure of how well a patient is able to perform ordinary tasks and carry out daily activities. [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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [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] 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] 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] Phantom: Used to absorb and/or scatter radiation equivalently to a patient, and hence to estimate radiation doses and test imaging systems without actually exposing a patient. It may be an anthropomorphic or a physical test object. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] 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] 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] Phenylbutyrate: An anticancer drug that belongs to the family of drugs called differentiating agents. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [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

402 Lung Cancer

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] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [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]

Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [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] 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

Dictionary 403

molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]

Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [NIH] Pneumonectomy: An operation to remove an entire lung. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [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]

404 Lung Cancer

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiates: 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] Predisposition: A latent susceptibility to disease which may be activated under certain

Dictionary 405

conditions, as by stress. [EU] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [NIH] 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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH]

406 Lung Cancer

Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] 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] 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] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [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 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]

Dictionary 407

Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein 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] 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] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease

408 Lung Cancer

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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation Oncology: A subspecialty of medical oncology and radiology concerned with the radiotherapy of cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body.

Dictionary 409

Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [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] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH]

Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiosensitization: The use of a drug that makes tumor cells more sensitive to radiation therapy. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radium: A radioactive element symbol Ra, atomic number 88, disintegration of uranium and is is used clinically as a source brachytherapy. [NIH]

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

Radon: A naturally radioactive element with atomic symbol Rn, atomic number 86, and atomic weight 222. It is a member of the noble gas family and released during the decay of radium and found in soil. There is a link between exposure to radon and lung cancer. [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] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or

410 Lung Cancer

other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [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 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] 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] 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] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] 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 chemotherapy: Treatment with anticancer drugs that is directed to a specific area. [NIH]

Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative 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

Dictionary 411

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] 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 cell carcinoma: A type of kidney cancer. [NIH] Renal Circulation: The circulation of the blood through the vessels of the kidney. [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] 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] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [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] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] 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] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It

412 Lung Cancer

does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [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] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [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] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] S-1: A drug that is being studied for its ability to enhance the effectiveness of fluorouracil and prevent gastrointestinal side effects caused by fluorouracil. It belongs to the family of drugs called anitmetabolites. [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] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH]

Dictionary 413

Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] 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] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] 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] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs

414 Lung Cancer

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] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] 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] Sentinel Lymph Node Biopsy: A diagnostic procedure used to determine whether lymphatic metastasis has occurred. The sentinel lymph node is the first lymph node to receive drainage from a neoplasm. [NIH] Sentinel lymph node mapping: The use of dyes and radioactive substances to identify the first lymph node to which cancer is likely to spread from the primary tumor. Cancer cells may appear first in the sentinel node before spreading to other lymph nodes and other places in the body. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [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] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH]

Dictionary 415

Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an 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] Silicosis: A type of pneumoconiosis caused by inhalation of particles of silica, quartz, ganister or slate. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

416 Lung Cancer

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [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] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [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]

Dictionary 417

Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [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] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] 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] Spinous: Like a spine or thorn in shape; having spines. [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] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Steady state: Dynamic equilibrium. [EU] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotactic radiosurgery: A radiation therapy technique involving a rigid head frame that is attached to the skull; high-dose radiation is administered through openings in the head frame to the tumor while decreasing the amount of radiation given to normal brain tissue. This procedure does not involve surgery. Also called stereotaxic radiosurgery and

418 Lung Cancer

stereotactic radiation therapy. [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] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] 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] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [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] 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] Subtraction Technique: Combination or superimposition of two images for demonstrating differences between them (e.g., radiograph with contrast vs. one without, radionuclide

Dictionary 419

images using different radionuclides, radiograph vs. radionuclide image) and in the preparation of audiovisual materials (e.g., offsetting identical images, coloring of vessels in angiograms). [NIH] Subtrochanteric: Below a trochanter. [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] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] 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] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] 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] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] 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

420 Lung Cancer

in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] 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] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] 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] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [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] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH]

Dictionary 421

Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thiorphan: A potent inhibitor of membrane metalloendopeptidase (enkephalinase). Thiorphan potentiates morphine-induced analgesia and attenuates naloxone-precipitated withdrawal symptoms. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Thoracoscopy: Endoscopic examination, therapy or surgery of the pleural cavity. [NIH] Thoracotomy: Surgical incision into the chest wall. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] 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] 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]

422 Lung Cancer

Thymosin: A family of heat-stable, polypeptide hormones secreted by the thymus gland. Their biological activities include lymphocytopoiesis, restoration of immunological competence and enhancement of expression of T-cell characteristics and function. They have therapeutic potential in patients having primary or secondary immunodeficiency diseases, cancer or diseases related to aging. [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] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tirapazamine: A drug that makes tumor cells more sensitive to radiation therapy. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue 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] Tobacco Industry: The aggregate business enterprise of agriculture, manufacture, and distribution related to tobacco and tobacco-derived products. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH]

Dictionary 423

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] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Agreement: A written agreement for the transfer of patients and their medical records from one health care institution to another. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group 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] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [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] 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] 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] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triad: Trivalent. [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]

424 Lung Cancer

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] Tungsten: A metallic element with the atomic symbol W, atomic number 74, and atomic weight 183.85. It is used in many manufacturing applications, including increasing the hardness, toughness, and tensile strength of steel; manufacture of filaments for incandescent light bulbs; and in contact points for automotive and electrical apparatus. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Unsaturated Fats: A type of fat. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH]

Dictionary 425

Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uteroglobin: A protein fraction of pregnant uterine fluid which can induce and regulate blastocystic development. Blastokinin is thought to be similar or identical to uteroglobin. Presence in uterine fluid regulated by progesterone. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of

426 Lung Cancer

vesicles on the skin. [EU] 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] Vindesine: Vinblastine derivative with antineoplastic activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus, head, and neck, and Hodgkin's and non-Hodgkin's lymphomas. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [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] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vocal cord: The vocal folds of the larynx. [NIH] War: Hostile conflict between organized groups of people. [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] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

Dictionary 427

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]

429

INDEX 3 3-dimensional, 46, 345 A Abdomen, 233, 345, 355, 359, 371, 385, 388, 390, 391, 399, 400, 401, 417, 418, 421 Abdominal, 345, 366, 376, 385, 399, 401 Aberrant, 25, 65, 72, 150, 158, 254, 277, 278, 345 Abscess, 298, 345 Acceptor, 345, 388, 399, 421, 423 Acetylcholine, 68, 120, 345, 359, 396 Acidity, 345, 401 Acne, 345, 386 Acne Vulgaris, 345, 386 Acrylonitrile, 345, 412 Actin, 247, 345, 394 Activities of Daily Living, 345 Acute leukemia, 218, 345, 371, 405, 426 Acute lymphoblastic leukemia, 345, 395 Acute lymphocytic leukemia, 345, 395 Acute myelogenous leukemia, 345, 346 Acute myeloid leukemia, 218, 234, 346 Acute nonlymphocytic leukemia, 346 Acute renal, 70, 346 Adaptability, 346, 358 Adduct, 9, 346 Adenine, 138, 346, 408 Adenoma, 40, 346 Adenosine, 265, 266, 346, 352, 402 Adenovirus, 55, 275, 346 Adjuvant, 31, 32, 34, 39, 46, 73, 87, 118, 198, 199, 269, 270, 305, 330, 346, 376 Adjuvant Therapy, 32, 39, 118, 270, 346 Adrenergic, 346, 367, 371, 419 Adverse Effect, 346, 350, 386, 415, 426 Aerobic, 346, 394, 399 Aerosol, 94, 137, 176, 189, 346, 426 Afferent, 346, 402 Affinity, 346, 347, 351, 416 Age Distribution, 347 Age Groups, 347 Aggressiveness, 59, 347 Agonist, 66, 262, 265, 347, 367, 396 Airway, 22, 25, 37, 63, 102, 347, 415 Algorithms, 347, 354 Alimentary, 347, 400 Alkaline, 347, 356, 361, 399, 409, 420 Alkaloid, 24, 347, 356, 360, 396, 397

Alkylating Agents, 263, 347, 420 Alkylation, 263, 347 Alleles, 4, 347, 388, 389 Allergen, 347, 414 Allergic Rhinitis, 347, 356 Allogeneic, 7, 347, 378 Alopecia, 347, 364 Alpha Particles, 347, 408 Alpha-fetoprotein, 347, 373 Alternative medicine, 5, 306, 347 Alternative Splicing, 241, 348, 406 Amifostine, 151, 159, 174, 181, 198, 348 Amino Acid Sequence, 348, 349, 372, 377 Amino Acid Substitution, 248, 348 Amplification, 252, 253, 348 Ampulla, 348, 369 Anaesthesia, 348, 383 Anal, 45, 63, 244, 348, 370, 374 Analgesic, 20, 348, 382, 387, 419 Analog, 46, 48, 244, 246, 348, 374, 375 Anaphylatoxins, 348, 362 Anatomical, 348, 359, 363, 366, 383, 413 Androgens, 348, 391 Anemia, 131, 221, 348, 374, 394 Anesthesia, 5, 297, 347, 349 Aneurysm, 349, 350, 425 Angiogenesis, 15, 34, 56, 61, 74, 110, 114, 118, 142, 150, 151, 158, 159, 199, 238, 349, 390 Angiogenesis inhibitor, 150, 158, 199, 349, 390 Animal model, 41, 43, 54, 62, 349, 424 Anions, 349, 386 Annealing, 349, 404 Anorexia, 58, 228, 234, 349, 376 Anthelmintic, 202, 349 Anthracycline, 44, 349, 365, 371 Antibacterial, 251, 349, 417 Antibiotic, 181, 349, 350, 365, 367, 371, 393, 417, 420 Antibiotic Prophylaxis, 181, 349 Antibodies, 55, 93, 242, 245, 246, 260, 267, 283, 284, 349, 352, 381, 383, 389, 393, 402, 409 Antibody therapy, 218, 229, 265, 349 Anticarcinogenic, 53, 349 Anticoagulant, 349, 366, 406 Antidepressant, 233, 349, 374

430 Lung Cancer

Antidote, 62, 349 Antigen-Antibody Complex, 350, 362 Antigen-presenting cell, 350, 365 Anti-infective, 350, 381, 386, 416 Anti-inflammatory, 20, 212, 350, 351, 357, 377, 382, 387, 397, 399, 419 Anti-Inflammatory Agents, 350, 351, 357 Antimetabolite, 350, 352, 366, 374, 392 Antineoplastic Agents, 263, 278, 347, 350, 426 Antioxidant, 30, 41, 53, 195, 211, 350, 375 Antipyretic, 350, 387 Antitumour, 93, 350 Antiviral, 350, 366, 385 Anus, 348, 350, 355, 361, 410 Anxiety, 12, 232, 350 Aorta, 350 Aortic Aneurysm, 66, 103, 350 Aphidicolin, 92, 350 Apnea, 350 Apoptosis, 13, 21, 42, 45, 48, 50, 54, 56, 58, 60, 62, 67, 72, 75, 89, 92, 108, 109, 115, 120, 121, 142, 150, 153, 158, 161, 175, 185, 187, 189, 197, 202, 203, 255, 256, 260, 261, 262, 276, 281, 350, 357, 372 Aqueous, 351, 352, 365, 381 Arachidonate 15-Lipoxygenase, 351, 388 Arachidonate Lipoxygenases, 351, 388 Arachidonic Acid, 351, 368, 387, 406 Arginine, 120, 348, 351, 396, 398, 408 Aromatic, 9, 267, 351, 378, 401, 418 Arterial, 95, 351, 382, 407, 420 Arteries, 350, 351, 354, 363, 392, 408, 421 Arteriolar, 351, 355 Arterioles, 351, 354, 356, 392 Artery, 4, 349, 351, 363, 400, 408 Artifacts, 27, 351 Asbestos, 9, 53, 85, 109, 267, 326, 327, 334, 351, 390, 391 Asbestosis, 334, 351 Aspergillosis, 185, 351 Aspiration, 5, 123, 203, 298, 351, 373 Aspirin, 20, 69, 351 Assay, 20, 35, 60, 247, 263, 351, 361 Astrocytes, 351, 352, 385 Astrocytoma, 352, 377 Asymptomatic, 258, 352 Atopic, 269, 352 ATP, 261, 352, 367, 377, 402, 407, 421, 423 Atypical, 52, 218, 352 Autoantibodies, 9, 65, 352 Autoantigens, 352

Autoimmune disease, 4, 269, 352, 394 Autologous, 7, 55, 200, 352 Autologous tumor cells, 7, 352 Autonomic, 345, 348, 352, 397 Axillary, 55, 352 Azacitidine, 234, 352 B Bacteriophage, 352, 423 Barbiturate, 352, 421 Basal Ganglia, 352, 375, 377 Base, 28, 30, 279, 280, 346, 352, 364, 365, 372, 373, 376, 387, 403, 420 Basement Membrane, 69, 352, 357, 372 Basophils, 352, 378, 387 Benchmarking, 83, 353 Benign, 5, 14, 277, 288, 346, 353, 375, 391, 395, 399, 409 Benign prostatic hyperplasia, 288, 353 Benzene, 353 Benzo(a)pyrene, 13, 353 Benzodiazepines, 297, 353 Beta carotene, 333, 353 Beta-Thromboglobulin, 353, 385 Bilateral, 141, 353 Bile, 353, 370, 375, 381, 388 Bile duct, 353, 375 Bilirubin, 353, 375 Bioassays, 296, 353 Biochemical, 27, 44, 54, 57, 109, 140, 184, 189, 347, 350, 353, 366, 374, 398, 401, 414, 421 Biochemical reactions, 353, 421 Biological response modifier, 353, 385 Biological therapy, 353, 379 Biomarkers, 9, 13, 17, 30, 37, 41, 42, 45, 53, 54, 88, 92, 100, 103, 120, 126, 183, 200, 258, 259, 353 Biophysics, 36, 354 Biopsy, 5, 53, 114, 176, 203, 233, 268, 354 Biopsy specimen, 53, 354 Biotechnology, 65, 70, 296, 306, 317, 354 Bladder, 13, 44, 280, 281, 326, 328, 353, 354, 359, 362, 394, 396, 406, 425 Blastocyst, 354, 362 Blood Coagulation, 354, 356, 421 Blood Glucose, 354, 380, 384 Blood pressure, 4, 76, 298, 328, 354, 357, 382, 393, 408, 416 Blood transfusion, 81, 354 Blood Volume, 297, 354 Blot, 244, 354 Body Fluids, 242, 353, 354, 416, 424

Index 431

Body Mass Index, 130, 354, 399 Bombesin, 69, 242, 354 Bone Density, 275, 354 Bone Marrow Cells, 355, 379, 394 Bone Marrow Transplantation, 44, 355 Bone metastases, 89, 90, 143, 178, 289, 355 Bone scan, 86, 178, 355, 413 Bowel, 268, 348, 355, 366, 384, 385, 396, 418 Bowel Movement, 355, 366, 418 Brachytherapy, 103, 355, 385, 386, 408, 409, 427 Bradykinin, 66, 150, 159, 242, 355, 386, 396 Brain metastases, 86, 91, 136, 139, 146, 183, 204, 219, 227, 282, 355 Branch, 155, 163, 246, 341, 355, 376, 389, 398, 400, 407, 416, 421 Breakdown, 355, 366, 375, 398 Bromine, 243, 355 Bronchi, 355, 371, 423 Bronchiectasis, 298, 355 Bronchioles, 273, 355 Bronchitis, 273, 296, 355, 360 Bronchoalveolar Lavage, 106, 355 Bronchoconstriction, 265, 266, 355 Bronchoscope, 64, 233, 355 Bronchoscopy, 203, 355 Bronchus, 115, 355 Bryostatin-1, 173, 355 Buccal, 30, 60, 355, 356, 389 Buccal mucosa, 30, 356 Budesonide, 13, 54, 356 C Calcium, 14, 33, 68, 275, 351, 356, 361, 382, 390, 400, 407, 415, 420 Calibration, 29, 37, 274, 356 Calpain, 62, 356 Camptothecin, 175, 356, 386 Capillary, 355, 356, 425 Capillary Permeability, 355, 356 Carbohydrate, 247, 356, 390, 404, 414 Carbon Dioxide, 356, 365, 374, 411, 424 Carcinoembryonic Antigen, 247, 356 Carcinogen, 19, 22, 27, 37, 333, 346, 353, 356 Carcinogenic, 23, 27, 347, 353, 356, 384, 398, 405, 424 Carcinoma in Situ, 12, 17, 52, 357 Cardiac, 66, 356, 357, 368, 371, 376, 394 Cardiotoxicity, 357, 371 Cardiovascular disease, 256, 357

Carotene, 19, 21, 30, 130, 175, 183, 208, 209, 333, 353, 357, 411 Carotenoids, 19, 85, 150, 157, 158, 165, 202, 208, 353, 357 Case report, 5, 86, 108, 357, 360 Case series, 5, 357, 360 Case-Control Studies, 57, 69, 357, 370 Caspase, 42, 54, 153, 161, 357 Catecholamine, 357, 367 Catheter, 233, 357 Cathode, 282, 357 Cations, 357, 386 Causal, 23, 43, 357, 370 Cause of Death, 62, 249, 270, 277, 357 Celecoxib, 27, 45, 60, 176, 231, 357 Cell Adhesion, 129, 156, 164, 241, 357 Cell Death, 19, 42, 55, 62, 75, 255, 256, 261, 262, 285, 350, 357, 371, 372, 377 Cell Differentiation, 358, 415 Cell Division, 36, 75, 352, 358, 371, 379, 385, 393, 402, 413, 420 Cell membrane, 239, 261, 358, 366, 375, 402, 416 Cell motility, 93, 358 Cell proliferation, 13, 32, 49, 53, 261, 262, 285, 350, 358, 407, 415 Cell Respiration, 358, 399, 411 Cell Size, 358, 374 Cell Survival, 20, 42, 91, 358, 379 Cellular adhesion, 238, 358 Cellulose, 358, 402 Central Nervous System, 345, 353, 358, 359, 368, 375, 377, 378, 387, 394, 414 Centrifugation, 358, 392 Ceramide, 42, 48, 55, 358 Cerebral, 135, 352, 358, 371, 377 Cerebral hemispheres, 352, 358, 377 Cerebrovascular, 357, 358 Cerebrum, 358 Cervical, 10, 243, 254, 275, 358 Cervix, 45, 358, 411 Chemical Warfare, 283, 359 Chemical Warfare Agents, 283, 359 Chemopreventive, 13, 18, 21, 27, 30, 37, 41, 44, 49, 52, 53, 54, 175, 359 Chemotactic Factors, 359, 362 Chemotherapeutic agent, 26, 42, 55, 246, 274, 359 Chest wall, 90, 114, 121, 141, 203, 359, 403, 421 Chin, 79, 92, 138, 193, 203, 359, 391 Cholecystokinin, 242, 359

432 Lung Cancer

Cholesterol, 4, 298, 353, 359, 363, 375 Choline, 142, 359 Cholinergic, 359, 396 Cholinesterase Inhibitors, 359, 367 Chondrocytes, 359, 373 Chromates, 267, 359 Chromatin, 350, 359 Chromic, 359 Chromosomal, 36, 38, 58, 65, 348, 359, 402, 412, 420 Chromosome Aberrations, 88, 360 Chronic Disease, 156, 164, 242, 334, 360 Chronic Obstructive Pulmonary Disease, 20, 57, 116, 207, 265, 270, 271, 273, 275, 300, 360 Cirrhosis, 157, 165, 282, 360 CIS, 107, 327, 360, 411 Cleave, 250, 360 Clinical Medicine, 360, 404 Clinical study, 289, 360 Clone, 43, 50, 258, 360 Cloning, 38, 48, 67, 96, 244, 354, 360 Codon, 79, 99, 120, 138, 360, 377 Cofactor, 66, 360, 396, 407, 421 Cognition, 4, 360 Cohort Studies, 20, 360, 370 Colchicine, 360, 424 Colitis, 269, 361, 384 Collagen, 241, 348, 352, 361, 372, 373, 376, 390, 403, 405 Collapse, 355, 361, 403, 415 Colorectal, 10, 21, 34, 53, 69, 96, 252, 277, 278, 334, 361, 407 Colorectal Cancer, 34, 53, 252, 277, 334, 361, 407 Combination Therapy, 154, 162, 361 Combined Modality Therapy, 31, 361 Comet Assay, 187, 361 Comorbidity, 137, 143, 179, 361 Compassionate, 147, 361 Complement, 9, 20, 348, 361, 362, 377, 386, 414 Complementary and alternative medicine, 171, 209, 362 Complementary medicine, 5, 171, 362 Complete remission, 219, 362, 411 Complete response, 141, 362 Compliance, 46, 362 Computational Biology, 9, 317, 362 Computed tomography, 14, 28, 49, 71, 101, 103, 113, 117, 134, 195, 199, 204, 354, 362, 413

Computerized tomography, 362 Conception, 252, 362, 373, 416, 418 Concomitant, 94, 156, 164, 176, 178, 198, 362 Concurrent therapy, 31, 362 Cones, 362, 402, 411 Confounding, 20, 363 Conjugated, 269, 311, 363, 364, 397 Connective Tissue, 354, 361, 363, 373, 375, 376, 389, 391, 412, 418, 420 Consciousness, 348, 363 Constipation, 4, 363 Constriction, 363, 386, 425 Constriction, Pathologic, 363, 425 Consultation, 17, 363 Consumption, 4, 24, 33, 130, 363, 376, 399 Continuous infusion, 155, 163, 363 Contraindications, ii, 363 Control group, 363, 405 Cooperative group, 363 Coordination, 15, 363, 394 Cornea, 363, 413, 425 Coronary, 4, 357, 363, 392 Coronary heart disease, 357, 363 Coronary Thrombosis, 363, 392 Corticosteroids, 363, 377 Cranial, 68, 127, 330, 363, 364, 396, 399 Cranial Irradiation, 68, 127, 330, 364 Creatinine, 133, 364 Creatinine clearance, 133, 364 Criterion, 83, 295, 364 Crossing-over, 364, 410 Cross-Sectional Studies, 364, 370 Croton Oil, 276, 364 Curative, 24, 39, 44, 58, 84, 95, 122, 127, 138, 364, 421 Cyclic, 274, 356, 364, 379, 396, 402, 406 Cyclin, 47, 66, 82, 212, 261, 364 Cyclophosphamide, 177, 208, 364 Cyclosporine, 155, 163, 191, 364 Cytidine, 352, 364 Cytochrome, 54, 72, 92, 364 Cytokine, 22, 55, 68, 245, 246, 284, 364, 373, 385, 413, 421 Cytomegalovirus, 364, 365, 375 Cytomegalovirus Infections, 365, 375 Cytoplasm, 350, 352, 358, 365, 370, 393, 394, 412, 420 Cytoprotection, 151, 159, 365 Cytoskeleton, 261, 365, 392 Cytostatic, 263, 365

Index 433

Cytotoxic, 24, 36, 55, 99, 204, 251, 260, 263, 264, 365, 409, 415 Cytotoxic chemotherapy, 204, 365 Cytotoxicity, 251, 252, 260, 263, 360, 365 D Dairy Products, 4, 365 Data Collection, 28, 34, 365 Daunorubicin, 365, 367 De novo, 55, 365 Decarboxylation, 365, 380, 398, 408 Decision Making, 49, 250, 365 Deletion, 67, 69, 252, 350, 365, 389 Delivery of Health Care, 365, 379 Denaturation, 365, 404 Dendrites, 365, 396 Dendritic, 55, 83, 241, 365, 391 Dendritic cell, 55, 83, 365 Density, 253, 274, 275, 354, 358, 365, 374, 398, 416 Dental Care, 4, 365 Deoxyglucose, 145, 178, 366 Deoxyuridine, 46, 366, 421 Depolarization, 366, 415 Dermal, 238, 366 Dermatitis, 269, 350, 366 Detergents, 366, 373 Detoxification, 23, 366 Deuterium, 366, 381 Diabetes Mellitus, 279, 366, 378, 380 Diagnostic procedure, 237, 250, 307, 366, 414 Diagnostic trial, 227, 366 Diaphragm, 366, 403 Diarrhea, 196, 252, 366 Diastolic, 366, 382 Dicumarol, 62, 366 Digestion, 347, 353, 355, 366, 385, 388, 400, 418 Digestive system, 236, 366, 394 Digestive tract, 23, 366, 415, 417 Dihydrotestosterone, 366, 410 Dilatation, 349, 355, 366, 405, 425 Dilatation, Pathologic, 366, 425 Dilation, 355, 366, 425 Diploid, 366, 402 Direct, iii, 11, 24, 27, 52, 86, 246, 259, 309, 360, 366, 367, 381, 410, 419 Discrimination, 264, 367 Disease Progression, 37, 226, 367 Disease Susceptibility, 23, 367 Dissection, 16, 66, 103, 301, 367, 389 Distal, 59, 84, 367, 368, 407

DNA Topoisomerase, 367, 377 Donepezil, 226, 227, 367 Dopamine, 24, 367, 396, 401 Dorsal, 367, 396, 404 Dose-limiting, 58, 367 Dose-rate, 125, 367 Dosimetry, 39, 367 Double-blind, 22, 130, 147, 181, 198, 218, 224, 226, 367 Double-blinded, 218, 224, 367 Doxorubicin, 151, 159, 217, 310, 367, 371 Drive, ii, vi, 36, 149, 265, 270, 291, 367 Drug Interactions, 310, 311, 368 Drug Resistance, 26, 53, 57, 65, 69, 95, 368 Drug Tolerance, 368, 422 Duodenum, 353, 368, 369, 418 Dyes, 352, 368, 374, 389, 414 Dysplasia, 12, 17, 53, 220, 277, 278, 368 Dyspnea, 11, 368, 408 E Echocardiography, 139, 368 Ectoderm, 368, 395 Ectopic, 101, 368 Edatrexate, 257, 368 Edema, 242, 368, 395 Effector, 345, 361, 368 Efferent, 241, 368 Efficacy, 7, 11, 12, 13, 17, 22, 35, 37, 42, 45, 47, 49, 51, 55, 57, 62, 79, 89, 97, 172, 182, 183, 197, 252, 257, 368 Eicosanoids, 52, 368 Elastic, 368, 416, 419 Elastin, 361, 368, 372 Elective, 195, 368 Electrocardiogram, 233, 368 Electrode, 357, 368 Electrophoresis, 105, 361, 369, 386 Embolism, 127, 369 Embryo, 256, 354, 358, 368, 369, 383 Embryology, 287, 369 Emetic, 364, 369 Emphysema, 207, 265, 270, 271, 273, 360, 369 Empirical, 10, 24, 369 Encapsulated, 369, 388 Endemic, 369, 417 Endocrine System, 369, 396 Endogenous, 26, 48, 55, 262, 352, 354, 356, 367, 368, 369, 398 Endometrial, 369 Endometriosis, 274, 369 Endometrium, 369

434 Lung Cancer

Endoscope, 369 Endoscopic, 5, 120, 123, 187, 289, 290, 355, 369, 390, 421 Endothelial cell, 238, 369, 373, 385, 421 Endothelium, 47, 369, 396, 403 Endothelium, Lymphatic, 369 Endothelium, Vascular, 369 Endothelium-derived, 369, 396 Endotoxin, 93, 145, 370, 424 Enterohepatic, 370, 419 Enterohepatic Circulation, 370, 419 Environmental Exposure, 60, 370, 398 Environmental Health, 23, 135, 316, 318, 370 Environmental Monitoring, 112, 282, 370 Environmental tobacco smoke, 74, 131, 370 Enzymatic, 250, 260, 348, 356, 357, 362, 370, 380, 404, 411 Enzyme, 20, 49, 52, 58, 62, 65, 239, 259, 262, 348, 351, 356, 357, 367, 368, 370, 372, 376, 378, 379, 386, 388, 392, 395, 396, 399, 400, 402, 404, 406, 407, 410, 415, 418, 421, 423, 424, 426, 427 Eosinophil, 370, 379 Epidemic, 300, 370, 417 Epidemiologic Studies, 29, 35, 370 Epidemiological, 8, 19, 30, 41, 44, 50, 60, 69, 90, 211, 212, 296, 370 Epidermal, 44, 69, 89, 90, 91, 97, 108, 124, 147, 157, 164, 194, 370, 387, 391 Epidermal Growth Factor, 44, 69, 89, 90, 97, 124, 147, 157, 164, 194, 370 Epidermal growth factor receptor, 44, 89, 90, 91, 97, 124, 147, 157, 164, 194, 370 Epidermis, 370, 387, 405 Epidermoid carcinoma, 370, 417 Epigastric, 371, 399 Epinephrine, 346, 367, 371, 396, 397, 424 Epirubicin, 177, 371 Epithelial Cells, 12, 17, 20, 22, 37, 49, 60, 244, 370, 371, 385 Epithelium, 37, 40, 45, 57, 58, 245, 352, 369, 371, 376 Epitope, 246, 371 Epoetin alfa, 221, 371 Erythema, 371, 425 Erythrocyte Volume, 354, 371 Erythrocytes, 348, 354, 356, 371, 410, 414 Erythropoiesis, 297, 371 Escalation, 44, 87, 152, 160, 171, 174, 195, 371

Esophageal, 273, 371 Esophagus, 44, 45, 366, 371, 418, 421, 426 Estrogen, 371, 391 Eukaryotic Cells, 350, 371, 383, 398 Evacuation, 363, 371 Evoke, 371, 418 Excipients, 257, 372 Excitation, 372, 374, 396 Exisulind, 21, 152, 160, 226, 372 Exocrine, 359, 372, 399 Exogenous, 48, 69, 250, 369, 372 Exon, 125, 265, 348, 372 Expiration, 372, 411 Extensive-stage small cell lung cancer, 190, 194, 215, 219, 224, 372 Extensor, 372, 407 External-beam radiation, 372, 386, 408, 427 Extracellular, 33, 101, 241, 253, 351, 363, 372, 373, 390, 416, 420 Extracellular Matrix, 241, 363, 372, 373, 390 Extracellular Matrix Proteins, 372, 390 Extracellular Space, 372 Extraction, 14, 24, 372 Extrapyramidal, 367, 372 Eye Infections, 346, 372 F Family Planning, 317, 372 Farnesyl, 13, 279, 372 Fat, 130, 351, 353, 354, 355, 357, 358, 363, 372, 388, 394, 399, 412, 416, 419, 424 Fatigue, 11, 232, 234, 373, 379 Fatty acids, 49, 368, 373, 388, 406, 416, 421 Feasibility Studies, 48, 373 Feces, 356, 363, 373, 418 Femoral, 373, 380 Femoral Neck Fractures, 373, 380 Femur, 373, 380 Fetoprotein, 247, 373 Fetus, 347, 373, 405, 425 Fibrin, 354, 373, 402, 421 Fibrinogen, 373, 403, 421 Fibroblast Growth Factor, 103, 373 Fibroblasts, 24, 43, 238, 373, 385 Fibrosis, 265, 269, 273, 298, 373, 408, 412, 413 Filgrastim, 224, 373 Fine-needle aspiration, 114, 123, 187, 373, 395 Fish Oils, 49, 373 Fistula, 77, 373

Index 435

Fixation, 373, 414 Flatus, 374, 375 Flow Cytometry, 103, 374 Fluorescence, 20, 374 Fluorescent Dyes, 374 Fluorouracil, 125, 208, 374, 412 Fluoxetine, 232, 233, 374 Folate, 19, 30, 44, 366, 374 Fold, 15, 17, 22, 62, 244, 248, 267, 374 Folic Acid, 167, 228, 257, 374 Follicles, 374 Follow-Up Studies, 260, 374 Forearm, 354, 375 Fractionation, 46, 260, 276, 329, 375 Free Radicals, 238, 239, 350, 375 Fungi, 244, 350, 351, 372, 375, 379, 392, 427 G Gadolinium, 222, 375 Gadolinium texaphyrin, 222, 375 Gallate, 154, 162, 375 Gallbladder, 345, 359, 366, 375 Gallstones, 4, 375 Gamma Rays, 375, 394, 408, 409 Ganciclovir, 246, 375 Ganglia, 345, 348, 375, 395 Ganglion, 375, 396 Ganglioside, 269, 375 Gap Junctions, 375, 419, 420 Gas, 29, 282, 356, 374, 375, 381, 394, 396, 397, 403, 409, 425, 426 Gastric, 34, 238, 298, 354, 370, 371, 376, 380, 400 Gastric Juices, 376, 400 Gastric Mucosa, 376, 400 Gastrin, 376, 381 Gastroenteritis, 355, 376 Gastrointestinal, 46, 256, 351, 355, 356, 359, 371, 376, 387, 412, 414, 418, 419, 424 Gastrointestinal Neoplasms, 351, 376 Gastrointestinal tract, 356, 359, 376, 388, 414, 424 Gelatin, 376, 378, 421 Gene Expression, 22, 26, 44, 53, 60, 75, 136, 146, 212, 240, 247, 248, 250, 271, 376 Gene Expression Profiling, 271, 376 Gene Therapy, 245, 267, 275, 346, 376 Gene-modified, 7, 376 General practitioner, 292, 293, 376 Generator, 249, 376 Genetic Code, 376, 397 Genetic Counseling, 377 Genetic Engineering, 252, 354, 360, 377

Genetic Markers, 58, 377 Genetic testing, 100, 377, 404 Genetics, 8, 11, 37, 38, 40, 41, 51, 88, 112, 135, 285, 295, 377, 393 Genistein, 188, 377 Genital, 377, 425 Genitourinary, 46, 377, 425 Genomics, 42, 96, 261, 377 Genotype, 40, 135, 377, 401 Germ Cells, 377, 398, 416 Germ-Line Mutation, 252, 377 Giant Cells, 377, 412 Gingivitis, 273, 377 Ginseng, 207, 209, 377 Gland, 287, 377, 389, 399, 400, 402, 406, 413, 418, 422 Glioblastoma, 262, 377 Glucocorticoid, 54, 356, 377 Glucose, 180, 195, 203, 354, 358, 366, 378, 380, 384, 402 Glucose Intolerance, 366, 378 Glutamic Acid, 374, 378, 396, 405 Glutathione Peroxidase, 22, 378, 413 Glutathione Transferase, 22, 378 Glycine, 131, 348, 378, 396, 414 Glycoprotein, 26, 126, 174, 196, 241, 245, 356, 373, 377, 378, 394, 421, 424 Goats, 365, 378 Governing Board, 378, 404 Grade, 378 Grading, 59, 378 Graft, 269, 378, 381, 383 Graft Rejection, 378, 383 Grafting, 378, 383 Gram-positive, 378, 394 Granulocyte, 66, 108, 373, 378 Granulocyte-Macrophage ColonyStimulating Factor, 108, 378 Grasses, 374, 379 Growth factors, 241, 379 Guanine, 138, 261, 379, 408 Guanylate Cyclase, 379, 396 H Habitat, 379, 394 Haemodialysis, 182, 379 Hair follicles, 274, 379 Halogens, 243, 379 Haploid, 379, 402 Health Care Costs, 266, 379 Health Expenditures, 379 Health Services, 49, 365, 379 Health Status, 34, 379

436 Lung Cancer

Heart attack, 328, 357, 379 Heart failure, 379, 408 Hematopoiesis, 241, 379 Heme, 353, 364, 379, 399 Hemodynamics, 78, 379 Hemoglobin, 76, 348, 371, 379, 380, 387 Hemoglobin A, 76, 380 Hemoglobinopathies, 376, 380 Hemorrhage, 380, 418 Hepatic, 265, 380, 388 Hepatocellular, 252, 265, 380 Hepatocellular carcinoma, 252, 265, 380 Hepatoma, 245, 380 Hereditary, 380, 411 Heredity, 345, 376, 377, 380 Herpes, 246, 380 Herpes Zoster, 380 Heterodimers, 50, 380, 423 Heterogeneity, 123, 139, 211, 242, 247, 346, 380 Heterotrophic, 375, 380 Hip Fractures, 275, 373, 380 Histamine, 348, 380 Histidine, 96, 380 Histology, 15, 22, 28, 135, 380, 399 Homeobox, 105, 380 Homeostasis, 238, 262, 381 Homodimer, 381, 423 Homogeneous, 139, 381 Homologous, 281, 347, 364, 376, 381, 394, 413, 414, 419 Hormone therapy, 346, 381, 391 Hospital Mortality, 66, 74, 381 Host, 43, 60, 123, 256, 260, 269, 284, 352, 381, 382, 383, 387, 412, 426 Housekeeping, 271, 381 Human Genome Project, 37, 381 Humoral, 33, 378, 381 Humour, 381 Hybrid, 360, 381 Hybridization, 381, 393 Hybridomas, 246, 381 Hydrogen Peroxide, 378, 381, 388 Hydrogenation, 353, 381 Hydrolysis, 55, 360, 381, 401, 407 Hydrophobic, 366, 381, 395 Hydroxylysine, 361, 382 Hydroxyproline, 348, 361, 382 Hygienic, 289, 382 Hyperalgesia, 242, 382 Hypercalcemia, 33, 382 Hyperfractionation, 184, 382

Hyperplasia, 12, 17, 40, 253, 382 Hypersensitivity, 252, 347, 370, 382, 387, 412, 414 Hypertension, 4, 262, 279, 357, 382 Hyperthermia, 89, 382, 395 Hypertrophy, 273, 353, 382 Hypnotic, 352, 382, 421 Hypoxia, 83, 105, 110, 184, 382 I Ibuprofen, 382, 387 Id, 166, 206, 268, 329, 330, 331, 332, 335, 340, 342, 382 Idiopathic, 110, 382, 412 Immune function, 382, 423 Immune response, 7, 25, 54, 65, 235, 246, 346, 350, 352, 378, 382, 383, 414, 418, 426 Immune system, 224, 229, 349, 350, 353, 382, 383, 388, 389, 390, 394, 425, 426 Immunity, 306, 382 Immunization, 382, 383, 405, 414 Immunodeficiency, 382, 422 Immunogenic, 25, 69, 266, 269, 382 Immunoglobulin, 349, 383, 393 Immunohistochemistry, 139, 383 Immunologic, 359, 382, 383, 409 Immunology, 3, 4, 11, 83, 93, 238, 346, 374, 383 Immunosuppressant, 347, 374, 383, 392 Immunosuppressive, 7, 364, 377, 383 Immunosuppressive therapy, 383 Immunotherapy, 61, 73, 83, 141, 240, 268, 353, 383, 395 Impairment, 175, 288, 372, 383, 391 Implant radiation, 383, 385, 386, 408, 427 Implantation, 114, 139, 362, 383 In situ, 20, 55, 56, 97, 238, 253, 383 In Situ Hybridization, 20, 383 Incision, 383, 385, 421 Indicative, 53, 244, 259, 288, 383, 400, 425 Infancy, 30, 383 Infarction, 353, 363, 383, 392 Infiltrating cancer, 384, 385 Infiltration, 241, 384 Inflammatory bowel disease, 242, 384 Inflammatory breast cancer, 141, 384, 400 Informed Consent, 15, 45, 384 Infusion, 95, 233, 384, 423 Inhalation, 54, 75, 94, 145, 346, 351, 384, 403, 415 Initiation, 33, 36, 37, 43, 47, 60, 384 Initiator, 32, 384 Inlay, 384, 411

Index 437

Inoperable, 21, 72, 80, 91, 103, 122, 129, 138, 173, 195, 205, 300, 301, 384 Inorganic, 360, 384, 403 Inotropic, 367, 384 Insight, 12, 17, 20, 30, 33, 42, 43, 49, 53, 61, 384 Insulator, 384, 394 Insulin, 153, 161, 279, 384, 395 Insulin-dependent diabetes mellitus, 384 Intensive Care, 123, 384 Intercellular Junctions, 261, 384 Interferon, 108, 140, 238, 385 Interferon-alpha, 108, 385 Interleukin-3, 156, 164, 199, 385 Interleukin-8, 142, 238, 385 Intermittent, 182, 385, 389 Internal Medicine, 7, 8, 36, 63, 100, 111, 129, 152, 155, 156, 157, 160, 163, 164, 165, 385, 390 Internal radiation, 385, 386, 408, 427 Interphase, 20, 385 Interstitial, 355, 372, 385, 386, 427 Intestinal, 4, 65, 70, 269, 357, 359, 385 Intestinal Mucosa, 359, 385 Intestine, 41, 284, 355, 361, 370, 385, 387 Intracellular, 89, 241, 242, 383, 385, 396, 406, 413, 415 Intraperitoneal, 44, 385 Intravenous, 5, 192, 384, 385 Intrinsic, 44, 60, 65, 347, 352, 385 Invasive, 12, 17, 52, 58, 185, 227, 239, 241, 249, 259, 277, 278, 330, 382, 384, 385, 390 Invasive cancer, 58, 384, 385 Involuntary, 370, 385, 394, 416 Iodine, 46, 311, 385, 386 Iodine-131, 46, 386 Ion Channels, 261, 351, 386, 419 Ionization, 386 Ionizing, 47, 248, 249, 347, 370, 386, 409 Ions, 282, 345, 352, 381, 386, 407, 416 Irinotecan, 151, 152, 153, 156, 159, 160, 161, 164, 179, 180, 182, 185, 186, 190, 191, 192, 193, 196, 197, 198, 200, 202, 203, 386 Irradiation, 31, 71, 83, 86, 95, 122, 132, 195, 282, 386, 427 Ischemia, 375, 386 Isoelectric, 244, 386 Isoelectric Focusing, 244, 386 Isoelectric Point, 386 Isoenzymes, 239, 386 Isothiocyanates, 41, 386

Isotretinoin, 54, 218, 386 J Joint, 109, 265, 386, 398, 419, 420 K Kallidin, 355, 386 Karyotype, 38, 386 Kb, 38, 241, 281, 316, 387 Keratin, 387 Keratinocytes, 238, 385, 387 Ketoprofen, 13, 387 Kinetic, 59, 386, 387 L Labile, 361, 387 Large cell carcinomas, 247, 387 Large Intestine, 361, 366, 385, 387, 410, 415 Laryngeal, 220, 298, 387 Laryngectomy, 298, 387 Larynx, 298, 387, 423, 426 Latent, 387, 404 Lavage, 84, 95, 144, 150, 158, 387 Legionellosis, 298, 387 Lethal, 242, 263, 279, 387 Leucine, 41, 387, 400 Leukocytes, 352, 354, 359, 385, 387, 393, 424 Leukocytosis, 140, 387 Leukotrienes, 49, 351, 368, 387 Library Services, 340, 388 Life cycle, 375, 388 Ligament, 388, 406 Ligands, 47, 241, 388 Limited-stage small cell lung cancer, 200, 219, 229, 232, 331, 388 Linear accelerator, 71, 388 Linkage, 8, 377, 388 Linkage Disequilibrium, 8, 388 Lip, 220, 388 Lipid, 48, 53, 55, 238, 239, 356, 359, 384, 388, 394 Lipid Peroxidation, 53, 238, 239, 388 Liposomal, 151, 159, 388 Lipoxygenase, 49, 351, 387, 388 Liver, 110, 269, 273, 278, 282, 326, 345, 347, 351, 353, 356, 360, 364, 366, 370, 373, 374, 375, 379, 380, 388, 412, 413, 424, 426 Liver cancer, 273, 347, 388 Liver Cirrhosis, 282, 388 Liver Neoplasms, 388, 426 Liver scan, 388, 413 Lobe, 388, 400 Lobectomy, 66, 74, 115, 116, 138, 388 Local therapy, 189, 388

438 Lung Cancer

Localization, 55, 383, 389 Localized, 36, 155, 163, 239, 240, 241, 245, 246, 251, 261, 264, 268, 272, 369, 374, 383, 389, 402, 425 Locomotion, 389, 402 Locoregional, 144, 157, 165, 389 Longitudinal Studies, 10, 364, 389 Long-Term Care, 41, 389 Loss of Heterozygosity, 39, 84, 389 Lung metastases, 217, 389 Lupus, 389, 420 Lymph node, 52, 55, 82, 84, 88, 90, 124, 127, 132, 143, 187, 225, 241, 280, 301, 352, 358, 388, 389, 397, 410, 412, 414 Lymph node mapping, 389 Lymphadenectomy, 78, 389 Lymphatic, 241, 269, 277, 298, 369, 383, 389, 391, 414, 416, 417, 422 Lymphatic Metastasis, 389, 414 Lymphatic system, 277, 389, 416, 417, 422 Lymphocyte, 241, 350, 389, 390 Lymphocytic, 260, 389 Lymphoepithelioma, 141, 389 Lymphoid, 54, 241, 349, 363, 389, 390 Lymphoma, 141, 175, 234, 245, 251, 259, 276, 279, 281, 390 Lymphoproliferative, 280, 281, 390 Lytic, 390, 414 M Macrophage, 20, 114, 128, 238, 379, 390 Magnetic Resonance Imaging, 375, 390, 413 Malignancy, 14, 22, 33, 41, 58, 140, 254, 277, 278, 280, 281, 390 Malignant mesothelioma, 111, 390, 391 Malignant tumor, 40, 275, 285, 357, 390, 394, 398 Malondialdehyde, 53, 390 Mammary, 257, 390 Marijuana Smoking, 60, 390 Marimastat, 34, 390 Mass Screening, 123, 390 Matrix metalloproteinase, 15, 34, 56, 97, 123, 196, 390 Mebendazole, 202, 390 Mediastinoscopy, 71, 109, 115, 123, 138, 390 Mediate, 47, 68, 367, 390 Mediator, 42, 238, 266, 359, 390, 414 Medical Records, 390, 412, 423 Medical Staff, 367, 391 MEDLINE, 317, 391

Megaloblastic, 366, 374, 391 Megestrol Acetate, 154, 162, 391 Melanin, 391, 401, 424 Melanocytes, 391 Melanoma, 72, 77, 218, 238, 239, 241, 244, 245, 248, 251, 260, 265, 276, 391 Memory, 55, 349, 391 Meningeal, 108, 391 Meninges, 358, 391 Meningioma, 269, 391 Mental, iv, 6, 236, 316, 318, 359, 360, 373, 391, 405, 407, 408, 414 Mental Disorders, 236, 391, 405 Mental Health, iv, 6, 236, 316, 318, 391, 405, 408 Mentors, 11, 51, 391 Mercury, 374, 391 Mesenchymal, 370, 378, 391 Mesothelioma, 58, 85, 268, 288, 327, 390, 391 Meta-Analysis, 68, 70, 130, 132, 391 Metabolic disorder, 259, 392 Metabolite, 392, 405 Metaplasia, 12, 17, 30, 53, 273, 392 Metastasis, 26, 34, 60, 71, 76, 77, 79, 85, 90, 94, 100, 110, 114, 115, 122, 123, 124, 132, 145, 152, 160, 173, 238, 239, 251, 254, 255, 277, 390, 392 Metastasize, 278, 392, 413 Metastatic cancer, 63, 225, 392 Methionine, 392, 419 Methotrexate, 209, 257, 392 Methyltransferase, 67, 128, 352, 392 MI, 67, 83, 87, 96, 110, 144, 172, 343, 392 Microbe, 392, 422 Microbiology, 79, 352, 392 Microcirculation, 388, 392, 403 Micronutrients, 19, 30, 392 Microorganism, 360, 392, 426 Microsomal, 74, 392 Microtubules, 392, 399 Migration, 114, 128, 241, 392 Milliliter, 354, 392 Mitomycin, 173, 193, 393 Mitosis, 350, 393 Mitotic, 96, 175, 202, 367, 371, 393, 420, 426 Mobility, 45, 49, 145, 241, 282, 393 Modeling, 8, 24, 36, 40, 51, 59, 200, 393 Modification, 23, 44, 74, 131, 187, 269, 348, 377, 393, 408 Molecular Probes, 64, 254, 393

Index 439

Monitor, 42, 57, 187, 233, 270, 271, 284, 356, 364, 393, 397 Monoclonal, 57, 218, 228, 234, 245, 246, 247, 252, 255, 311, 381, 386, 393, 408, 423, 427 Monoclonal antibodies, 218, 228, 234, 245, 246, 247, 252, 393, 423 Monocytes, 238, 385, 387, 393, 421 Monogenic, 23, 393 Mononuclear, 9, 68, 393, 424 Monotherapy, 87, 393 Morphogenesis, 256, 294, 393 Morphological, 47, 92, 246, 296, 369, 391, 393 Morphology, 22, 393 Motility, 49, 75, 124, 393, 414 Motion Sickness, 393, 395 Mucociliary, 394, 415 Mucolytic, 355, 394 Mucosa, 58, 63, 376, 389, 394, 418 Mucositis, 394, 421 Multicenter study, 226, 394 Multidrug resistance, 26, 394 Multiple Myeloma, 234, 279, 394 Multiple sclerosis, 269, 394 Multivalent, 379, 394 Mutagen, 353, 394 Mutagenic, 347, 394 Mycobacterium, 199, 394 Myelin, 394 Myelodysplasia, 234, 394 Myelodysplastic syndrome, 218, 394, 415 Myelogenous, 394 Myeloma, 244, 394 Myelosuppression, 394, 426 Myocardium, 392, 394 Myofibrils, 356, 394 N Naive, 55, 394 Nasopharynx, 389, 395 Nausea, 252, 274, 376, 395 Nebulizer, 249, 395 Need, 3, 7, 16, 21, 29, 83, 239, 274, 278, 282, 287, 289, 294, 297, 298, 299, 311, 335, 336, 346, 390, 395, 422 Needle biopsy, 373, 395 Nematocide, 390, 395 Neoadjuvant Therapy, 180, 395 Neoplasia, 40, 395 Neoplasm, 43, 233, 389, 395, 399, 412, 414, 424

Neoplastic, 7, 39, 241, 245, 248, 249, 250, 253, 267, 274, 277, 296, 381, 389, 390, 395, 412 Nephrosis, 395 Nephrotic, 133, 395 Nephrotic Syndrome, 133, 395 Neprilysin, 262, 395 Nervous System, 346, 358, 390, 395, 396, 418, 419, 420 Networks, 14, 251, 395 Neural, 14, 69, 118, 248, 250, 251, 346, 373, 381, 395, 396, 416 Neural Crest, 248, 395 Neural tube defects, 373, 396 Neuroendocrine, 57, 118, 242, 396 Neurologic, 281, 282, 377, 396 Neuromuscular, 345, 396 Neuromuscular Junction, 345, 396 Neuronal, 261, 396 Neurons, 365, 375, 396, 419 Neuropeptide, 61, 68, 242, 396 Neurotoxicity, 396, 426 Neurotransmitter, 345, 346, 348, 354, 355, 359, 367, 378, 380, 386, 396, 397, 415, 418, 419 Neutrons, 347, 386, 396, 408 Neutrophil, 238, 396 Nickel, 112, 267, 396 Nicotine, 24, 68, 120, 305, 396 Nitric Oxide, 279, 396 Nitrocamptothecin, 229, 397 Nitrogen, 274, 347, 348, 364, 372, 374, 397, 423 Node-negative, 39, 397 Nonverbal Communication, 397, 407 Norepinephrine, 346, 367, 396, 397 NSAIDs, 20, 57, 212, 397 Nuclear Proteins, 105, 397 Nuclei, 347, 376, 377, 390, 393, 396, 397, 407 Nucleic acid, 248, 253, 260, 261, 265, 267, 272, 277, 278, 376, 381, 383, 397, 408, 417 Nucleoproteins, 397 Nucleus, 350, 352, 359, 364, 365, 366, 371, 375, 393, 396, 397, 407, 418 O Occult, 78, 397 Occupational Exposure, 23, 61, 88, 397 Odds Ratio, 397, 411 Odour, 351, 397 Ointments, 397, 399, 416

440 Lung Cancer

Oncogene, 17, 38, 73, 84, 93, 96, 99, 114, 131, 189, 204, 247, 250, 272, 398 Oncogenic, 75, 398, 407 Opacity, 365, 398 Opioid Peptides, 395, 398 Oral Health, 4, 297, 398 Organelles, 358, 365, 391, 393, 398 Ornithine, 260, 398, 408 Ornithine Decarboxylase, 260, 398 Osteoarthritis, 387, 398 Osteogenic sarcoma, 398 Osteolytic, 71, 398 Osteoporosis, 275, 298, 398 Osteosarcoma, 262, 398, 407 Otorhinolaryngology, 298, 398 Outpatient, 45, 188, 398 Ovarian epithelial cancer, 218, 398 Ovaries, 398, 411 Ovary, 44, 244, 398, 418 Overall survival, 39, 91, 270, 398 Overexpress, 26, 399 Overweight, 166, 298, 399 Oxaliplatin, 171, 399 Oxidation, 345, 350, 351, 364, 378, 379, 388, 399 Oxidative metabolism, 387, 399 Oxides, 378, 399 Oxygen Consumption, 399, 411 Oxygenase, 44, 176, 399 P P53 gene, 124, 247, 252, 262, 399, 407 Palliative, 5, 63, 67, 75, 141, 175, 399, 421 Pancreas, 152, 161, 280, 281, 328, 345, 354, 366, 384, 399, 413, 424 Pancreatic, 5, 34, 265, 269, 273, 282, 359, 371, 399 Pancreatic cancer, 5, 265, 269, 273, 282, 371, 399 Papilloma, 245, 399 Paraffin, 16, 399 Paranasal Sinuses, 399, 415 Paraneoplastic syndrome, 133, 329, 399 Parasite, 390, 399 Parathyroid, 33, 400, 420 Parathyroid Glands, 400 Parathyroid hormone, 33, 400 Parietal, 400, 403 Parotid, 400, 412 Paroxysmal, 11, 400 Pathogenesis, 12, 17, 33, 43, 52, 68, 120, 242, 272, 400

Pathologic, 16, 29, 64, 96, 112, 180, 264, 350, 354, 363, 382, 400, 407 Pathologic Processes, 350, 400 Pathologist, 17, 400 Patient Education, 328, 338, 340, 343, 400 Patient Satisfaction, 34, 400 Patient Selection, 115, 400 Peau d'orange, 384, 400 Pelvic, 369, 400, 406 Pelvis, 233, 345, 398, 400, 425 Pepsin, 400 Pepsin A, 400 Peptic, 273, 400 Peptic Ulcer, 273, 400 Peptide, 65, 70, 81, 99, 238, 242, 244, 262, 294, 348, 359, 373, 387, 398, 400, 406, 407, 410 Perennial, 401, 423 Performance status, 180, 185, 226, 401 Perfusion, 382, 401 Pericardium, 401, 420 Periodontitis, 273, 377, 401 Perioperative, 81, 401 Peripheral blood, 9, 44, 68, 224, 235, 385, 401, 405 Peritoneal, 385, 401 Peritoneal Cavity, 385, 401 Petroleum, 399, 401 PH, 27, 114, 127, 137, 204, 265, 288, 354, 401 Phantom, 14, 250, 401 Pharmacodynamics, 44, 401 Pharmacokinetic, 10, 189, 199, 401 Pharmacologic, 25, 27, 155, 163, 191, 349, 364, 401, 422 Phenotype, 22, 26, 27, 39, 52, 54, 102, 242, 250, 252, 255, 401 Phenylalanine, 400, 401, 424 Phenylbutyrate, 234, 401 Phorbol, 276, 401 Phospholipases, 401, 415 Phospholipids, 372, 401 Phosphorus, 33, 356, 400, 402 Phosphorylase, 356, 402 Phosphorylation, 47, 51, 261, 402, 407 Photodynamic therapy, 231, 402 Phototherapy, 265, 402 Phototransduction, 261, 402 Physiologic, 30, 36, 331, 347, 392, 402, 406, 410 Pigments, 357, 402, 411 Pilot Projects, 57, 402

Index 441

Pilot study, 60, 73, 79, 95, 402 Pituitary Gland, 373, 402 Plants, 259, 276, 347, 356, 359, 377, 378, 393, 397, 402, 422, 423 Plasma, 68, 85, 87, 261, 264, 349, 353, 354, 358, 369, 373, 376, 378, 380, 394, 402, 403, 407, 414 Plasma cells, 349, 394, 402 Plasmid, 26, 247, 402, 425 Plasmin, 402, 403 Plasminogen, 105, 175, 402, 403 Plasminogen Activators, 402, 403 Platelet Activation, 403, 415 Platelet Aggregation, 348, 396, 403, 421 Platelets, 353, 356, 394, 396, 403, 413, 414 Platinum Compounds, 44, 399, 403 Pleura, 136, 144, 268, 403 Pleural, 144, 403, 421 Pleural cavity, 403, 421 Pneumoconiosis, 403, 415 Pneumonectomy, 129, 139, 403 Pneumonia, 273, 275, 363, 403 Pneumonitis, 107, 123, 129, 172, 179, 403 Pneumothorax, 127, 403 Podophyllotoxin, 371, 403 Point Mutation, 43, 248, 281, 403 Poisoning, 376, 391, 395, 403 Polymerase, 119, 124, 156, 164, 243, 265, 350, 404 Polymerase Chain Reaction, 119, 124, 156, 164, 243, 265, 404 Polymorphic, 23, 241, 271, 359, 404 Polymorphism, 74, 79, 82, 92, 99, 100, 101, 115, 120, 124, 125, 146, 279, 404 Polyp, 277, 404 Polyposis, 361, 404 Polysaccharide, 81, 350, 358, 404 Posterior, 348, 367, 399, 404, 413 Postmenopausal, 398, 404 Postoperative, 72, 106, 143, 297, 298, 330, 404 Postsynaptic, 404, 415, 419 Potentiates, 66, 152, 161, 404, 421 Potentiation, 195, 359, 404, 415 Practicability, 373, 404 Practice Guidelines, 318, 329, 330, 331, 332, 404 Precancerous, 13, 359, 372, 404, 405 Preclinical, 25, 34, 48, 52, 58, 263, 404 Predisposition, 23, 112, 258, 271, 279, 280, 283, 404 Preleukemia, 394, 405, 415

Premalignant, 53, 60, 242, 404, 405 Prenatal, 369, 405 Preoperative, 118, 176, 180, 405 Presynaptic, 396, 405, 419, 420 Prevalence, 6, 21, 25, 38, 139, 266, 288, 397, 405 Prickle, 387, 405 Primary endpoint, 22, 405 Primary Prevention, 36, 405 Primary tumor, 47, 52, 150, 158, 241, 248, 253, 268, 405, 414 Probe, 68, 281, 405 Prodrug, 245, 405 Progeny, 29, 377, 405 Progesterone, 405, 425 Prognostic factor, 76, 104, 123, 126, 132, 135, 174, 196, 197, 247, 301, 405 Progression, 12, 13, 17, 20, 33, 35, 36, 37, 39, 40, 41, 52, 57, 58, 74, 81, 84, 91, 97, 99, 111, 116, 197, 239, 248, 250, 252, 253, 262, 270, 271, 277, 278, 281, 284, 349, 405, 424 Progressive, 358, 360, 368, 371, 379, 398, 403, 405, 408, 424 Projection, 253, 254, 397, 405 Proline, 361, 382, 405 Promoter, 18, 32, 37, 48, 50, 73, 105, 150, 158, 247, 405 Prone, 27, 275, 287, 406 Prophylaxis, 279, 406 Prospective study, 71, 72, 122, 124, 127, 406 Prostaglandin, 26, 52, 406, 421 Prostaglandins A, 406 Prostate gland, 287, 406 Prostatic Hyperplasia, 406 Prostatitis, 288, 406 Prosthesis, 141, 406 Protease, 361, 406 Protein C, 281, 348, 352, 360, 387, 406, 424 Protein Isoforms, 348, 406 Protein Kinases, 262, 407 Protein p53, 79, 407 Protein S, 16, 47, 48, 241, 244, 296, 354, 377, 407, 412, 420 Protein-Tyrosine Kinase, 377, 407 Proteinuria, 394, 395, 407 Proteolytic, 241, 361, 373, 402, 403, 407 Prothrombin, 407, 421 Protocol, 5, 11, 15, 16, 24, 46, 47, 88, 407 Protons, 347, 381, 386, 407, 408 Proto-Oncogene Proteins, 399, 407

442 Lung Cancer

Proto-Oncogene Proteins c-mos, 399, 407 Proximal, 367, 405, 407 Proxy, 29, 142, 212, 407 Psoriasis, 269, 274, 350, 407 Psychic, 391, 407, 413 Psychotherapy, 45, 407 Public Health, 16, 21, 23, 27, 35, 111, 139, 152, 156, 160, 164, 288, 318, 326, 353, 407 Public Policy, 317, 408 Pulmonary Artery, 354, 408 Pulmonary Fibrosis, 110, 112, 182, 408 Pulmonary hypertension, 265, 408 Pulse, 393, 408 Purifying, 244, 276, 366, 408 Purines, 408, 414 Purulent, 345, 408 Putrescine, 398, 408, 417 Pyridoxal, 398, 408 Pyrimidines, 408, 414 Q Quinones, 263, 408 R Race, 30, 33, 34, 386, 392, 408 Radioactive, 355, 381, 383, 385, 386, 388, 389, 393, 397, 398, 408, 409, 413, 414, 420, 424, 427 Radioactivity, 364, 409 Radiography, 89, 239, 251, 258, 293, 409 Radioimmunotherapy, 361, 409 Radioisotope, 78, 89, 371, 409 Radiolabeled, 46, 386, 408, 409, 427 Radiological, 19, 250, 251, 292, 300, 409 Radiologist, 251, 409 Radiology, 11, 13, 28, 45, 46, 59, 88, 205, 233, 293, 297, 408, 409 Radiopharmaceutical, 27, 376, 409 Radiosensitization, 154, 162, 409 Radium, 144, 188, 192, 193, 200, 409 Radon, 29, 90, 101, 211, 212, 291, 292, 333, 334, 409 Randomized Controlled Trials, 28, 102, 409 Ras gene, 39, 250, 410 Reactive Oxygen Species, 41, 410 Reagent, 250, 410 Recombinant, 25, 49, 55, 66, 156, 164, 199, 245, 247, 260, 263, 410, 425 Recombination, 40, 281, 376, 377, 410 Rectal, 12, 17, 273, 410 Rectum, 350, 355, 361, 366, 374, 375, 384, 387, 406, 410 Recur, 59, 410

Recurrence, 12, 17, 39, 42, 59, 86, 106, 137, 217, 220, 359, 410 Red blood cells, 371, 394, 399, 410 Reductase, 54, 62, 392, 410, 421 Refer, 1, 347, 355, 361, 374, 375, 380, 389, 394, 396, 409, 410, 422 Refraction, 410, 417 Refractory, 178, 192, 220, 231, 410 Regeneration, 373, 410 Regimen, 176, 177, 180, 182, 216, 225, 304, 368, 410, 412 Regional chemotherapy, 44, 410 Regional lymph node, 39, 277, 410 Registries, 32, 35, 125, 334, 410 Relapse, 79, 114, 410 Relative risk, 17, 143, 410 Remission, 219, 410, 411 Renal cell carcinoma, 133, 411 Renal Circulation, 354, 411 Reproductive system, 406, 411 Resection, 39, 42, 58, 59, 77, 78, 84, 90, 106, 108, 110, 113, 128, 140, 144, 245, 301, 411 Residual disease, 140, 411 Respiration, 106, 195, 196, 265, 350, 356, 393, 399, 411 Respiratory distress syndrome, 265, 298, 411 Restoration, 55, 411, 422, 426 Retina, 362, 402, 411, 425 Retinal, 402, 411 Retinoblastoma, 7, 66, 252, 411 Retinoid, 50, 54, 411 Retinol, 19, 183, 411 Retreatment, 196, 411 Retrospective, 20, 29, 57, 66, 74, 76, 174, 412 Retrospective study, 66, 74, 76, 412 Retroviral vector, 247, 248, 376, 412 Retrovirus, 43, 67, 68, 69, 246, 291, 412 Rheumatism, 382, 412 Rheumatoid, 269, 387, 412 Rheumatoid arthritis, 269, 387, 412 Rhinitis, 242, 269, 412 Ribose, 346, 364, 412 Ribosome, 412, 423 Rigidity, 402, 412 Risk factor, 4, 10, 16, 23, 35, 39, 51, 61, 79, 111, 122, 131, 156, 164, 298, 370, 406, 410, 412 Risk patient, 58, 83, 412 Rubber, 88, 345, 412

Index 443

S S-1, 263, 412 Salivary, 364, 365, 366, 399, 412, 418 Salivary glands, 364, 365, 366, 412 Salvage Therapy, 361, 412 Sarcoidosis, 5, 112, 298, 412 Sarcoma, 260, 269, 412 Sargramostim, 235, 413 Scans, 233, 268, 413 Scatter, 401, 413 Sclera, 413, 425 Sclerosis, 238, 394, 413 Secondary tumor, 268, 392, 413 Secretion, 7, 33, 345, 354, 370, 380, 381, 384, 413, 423 Secretory, 413, 419 Sedimentation, 358, 413, 424 Segmentation, 14, 413 Segregation, 410, 413 Seizures, 377, 400, 413 Selenium, 53, 54, 167, 200, 413 Selenomethionine, 54, 413 Self Care, 345, 413 Semen, 406, 413 Semisynthetic, 356, 371, 414 Senescence, 243, 414 Senile, 203, 398, 414 Sensibility, 348, 382, 414 Sensitization, 44, 189, 414 Sensor, 282, 414 Sentinel Lymph Node Biopsy, 185, 414 Sentinel lymph node mapping, 71, 414 Sepsis, 242, 269, 414 Sequence Analysis, 68, 414 Sequence Homology, 244, 414 Sequencing, 61, 404, 414 Serine, 48, 120, 407, 414 Serologic, 9, 414 Serotonin, 374, 396, 414, 423 Serous, 369, 403, 414 Serum, 9, 19, 33, 39, 52, 70, 90, 103, 116, 118, 196, 247, 348, 361, 414, 424 Shedding, 32, 414 Shock, 25, 89, 415 Signal Transduction, 31, 40, 43, 47, 57, 261, 281, 415 Signs and Symptoms, 410, 411, 415 Silicosis, 334, 415 Sinusitis, 297, 415 Skeletal, 147, 348, 359, 394, 415, 416 Skeleton, 275, 345, 373, 386, 406, 415 Skull, 396, 415, 417, 420

Sleep apnea, 298, 415 Small intestine, 368, 381, 385, 415 Smoking Cessation, 5, 6, 16, 44, 69, 100, 415 Smoldering leukemia, 394, 415 Smooth muscle, 242, 273, 348, 354, 356, 380, 415, 416, 418 Sneezing, 414, 416 Soaps, 373, 416 Social Environment, 288, 408, 416 Social Security, 409, 416 Sodium, 402, 416 Sodium Channels, 402, 416 Soft tissue, 274, 354, 415, 416 Solid tumor, 27, 89, 147, 157, 164, 199, 245, 246, 251, 349, 367, 416 Solvent, 276, 353, 416 Soma, 416 Somatic, 36, 40, 41, 238, 377, 381, 393, 416, 420 Somatic cells, 41, 238, 377, 393, 416 Somatic mutations, 36, 416 Sound wave, 409, 416 Spasm, 242, 416, 420 Specialist, 175, 336, 366, 416 Specificity, 51, 241, 242, 263, 264, 274, 346, 351, 405, 416 Spectrometer, 282, 417 Spectrum, 34, 38, 39, 41, 51, 83, 242, 259, 417 Sperm, 348, 359, 416, 417, 424 Spermidine, 398, 417 Sphincter, 387, 417 Spinal cord, 351, 352, 358, 359, 375, 391, 395, 396, 417 Spinous, 370, 387, 417 Spleen, 364, 389, 412, 417 Sporadic, 411, 417 Sputum, 17, 37, 53, 95, 194, 227, 239, 240, 245, 246, 249, 251, 254, 258, 268, 289, 296, 417 Squamous cell carcinoma, 76, 172, 246, 272, 371, 397, 417, 426 Squamous cells, 417 Standard therapy, 270, 304, 417 Steady state, 33, 417 Stereotactic, 46, 119, 134, 417 Stereotactic radiosurgery, 46, 417 Sterile, 400, 418 Sterility, 364, 418 Steroids, 363, 377, 418 Stimulant, 242, 380, 386, 418

444 Lung Cancer

Stimulus, 50, 368, 372, 385, 386, 418, 421 Stomach, 41, 273, 275, 284, 345, 366, 371, 376, 381, 387, 395, 400, 401, 415, 417, 418 Stool, 361, 387, 418 Strand, 19, 124, 361, 404, 418 Stress, 96, 265, 275, 357, 376, 395, 405, 412, 418, 425 Stroke, 4, 207, 236, 316, 328, 357, 418 Stromal, 24, 355, 369, 418 Stromal Cells, 24, 355, 418 Styrene, 412, 418 Subacute, 383, 415, 418 Subclinical, 383, 413, 418 Subcutaneous, 151, 159, 368, 418 Submaxillary, 370, 418 Subspecies, 416, 418 Substance P, 392, 413, 418 Substrate, 27, 262, 263, 418 Substrate Specificity, 263, 418 Subtraction Technique, 89, 418 Subtrochanteric, 380, 419 Sulfur, 274, 372, 378, 392, 419 Sulindac, 13, 419 Supplementation, 30, 53, 200, 419 Support group, 334, 419 Supportive care, 75, 78, 201, 227, 419 Suppression, 24, 56, 60, 262, 274, 366, 419 Surfactant, 265, 419 Survival Rate, 13, 14, 32, 46, 62, 239, 240, 249, 251, 253, 268, 278, 280, 298, 398, 419 Sympathomimetic, 367, 371, 397, 419 Symphysis, 359, 406, 419 Symptomatic, 89, 138, 419 Synapses, 261, 359, 419, 420 Synaptic, 396, 415, 419, 420 Synaptic Transmission, 396, 419 Synaptic Vesicles, 419, 420 Synergistic, 9, 17, 55, 59, 150, 159, 420 Systemic disease, 273, 420 Systemic lupus erythematosus, 4, 269, 420 Systolic, 382, 420 T Taxanes, 119, 201, 243, 295, 420 Technetium, 143, 178, 204, 420 Telomerase, 36, 48, 72, 80, 84, 243, 420 Telomere, 36, 48, 243, 420 Temozolomide, 136, 204, 420 Temporal, 32, 35, 89, 420 Teratogenic, 347, 386, 420 Terminator, 360, 420 Testosterone, 410, 420 Tetany, 400, 420

Tetracycline, 251, 420 Thalidomide, 215, 216, 217, 306, 421 Therapeutics, 56, 125, 179, 185, 199, 202, 238, 244, 262, 291, 305, 311, 421 Thermal, 351, 396, 404, 421 Thioredoxin, 54, 421 Thiorphan, 395, 421 Thoracoscopy, 123, 421 Thoracotomy, 128, 421 Thorax, 27, 106, 111, 112, 113, 128, 132, 139, 197, 345, 390, 421 Threonine, 407, 414, 421 Threshold, 36, 250, 275, 382, 421 Thrombin, 238, 373, 403, 406, 407, 421 Thrombolytic, 403, 421 Thrombomodulin, 406, 421 Thrombosis, 353, 407, 418, 421 Thromboxanes, 351, 368, 421 Thymidine, 46, 246, 265, 421 Thymidine Kinase, 246, 421 Thymidylate Synthase, 119, 421 Thymosin, 26, 114, 275, 422 Thymus, 382, 389, 422 Thyroid, 66, 139, 386, 400, 422, 424 Thyroid Gland, 400, 422 Tin, 143, 403, 422 Tirapazamine, 224, 225, 422 Tissue Polypeptide Antigen, 79, 247, 422 Tobacco Industry, 5, 422 Tolerance, 151, 159, 346, 378, 422 Topical, 28, 381, 386, 399, 416, 422 Topoisomerase inhibitors, 386, 397, 422 Topotecan, 31, 80, 139, 177, 190, 200, 231, 294, 310, 422 Toxicity, 25, 31, 48, 58, 79, 106, 195, 218, 226, 260, 263, 357, 368, 391, 422, 426 Toxicology, 75, 79, 115, 145, 318, 422 Toxin, 370, 422 Trace element, 70, 396, 422 Trachea, 355, 387, 422, 423 Transcriptase, 412, 420, 423 Transduction, 47, 246, 415, 423 Transfection, 354, 376, 423 Transfer Agreement, 48, 423 Transferases, 100, 423 Transforming Growth Factor beta, 117, 423 Transfusion, 423 Translation, 47, 58, 247, 348, 423 Translational, 7, 11, 15, 18, 27, 31, 35, 41, 46, 47, 56, 57, 61, 423 Translocation, 36, 38, 56, 423

Index 445

Transmitter, 345, 351, 367, 386, 390, 397, 419, 420, 423 Trastuzumab, 141, 234, 423 Treatment Failure, 27, 423 Trees, 276, 412, 423 Triad, 96, 423 Tryptophan, 361, 414, 423 Tubulin, 179, 202, 392, 424 Tumor marker, 9, 70, 71, 85, 97, 246, 354, 422, 424 Tumor model, 16, 92, 424 Tumor Necrosis Factor, 238, 421, 424 Tumor suppressor gene, 12, 13, 17, 37, 65, 67, 96, 129, 246, 252, 262, 389, 399, 424 Tumorigenic, 272, 424 Tumour, 24, 69, 91, 110, 111, 127, 151, 159, 263, 350, 375, 424 Tungsten, 357, 424 Tunica, 394, 424 Tyrosine, 43, 44, 47, 56, 89, 115, 157, 164, 194, 367, 407, 424 U Ultrasonography, 187, 424 Unconscious, 382, 424 Unsaturated Fats, 373, 424 Uranium, 57, 212, 409, 420, 424 Urea, 398, 424 Urease, 396, 424 Urethra, 353, 406, 425 Urinary, 13, 52, 359, 377, 424, 425 Urine, 33, 212, 259, 353, 354, 364, 370, 407, 425 Urogenital, 377, 425 Urokinase, 175, 425 Urticaria, 269, 425 Uteroglobin, 254, 255, 425 Uterus, 358, 369, 398, 405, 411, 425 Uvea, 425 Uveitis, 269, 425 V Vaccine, 7, 25, 102, 235, 266, 269, 346, 407, 425 Vagina, 358, 411, 425 Vascular, 14, 47, 85, 117, 144, 196, 238, 354, 369, 383, 388, 392, 396, 403, 422, 425 Vascular endothelial growth factor, 85, 144, 196, 425

Vasoconstriction, 265, 371, 425 Vasodilation, 242, 348, 425 Vasodilator, 355, 367, 380, 425 VE, 27, 425 Vector, 7, 55, 245, 246, 248, 423, 425 Vein, 233, 349, 385, 397, 400, 425 Venom, 75, 425 Venous, 353, 407, 425 Venules, 354, 356, 369, 392, 425 Vertebrae, 86, 417, 425 Vesicular, 380, 392, 425 Veterinary Medicine, 317, 426 Vinblastine, 193, 424, 426 Vinca Alkaloids, 426 Vincristine, 26, 177, 198, 424, 426 Vindesine, 185, 426 Vinyl Chloride, 113, 426 Viral, 16, 43, 242, 246, 249, 256, 265, 284, 297, 350, 377, 398, 412, 423, 424, 426 Viral vector, 246, 426 Virulence, 422, 426 Virus, 110, 246, 265, 352, 377, 385, 412, 423, 426 Vitro, 7, 20, 27, 33, 42, 43, 66, 70, 107, 146, 150, 157, 159, 165, 175, 189, 211, 246, 273, 376, 383, 404, 426 Vivo, 7, 24, 27, 33, 35, 40, 43, 52, 56, 58, 59, 61, 70, 74, 107, 146, 150, 157, 159, 165, 175, 184, 246, 263, 283, 376, 383, 419, 421, 426 Vocal cord, 298, 426 W War, 359, 426 Wart, 245, 426 White blood cell, 345, 349, 373, 378, 387, 389, 390, 394, 396, 402, 426 Windpipe, 355, 422, 426 Wound Healing, 373, 390, 426 X Xenograft, 257, 349, 424, 426 X-ray therapy, 386, 427 Y Yeasts, 375, 401, 427 Z Zygote, 362, 427 Zymogen, 406, 427

446 Lung Cancer

Index 447

448 Lung Cancer