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

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Liver 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: 0-597-84010-5 1. Liver Cancer-Popular works. I. Title.

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

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

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

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

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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON LIVER CANCER .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Liver Cancer.................................................................................. 7 E-Journals: PubMed Central ....................................................................................................... 36 The National Library of Medicine: PubMed ................................................................................ 40 CHAPTER 2. NUTRITION AND LIVER CANCER ................................................................................ 87 Overview...................................................................................................................................... 87 Finding Nutrition Studies on Liver Cancer................................................................................. 87 Federal Resources on Nutrition ................................................................................................... 89 Additional Web Resources ........................................................................................................... 90 CHAPTER 3. ALTERNATIVE MEDICINE AND LIVER CANCER.......................................................... 91 Overview...................................................................................................................................... 91 National Center for Complementary and Alternative Medicine.................................................. 91 Additional Web Resources ........................................................................................................... 98 General References ..................................................................................................................... 100 CHAPTER 4. DISSERTATIONS ON LIVER CANCER ......................................................................... 103 Overview.................................................................................................................................... 103 Dissertations on Liver Cancer ................................................................................................... 103 Keeping Current ........................................................................................................................ 103 CHAPTER 5. CLINICAL TRIALS AND LIVER CANCER .................................................................... 105 Overview.................................................................................................................................... 105 Recent Trials on Liver Cancer.................................................................................................... 105 Keeping Current on Clinical Trials ........................................................................................... 122 CHAPTER 6. PATENTS ON LIVER CANCER .................................................................................... 125 Overview.................................................................................................................................... 125 Patents on Liver Cancer............................................................................................................. 125 Patent Applications on Liver Cancer ......................................................................................... 133 Keeping Current ........................................................................................................................ 151 CHAPTER 7. BOOKS ON LIVER CANCER ........................................................................................ 153 Overview.................................................................................................................................... 153 Book Summaries: Federal Agencies............................................................................................ 153 Book Summaries: Online Booksellers......................................................................................... 156 The National Library of Medicine Book Index ........................................................................... 159 Chapters on Liver Cancer........................................................................................................... 159 CHAPTER 8. MULTIMEDIA ON LIVER CANCER ............................................................................. 161 Overview.................................................................................................................................... 161 Video Recordings ....................................................................................................................... 161 Audio Recordings....................................................................................................................... 165 Bibliography: Multimedia on Liver Cancer ............................................................................... 167 CHAPTER 9. PERIODICALS AND NEWS ON LIVER CANCER .......................................................... 169 Overview.................................................................................................................................... 169 News Services and Press Releases.............................................................................................. 169 Newsletter Articles .................................................................................................................... 174 Academic Periodicals covering Liver Cancer ............................................................................. 174 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 177 Overview.................................................................................................................................... 177 U.S. Pharmacopeia..................................................................................................................... 177 Commercial Databases ............................................................................................................... 178 Researching Orphan Drugs ....................................................................................................... 179

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APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 183 Overview.................................................................................................................................... 183 NIH Guidelines.......................................................................................................................... 183 NIH Databases........................................................................................................................... 185 Other Commercial Databases..................................................................................................... 188 The Genome Project and Liver Cancer....................................................................................... 188 APPENDIX B. PATIENT RESOURCES ............................................................................................... 193 Overview.................................................................................................................................... 193 Patient Guideline Sources.......................................................................................................... 193 Finding Associations.................................................................................................................. 200 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 203 Overview.................................................................................................................................... 203 Preparation................................................................................................................................. 203 Finding a Local Medical Library................................................................................................ 203 Medical Libraries in the U.S. and Canada ................................................................................. 203 ONLINE GLOSSARIES................................................................................................................ 209 Online Dictionary Directories ................................................................................................... 211 LIVER CANCER DICTIONARY................................................................................................. 213 INDEX .............................................................................................................................................. 281

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

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

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

Hepatocellular Carcinoma and Hepatitis C in the United States Source: Hepatology. 36(5 Supplemental 1): S74-S83. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Chronic infection with hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). This article explores the interrelationship between HCC and hepatitis C. In general, HCC develops only after two or more decades of HCV infection and the increased risk is restricted largely to patients with cirrhosis (scarring) or advanced fibrosis. Factors that predispose to HCC among HCV-infected persons include male sex, older age, hepatitis B virus (HBV) coinfection, heavy alcohol intake, and possibly diabetes and a transfusion-related source

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of HCV infection. Viral factors play a minor role. The likelihood of development of HCC among HCV-infected persons is difficult to determine because of the lack of adequate long term cohort studies; the best estimate is 1 to 3 percent after 30 years. Once cirrhosis is established, however, HCC develops at an annual rate of 1 to 4 percent. Successful antiviral therapy of patients with HCV-related cirrhosis may reduce their future risk for HCC. The incidence of and mortality caused by all HCC has doubled in the United States over the past 25 years, an increase that has affected all ethnic groups, both sexes, and younger age groups. Given the current prevalence of HCV infection among persons 30 to 50 years of age, the incidence and mortality rates of HCC are likely to double in the United States over the next 10 to 20 years. Future research should focus on improving understanding of the incidence and risk factors for HCC, causes of HCV-related carcinogenesis (development of cancer), means of early detection, and better treatment for HCC. 5 figures. 3 tables. 88 references. •

Refractory Pancreatitis Secondary to Ruptured Hepatocellular Carcinoma into the Common Bile Duct Source: Digestive Diseases and Sciences. 46(5): 1029-1033. May 2001. Contact: Available from Kluwer Academic Publishers. Customer Service Department, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Distribution Centre, P.O. Box 322, 3300 AH Dordrecht, The Netherlands. 31 78 6392392. Fax: 31 78 6546474. E-mail: [email protected]. Summary: Hepatocellular carcinoma (HCC, liver cancer) is a common disease worldwide and continues to be the leading cause of death of males in Taiwan (from where this article originates). Jaundice is present in 19 to 44 percent of cases of HCC at the time of diagnosis and is usually attributed to the preexisting liver cirrhosis (scarring) or extensive hepatic parenchymal (the liver body) destruction by tumor. Icteric hepatoma (a type of liver tumor) is characterized by intermittent obstructive jaundice with associated complications, such as cholangitis (inflammation of the bile ducts) and hemobilia. In this article, the authors report the first case of icteric hepatoma that initially presented as pancreatitis in addition to obstructive jaundice. The 59 year old man was admitted with a 2 week history of tea colored urine, intermittent tarry stool, vomiting, and postprandial epigastralgia (pain in the stomach after meals) with radiation to his back. He denied alcohol abuse and drugs consumption and he had never experienced pancreatitis. After 8 days of hospital treatment, the patient was released and able to eat a normal diet at an outpatient visit one month later. However, he was rehospitalized 8 weeks later with another episode of pain; surgical treatment was implemented. The patient died of multisystem organ failure on the 32nd postoperative day. For this case, the treatment was focused on two goals. First, the consequences of the biliary obstruction including the pancreatitis should be resolved by nonoperative methods, if available. Second, the origin of the migrating tumor should be eradicated either by transarterial chemoembolization or hepatic (liver) resection. The present case was not suitable for hepatic resection or hepatic artery ligation because of intrahepatic metastasis of both lobes and portal vein thrombosis (clotting) seen at exploration. Although palliation could be satisfactorily given, the prognosis continues to be dismal. 4 figures. 11 references.

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Risk Factors for Hepatocellular Carcinoma: Synergism of Alcohol with Viral Hepatitis and Diabetes Mellitus Source: Hepatology. 36(5): 1206-1213. November 2002.

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Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Risk factors associated with hepatocellular carcinoma (HCC, liver cancer) are well documented, but the synergisms between these risk factors are not well examined. This article reports on a hospital-based, case-control study that included 115 HCC patients and 230 non-liver cancer control patients. Odds ratios were 15.3 for anti-HCV antigen, 12.6 for hepatitis B surface antigen (HBsAg), 4.5 for heavy alcohol consumption, and 4.3 for diabetes mellitus. Synergistic interactions on the additive model were observed between heavy alcohol consumption and chronic hepatitis virus infection and diabetes mellitus. Independent of the effect of HCV, HBV, and diabetes mellitus, heavy alcohol consumption contributes to the majority of HCC cases (32 percent), whereas 22 percent, 16 percent, and 20 percent were explained by HCV, HBV, and diabetes mellitus, respectively. The authors conclude that the significant synergy between heavy alcohol consumption, hepatitis virus infection, and diabetes mellitus may suggest a common pathway for hepatocarcinogenesis (development of liver cancer). 3 tables. 38 references. •

Detection of Hepatitis B Virus (HBV) in HBsAG Negative Individuals with Primary Liver Cancer Source: Digestive Diseases and Sciences. 36(8): 1122-1129. August 1991. Summary: The importance of chronic hepatitis B virus (HBV) infection in the development of primary liver cancer has been established by epidemiological studies. This article discusses the detection of HBV in HBsAG negative individuals with primary liver cancer. The authors report the use of the polymerase chain reaction to detect HBV DNA in the serum and liver of these patients. This technique allows both for the detection and cloning of HBV variants. The authors contend that the laboratory values obtained with this technique reinforce the role of HBV in the pathogenesis of this tumor. 5 figures. 39 references. (AA-M).

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Preventing Hepatitis B in People in Close Contact with Hepatocellular Carcinoma Patients Source: Public Health Reports. 112(1): 63-65. January-February 1997. Contact: Available from Public Health Reports. Room 1855, JFK Federal Building, Boston, MA 02203. (617) 565-1440. E-mail: [email protected]. Summary: This article reports on a study to determine the prevalence of testing for hepatitis B virus (HBV) infection in the clinical management of primary liver cancer (hepatocellular carcinoma). The authors reviewed the records of 78 patients treated for hepatocellular carcinoma in hospitals in the Puget Sound area in 1988 and early 1989 and reviewed all 1990 U.S. death certificates on which primary liver cancer was listed. The records of 50 (64 percent) of 78 hepatocellular carcinoma patients contained no evidence that the patient's hepatitis B surface antigen (HBsAg) status had been determined. In addition, of 4,353 people who died in 1990 for whom the diagnosis of primary liver cancer was listed on the death certificate, HBV infection was also listed for only 136 (3 percent), much less than expected based on case series. Many patients with hepatocellular carcinoma are not tested for HBV infection, suggesting that their close contacts are also not evaluated for HBV infection and the need for vaccination. Hepatitis B vaccination of close personal contacts of HBV-infected hepatocellular carcinoma patients is an important strategy for preventing HBV transmission. 14 references. (AAM).

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Hepatitis B Carriage Explains the Excess Rate of Hepatocellular Carcinoma for Maori, Pacific Island and Asian People Compared to Europeans in New Zealand Source: International Journal of Epidemiology. 28(2): 204-210. April 1999. Contact: Available from Oxford University Press. Journals Subscription Department, Great Clarendon Street, Oxford OX2 6DP, UK. 44 (0)1865 267907. Fax 44 (0)1865 267485. Summary: This article reports on a study undertaken to determine the prevalence of hepatitis B surface antigen (HBsAg) carriers among cases of hepatocellular carcinoma (HCC), and the population attributable risk of HBsAg carriage for HCC, by ethnicity in New Zealand. The authors reviewed the hospital notes of HCC cases registered with the New Zealand Cancer Registry for the years 1987 to 1994. The HBsAg status was determined for 193 cases of HCC. The HBsAg carrier prevalence for non Europeans with HCC was markedly higher than that for Europeans (76.7 percent for Maori, 80.0 percent for Pacific Island people, and 88.5 percent for Asians, compared to 6.0 percent for Europeans). In addition to the effect of ethnicity, HCC cases younger than 60 years were more likely to be HBsAg carriers than those older than 60. The estimated population attributable risk of HBsAg for HCC, within each ethnic group, was only marginally less than the HBsAg prevalence due to the high relative risk of HBsAg carriage for HCC. The standardized incidence rate ratios of HCC for Maori, Pacific Island people, and Asians compared to Europeans were 9.6, 20.4, and 22.3, respectively. HCC attributable to HBsAg carriage explained 79 percent, 83 percent, and 92 percent of the excess standardized rate for Maori, Pacific Islanders, and Asians, respectively. The authors conclude that their data predict that 75 to 90 percent of the cases of HCC that will occur in the target population (subpopulations of New Zealand) will occur among HBsAg carriers and are therefore potentially detectable by ongoing screening. 5 tables. 28 references. (AA-M).

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Worldwide Immunization Program Targets Hepatitis B and Liver Cancer Source: Journal of the National Cancer Institute. 83(10): 666-668. May 15, 1991. Summary: This article reports on the worldwide immunization program that targets hepatitis B and liver cancer. Three doses of hepatitis B vaccine have been shown to be 95 percent effective in preventing chronic hepatitis B virus (HBV) infection, the cause of over four-fifths of the world's primary liver cancers. The article details the work of the International Task Force on Hepatitis B Immunization, an independent body of health professionals from eight countries that was created in 1986. A major accomplishment of the Task Force has been to foster more international acceptance of the hepatitis B vaccine and the concept of universal childhood immunization, even in areas with a relatively low prevalence for HBV, such as the United States. 1 figure.

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Successful Treatment of Bleeding Due to Ileal Varices in a Patient with Hepatocellular Carcinoma Source: European Journal of Gastroenterology and Hepatology. 13(1): 63-66. January 2001. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London SE1 1GB, UK 44(0)20-7940-7502. Fax: 44(0)20-7940-7574. Website: http://www.eurojgh.com/. Summary: This case report concerns a 62 year old female who was known to have cirrhosis (liver scarring) and advanced hepatocellular carcinoma (HCC, liver cancer). An endoscopic examination showed no evidence of hemorrhaging (bleeding) due to either

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esophageal or gastric varices (twisted, dilated veins). Angiographic studies demonstrated extravasation (blood escaping into the tissues) from the ileal varices. There was a prominent arterio-portal shunt in the liver, and the shunt was considered to be a contributing factor to induce portal hypertension (high blood pressure in the blood supply of the liver) and variceal bleeding in the ileum. Therefore, transcatheter arterial embolization was performed, but was unsuccessful. As a result, the patient underwent a laparotomy, and a dilatating ileocecal vein and a communicating ovarian vein were selectively ligated. Following the procedure, the hemorrhaging stopped and she then recovered. The patient is doing well 21 months after surgery at the time of writing. 4 figures. 1 table. 39 references. •

Screening Tests for Hepatocellular Carcinoma in Patients with Chronic Hepatitis C: A Systematic Review Source: Hepatology. 36(5 Supplemental 1): S84-S92. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This systematic review article addresses two areas: the efficacy of using screening tests for hepatocellular carcinoma (HCC, liver cancer) in improving outcomes in chronic hepatitis C (HCV); and the sensitivity and specificity of screening tests for HCC in chronic HCV infection. The authors searched MEDLINE and other electronic databases for publications between January 1985 and March 2002. Additional articles were identified by reviewing pertinent articles and journals and by querying experts. Data collection involved paired reviewers who assessed the quality of each study and abstracted data. One nonrandomized prospective cohort study suggested that HCC was detected earlier and was more often resectable in patients who had twice yearly screening with serum alpha-fetoprotein (AFP) and hepatic ultrasound than in patients who had usual care. Twenty-four studies, which included patients with chronic hepatitis B or C or both, addressed the sensitivities and specificities of screening tests. They were relatively consistent in showing that the sensitivity of serum AFP for detecting HCC usually was moderately high at 45 percent to 100 percent, with a specificity of 70 to 95 percent. The few studies that evaluated screening with ultrasound reported high specificity, but variable sensitivity. The authors conclude that screening of patients with chronic hepatitis C with AFP and ultrasound may improve detection of HCC, but studies are needed to determine whether screening improves clinical outcomes. 2 figures. 1 table. 51 references.

Federally Funded Research on Liver Cancer The U.S. Government supports a variety of research studies relating to liver cancer. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions.

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

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

Project Title: A5: DIETHYL NITROSAMINE ON DNA ADDUCTS IN RAT: OVARIAN HORMONES ON LIVER CANCER Principal Investigator & Institution: Hood, Darryl B.; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADENOVIRUS CARCINOMA

P53

CONSTRUCT

FOR

HEPATOCELLULAR

Principal Investigator & Institution: Belani, Chandra; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001 Summary: The object of this study is to determine the safety of percutaneously delivered, intralesionally injected adeno-virus p53 construct (adeno-p53) in patients with hepatocellular carcinomas (HCC) and to investigate the potential anti-tumor effects of intralesional adeno-p53 given by monthly percutaneous injections. HCC is one of the three most common tumors to afflict humans. There is a great need for non-cytotoxic drugs for HCC in view of the underlying cirrhosis & the limitation of the diseased liver to withstand the hepatotoxic actions of almost all of the currently available cancer chemotherapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ARSENIC EFFECTS ON GLUCOCORTICOID RECEPTOR ACTION Principal Investigator & Institution: Bodwell, Jack E.; Physiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 18-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant): The overall goal of this research project is to determine the contribution of arsenic (As) exposure to human disease risk. There is growing worldwide concern about the human health effects of chronic, low level arsenic exposure. Arsenic in drinking water has been associated with an increased risk of developing type 2 diabetes, vascular and cardiovascular diseases, reproductive and developmental problems, and several kinds of cancer, notably lung, skin, bladder and liver cancer. We had previously shown that arsenic inhibited glucocorticoid hormonemediated transcriptional gene regulation. We hypothesize that direct biochemical disruption of OR function by arsenic contributes to the pathophysiology of the diseases associated with chronic arsenic exposure. Recent experiments demonstrated that mutant GRs lacking either the N-terminal domain or the C-terminal ligand-binding domain had a similar response to As as wild-type OR. This suggested that the effects of arsenic are

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primarily mediated through the middle DNA binding domain (DBD). We also have preliminary data suggesting that As binds stoichiometrically to GR at very low intracellular concentrations of As. The specific goal of this project is to determine the biochemical basis for effects of arsenic on GR signaling, focusing principally on As effects on the DBD of OR. In particular, using model mammalian hepatocyte-derived cell lines, wild-type and mutant forms of OR, genetic constructs containing model GRresponsive genes, and various biochemical and genetic techniques, we will examine this question in detail with the following specific aims: 1) Determine the arsenic-OR binding stoichiometry and site(s) of interaction using mass spectrometry and site-directed mutagenesis of OR; 2) Determine the effects of arsenic on the normal functions of the GR DBD, examining in particular whether As alters: a) the formation of cytosolic GR dimers or their transport to the nucleus using mutant and tagged GRs in combination with immunoprecipitation and Western analysis; b) OR monomer-timer interactions with their glucocorticoid response element (GRE) DNA recognition sequences using gel shift and BlAcore analyses; or c) the interaction of OR-GRE complexes with co-activators and other transcription factors using a Chromatin Immuno-Precipitation (ChIP) assay; and 3) mutational analysis of the OR DBD to confirm the key results of specific aims 1 and 2. The goal of these aims is to develop a more detailed understanding of the molecular basis for the effects of arsenic on steroid receptor signaling. This will be important for determining the contribution of these effects to the overall human health effects of arsenic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOMARKERS TO MOLECULAR INTERVENTIONS IN AFLATOXIN EXPOSED INDIVIDUALS Principal Investigator & Institution: Kensler, T W.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: Project II. Development and application of biomarkers to molecular interventions in aflatoxin-exposed individuals. A major goal of public health practice is disease prevention. Recent advances in our understanding of the fundamental mechanisms of carcinogenesis have provided opportunities to reduce human cancer incidence through molecular, chemopreventive interventions. However, use of cancer endpoints in the evaluation of new intervention strategies ensures slow and costly progress. The development of intermediate biomarkers is essential to the timely development and maturation of the field of chemoprevention. The continuing goal of these studies is to determine whether biomarkers of aflatoxicosis caused by consumption of aflatoxin-contaminated foods can be modulated by ingestion of oltipraz or chlorophyllin. Both oltipraz and chorophyllin are effective inhibitors of aflatoxininduced hepatocarcinogenesis in animal models, although their mechanisms of action appear to be distinct. It is our hypothesis that levels of biomarkers for the biologically effective dose of aflatoxin will be predictive for assessing the efficacy of chemopreventive interventions in aflatoxin-exposed individuals. Results in rats during the initial grant period suggest that measurements of the levels of aflatoxin-N7-guanine in urine and aflatoxin-albumin adducts in serum reflect aflatoxin-induced genotoxicity in target organs. Moreover, animals fed oltipraz exhibited marked reductions in the levels of these biomarkers in parallel with reductions in the levels of hepatic aflatoxinDNA adducts and liver cancer incidence. Molecular epidemiology studies have also firmly established these biomarkers as indices of aflatoxin exposure in humans and for subsequent risk of developing hepatocellular carcinoma. The proposed studies seek to

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continue the development and application of biomarkers to chemoprevention in populations at high risk for aflatoxin exposure and liver cancer. An additional biomarker of considerable promise is 8-hydroxy-2 prime- deoxyguanosine (8-OHdG). Several laboratories have shown recently that treatment of animals with aflatoxin B1 elevates levels of 8-OhdG in hepatic DNA. The proposed studies will evaluate whether measurement of 8-OHdG excretion in urine is a useful, modulatable endpoint for assessing chemopreventive efficacy. These studies will utilize urine samples collected from rats and humans that have recently undergone chemopreventive interventions with oltipraz. These studies will also be extended by conducting a clinical intervention with the anticarcinogen chlorophyllin in individuals from Qidong, Peopl~s Repubic of China, who are exposed to aflatoxins in their diets and are subsequently at high risk for development of liver cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANCER CONTROL IN A VIETNAMESE AMERICAN POPULATION Principal Investigator & Institution: Jackson, J C.; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 05-MAY-2000; Project End 30-APR-2004 Summary: (Adapted from the Applicant's Abstract): Little is known about the disease prevention behavior of Southeast Asian immigrants, and few studies have addressed cancer control in this disadvantaged population. However, it is known that two malignancies in particular, carcinoma of the cervix and hepatocellular carcinoma, occur more frequently among Vietnamese Americans than among individuals of an, other race/ethnicity. Almost all invasive cervical cancers could be prevented by Papanicolaou testing, and up to 80 percent of liver cancers could be prevented by hepatitis B vaccination. There is a clear need for programs that can successfully enhance the uptake of Papanicolaou testing among Vietnamese women; and increase the proportion of Vietnamese adults who have been tested for evidence of hepatitis B infection (and, therefore, have either been vaccinated, are screened for hepatocellular carcinoma, or know they are immune). Cancer control programs targeting less acculturated immigrant groups should be based on a thorough understanding of culturally based attitudes and practices. The study has three specific objectives: collect qualitative and quantitative data about the cervical and liver cancer prevention behavior of Vietnamese Americans; design a culturally and linguistically appropriate household cancer control intervention targeting cervical cancer, hepatitis B infection, and hepatocellular carcinoma among Vietnamese; and evaluate the intervention program's acceptability to the Vietnamese community as well as its feasibility in terms of program delivery. Community involvement will be emphasized. The PRECEDE framework and qualitative methods will be used to guide the development of a quantitative survey instrument. Qualitative and quantitative findings will both be used to develop the intervention components. All interventions will be delivered by bicultural Vietnamese outreach workers. A total of 60 Seattle households that under-use preventive care will receive the intervention program; these households will be identified from a population-based survey of 650 households. Intervention components will include home visits, barrier specific counseling, the use of videotapes and print materials, and logistic assistance. A comprehensive process evaluation of the intervention will be conducted. If the intervention program proves to be acceptable and feasible, the investigators will subsequently apply for funding to conduct a randomized controlled trial and evaluate the effectiveness of the program with respect to outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEFECTIVE INTERFERENCE OF HEPADNAVIRUS IN NATURE Principal Investigator & Institution: Shih, Chiaho; Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 23-DEC-1996; Project End 31-DEC-2004 Summary: Our long-term goal is to understand the pathobiology associated with viral hepatitis and liver cancer. Hepatitis B virus (HBV) is the 4th most common infectious agent in humans. Chronic infection with HBV is tightly associated with the development of liver cancer. Although both hot immune and viral factors are believed to contribute to the establishment of chronic infection, the mechanism of HBV chronic infection remains to be fully explored. Defective interfering (DI) particles have been found in many RNA and DNA viruses of bacteria, plants, and animals, and are known to be associated with persistent infection in tissue culture. However, the existence of DI particles has not yet been demonstrated in human natural infections since their first discovery in influenza virus by von Magnus (1947) in the laboratory setting. Using a new approach, we provided the first experimental evidence for the existence of DI-like viruses in human chronic HBV carriers. Functional characterization of these naturallyoccurring "core intentional deletion variants" (CID) of HBV reveals all of the characteristic features of DI particles. In this application, we propose to study the biological significance of CID variants in patients and woodchuck animal model. We will investigate the phenomenon of fluctuating titers of HBV CID variants in human patients. In addition, we propose to investigate if woodchuck hepatitis virus (WHV) core internal deletion variants, which we have found recently (manuscript submitted) also behave like DI particles in tissue culture. Finally, we will continue our studies of the mechanism of defective interference of HBV CID variants by both genetic and biochemical approaches. A "repressor-like model" versus a "preferential replication" model will be distinguished. Successful completion of this work will have important implications for chronic viral hepatitis which leads to the development of highly malignant liver cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DNA REPAIR AND CANCER PRONE HEREDITARY HUMAN DISEASE Principal Investigator & Institution: Friedberg, Errol C.; Professor and Chair; Pathology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 01-FEB-1987; Project End 31-JAN-2003 Summary: The long-term objectives of this proposal are to investigate the relationship of defective repair of DNA damage to cancer in humans. To this end mutational inactivation of various DNA repair genes in mice by targeted gene replacement is being used as an experimental strategy. A mouse strain has been generated which carries homozygous deletions in the nucleotide excision repair (NER) gene XPC. This strain is exceptionally prone to ultraviolet (UV) radiation-induced skin cancer. Experiments are in progress to determine predisposition to liver cancer associated with exposure to the liver carcinogen 2-acetylaminofluorene, the repair of which requires the process of NER in mammals. XPC-1- mice that are additionally heterozygously or homozygously defective in the p53 tumor suppresser gene exhibit an even greater predisposition of skin cancer. Studies are proposed to investigate the mechanism of this synergistic interaction, in particular whether abrogation of the G1->S checkpoint function or of the apoptotic function of the p53 gene (or both), mediates this effect. Dr. Friedberg will generate a mouse strain by targeted gene replacement that is homozygous defective in

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Liver Cancer

the HAP1 gene which encodes the major apurinic/apyrimidinic (AP) endonuclease required for the process of base excision repair (BER) in mice. Such a mutant mouse is expected to be defective in the repair of various types of spontaneous base damage in DNA, particularly that generated by oxidative metabolism. Crosses will be made between the XPC-1- (NER-defective) mouse, the HAP1-/- (BER-defective) mouse and mice defective in the mismatch repair defective mouse MSH2, in order to investigate the role of all three known excision repair pathways in both spontaneous and environmental carcinogen-induced cancer in mammals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY DETECTION OF LIVER CANCER AND HEPATITIS Principal Investigator & Institution: Block, Timothy M.; Professor and Director; Biochem & Molecular Pharmacol; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The goal of this proposal is to develop methods for the early detection of hepatocellular carcinoma (HCC) and hepatitis. The hypothesis that changes in the amount or modification of serum polypeptides correlate with the onset of HCC or hepatitis will be determined. Individuals chronically infected with hepatitis B or C virus (HBV, HCV) are at high risk for the development of HCC and hepatitis, with disease progression occurring after many years. Serum polypeptides from individuals at different stages in the disease continuum will be resolved by "Proteomic" 2-dimensional gel analysis. Our preliminary evidence and the work of others demonstrate that 2D gel technology has advanced to the point where expressed protein profiles of biological samples can be reproducibly resolved. Polypeptides that correlate (by their appearance, disappearance or post translational modification) with disease status will be identified. Correlating polypeptides will be characterized by a variety of methods available to us: data base reference, immunological methods or micro sequencing. Identification of biomarkers that help in the diagnosis and prediction of liver disease in this high-risk population will have enormous public health benefit, given the limitations on current methods. It will also provide insights about the mechanisms of progression of this disease family and offer a platform technology for the use of proteome diagnostics in other areas of cancer detection and liver decompensation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EARLY PHASE I AND II CANCER CLINICAL TRIALS Principal Investigator & Institution: Baez, Luis; University of Puerto Rico Med Sciences Medical Sciences Campus San Juan, Pr 00936 Timing: Fiscal Year 2001; Project Start 18-MAY-2001; Project End 30-APR-2004 Summary: Presently, several clinical Phase III clinical trials are ongoing at the University of Puerto Rico and affiliated Institutions for the treatment of our cancer patients. We are acutely aware of the need for an early clinical trial program at our Institution. The goal of this pilot project is to establish a program of early phase clinical trials at the University of Puerto Rico. To establish this program, we are starting a collaboration with Dr. Daniel Sullivan of the H. Lee Moffitt Cancer Center (HLMCC). This collaboration will emphasize the development of Phase I and Phase III clinical trials, targeting our Puerto Rican population. In addition, we propose to develop basic science infrastructure that will support investigator-initiated studies. Via this collaboration, the HLMCC, will have access to a unique population of patients that have a higher prevalence of specific

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malignancies in Puerto Rico, such as, esophageal, cervical, penile, anal, breast, and liver cancers. We propose to achieve these goals through the following three specific aims. In specific aim 1, we will evaluate the facilities of UPR and PRCC to conduct early Phase I and Phase II clinical trials. We will identify the availability of the infrastructure to perform pharmacokinetic, pharmacodynamic, and molecular analyses. In specific aim 2; we will delineate a plan to establish an early phase clinical trials program within the PRCC. Clinical and basic investigators from the UPR and HLMCC will join efforts in the development of specific clinical trials. Finally, in specific aim 3; we will initiate clinical trials that are based on basic research data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF HEPATOCELLULAR CARCINOMA Principal Investigator & Institution: Ko, Cynthia W.; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The goals of the proposed research project are: 1) to prepare and train the candidate for a career in academic gastroenterology by providing the necessary environment, education, and research support, and 2) to gain insight into the epidemiology of hepatocellular carcinoma in the United States. The candidate is a clinically trained gastroenterologist with additional training in basic epidemiology and biostatistics. As part of this proposal, she will be provided with more advanced training in both general and applied epidemiology and biostatistics. The candidate will be supported and mentored by Dr. John Potter. Her progress will be monitored by the sponsor and the Division of Gastroenterology. The Department of Medicine and Division of Gastroenterology will provide full commitment and support toward the development of the candidate's independent research career. The focus of the scientific portion of this proposal is on hepatocellular carcinoma, a common tumor worldwide the incidence of which is also rising in the United States. Much of this increase can be attributed to the current epidemic of hepatitis C. The epidemiology of hepatocellular carcinoma has not been extensively studied in this country, and few studies have recruited population-based cases and controls. Well-recognized environmental risk factors for hepatocellular carcinoma include chronic viral hepatitis, other chronic liver diseases, and exposure to aflatoxins. However, risk factors that predispose patients with chronic liver disease to hepatocellular carcinoma are not well defined. It is likely that genetic risk factors for hepatocellular carcinoma exist, since familial and ethnic clustering of the tumor are well documented, iron is a recognized co-factor for the development of malignancy in other sites. Hemochromatosis is an inherited disorder in which excess iron accumulates in the liver, heart, pancreas, and other organs. A gene for hemochromatosis, HFE, has recently been identified. Patients with hemochromatosis are at up to 200-fold increased risk of developing hepatocellular carcinoma. We hypothesize that HFE mutations are risk factors for HCC in patients either with or without underlying liver disease. Thus, the specific aims of tills proposal are: 1) to determine whether mutations in the HFE gene are a risk factor for hepatocellular carcinoma; and 2) to recruit a cohort of patients with chronic hepatitis C for prospective studies of the epidemiology of hepatocellular carcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF HEPATOCELLULAR HEPATITIS B VIRUS IN 3 POPULATIONS

CARCINOMA

&

Principal Investigator & Institution: London, W T.; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2002 Summary: (Applicant's Description) Prospective studies of 60,984 men in Haimen City, China and 19,469 men in Senegal, west Africa revealed a 14-fold greater death rate from hepatocellular carcinoma (HCC) among the Haimen (168 per 100,000) than the Senegalese cohort (12 per 100,000). Even though chronic infection with hepatitis B virus (HBV) is the major risk factor for HCC in both populations, the age-adjusted prevalence of chronic infection is about 20% in both cohorts. Exposure to aflatoxin, a postulated major risk factor for HCC, is also similar or greater in the Senegalese population. The prevalence of viremia (HBV DNA in serum) among HBV carriers throughout adult life, however, is much higher among the Chinese than the Senegalese population. Nevertheless, within the Chinese cohort, viremia at study entry is not a risk factor for HCC after four years of follow-up. The aims of this project focus on factors that may account for variation in HCC risk in the Chinese and Senegalese cohorts and a cohort of Asian-American HBV carriers living in the Philadelphia area. Continued tracking of these three cohorts will test the hypothesis that with longer duration of follow-up, H B V v iremia and liver damage at study entry are associated with person-specific risks of HCC and that aflatoxin-B1 (AFB1)-albumin adducts are a s s ociated with development of HCC among viremic individuals and/or genotypically determined poor detoxifiers of AFB1 (in collaboration with Project 2). In close cooperation with the studies of WHV in woodchucks (Project 3), an intensive longitudinal study of 1000 male and female HBV carriers in these three populations will be conducted to: a) examine whether perturbations of the stability of HBV serum markers are associated with acute illnesses, aflatoxin exposure, and/or outgrowth of viral mutants; b) assay hepatocyte turnover and immune responses in liver biopsies; c) correlate these measures with viral load; d) examine the relationship of sex differences in changes in HBV serum markers over time to the lower HCC risk of female HBV carriers. Because present studies show that an episode of acute hepatitis in adulthood approximately doubles HCC risk among both HBV carriers and non-carriers, the causes and outcomes of 200 cases of acute hepatitis in Haimen City will be characterized. This research will lead to a new level of understanding of the factors that lead to HCC and to new strategies for the prevention of this lethal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPRESSION & ROLE OF TA1 ONCOFETAL GENE--LIVER CANCER Principal Investigator & Institution: Thompson, Nancy L.; Associate Professor (Research); Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-JAN-2004 Summary: (adapted from the investigator's abstract) TA1 was cloned as a cDNA with high level expression in rat hepatoma cell lines and fetal liver but not in normal adult liver. It's coding region is highly conserved, encoding a predicted 241 amino acid hydrophobic peptide with 6 or 7 transmembrane domains that is 94 percent identical to the human lymphocyte immediate early gene E16. Although homologs have recently been cloned in Xenopus, Schistosoma and C. elegans, its specific function remains unknown. TA1/E16 bears significant homology with yeast amino acid permeases and mammalian cationic amino acid transporters, strongly suggesting such a function. We

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have reported evaluated E16 expression in a variety of primary human cancer specimens relative to normal tissue, suggesting that upregulation of E16/TA1 expression is a common event in tumorigenesis. We have further demonstrated transient expression in acute rat liver injury and induced expression in normal hepatocytes in vitro following arginine depletion, findings consistent with the exploitation by tumor cells of a normal function in amino acid transport. The focus of this proposal is to examine the regulation and function of TA1/E16 in hepatic cells and its role in carcinogenesis. The hypothesis we propose to test is that while expression of TA1/E16 is tightly regulated in normal hepatic cells, consistutive high level expression contributes to the malignant phenotype, most likely by conferring a growth and/or survival advantage related to amino acid transport activity. In this proposal, we will use rat and human models in which to examine TA1 expression during hepatocarcinogenesis in vivo and compare its regulation in transformed and nontransformed hepatic cells in vitro. We will also determine the consequences of constitutive TA1 overexpression and blocked expression in heptatic cells on phenotype and the functional association of TA1 with CD98hc/4F2, a cell surface molecule implicated in integrin activation and amino acid transport. These studies will provide mechanistic insight into TA1 function and its role in liver carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENOTOXICITY OF ESTROGEN-AND ANTI-ESTROGEN-DNA ADDUCTS Principal Investigator & Institution: Shibutani, Shinya; Pharmacological Sciences; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 13-MAY-1998; Project End 31-JUL-2007 Summary: (provided by applicant): Tamoxifen, an antiestrogen used in the endocrine therapy and chemoprevention of breast cancer, induces liver cancer in rodents and is associated with endometrial cancer in women. Estrogens also are implicated in the etiology of endometrial and breast cancer. The carcinogenicity of these agents may be mediated through their genotoxic effects. The goals of this research are to establish a mechanism for the genotoxicities of tamoxifen and estrogen and to find a safer alternative to tamoxifen. Oligodeoxynucleotides containing a single defined DNA adduct will be prepared by automated DNA synthesis. Using these site-specifically modified oligodeoxynucleotides, the mutagenic and repair potential of estrogen and anti-estrogen DNA adducts in mammalian cells will be determined. The three dimensional structure of tamoxifen- and estrogen adducts in DNA duplex also will be established, permitting us to understand the process of mutagenic and repair events which occur at lesion sites. Such modified oligodeoxynucleotides also will be employed as standards in ultrasensitive 32P-postlabeling and HPLC/electrochemical detector analyses designed to quantify DNA adducts and oxidatively damaged lesions in the tissues of rodents and monkeys treated with these drugs. Taken together, this information can be used to predict genotoxicity. Translational studies have been designed to detect adducts in the endometrial DNA of patients undergoing treatment with tamoxifen or toremifene. These experiments will provide biomarkers for molecular epidemiological studies and explore the relationship between tamoxifen therapy and the development of endometrial cancer in women treated with this drug. This research should lead to a safer alternative for women undergoing breast cancer therapy and for chemoprevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLYPICAN-3: A NOVEL MARKER FOR HEPATOCELLULAR CARCINOMA Principal Investigator & Institution: Filmus, Jorge E.; Sunnybrook & Women's Coll Hlth Scis Ctr Health Sciences Centre Toronto, Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Human hepatocellular carcinoma (HCC) is usually asymptomatic at early stages. As a result, HCC is generally at an advanced stage when discovered, and the therapeutic options very limited. HCC is associated with chronic liver injury, primarily chronic viral hepatitis and alcoholic liver disease. The risk of developing HCC is 50 - 100 fold greater in individuals with chronic hepatitis B virus infection than in non-infected individuals, and the incidence of HCC in cirrhotic carriers of hepatitis C virus (HCV) may be as high as 5% per year. In principle, therefore, screening protocols are justified for chronic HBV carriers and cirrhotic HCV patients. The only molecular marker that has been widely used for the diagnosis and detection of HCC is alfafetoprotein (AFP). However, AFP expression is significantly increased in a considerable number of patients with non-malignant chronic liver diseases. Thus, more specific markers for HCC are required. Results recently obtained in this laboratory have shown that a protein called glypican-3 (GPC3) can be detected in most HCC tissue sections but it is undetectable in normal liver or benign liver disease. In addition, examination of a limited number of patients has shown that whereas GPC3 is undetectable in the serum of healthy individuals, its levels are significantly elevated in a large proportion of HCC patients. These results suggest, therefore, that GPC3 could be a better marker than AFP for the diagnosis and detection of HCC. The main goal of this study is to test this hypothesis. To this end, serum GPC3 and AFP will be measured in a cohort of 100 patients with HCC, and in patients with benign liver disease. The specificity and sensitivity of both markers will then be compared. GPC3 levels will also be assessed in 50 additional tissue sections from HCC patients, and a similar number of sections from various benign liver diseases. Another objective of this project is to investigate whether GPC3 could be used as a marker of tumor burden in experimental cancer. If this is the case this study will provide a tool that will simplify the search of novel treatments for HCC, and may open the possibility of using GPC3 measurement for the follow-up of HCC patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HCV INFECTION--RISK FACTORS FOR PROGRESSION Principal Investigator & Institution: Stuver, Sherri O.; Assistant Professor; Epidemiology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): For individuals who are infected with hepatitis C virus (HCV), knowledge of co-factors affecting the occurrence of liver disease is crucial. However, the mechanisms of HCV-associated pathogenesis, particularly with regard to the role of the virus and the host immune response, remain unclear. The primary goal of the proposal is to elucidate the natural history of HCV infection with respect to progression to hepatocellular carcinoma (HCC) and other health outcomes in a Japanese community-based population in which infection with HCV is highly endemic. As part of an annual ultrasonographic tomography screening program in this population, nearly 1,000 adult residents with HCV have been under surveillance for liver cancer since 1994. The proposed study will extend the observation of this cohort,

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with the additional collection and analysis of virologic, epidemiologic, and clinical data. The specific aims of the research are: to determine the predictive value of markers of HCV infection in the development of liver damage and HCC; to estimate the effect of host-related factors, including heavy alcohol consumption, cigarette smoking, and diet, on HCV-induced liver disease progression and hepatocarcinogenesis; to examine the role of co-infection with hepatitis B virus and human T-lymphotropic virus type I in the natural history of HCV; to characterize the function of host immune status and response in the persistence of HCV infection as well as in the progression of liver disease and HCC among HCV carriers; to evaluate the utility of serologic markers of liver damage in predicting the development of HCC in individuals infected with HCV; to identify predictors of extrahepatic morbidity and mortality among HCV carriers. The uniqueness of the study population and the richness of the data parameters combined with the extensive experience of the assembled multi-disciplinary team provide an important opportunity to increase our understanding of the natural history of HCV and to contribute to our ability to identify and potentially treat those carriers who are at increased risk of an adverse outcome related to their HCV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPADNAVIRAL GENOME REPLICATION AND TEMPLATE SWITCHING Principal Investigator & Institution: Loeb, Daniel D.; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 29-MAY-2003; Project End 30-APR-2008 Summary: Hepatitis B virus (HBV) is the most prevalent human tumor virus. It is estimated that chronic HBV infection causes 1,000,000 cases of liver cancer annually. HBV must actively replicate within liver cells to maintain its chronic infection. We work to understand how HBV carries out the individual steps by which it replicates its genome in order to understand how this virus contributes to human cancer. To date, most insights into hepadnavirus DNA replication have come through the study of the avian hepadnavirus, duck hepatitis B virus (DHBV). Over the past decade, our laboratory has made multiple contributions to the understanding of hepadnavirus DNA replication by studying DHBV. During this last funding period our most significant progress was made in elucidating the mechanism of the templates switches during the synthesis of plus-strand DNA of DHBV. These analyses have elucidated two fundamental mechanisms that contribute to the template switching during avian hepadnavirus plus-strand synthesis: (1) a local DNA secondary structure that suppresses in situ priming, and therefore contributes to primer translocation; and (2) a long-distance DNA secondary structure that juxtaposes the donor and acceptor templates for primer translocation and circularization. We propose to develop a mechanistic understanding of HBV DNA replication that builds on and exceeds our current understanding of DHBV DNA replication. This project has three aims: (I) To characterize the process of minus-strand synthesis with an emphasis on the mechanism of the template switch after the synthesis of the fourth nucleotide of minus-strand DNA; (II)To characterize the mechanisms that are important for the crucial events during plusstrand DNA synthesis. These events include the specificity of primer generation and the initiation of plus-strand DNA synthesis, the regulation of in situ priming, and the mechanisms of the two plus-strand template exchanges, primer translocation and circularization; and (III)To determine the mechanisms by which cccDNA amplification is regulated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPADNAVIRUS ASSOCIATED HEPATOCELLULAR CARCINOMA Principal Investigator & Institution: Rogler, Charles E.; Professor; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 01-APR-1984; Project End 30-APR-2006 Summary: (Adapted from the Investigator's abstract): Infection of humans with hepatitis B viruses cause acute and persistent infections of worldwide significance. Persistent infections, in particular, are associated with a very high risk of hepatocellular carcinoma (HCC). HCCs arise in HBV carriers after long periods of immunologically driven liver disease that is characterized by periods of inflammation, regeneration, cirrhosis and finally HCC. One of the hallmarks of HCCs arising in I-IBV carriers is the presence of clonally amplified viral DNA integrations. Our laboratory has carried out studies to understand the mechanisms by which viral DNA integrations may act as mutagenic agents during hepatocarcinogenesis. Our approach has been to study the natural history and frequency of integrations in clonal populations of cells. These studies have implicated a minor form of hepadnavirus DNA, specifically, double strand linear (DSL) viral DNA molecules as the precursors for integration and have also shown that DSL DNAs integrate at a higher frequency than wild type DNAs. Furthermmore, we have shown that integrations can be lost from the cells along with cellular DNA in a "hit and run" mutagenesis mechanism. In the current proposal we will utilize a new assay system that can detect single integrations to study integration frequencies of DSL versus WT viral DNA and follow the dynamic flux of integrations in cell culture. We will pursue integration studies during infection of primary hepatocytes under conditions that cause DNA damage and we will also utilize mutational analysis to test the hypothesis that topoisomerase I (top 1) acts as a regulator of viral replication and integration. These studies will increase our understanding of the genetic and physiologic controls of integration and their mutagenic impact on the host cell. Finally, in a new area of research, we will utilize cDNA microarrays to investigate the effects of the HBV X regualtory protein on the transcriptome of murine liver stem cells in both the liver progenitor and hepatocytic differentiation states. These studies will begin to help us understand the impact ofHBx on transcriptional regulation from a global perspective. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPADNAVIRUS INFECTIONS AND LIVER CANCER Principal Investigator & Institution: Mason, William S.; Senior Member; Institute for Cancer Research Philadelphia, Pa 19111 Timing: Fiscal Year 2001; Project Start 01-SEP-1982; Project End 31-MAR-2005 Summary: Certain key aspects of hepadnavirus biology, including the mechanisms controlling resolution of an infection, and infection progressing to neoplastic transformation, have not yet been elucidated. For example, (i) we don't understand how transient infections can resolve rapidly even after infection of the entire hepatocyte population, or what may initiate the resolution of chronic infections after years or even decades of virus production. (ii) We do not yet know2 the process ov virus quasi-species evolution during chronic infections and its relationship to disease outcome, or the outcome of antiviral therapy. (iii) The cellular changes leading to hepatocellular carcinoma during a hepadnavirus infection have not yet been described. (iv) We still don't know the in vivo role of the X gene product, which is required for infection, but not for virus production by transfected cell lines. Without this knowledge, the possibilities for treating and even curing chronic infections is limited. However, recent technical advances, and refinements of older procedures, now make it feasible to begin

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to address these problems in greater detail. The specific aims of our research are therefore to use woodchuck hepatitis virus. 1) To determine the mechanisms of virus loss during recovery from a transient infection. Experiments will be carried out to determine the kinetics and cumulative loss of hepatocytes during recovery from a transient infection, and possible mechanisms by which this may occur. 2) To determine how viruses evolve during the course of a chronic infection. In the interim, mechanisms underlying more conventional antiviral approaches are being analyzed. The proposed experiments focus on the mechanism of virus evolution with a clear practical significance, the outgrowth of drug resistant populations during therapy with antiviral nucleosides. 3) To characterize pre-neoplastic lesions. A long-term goal of antiviral therapy is to reverse neoplastic transformation leading to HCC. Studies will therefore be undertaken to identify molecular markers and/or determinants of this progression, as a basis for evaluation neoplastic disease progression in chronic hepatitis. 4) To determine the role of the X gene product in initiation/maintenance of an infection in cell culture and in the woodchuck liver. There is an absolute requirement for the X gene product of viral reproduction in vivo, making it an ideal therapeutic target. Experiments are described to determine where in the virus life cycle X is required. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEFINITION

HEPATIC

CANCER

THERAPY

MONITORING

&

ORGAN

Principal Investigator & Institution: Meyer, Charles R.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The goal of this application is to apply software tools developed under previous funding to aid in the solution of significant clinical problems in liver cancer and radiation therapy treatment planning. Specifically, we propose to provide computed decision support for liver cancer therapy treatment by enhancing the ability to detect and quantify small intensity and morphological changes in serial follow-up exams, referred to as interval exams. The utility of the ability to register the 3D data set obtained from a current exam with the 3D data set from an earlier exam, and then subtract the coregistered data sets to enhance differences has already been demonstrated for interval brain examinations[7-11]. Because the liver is a soft, malleable organ, the ability to rountinely apply such a process to liver cancer requires the use of automatic nonlinear registration techniques, i.e. warping. Because the conformation of the liver is severely dependent on patient position on the imaging exam table and degree of inspiration during breath holding, simple linear registration methods fail. We hypothesize that the method will be capable of detecting important early changes that would typically be unnoticed by experienced radiologists/oncologists. Such changes include regrowth of previously treated lesions, or the appearance of new metastatic lesions. Such techniques are useful for the spectrum of lesions encountered including single or multifocal lesions, as well as diffuse lesions. Phantom studies will be performed to help quantify differences and variances for the technique and readers. Studies on clinical data will assess the performance of the technique using real patient data. We additionally propose to develop a robust method of accurately outlining organs in patient data sets to assist organ definition for radiation therapy treatment planning requiring dose-volume histograms to objectively quantify and optimize the plan. Currently manual outlining of normal organs is the rate limiting process associated with patient throughput in many institutions. Such definition would

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not only speed patient throughput, but also make the quantitative planning technique more widely accessible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPATITIS VIRUS, ALCOHOL EXPOSURE AND OXIDATIVE STRESS Principal Investigator & Institution: Hassan, Manal M.; Gastrointestinal Med Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) Hepatitis C virus (HCV) infection and alcohol abuse are the 2 major risk factors for hepatocellular carcinoma (HCC) in this country. The higher prevalence of HCV infection in the general population has resulted in a significant increase of the incidence of HCC in the United States. Although both HCV and alcohol can independently induce liver disease, exposure to both agents may accelerate the course of liver pathology and/or lead to more severe injury. The mechanism underlying the synergistic effect of HCV and alcohol intake is not well understood. One hypothesis is that both HCV and alcohol intake may contribute to chronic hepatitis, cirrhosis and subsequent liver cancer through enhanced oxidative stress. It is known that alcohol could induce oxidative stress and lipid peroxidation. Interestingly, a recent study has reported that HCV encodes a selenium (Se)-dependent antioxidant enzyme, glutathione peroxidase, GPx, and GPx may have a regulatory role in HCV replication. The virus-induced overexpression of GPx may lead to a decreased level of Se in the host due to the competition of HCV for Se. In fact, patients with HCV have been shown to have a significant decline in their serum Se. On the other hand, the hepatotoxicity of ethanol and its associated malnutrition will further reduce the cellular Se level. This additive decline in the Se level will make the cell more susceptible to reactive oxygen species (ROS). Previous studies have shown an association between oxidative DNA damage and either alcohol exposure or chronic viral infection. It seems that chronic HCV infection may lead to an increased ROS, overexpression of GPx and reduced serum level of Se. When the Se-GPx level is low, the virus will be more provoked for replication, leading to a higher viral load in the infected cell. Eighty newlydiagnosed HCC patients will be recruited from University of Texas MD Anderson Cancer Center (UTMDACC). The current project will explore the effect of dietary selenium intake and its interaction with HCV and alcohol intake in HCC in a casecontrol study. Eighty healthy individuals (first control group), matched with cases by age, sex and ethnicity, will be recruited from the patients non-blood relatives and friends from UTMDACC. To have a control group with comparable prevalence of HCV infection, 80 patients with liver cirrhosis, who have no evidence of HCC (second control group), will be recruited from Baylor College of Medicine. Information on alcohol intake, dietary Se intake and other risk factors will be collected by a questionnaire. The frequency and profile of hepatitis B virus (HBV) and HCV infection will be determined by measuring serum HBsAg, anti-HBC, anti-HCV, and HCV-RNA. Oxidative stress will be evaluated by measuring the levels of serum Se, GPx activity, lipid peroxides, and 8hydroxy-deoxyguanosine (8-OH-dG), a marker of oxidative DNA damage. The expression of GPx and the level of 8-OH-dG will also be measured in tissue samples from cirrhotic and HCC patients. Serum Se, GPx activity, lipid peroxides and oxidative DNA damage will be measured in relation to HCV and alcohol intake history. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERSTITIAL DRUG DELIVERY TO THERMOABLATED LIVER TUMORS Principal Investigator & Institution: Gao, Jinming; Biomedical Engineering; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 09-MAY-2002; Project End 30-APR-2006 Description (provided by applicant): This research effort is a long-term commitment to develop intratumoral drug delivery as a local chemotherapy to supplement twnor thermoablation for the treatment of liver cancers. In this treatment, image-guided thermoablation first destroys the majority of the tumor tissue by heat. The drug delivery device, in the shape of a cylindrical millirod, is then implanted into the thermoablated tumors to kill any cancer cells remaining after thermoablation. The objective of the proposed application is to develop and evaluate drug delivery systems that can modulate the release of doxorubicin, an anticancer drug, for intratumoral drug delivery to thermoablated tumor tissues. The central hypothesis is that polymer millirods with dual release kinetics-an initial burst release followed by a sustained release of drugs-can provide the maximal therapeutic effect to supplement thermoablation in the treatment of liver tumors. To test this central hypothesis, we will carry out the following four specific aims: (1) rational design of polymer millirods with dual release kinetics by mathematical models; (2) development and characterization of polymer millirods with dual release kinetics; (3) pharmacokinetic analysis of implanted polymer millirods in rabbit VX-2 liver tumors; (4) validation of drug efficacy by monitoring of tumor size and histology analysis. Successful execution of the proposed application will establish a solid pharmacological basis and bioengineering foundation for the development of drug delivery systems for intratumoral drug delivery. In combination with image-guided thermoablation, this therapeutic procedure should provide an innovative, minimally invasive and less toxic therapy for the treatment of liver tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIGAND-DIRECTED DELIVERY OF ANTI-CANCER DRUGS Principal Investigator & Institution: Rheinstein, Peter H.; Cell Works, Inc. Holabird Business Park Baltimore, Md 21224 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: (Applicant's Description) The development of a ligand-directed, liverspecific, 5-flurouracil containing neoglycoconjugate is proposed for the treatment of hepatocellular carcinoma. This neoglycoconjugate is comprised of the liver-specific ligand YEE(ahGalNac)3 covalently linked to a 5FU pro-drug via a small molecular weight linker. The resultant construct is homogeneous, defined, chemically biodegradable and capable of specifically delivering it's drug payload via receptormediated endocytosis. Preliminary studies have shown that the neoglycoconjugate is taken up specifically and at an enhanced rate by hepatocytes resulting in increased bioeffectiveness. In vivo biodistribution experiments revealed the neoglycoconjugate is delivered rapidly and specifically to the liver of mice. The object of the proposed studies is to demonstrate the feasibility of the liver specific neogycoconjugate as an effective chemotherapeutic treatment. To accomplish this end, initially a range of concentrations will be determined by intravenous injection into mice. Subsequently, tumor pharmacokinetics, and bioeffectiveness will be determined by intravenous injection into immunodeficient mice bearing HCC xenografts. These studies are designed to satisfy FDA regulations concerning non-clinical testing of therapeutic drugs. Phase I will be extended to consider the commercial scale production of the neoglycoconjugate and

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toxicity testing in larger animals in Phase II. These studies will subsequently be extended to Phase I clinical trials. PROPOSED COMMERCIAL APPLICATION: Hepatocellular carcinoma (HCC) is untreatable. Infections with hepatitis virus and cirrhosis are major risk factors for liver cancer. HCC is a major health problem worldwide with 0.5-1 million deaths per year. In 1998, 13,900 deaths in the U.S. were related to liver cancer and in other areas, such as China and Southeast Asia, as many as 50% of all cancers are attributed to liver cancer. Potentially any drug may be inserted within the liverspecific ligand-linker-prodrug construct. A virtually untapped market is available for new drug treatment regimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIVER CANCER CONTROL AMONG NORTH AMERICAN CHINESE Principal Investigator & Institution: Taylor, Victoria C.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Little is known about the disease prevention behavior of Chinese in North America, and few studies have addressed cancer control in this group. However, Chinese American men and women are four times more likely to be diagnosed with liver cancer than their non-Latino White counterparts. This excess risk is attributable to high rates of hepatitis B virus (HBV) infection combined with low levels of hepatitis B vaccination coverage. The goal of this research is to increase the proportion of less acculturated Chinese adults who have been tested for HBV (and, therefore, either have been vaccinated, are screened for liver cancer, or know they are immune to the disease). Objectives are to: obtain qualitative and quantitative information about the liver cancer prevention behavior of Chinese Americans and Canadians; develop a culturally and linguistically appropriate outreach intervention targeting hepatitis B and liver cancer among Chinese; and conduct a randomized controlled trial to evaluate the effectiveness, feasibility, and acceptability of the intervention program. To increase the generalizability of our findings, the research will be conducted in two cities: Seattle, Washington and Vancouver, British Columbia. The project will emphasize community involvement. PRECEDE and qualitative methods (i.e., forty in-depth interviews and eight focus groups) will be used to develop a quantitative survey instrument as well as intervention components. Six hundred Chinese men and women aged 18-64 who have not been serologically tested for HBV will be identified from a community-based survey of 1,200 individuals, and randomized to intervention or control status. Individuals in the experimental group will receive an outreach worker intervention (which will include a home visit and follow-up telephone call, tailored counseling and logistic assistance, and the use of audiovisual and print materials). Outcome evaluation will be based on data from a follow-up survey as well as medical record verification. If effective, our outreach intervention could be used by health care facilities and community organizations serving less acculturated Chinese in North America. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIVER CENTER Principal Investigator & Institution: Bissell, Dwight M.; Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 01-JUL-1985; Project End 31-MAY-2007

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Summary: (provided by applicant) The Liver Center of the University of California, San Francisco is an inter-disciplinary consortium of basic and clinical scientists dedicated to understanding the biology and pathobiology of the liver and the treatment of liver diseases. From its inception in 1975, it has undergone continual evolution to meet current scientific challenges, with its Executive Committee monitoring research progress and creating initiatives to open up new areas. The main lines of Center research at present are represented by five inter-related themes: (1) Immunology; (2) Metabolism, Injury and Repair; (3) Genetics and Development; (4) Liver Cancer; and (5) Viral hepatitis. Three themes-Immunology, Genetics and Development, and Liver Cancerhave emerged during the current funding period through recruitment of new members and alliances with organized research units. A major initiative over the past two years has involved the UCSF Cancer Center and resulted in preparation of an application for an NCI SPORE in liver cancer. The Center supports four core facilities: (1) Cell and Tissue Biology; (2) Clinical and Translational Research; (3) Microscopy and Advanced Imaging; (4) Molecular Analysis. The four scientific Cores not only provide direct research support but are a venue for new collaborations and an entry point for new members. Finally, the Center fosters scientific exchange through a Visiting Scientist Program, a Seminar Series, and its Annual Scientific Retreat. In the 2000-01 academic year, these programs brought five leading researchers in basic biology or translational science whose work has particular relevance to the research themes of the Center. The Center continues to expand its support of member science through strategic partnerships, most recently with the Veterans Administration, the UCSF Cancer Center, and the graduate program in Biomedical Sciences. In addition to these affiliations, the Center enjoys close links with the UCSF programs in Immunology and Developmental Biology, respectively. Its funding base continues to grow, and support from the institution is sustained and strong. The opportunities in basic biology and in the application of basic science to clinical liver disease have never been greater, and the Center is poised to catalyze discovery in these areas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIVER REGENERATION IN MAN--EFFECTS OR ADJUVANT THERAPY Principal Investigator & Institution: Fong, Yuman; Associate Professor; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-JUL-1997; Project End 31-JAN-2006 Summary: (provided by applicant): Cancers involving the liver are responsible for over one million deaths a year. At present, liver resection represents the only potentially curative treatment. However, in the majority of patients, tumor recurs, because microscopic disease remain undetected at the time of liver resection. This R01 is one of four submissions in an Interactive Research Project Grants. Using shared resources, including animal models, central isotope facility, Positron Emission Tomography (PET) facility, Magnetic Resonance (MR) facility, and patients, these grants seek to improve survival of patients with liver cancer. The current submission examines the cellular alterations underlying liver regeneration and the resultant biological determinants for the optional timing of adjuvant therapy after resection of tumors. In experimental models, the liver regenerative process stimulates growth of residual tumor. Adjuvant chemotherapy or oncolytic viral therapy strives to eradicate microscopic residual tumor. Theoretically, early adjuvant therapy is desirable. However, clinicians are reluctant to institute adjuvant therapy within four weeks after liver resection for fear that such therapy may detrimentally alter liver regeneration. In the previous grant study period,

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we showed that characteristic changes in cellular phospholipids and high energy phosphates can be detected by MR spectroscopy in animals and be used as a surrogate marker for liver recovery in planning of safe adjuvant therapy. We further demonstrated that such characteristic MR spectroscopic changes can be detected in man. Non-invasive measure of DNA synthesis by 124I-IUDR PET scanning was also validated in animals and used to predict safe administration not only of chemotherapy but also of 125I-IUDR as anti-tumor therapy. Two new advances that are reaching clinical testing and utilization are 1) pre-operative unilateral portal vein embolization as a means of producing contralateral liver hypertrophy to extend the possibilities of resective therapy, and 2) oncolytic viral therapies that also exploit cell proliferation for tumor targeting. In the current proposal, we seek to extend our MR spectroscopy observations to study of liver and tumor metabolism after portal vein embolization in order to characterize hepatocyte alterations during regeneration without the confounding issues of major surgery, but more importantly to determine if tumor proliferation is enhanced in man during regeneration. We also seek to determine if MR or PET can be used to determine tumor sensitivity and liver toxicity in response to viral oncolytic therapy. Finally, the use of 124I-IUDR PET validated in animals as a non-invasive measure of DNA synthesis in the previous grant period will be extended to a human trial. Thus, the specific goals of this application are to determine the comparative cellular proliferative rates of hepatocyte versus residual tumor after liver resection, to determine if these changes in proliferative rates can be determined non-invasively in vivo, with the hope that an adjuvant strategy exploiting the differential changes in tumor and hepatocyte proliferation may provide the basis for future therapy in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BIOMARKERS FOR HUMAN LIVER CANCER Principal Investigator & Institution: Groopman, John D.; Associate Director of Cancer Prevention; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: Molecular Biomarkers for Human Liver Cancer Hepatocellular carcinoma is one of the most common cancers in parts of China and sub-Saharan Africa and the poor prognosis of this tumor results in it being one of the three leading causes of cancer deaths world-wide with at least 250,000 deaths per year. Human epidemiology and experimental data have provided the statistical association and biological information necessary to implicate aflatoxins and chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) as major risk factors for this cancer in these high-risk areas. The degree that aflatoxins and HBV/HCV contribute to the causation of this disease may be affected by a number of factors including; the level of carcinogen exposure, intrinsic cytochrome P-450 and glutathione-S-transferase activation/detoxification pathways for aflatoxins, and the nutritional status of the person. Primary prevention measures by vaccination against HBV and food safety techniques to lower aflatoxin exposure could significantly lower liver cancer rates. HBV vacccination should be an effective contributor to prevention if people can be inoculated prior to infection, which generaly occurs before age two in Asia and Africa. Unfortunately, a vaccine has yet to be developed for HCV. For aflatoxins a similar targeted intervention could be envisaged, but for this to be effective requires determination of the relative roles and mechanisms of action of aflatoxin and HBV/HCV in the etiopathogenesis of liver cancer. Our hypothesis is that levels of formation and persistence of aflatoxin biomarkers reflect intrinsic risk of disease development from aflatoxin exposures. Briefly, the aims of this project are: a) To define the precise temporal relationships between dietary exposure to

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afltoxins and the formation and persistence of its serum albumin adducts and the kinetics of formation and removal of urinary metabolites of aflatoxin exposures including the DNA adducts and oxidative metabolites such as aflatoxin M1, Q1, P1 and the mercapturic acids as modulated by HBV and/or HCV infection, nutriture and metabolic polymorphism status. The relation between exposure and marker levels will be examined in two populations at high risk for liver cancer in West Africa and Qidong County, P.R.C. b) To determine the impact of primary prevention strategies in Guinea (West Africa) using a targeted contamination reduction strategy in community settings towards the reduction of aflatoxin biomarkers levels, and c) To continue to follow- up a prospective cohort in rural China to examine the relation and interaction between aflatoxin biomarker levels, intrinsic risk factors and disease outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BIOMARKERS OF EXPOSURE AND SUSCEPTIBILITY IN HUMAN COLON CANCER Principal Investigator & Institution: Strickland, Paul T.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: A major route of exposure to environmental carcinogens is through the diet. Epidemiological studies indicate the 20 to 50 percent of all human cancers can be attributed to dietary causes. The frequent consumption of animal fat, red meats, or grilled/smoked meats has been associated with increased risk for cancers of the gastrointestinal tract and pancreas. In contrast to the strong association between aflatoxin and liver cancer described in other projects in this program, the specific etiologic agents responsible for causing many diet- associated human cancers have yet to be determined. Two classes of chemical carcinogens, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (Has), have been indentified in grilled or fried meats. These chemicals produce a variety of cancers, including colon, stomach, breast, and liver cancers, in experimental animal models. The overall goals of this project are to investigate the role of these dietary carcinogens in colon carcinogenesis in humans, and to identify susceptibility factors (effect modifiers) that modulate the metabolism of these carcinogens and, ultimately, colon polyp/cancer risk. Our work hypothesis is that ingestion of dietary carcinogens formed in meat during cooking is a causative factor in the formation of colon polys, preneoplastic lesions that occur early in the process of human colon cancer development. This project (Aim 1 and 2) will examine inter- individual differences in urinary HA and PAH metabolite profiles in subjects ingesting fried or broiled meat during controlled feeding studies. Relevant metabolic phenotypes and potential confounders will be assessed to investigate their role in intra-and inter-individual differences. These studies should provide insight into the biological basis for inter-individual variation in response to ingestion of carcinogens found in cooked meats. This project ( Aim 3 and 4) will also evaluate the association of these biomarkers of exposure and metabolism with risk of colon polyp development in a case-control and a case-case study. The identification of critical metabolic and dietary determinants of colon polyp risk should lead to new approaches for prevention of colon polyps and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR DITHIOLETHIONES

MECHANISMS

OF

CHEMOPREVENTION--

Principal Investigator & Institution: Kensler, Thomas W.; Professor; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-SEP-1985; Project End 31-JAN-2004 Summary: Cancer prevention involving reduction or elimination of human exposure to environmental carcinogens may not always be possible. Inhibition of the development of cancer by the administration of anticarcinogenic age may offer a practical alternative for reducing human cancer burden. However, the successful utilization of chemopreventive interventions will require solid mechanistic understanding of the action(s) of these agents. The proposed studies will continue to investigate the modes of protection afforded by oltipraz and other 1,2-dithiole-3-thiones on aflatoxin (AFB1) hepatocarcinogenesis in the rat. Oltipraz is an effective and potent inhibitor of experimental carcinogenesis induced by many agents in many tissues. Oltipraz is currently being evaluated in Phase I and II clinical chemoprevention trials. This project will continue the development and evaluation of dithiolethiones more active than oltipraz on a) inhibition of AFB1-induced tumorigenesis in rats; b) altered AFB- DNA adduct formation; and c) induction of carcinogen detoxication ("phase 2") enzymes. Using a large series of analogs synthesized previously, the structure-activity relationships for inhibition of cytochrome P450 activation of AFB1 metabolism will also be determined. Using molecular genetic approaches, the identification and characterization of genes induced by dithiolethiones in rat liver will be continued together with elucidation of the role(s) of these gene products in protection against aflatoxin toxicity and carcinogenicity. Several novel inducible genes recently identified may protect against inflammation and oxidative stress. Finally, the chemopreventive actions and efficacy of oltipraz will be evaluated in a unique experimental model, the tree shrew, in which infection with human hepatitis B virus and exposure to AFB1 synergistically enhance the incidence of liver cancer, as occurs in humans. Collectively, these multifaceted, integrated studies will more fully define the chemical, molecular, biochemical and biological mechanisms of action of this versatile class of chemoprotective agents. The long-term goal of this project is to facilitate the most efficient and effective use dithiolethiones as protective agents in human populations exposed to environmental toxicants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUTATIONS IN HUMAN P53 SEQUENCES OF A P53 KNOCK-IN MOUSE Principal Investigator & Institution: Hollstein, Monica C.; German Cancer Research Center Im Neuenheimer Feld 280 Heidelberg, Timing: Fiscal Year 2001; Project Start 15-JUL-1999; Project End 30-JUN-2002 Summary: The long-term objectives of this proposal are to test a humanized genetargeted p53 tumor suppressor gene knock-in mouse as an experimental tool for molecular epidemiology, chemoprevention, and cancer therapy studies. This new model is designed to reflect and predict more faithfully than the currently used mouse models, human in vivo mutagenesis, carcinogenesis and responses to therapeutic drugs that target p53 protein. The specific aims are 1) to induce tumor mutations in human p53 sequences of knock-in mice exposed to human carcinogens, and compare them to human tumor p53 mutation spectra; 2) to test whether a p53 hotspot mutation common in aflatoxin-associated human liver cancers occurs in liver tumors of aflatoxin B1-

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exposed, hepatitis B virus-transgenic/human p53 knock-in mice; 3) to generate mouse strains that harbor a mutant human p53 sequence identical to one of the inherited p53 mutations of cancer-prone Li-Fraumeni families. These p53 mutant mouse strains provide a new animal model, with an allelic configuration that parallels the human situation, for testing chemotherapeutic agents and chemopreventive dietary factors; 4) to replace mouse regulatory sequences with human elements, and determine how this alters p53 expression; these data may be useful in developing next generation p53 knock-in mouse strains. The research plan involves: 1) Construction of gene-targeting plasmids; 2) Generation of gene-targeted mouse strains in which exons 5-9 of the endogenous mouse p53 gene have been replaced by the corresponding human segment; 3) Treatment of p53 knock-in strains with human carcinogens; 4) Analysis of tumors and normal tissues for p53 mutations, and alterations in p53 message and protein. The methods to be used are: (a) Standard cloning procedures for plasmid construction; (b) gene-targeted technology with ES cells, and knock-in/knock-out strategies; (c) mouse breeding and treatment with carcinogens; (d) DNA sequencing, PCR and RT-PCR amplification; (e) immunohistochemistry; (f) mutation analysis by DGGE and allelespecific PCR. New pharmaceuticals designed to regenerate tumor suppressor functions of a mutated p53 in humans can be tested in vivo in these humanized" mice because they have a core domain identical to the human p53 protein rather than the mouse p53 protein. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOPHYSIOLOGY AND TREATMENT OF DISORDERS IN THE DISTAL Principal Investigator & Institution: Grompe, Markus C.; Professor; Molecular and Medical Genetics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-DEC-1993; Project End 30-NOV-2004 Summary: (Copied from Applicant Abstract): Homogentisic acid dioxygenase (HGD), maleylacetoacetate isomerase (MAI) and fumarylacetoacetate hydrolase (FAH) sequentially catalyze the terminal degradation of tyrosine into Krebs cycle intermediates. Deficiency of HGD causes the human disorder alkaptonuria, (AKU) deficiency of FAH causes tyrosinemia type I (HT1) and the phenotype of MAI deficiency in man is unknown. HT1 is characterized by severe liver dysfunction, renal tubular damage and finally liver cancer. Previously we have generated a murine model of HT 1 and shown that the drug NTBC can prevent the neonatal lethality and liver dysfunction of FAH deficient mice. We also demonstrated a strong selective growth advantage of FAH expressing cells in mutant liver. This in vivo selection resulted in a near complete repopulation of diseased liver with healthy tissue and raised the hope that human HT1 may be curable by gene therapy. To broaden our understanding of the pathophysiology and potential therapy of HT1we have now also established murine models of HGD and MAI deficiency. This application pertains to the use of murine models of enzyme deficiencies in tyrosine catabolism to explore the biology of novel strategies for liver and kidney gene therapy, to better understand the etiology of hepatic cancer in HT1 and dissect the pathophysiology of the diseases in this pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT--GASTROINTESTINAL CANCER Principal Investigator & Institution: Haile, Robert W.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024

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Timing: Fiscal Year 2001; Project Start 01-APR-1980; Project End 30-NOV-2005 Summary: The overall goal of our Program is to conduct research on the causes, prevention, and therapy of gastrointestinal (GI) cancers. We aim to have a strong translational component to our research that is enhanced by a close integration of the basic sciences with clinical and epidemiological research. With respect to etiological research, primary areas of interest include: a) assessing the roles of putative candidate genes, such as NAT 1 and 2 in colorectal cancer; b) studying prevalence and determinants of epigenetic events, such as hypermethylation of the estrogen receptor5 gene promoter, in colorectal tumor samples; c) characterizing population-based parameters for genes already accepted as causes of these cancers such as the mismatch repair genes in colorectal cancer; and d) how environmental factors may interact with these genetic factors. With respect to clinical research, an emerging them in our Program is to identify and understand why cancer patients or subjects with selected precursor lesions, such as Barrett's esophagus or colorectal polyps, have differential responses to therapeutic interventions. Increasingly, we are using molecular markers to develop a profile of patients who do or do not respond to a given therapy. This type of research involves a close collaboration between molecular biologists, clinicians, and epidemiologists. It has obvious and strong translational potential, since one goal, already being realized in some of our management of patients with Barrett's esophagus, is to tailor a given intervention to a given patient based on their likelihood of responding. In addition, we have strength in hepatitis research and hepatology, with four clinical research centers at USC (Hepatitis, Hepatitis C Virus, Alcohol, NIDDK). Given this existing expertise, we believe we have the potential for an active research program in liver cancer, and have established an infrastructure with monthly meetings to develop a research program in this area. To further enhance our already substantial research program in GI cancer, we are focusing on two near-term goals: 1) even better integration across the basic, clinical, and population-based sciences, and 2) strengthening our capabilities to apply high volume molecular technologies to ongoing and planned studies. Members of the GI Program currently have over $10,000,0000 in research support. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMICS OF HEPATIC CARCINOGENESIS Principal Investigator & Institution: Angeletti, Ruth H.; Associate Professor; Developmtl & Molecular Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 16-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): Hepatocellular carcinoma is the one of most frequent causes of death by cancer in the world. There is no reliable diagnosis prior to late stages of disease and no hope for cure except surgery. The overall goal of the proposal is to discover and identify distinctive alterations of protein expression in early precancerous lesions isolated from their physiological microenvironment. The data obtained will provide early molecular markers with diagnostic and therapeutic potential for early intervention in human liver cancer. We propose to apply innovative proteomics and laser capture microdissection microscopy (LCM) to study a wellcharacterized animal model of liver carcinogenesis (RH) that exhibits well-defined, synchronous stages of initiation and progression of liver cancer that are strikingly similar to those in liver cancer in humans. In the R21 phase, we will focus on demonstrating our ability to generate useful patterns/profiles with combined LCM and protein technologies using control tissue/serum and one preneoplastic stage of the biological model system. In the R33 phase, we will apply the pattern/profile generation

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technologies to the cells and sera of each of the early stages and control paradigms so that we can identify candidate markers and targets. We will use both global and targeted proteomics strategies to: 1) identify difference proteins in cells early in the development of liver cancer; 2) identify unique serum markers at early stages; 3) determine progressive changes in tubulin isotype composition, which is associated with development of drug resistance; and 4) identify changes in proteins associated with the cytoskeletal scaffold. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RADIATION DOSE ESCALATION FOR FOCAL LIVER CANCER Principal Investigator & Institution: Dawson, Laura A.; Radiation Oncology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 11-JAN-2001; Project End 31-DEC-2005 Summary: It is known that partial volumes of liver can tolerate a tumoricidal dose of therapeutic radiation if sufficient normal liver is spared. However, the exact relationship between dose, volume of normal liver spared, and risk of complication has not been established. The development of 3D radiation treatment planning technology has allowed for a reduction in the volume of normal liver irradiated (more accurate targeting) and provided quantification of the volume of normal liver treated. A mathematical model to predict the normal tissue complication probability (NTCP) for an individual treatment plan has been developed as well. We have utilized 3D technology and an NTCP model to safely escalate the dose of focal hepatic radiation in prior and current phase I clinical trials conducted over the past 10 years. Local control and survival data are encouraging. However, the parameters of the model currently utilized are based on data with substantial uncertainties related to liver motion and patient setup. In specific Aim 1, we plans to complete a phase one study to determine the maximum safe dose of radiation for focal liver malignancies, while accounting for positional uncertainties in the NTCP parameter definitions, allowing delivery of significantly higher doses of radiation than was possible using our earlier approach. Current planning techniques require the inclusion of a margin of normal liver for these uncertainties, to ensure adequate target coverage. In Specific Aim 2, we hypothesize that reduction of liver motion together with investigation of patient setup will allow for treatment of smaller target volumes, which will subsequently permit an increase in the dose delivered without increasing the risk of RILD (radiation induced liver disease). In Specific Aim 3 we will evaluate outcome of patients treated on a phase II trial, to determine if application of improved estimates of parameters for the NTCP model, and reduction in the volume of normal liver irradiated will allow safe delivery of higher radiation doses resulting in improved survival rates in patients with intrahepatic malignancies that warrant further study in a phase III setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RADIATION THERAPY WITH ACTIVE BREATHING CONTROL Principal Investigator & Institution: Wong, John W.; Director, Clinical Physics; William Beaumont Hospital Research Inst Suite 501 Royal Oak, Mi 48073 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-APR-2002 Summary: The success of cancer treatment with external beam radiation therapy depends critically on the adequate coverage of the tumor. Treatment variation due to daily setup variation and organ motion must be taken into account. Typically, a treatment margin is added to make allowance for these variations. It is generally

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desirable to have a small treatment margin. A higher dose can then be prescribed without inflicting serious failure. However, improper reduction of the margin will greatly increase the risk of local failure. The problem of margin reduction is particularly important for treatment of tumors in the lungs and upper abdomen. The dismal prognosis of these diseases compels the use of higher dose for treatment. Yet, attempt to do so is severely hampered by the large margin needed to cover the tumor motion while the patient breathes. The applicants hypothesize that treatment of tumors in the thorax and abdomen is much more effective when breathing motion is minimized. To do so, the approach of active breathing control (ABC) is developed to immobilize breathing motion temporarily and reproducibly. At any pre-selected phase in the breathing cycle, an ABC apparatus temporarily restricts airflow to and from the patient, thereby immobilizing breathing motion. The period of active breath hold is that which can by comfortably maintained by the patient. With ABC, radiation is turned on and off manually, and only, during the period of active breath hold. The need of complex control of the treatment machine is thus avoided. The ABC procedure can be applied for three dimensional (3D) CT scanning and treatment such that the patient information used in planning reproduces that during treatment. In this proposal, an ABC apparatus will be used to acquire 3D CT scans of 40 patients with lung and liver cancer at 8 different phases in the breathing cycle. The merit of treatment with ABC is evaluated by comparing the dosimetry of a 3D treatment plan where breathing motion is immobilized at one respiratory phase with that were 3D organ motion exists, as modeled by the 8 scans. Clinical feasibility of treatment with ABC will also be tested on 25 patients undergoing conventional treatment by studying the reproducibility and acceptance of the procedure by the patients and the treatment personnel. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REDOX MECHANISM OF CANCER PREVENTION BY SELENIUM Principal Investigator & Institution: Gladyshev, Vadim N.; Biochemistry; University of Nebraska Lincoln 14Th and R Sts Lincoln, Ne 68588 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) Recent human clinical trials have demonstrated a cancer-chemopreventive effect of dietary selenium, and several additional trials are underway. However, the molecular basis for chemoprevention by this essential trace element remains unknown. Furthermore, it is not clear why dietary supplementation with selenium prevents some cancers, such as those of the prostate, colon, and lung, but is ineffective against others, such as melanoma. On the basis of preliminary studies, it is suggested that cancers can be divided into at least 2 major types on the basis of regulation of selenoprotein expression: Type I cancers are characterized by a reduced expression of selenoproteins and a consequent disruption of redox homeostasis compared with corresponding normal tissue, whereas selenoprotein abundance and cellular redox parameters are unaffected in Type II cancers. Selenium supplementation within normal dietary levels is known to increase both selenoprotein expression and antioxidant defenses. It is proposed that: (1) antioxidant selenoproteins, rather than low molecular weight selenium-containing oxidants, contribute to the chemopreventive effect of selenium, and that (2) selenium is effective against cancers of Type I but not against those of Type II. These hypotheses will be addressed with the use of transgenic mice that overexpress either transforming growth factor a (and develop Type I liver cancer) or the c-Myc proto-oncogene (and develop Type II liver cancer). These animals will be maintained on selenium-deficient, selenium-sufficient, or selenium-enriched diets, after which the incidence, grade, multiplicity, and size of tumors will be

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determined and correlated with selenium-induced changes in selenoprotein expression and markers of redox homeostasis. In addition, DNA, microarray technology will be applied to define the pattern of gene expression induced by selenium deficiency or supplementation in normal and cancer tissue from transgenic mice. These approaches should yield insight into the mechanism of the anticancer effect of selenium and may lead to the identification of human cancers most susceptible to selenium chemoprevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF MDR GENE EXPRESSION IN LIVER CANCERS Principal Investigator & Institution: Kuo, Macus T.; Professor; Molecular Pathology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 09-MAY-1997; Project End 31-AUG-2005 Summary: (provided by applicant): Expression of the multidrug resistance gene (MDR1) is frequently upregulated in human hepatocellular carcinomas (HCC). In rodents, MDR1 homologous mdr1a and mdr1b are consistently upregulated during heptocarcinogenesis in many different carcinogenic programs. These observations suggest that activation of mdr1 expression and hepatocarcinogenetic programs may share overlapping pathways. As a first step to test this hypothesis, we investigated the activation mechanisms of rat mdr1b in cultured cells induced by hepatocarcinogen 2acetylaminofluorene (AAF). We found that the NF-KB signal is involved in the upregulation of mdr1b expression. Activation of NF-KB and elevated expression of MDR1 by the carcinogen also can be seen in human hepatoma cells. The goals of our research are to determine how NF-KB signaling is activated for the upregulation of mdr1b gene expression during hepatocarcinogenesis, and whetheractivation of this signal plays a role in the development of liver cancer. Three specific aims are proposed. The first aim is to determine the upstream and downstream signals of NF-KB in AAFinduced mdr1b expression. The possible involvement of phosphoinosite 3 kinase (PI3K) and Akt as upstream signal and transcriptional coactivators as downstream signal in chromatin will be investigated. The second aim is to determine whether the same signal also involved in the upregulation of mdr1b regulation in vivo. Adenoviral vectors will be used to deliver inhibitors of the NF-KB signal to the liver to investigate whether modulation of this signal would alter the expression of mdr1b. The last aim is to investigate whether NF-KB plays a role in hepatocarcinogenesis. Nontoxic adenoviral vector will be used to target recombinant DNA constructs to the liver to determine whether intervention of NF-KB signal would affect the rate of AAF-induced liver cancer development. We hope from this research, which includes in vitro cell culture and in vivo animal and tumor models, to gain important molecular insights into the genetic resolution of drug resistance and hepatocarcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF METHIONINE ADENOSYLTRANSFERASE IN LIVER Principal Investigator & Institution: Lu, Shelly Chi-Loo.; Professor of Medicine; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2006 Summary: Methionine adenosyltransferase (MAT) is a critical enzyme which catalyzes the formation of S-adenosylmethionine (SAM). In mammals, two different genes,

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MAT1A and MAT2A, encode for two homologous MAT catalytic subunits. MAT1A is expressed only in liver whereas MAT2A is widely distributed. In the past funding cycle we shwed that in adult liver, increased expression of MAT2A is associated with rapid growth or de-differentiation of the liver. Using a cell line model that differ only in the type of MAT expressed, we showed that the type of MAT expressed by the cell influences the rate of cell growth. Cells expressing MAT1A exhibited the slowest rate of cell growth while the opposite was true of MAT2A expression. A change in the SAM level and methylation status mediate this effect. Thus, SAM treatment increased intracellular SAM and global DNA methylation levels and inhibited the rate of growth of HuH-7 cells. To understand transcriptional regulation, we cloned the 5'- flanking region of both human MAT genes. For both Mat genes, methylation of the promoter correlated with decreased expression and cell type-specific transcription factors may regulate their expression. We also have showed increased binding of transcription factors to two key regions of the MAT2A promoter in hepatocellular carcinoma (HCC). To better understand the role of MAT1A in normal liver development and response to injury, we have created a MAT1A knockout mouse model. The following aims represent logical continuation of our studies to: 1. Examine transcriptional regulation of MAT2Aidentify key cis-acting elements and trans-activating factors important for the activity of this promoter, determine if the transcriptional activity is regulated by methylation and if there are cell type-specific transcription factors involved in mediating the expression of MAT2A; 2. Examine transcriptional regulation of MAT1A- the same types of analysis for MAT2A will be carried out for MAT1A as well; 3. Elucidate the mechanism of SAM's inhibitory effect on liver cancer cell growth and examine its in vivo applicability- use microarray technology to see whether SAM treatment and MAT expression alter the expression of genes important in cell growth, create an in vivo HCC model and examine the applicability of SAM in treating liver cancer; and 4. Examine the role of MAT1A in normal liver development and response to injury- using the MAT1A knockout mouse, examine normal liver development, the effect of choline deficient diet and thioacetamide on development of liver injury and malignant degeneration, and liver regeneration in response to 2/3 partial hepatectomy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SALINE ENHANCED RADIOFREQUENCY ABLATION FOR LIVE TUMORS Principal Investigator & Institution: Curley, Michael G.; President; E.P., Ltd 35 Medford St, Ste 204 Somerville, Ma 02143 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-MAY-2004 Summary: (Adapted from Applicant's Abstract): Liver cancer, especially colorectal cancer, is a significant health concern. In the United States, half of the 157,000 new cases of colorectal cancer will lead to metastases in the liver, which will lead to over 17,000 deaths. And while not as significant a health risk as colorectal metastasis, hepatocellular carcinoma is being diagnosed with increasing frequency. The current standard of practice for treating liver cancer is surgical resection, but only 10% of patients are eligible for this procedure. Thermal ablation using radiofrequency is a promising alternative therapy, but it can only treat small tumors. The applicants propose to continue development of a saline-enhanced radiofrequency ablation system for treating large liver tumors. The system uses radiofrequency energy to heat tissue, but this would be complimented with simultaneous injection of warm saline through the electrode and into the tissue The injected saline flows through the extracellular space and convects the thermal energy deep into the tissue. Consequently, it would be possible to treat

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significantly larger tumor volumes than previously possible. The technique has been reported to created thermal lesions whose volumes are 90 times as large as those created with conventional radiofrequency electrodes. The method would therefor enable percutaneous thermal ablation therapy to be used on larger tumors, greatly increasing the number of patients eligible for therapy. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPECIES DIFFERENCE IN THE BIOTRANSFORMATION OF AFLATOXIN Principal Investigator & Institution: Eaton, David L.; Professor and Associate Dean; Environmental Health; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-MAY-1991; Project End 31-JUL-2004 Summary: Numerous studies have demonstrated that biologically active, natural components of the diet may confer resistance to chemical carcinogens via induction and/or inhibition of biotransformation enzymes. In particular, specific chemical components of the diet, such as flavonoids, isocyanates, glucosinolates, indoles, dithiolthiones, and polyphenols have been identified as effective inducers and/or inhibitors of carcinogen activation/detoxification pathways in animal models. There is much supporting data from human epidemiological studies on the important relationship between diet and cancer in humans, although the diversity and complexity of the diet, and uncertainty of specific exposures, in such studies makes identification of specific active components nearly impossible. Although animal models are useful for "hypothesis testing", species differences in carcinogen activation and detoxification pathways, as well as differences in gene regulation and expression in response to inducers, make extrapolation of animal data to the human situation tentative, at best. Thus, there is a need to develop model systems that utilize human cells/tissues to determine the efficacy of specific dietary components and/or putative chemoprotectant drugs to favorably modify the biotransformation of human carcinogens. One such model human carcinogen is aflatoxin B1. Aflatoxins are mycotoxins produced by the common fungal molds, Aspergillus flavus and Aspergillus parasiticus. Worldwide, aflatoxins are considered a major public health problem because of their potent carcinogenic effects. Human epidemiological data has documented that humans are susceptible to AFB-induced hepatocarcinogenesis, especially in combination with hepatitis B virus infection. However, there are large species differences in the susceptibility to aflatoxin carcinogenesis. Rats are highly sensitive, whereas mice are very resistant. The mechanism for this difference is associated with the expression of a specific enzyme, glutathione S-transferase A3-3 (mGSTA3-3), which is present in the livers of mice, but not rats. Treatment of rats with the drug, oltipraz, or the food additive, ethoxyquin, protects rats from aflatoxin-induced liver cancer. The mechanism for this protection is due to the ability of these chemicals to "turn on" a gene for a glutathione S-transferase, rGSTA5-5, that is normally not expressed in rat liver, but which efficiently detoxifies aflatoxin. Human liver tissue has very low ability to detoxify aflatoxin -- in fact, worse than the poor ability of rats. There has been considerable interest in devising a dietary or chemointervention strategy for humans that increases resistance to AFB by induction of GSTs. The long range goals of this proposal are to: 1) establish in vitro models that utilize isolated human hepatocytes in culture and human cDNA expressing yeast, to assess the efficacy of specific dietary components as putative chemoprotectors against AFB and other chemical carcinogens, and 2) complete the

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characterization of species differences in glutathione S-transferases with activity toward AFB-epoxide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED RADIOACTIVE PARTICLES FOR LIVER TUMOR THERAPY Principal Investigator & Institution: Tapolsky, Gilles H.; Ferx, Inc. 12365 Montview Blvd Aurora, Co 80010 Timing: Fiscal Year 2002; Project Start 25-SEP-2000; Project End 31-AUG-2004 Summary: (provided by applicant): The ability to deliver high doses of radiation (up to 200 Gy and higher) to a tumor without significant damage to surrounding tissue would be a significant advancement in the radiation therapy of solid tumors. FeRx proposes to complete the preclinical and clinical development of targeted radioactive microparticles for the site-specific delivery of radionuclides to liver tumors. Magnetic Targeted Carriers (MTCs) are 0.5 to 5 micron particles composed of metallic iron and activated carbon. Results of SBIR phase I studies indicated that In111, Re188, and Y90 were efficiently and strongly bound to MTCs. Using a small externally positioned magnet, MTCs were effectively targeted to a swine liver where they were trapped. FeRx?s objectives are 1) to perform preclinical studies to support an Investigational Device Exemption submission and 2) to conduct a Phase I/Il safety and tolerability study in patients with liver cancer. In the first year, FeRx will complete the development of (90Y-DOTA)-MTCs, perform biodistribution studies in rabbits and swine, investigate the intra-tumoral biodistribution, and assess the radiotoxicity of high doses of localized radiation. In the second year, FeRx will submit an IDE and commence a phase I/II trial in patients with liver cancer to evaluate safety, tolerability, and preliminary efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE EPIDEMIOLOGY OF HEPATITIS C INFECTION IN THAILAND Principal Investigator & Institution: Nelson, Kenrad E.; Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-AUG-2004 Summary: The proposed research program will involve integrated collaborative studies of the epidemiology, biology and natural history of hepatitis C virus (HCV) infections in Northern Thailand. Infections with HCV are a worldwide health problem and are a major cause of chronic liver disease, liver cancer and cirrhosis. It is estimated that 4 million persons in the United States and 180 million persons worldwide are infected with HCV. After infection 80 percent of individuals will become chronic carriers and 20 percent of them will progress to chronic liver disease or cancer in the next 15-20 years. Epidemiologic studies in some populations have found high rates of HCV in injection drug users and lower but elevated rates from sexual and perinatal transmission. However, infections in many individuals are cryptogenic. The reasons for the persistence of HCV infection in such a high proportion of infected individuals is not clear. However, the virus is genetically quite diverse and viral variation with the emergence of new quasispecies usually occurs in chronically infected people. Furthermore the epidemiology and transmission of HCV is intertwined with HIV, so many persons who are infected with both viruses may be immunosuppressed. The studies we have planned will involve comprehensive investigations of the epidemiology, virology and natural history of HCV infections in various populations in Northern Thailand, most of whom are being evaluated for HIV infection. Liver cancer is

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one of the leading causes of cancer in Thailand and HCV prevalence in blood donors is 8-10 fold greater than in the U.S. The study populations will include injection drug users, sex workers, STD patients, military recruits, blood donors and their spouses and general community populations. Through the transfer of technology for HCV research to our collaborators, we hope to focus on understanding the biology and epidemiology of HCV and the development of more effective prevention of HCV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF HCDC4 IN HEPATOCELLULAR CARCINOMA Principal Investigator & Institution: Li, Kaiyi; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The overall goal of this study is to address the potential role of hCdc4 as a tumor suppressor gene in hepatocellular carcinoma (HCC). Our recent studies indicated that cyclin E, an oncogene overexpressed in 70% of HCC, played a substantial role on proliferation and survival and could serve as a promising therapeutic target for HCC. We also showed that downregulation of hCdc4, a recentlyidentified tumor suppressor candidate in breast cancer, could markedly trigger cyclin E protein accumulation in HCC cells. We hypothesize that deficiency of hCdc4 is one of the key factors causing cyclin E overexpression in HCC. To test this hypothesis, HCC specimen will be analyzed for hCdc4 alteration at DNA, RNA, and protein levels. Specifically, 100 HCC samples and their corresponding noncarcerous liver tissues will be collected at Houston area in Texas. RT-PCR product from HCC and their matched noncarcerous liver tissues will be applied to screen for hCdc4 mutation by direct sequencing. To determine if any alteration occurs in transcriptional or posttranscriptional level, the expression level of hCdc4 will be assessed by Northern blot and Western blot from HCC specimen with intact hCdc4 gene. We will also determine if hCdc4 status is correlated to cyclin E overexpression and if hCdc4 can serve as a prognostic factor for HCC patients. In addition to studies in patient samples, the effects caused from hCdc4 deficiencies on HCC will be evaluated using a transgenic mouse model. We will generate transgenic mice expressing a dominant negative hCdc4 mutant driven by a liver specific promoter. Alternatively, we will generate transgenic mice with hCdc4 expression suppressed by RNA interference approach. We have demonstrated that stable expression of a small interfering RNA against Cdc4 in a mouse cell line led to decrease of Cdc4 expression and elevation of cyclin E protein level. We will test whether the similar effects can be extended and reproduced in the transgenic mice. The transgenic lines generated by these two approaches will be systematically analyzed for both hCdc4 and cyclin E expression. Histopathological studies will also be performed in the transgenics to determine HCC-related phenotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VALIDATION OF FUMONISIN AND MICROCYSTIN BIOMARKERS Principal Investigator & Institution: Wang, Jia-Sheng; None; Texas Tech University Box 42013 Lubbock, Tx 79409 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The long-term goal of this research project is to study relationships between exposure to fumonisins and microcystins and human liver and esophageal cancer risks in high-risk populations. Fumonisins and microcystins are newly identified environmental biotoxins that are produced by toxicogenic fungi and

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cyanobacteria, respectively. Fumonisins are carcinogens and both fumonisins and microcystins are strong tumor promoters in animal models. Human populations in certain areas of world are exposed to higher levels of these toxins in their daily life mainly through contaminated dietary components and/or drinking water. Both of these toxins have been etiologically linked to high incidence of human primary liver cancer and esophageal cancer in several areas of South Africa and China. Although analytical methods for detecting these toxins in environmental samples have been reported and potential biomarkers, such as disruption of sphingolipids metabolism by fumonisins and inhibition of protein phosphatases by microcystins, have been found in animal models, validation of these biomarkers in humans, especially in high-risk populations, has not been done or reported. To date, methods are still lack for simultaneously detection of these toxins in environmental samples and human body fluids, which are critical for assessment of human cancer risks, because co-exposure to these biotoxins in high-risk populations has been widely reported. In this exploratory research project, we will develop and validate analytical array methods to simultaneously measure these biotoxins in both environmental samples and human body fluids. We will use molecular epidemiological tools to validate methods for biomarkers in body fluids of cases of primary liver cancer and esophageal cancer and controls. The working hypothesis underlying this research proposal is that long-term exposure to fumonisins and microcystins may induce synergistic carcinogenic effects in high-risk individuals and application of validated biomarkers can improve the quantitative estimation of human cancer risk from exposure to these biotoxins. The specific aims are: 1) to develop rapid and sensitive analytical array method(s) for measuring fumonisin and microcystin biomarkers based on previously developed immunoaffinity-HPLC method for aflatoxins and/or HPLC-enzyme-linked immunosorbent assay for microcystins; 2) to validate method(s) for measuring biomarkers of microcystins and fumonisins in food, water, and body fluids such as blood and urine samples collected from two one-week longitudinal biomonitoring studies in human subjects from high-risk areas of primary liver cancer and esophageal cancer, and 3) to perform molecular epidemiological studies in two high-risk populations of primary liver cancer and esophageal cancer in Qidong and Huaian, P.R. China, for exploring cancer risks from exposures to fumonisins and microcystins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “liver 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 liver cancer in the PubMed Central database: 3 4

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

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

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A methylated oligonucleotide inhibits IGF2 expression and enhances survival in a model of hepatocellular carcinoma. by Yao X, Hu JF, Daniels M, Shiran H, Zhou X, Yan H, Lu H, Zeng Z, Wang Q, Li T, Hoffman AR.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151856

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A Novel AP-1 Element in the CD95 Ligand Promoter Is Required for Induction of Apoptosis in Hepatocellular Carcinoma Cells upon Treatment with Anticancer Drugs. by Eichhorst ST, Muller M, Li-Weber M, Schulze-Bergkamen H, Angel P, Krammer PH.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86378

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A Trans-Activator Function is Generated by Integration of Hepatitis B Virus PreS/S Sequences in Human Hepatocellular Carcinoma DNA. by Caselmann WH, Meyer M, Kekule AS, Lauer U, Hofschneider PH, Koshy R.; 1990 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53815

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Abnormal Structure and Expression of p53 Gene in Human Hepatocellular Carcinoma. by Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR, Ozturk M.; 1990 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53607

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Activation of the c-Ki-ras Oncogene in Aflatoxin B1-Induced Hepatocellular Carcinoma and Adenoma in the Rat: Detection by Denaturing Gradient Gel Electrophoresis. by Soman NR, Wogan GN.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46017

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Allele Loss on Chromosome 16 Associated With Progression of Human Hepatocellular Carcinoma. by Tsuda H, Zhang W, Shimosato Y, Yokota J, Terada M, Sugimura T, Miyamura T, Hirohashi S.; 1990 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54623

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Apolipoprotein B mRNA-Editing Protein Induces Hepatocellular Carcinoma and Dysplasia in Transgenic Animals. by Yamanaka S, Balestra ME, Ferrell LD, Fan J, Arnold KS, Taylor S, Taylor JM, Innerarity TL.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41181

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Chlorophyllin intervention reduces aflatoxin --DNA adducts in individuals at high risk for liver cancer. by Egner PA, Wang JB, Zhu YR, Zhang BC, Wu Y, Zhang QN, Qian GS, Kuang SY, Gange SJ, Jacobson LP, Helzlsouer KJ, Bailey GS, Groopman JD, Kensler TW.; 2001 Dec 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64728

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Comparative Sequence Analysis of the Core Protein and Its Frameshift Product, the F Protein, of Hepatitis C Virus Subtype 1b Strains Obtained from Patients with and without Hepatocellular Carcinoma. by Ogata S, Nagano-Fujii M, Ku Y, Yoon S, Hotta H.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130847

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Construction and high cytoplasmic expression of a tumoricidal single-chain antibody against hepatocellular carcinoma. by Sandee D, Tungpradabkul S, Tsukio M, Imanaka T, Takagi M.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128817

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Differential prevalence of hepatitis C virus subtypes in healthy blood donors, patients on maintenance hemodialysis, and patients with hepatocellular carcinoma in Surabaya, Indonesia. by Soetjipto, Handajani R, Lusida MI, Darmadi S, Adi P, Soemarto, Ishido S, Katayama Y, Hotta H.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229426

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Evaluation of Quantitative PCR and Branched-Chain DNA Assay for Detection of Hepatitis B Virus DNA in Sera from Hepatocellular Carcinoma and Liver Transplant Patients. by Chen T, Luk JM, Cheung ST, Yu WC, Fan ST.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86641

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Extensive Oxidative DNA Damage in Hepatocytes of Transgenic Mice with Chronic Active Hepatitis Destined to Develop Hepatocellular Carcinoma. by Hagen TM, Huang S, Curnutte J, Fowler P, Martinez V, Wehr CM, Ames BN, Chisari FV.; 1994 Dec 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45529

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Gene Expression Patterns in Human Liver Cancers. by Chen X, Cheung ST, So S, Fan ST, Barry C, Higgins J, Lai KM, Ji J, Dudoit S, Ng IO, van de Rijn M, Botstein D, Brown PO.; 2002 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117615

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Genetic Heterogeneity of Hepatocellular Carcinoma. by Unsal H, Yakicier C, Marcais C, Kew M, Volkmann M, Zentgraf H, Isselbacher KJ, Ozturk M.; 1994 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43041

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Hepatitis C Virus Infection is Associated with the Development of Hepatocellular Carcinoma. by Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S, Watanabe Y, Koi S, Onji M, Ohta Y, Choo Q, Houghton M, Kuo G.; 1990 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54573

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Hepatitis C Virus RNA in Southern African Blacks with Hepatocellular Carcinoma. by Bukh J, Miller RH, Kew MC, Purcell RH.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45977

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Hepatocyte Growth Factor Inhibits Growth of Hepatocellular Carcinoma Cells. by Shiota G, Rhoads DB, Wang TC, Nakamura T, Schmidt EV.; 1992 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48239

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Identification of frequent cytogenetic aberrations in hepatocellular carcinoma using gene-expression microarray data. by Crawley JJ, Furge KA.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151177

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Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver. by Xu XR, Huang J, Xu ZG, Qian BZ, Zhu ZD, Yan Q, Cai T, Zhang X, Xiao HS, Qu J, Liu F, Huang QH, Cheng ZH, Li NG, Du JJ, Hu W, Shen KT, Lu G, Fu G, Zhong M, Xu SH, Gu WY, Huang W, Zhao XT, Hu GX, Gu JR, Chen Z, Han ZG.; 2001 Dec 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64988

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Liver repopulation with xenogenic hepatocytes in B and T cell-deficient mice leads to chronic hepadnavirus infection and clonal growth of hepatocellular carcinoma. by Petersen J, Dandri M, Gupta S, Rogler CE.; 1998 Jan 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18210

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Low Frequency of p53 Mutations Observed in a Diverse Collection of Primary Hepatocellular Carcinomas. by Buetow KH, Sheffield VC, Zhu M, Zhou T, Shen F, Hino O, Smith M, McMahan BJ, Lanier AP, London WT, Redeker AG, Govindarajan S.; 1992 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50184

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Mutant Woodchuck Hepatitis Virus Genomes From Virions Resemble Rearranged Hepadnaviral Integrants in Hepatocellular Carcinoma. by Kew MC, Miller RH, Chen H, Tennant BC, Purcell RH.; 1993 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47744

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Retroviral-Mediated Gene Therapy for the Treatment of Hepatocellular carcinoma: An Innovative Approach for Cancer Therapy. by Huber BE, Richards CA, Krenitsky TA.; 1991 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52441

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Somatic mutations of the [beta]-catenin gene are frequent in mouse and human hepatocellular carcinomas. by Coste AD, Romagnolo B, Billuart P, Renard CA, Buendia MA, Soubrane O, Fabre M, Chelly J, Beldjord C, Kahn A, Perret C.; 1998 Jul 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21165

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Spontaneous hepatocellular carcinoma is reduced in transgenic mice overexpressing human O6- methylguanine-DNA methyltransferase. by Zhou ZQ, Manguino D, Kewitt K, Intano GW, McMahan CA, Herbert DC, Hanes M, Reddick R, Ikeno Y, Walter CA.; 2001 Oct 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60094

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Susceptibility to Hepatocellular Carcinoma is Associated with Genetic Variation in the Enzymatic Detoxification of Aflatoxin B1. by McGlynn KA, Rosvold EA, Lustbader ED, Hu Y, Clapper ML, Zhou T, Wild CP, Xia X, Baffoe-Bonnie A, Ofori-Adjei D, Chen G, London WT, Shen F, Buetow KH.; 1995 Mar 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42488

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The aflatoxin B1 formamidopyrimidine adduct plays a major role in causing the types of mutations observed in human hepatocellular carcinoma. by Smela ME, Hamm ML, Henderson PT, Harris CM, Harris TM, Essigmann JM.; 2002 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124458

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Tissue-specific expression of herpes simplex virus thymidine kinase gene delivered by adeno-associated virus inhibits the growth of human hepatocellular carcinoma in athymic mice. by Su H, Lu R, Chang JC, Kan YW.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28403

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Transcriptional Regulation of Basic Fibroblast Growth Factor Gene by p53 in Human Glioblastoma and Hepatocellular Carcinoma Cells. by Ueba T, Nosaka T, Takahashi JA, Shibata F, Florkiewicz RZ, Vogelstein B, Oda Y, Kikuchi H, Hatanaka M.; 1994 Sep 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44736

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Woodchuck hepatitis virus X protein is present in chronically infected woodchuck liver and woodchuck hepatocellular carcinomas which are permissive for viral replication. by Dandri M, Schirmacher P, Rogler CE.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190481

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

A biologically based model for liver cancer risk in the Swedish thorotrast patients. Author(s): Heidenreich WF, Nyberg U, Hall P. Source: Radiation Research. 2003 May; 159(5): 656-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710877&dopt=Abstract

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A case report of synchronous double primary liver cancers combined with early gastric cancer. Author(s): Chang JY, Kim BH, Hong SW, Kim YW, Oh JH. Source: Korean J Intern Med. 2003 June; 18(2): 115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872450&dopt=Abstract

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

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A case-control study on family history of liver cancer as a risk factor for hepatocellular carcinoma in North Italy. Brescia HCC Study. Author(s): Donato F, Gelatti U, Chiesa R, Albertini A, Bucella E, Boffetta P, Tagger A, Ribero ML, Portera G, Fasola M, Nardi G. Source: Cancer Causes & Control : Ccc. 1999 October; 10(5): 417-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10530612&dopt=Abstract

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A cyclin-dependent kinase inhibitor (p21(WAF1/CIP1)) affects thymidine incorporation in human liver cancer cells. Author(s): Gong Y, Deng S, Zhang M, Wang G, Minuk GY, Burczynski F. Source: British Journal of Cancer. 2002 February 12; 86(4): 625-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870547&dopt=Abstract

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A ligand for peroxisome proliferator activated receptor gamma inhibits cell growth and induces apoptosis in human liver cancer cells. Author(s): Toyoda M, Takagi H, Horiguchi N, Kakizaki S, Sato K, Takayama H, Mori M. Source: Gut. 2002 April; 50(4): 563-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889080&dopt=Abstract

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A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer. Author(s): Iwashita Y, Tahara K, Goto S, Sasaki A, Kai S, Seike M, Chen CL, Kawano K, Kitano S. Source: Cancer Immunology, Immunotherapy : Cii. 2003 March; 52(3): 155-61. Epub 2003 February 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649744&dopt=Abstract

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A phase I study of chemoembolization with cisplatin, thiotepa, and lipiodol for primary and metastatic liver cancer. Author(s): Feun LG, Reddy KR, Scagnelli T, Yrizarry JM, Guerra JJ, Russell E, Schwartz M, Savaraj N, Livingstone AS, Levi JU, Jeffers LJ, Ardalan B, Schiff ER. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 1999 August; 22(4): 375-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440193&dopt=Abstract

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A phase II study of m-AMSA in patients with primary liver cancer. Author(s): Falkson G, Coetzer B, Klaassen DJ. Source: Cancer Chemotherapy and Pharmacology. 1981; 6(2): 127-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6895485&dopt=Abstract

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A promising technique for liver cancer? Author(s): Fong Y. Source: Cancer J Sci Am. 1999 November-December; 5(6): 339-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606474&dopt=Abstract

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A prospective study of blood transfusion history and liver cancer in a high-endemic area of Japan. Author(s): Fujino Y, Mizoue T, Tokui N, Yoshimura T. Source: Transfusion Medicine (Oxford, England). 2002 October; 12(5): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383335&dopt=Abstract

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A reanalysis of liver cancer incidence in Danish patients administered thorotrast using a two-mutation carcinogenesis model. Author(s): Leenhouts HP, Brugmans MJ, Andersson M, Storm HH. Source: Radiation Research. 2002 November; 158(5): 597-606. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385637&dopt=Abstract

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Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis. Author(s): Lu M, Nakamura RM, Dent ED, Zhang JY, Nielsen FC, Christiansen J, Chan EK, Tan EM. Source: American Journal of Pathology. 2001 September; 159(3): 945-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549587&dopt=Abstract

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Absence of Helicobacter species in the liver of patients with primary or metastatic liver cancer. Author(s): Wadstrom T, Abu Al-Soud W, Ljungh A, Nilsson HO, Stenram U. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 532-3; Author Reply 533. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883500&dopt=Abstract

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Absence of Helicobacter spp in the liver of patients with primary or metastatic liver cancer. Author(s): Coppola N, De Stefano G, Marrocco C, Scarano F, Scolastico C, Tarantino L, Piccinino F, Sagnelli E, Giorgio A, Filippini P. Source: Hepatology (Baltimore, Md.). 2002 November; 36(5): 1300-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395348&dopt=Abstract

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Adenovirus with insertion-mutated E1A selectively propagates in liver cancer cells and destroys tumors in vivo. Author(s): Zhao T, Rao XM, Xie X, Li L, Thompson TC, McMasters KM, Zhou HS. Source: Cancer Research. 2003 June 15; 63(12): 3073-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810631&dopt=Abstract

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Adoptive immunotherapy of primary and metastatic liver cancer via hepatic artery catheter. Author(s): Matsuhashi N, Moriyama T, Nakamura I, Ishikawa T, Ohnishi S, Nakagama H, Imawari M, Takaku F. Source: European Journal of Cancer (Oxford, England : 1990). 1990; 26(10): 1106-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2148889&dopt=Abstract

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Aflatoxin and liver cancer in Sudan. Author(s): Omer RE, Bakker MI, van't Veer P, Hoogenboom RL, Polman TH, Alink GM, Idris MO, Kadaru AM, Kok FJ. Source: Nutrition and Cancer. 1998; 32(3): 174-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10050268&dopt=Abstract

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Aflatoxin and liver cancer. Author(s): Jackson PE, Groopman JD. Source: Bailliere's Best Practice & Research. Clinical Gastroenterology. 1999 December; 13(4): 545-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10654919&dopt=Abstract

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Aflatoxin, hepatitis and worldwide liver cancer risks. Author(s): Henry SH, Bosch FX, Bowers JC. Source: Advances in Experimental Medicine and Biology. 2002; 504: 229-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922091&dopt=Abstract

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Alcohol consumption as a major risk factor for the rise in liver cancer mortality rates in Japanese men. Author(s): Makimoto K, Higuchi S. Source: International Journal of Epidemiology. 1999 February; 28(1): 30-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10195660&dopt=Abstract

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Alpha-fetoprotein and/or liver ultrasonography for liver cancer screening in patients with chronic hepatitis B. Author(s): Wun YT, Dickinson JA. Source: Cochrane Database Syst Rev. 2003; (2): Cd002799. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804438&dopt=Abstract

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Alphafetoprotein levels of liver cancer patients and controls in a European population. Author(s): Trichopoulos D, Sizaret P, Tabor E, Gerety RJ, Martel N, Munoz N, Theodoropoulos G. Source: Cancer. 1980 August 15; 46(4): 736-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6156754&dopt=Abstract

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Alterations of P19ARF in rodent hepatoma cell lines but not in human primary liver cancer. Author(s): Laes J, Parada LA, Johansson B, Levan G, Szpirer C, Szpirer J. Source: Cancer Genetics and Cytogenetics. 2000 March; 117(2): 118-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704681&dopt=Abstract

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An analysis for death causes in 45 cases of liver cancer treated with traditional Chinese drugs. Author(s): Yang Z, Sui X. Source: J Tradit Chin Med. 1999 June; 19(2): 97-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10681863&dopt=Abstract

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An empirical study of the use of living versus deceased study subjects: associations with liver cancer in the selected cancers study. Author(s): Hall HI, Caplan LS, Coughlin SS, Levine RS, Zhu K. Source: Annals of Epidemiology. 2002 January; 12(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750235&dopt=Abstract

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An increased standardised mortality ratio for liver cancer among polyvinyl chloride workers in Taiwan. Author(s): Wong RH, Chen PC, Du CL, Wang JD, Cheng TJ. Source: Occupational and Environmental Medicine. 2002 June; 59(6): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040117&dopt=Abstract

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Analysis of the beta-catenin/T cell factor signaling pathway in 36 gastrointestinal and liver cancer cells. Author(s): Ikenoue T, Ijichi H, Kato N, Kanai F, Masaki T, Rengifo W, Okamoto M, Matsumura M, Kawabe T, Shiratori Y, Omata M. Source: Japanese Journal of Cancer Research : Gann. 2002 November; 93(11): 1213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460462&dopt=Abstract

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Antitumoral effects of recombinant adenovirus YKL-1001, conditionally replicating in alpha-fetoprotein-producing human liver cancer cells. Author(s): Kim J, Lee B, Kim JS, Yun CO, Kim JH, Lee YJ, Joo CH, Lee H. Source: Cancer Letters. 2002 June 6; 180(1): 23-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911966&dopt=Abstract

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Are deaths from liver cancer, kidney cancer, and leukemia clustered in San Antonio? Author(s): Zhan FB. Source: Tex Med. 2002 October; 98(10): 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391737&dopt=Abstract

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Aspiration cytology in the diagnosis of liver cancer. Author(s): De Cock KM, Gatei DG, Shah MV. Source: East Afr Med J. 1981 September; 58(9): 636-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6274606&dopt=Abstract

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Basic science focus of third international symposium on liver cancer and hepatitis. Author(s): Skolnick AA. Source: Jama : the Journal of the American Medical Association. 1996 November 13; 276(18): 1457-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8903244&dopt=Abstract

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Bcl-2 related proteins are dramatically induced at the early stage of differentiation in human liver cancer cells by a histone deacetylase inhibitor projecting an antiapoptotic role during this period. Author(s): Wakabayashi K, Saito H, Ebinuma H, Saito Y, Takagi T, Nakamura M, Umezawa A, Hata J, Ishii H. Source: Oncol Rep. 2000 March-April; 7(2): 285-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10671672&dopt=Abstract

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Biochemical profile in liver cancer patients. Author(s): Rasheed A, Iqtidar A. Source: Zhongguo Yao Li Xue Bao. 1995 July; 16(4): 366-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7668112&dopt=Abstract

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Blood transfusion as a risk factor for cirrhosis and liver cancer: a matched case-control study. Author(s): Fukuda A, Sugimachi K, Tokudome S, Ikeda M, Koga S, Hirohata T. Source: Journal of the National Cancer Institute. 1989 August 2; 81(15): 1189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2746672&dopt=Abstract

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Can increased treatment of hepatitis C stem the tide of liver cancer? Author(s): Twombly R. Source: Journal of the National Cancer Institute. 2002 July 17; 94(14): 1050-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122094&dopt=Abstract

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Cancer incidence near municipal solid waste incinerators in Great Britain. Part 2: histopathological and case-note review of primary liver cancer cases. Author(s): Elliott P, Eaton N, Shaddick G, Carter R. Source: British Journal of Cancer. 2000 March; 82(5): 1103-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10737393&dopt=Abstract

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Cell proliferation index and the expression of p53 and Bcl-2 in tumorous and nontumorous lesions of hepatocellular carcinoma and metastatic liver cancer. Author(s): Yoon DS, Cheong JH, Park YN, Kwon SW, Chi HS, Kim BR. Source: Yonsei Medical Journal. 1998 October; 39(5): 424-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9821791&dopt=Abstract

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Changes in survival patterns in urban Chinese patients with liver cancer. Author(s): Hao XS, Chen KX, Wang PP, Rohan T. Source: World Journal of Gastroenterology : Wjg. 2003 June; 9(6): 1212-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800226&dopt=Abstract

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Characterization of aflatoxin BI (AFB) in human liver cancer. Author(s): Stora C, Dvorackova I, Ayraud N. Source: Res Commun Chem Pathol Pharmacol. 1981 January; 31(1): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6789415&dopt=Abstract

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Chemoembolization for primary liver cancer. Author(s): Achenbach T, Seifert JK, Pitton MB, Schunk K, Junginger T. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2002 February; 28(1): 37-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869011&dopt=Abstract

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Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Author(s): Egner PA, Wang JB, Zhu YR, Zhang BC, Wu Y, Zhang QN, Qian GS, Kuang SY, Gange SJ, Jacobson LP, Helzlsouer KJ, Bailey GS, Groopman JD, Kensler TW. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 December 4; 98(25): 14601-6. Epub 2001 November 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724948&dopt=Abstract

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Cholangiocarcinoma: the “other” liver cancer on the rise. Author(s): Davila JA, El-Serag HB. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3199-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492212&dopt=Abstract

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Cirrhosis and primary liver cancer amongst first generation migrants in England and Wales. Author(s): Haworth EA, Soni Raleigh V, Balarajan R. Source: Ethnicity & Health. 1999 February-May; 4(1-2): 93-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10887465&dopt=Abstract

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Cisplatin gel treatment of unresectable liver cancer. Author(s): Kerr C. Source: The Lancet Oncology. 2003 April; 4(4): 199. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681253&dopt=Abstract

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Clinical advances in primary liver cancer in China. Author(s): Wu M. Source: Hepatogastroenterology. 2001 January-February; 48(37): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268987&dopt=Abstract

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Clinical utility and safety of MultiHance in magnetic resonance imaging of liver cancer: results of multicenter studies in Europe and the USA. Author(s): Hamm B, Kirchin M, Pirovano G, Spinazzi A. Source: Journal of Computer Assisted Tomography. 1999 November; 23 Suppl 1: S53-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608398&dopt=Abstract

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Cloning and characterization of F-LANa, upregulated in human liver cancer. Author(s): Ying H, Yu Y, Xu Y. Source: Biochemical and Biophysical Research Communications. 2001 August 17; 286(2): 394-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11500051&dopt=Abstract

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Combined alpha fetoprotein testing and ultrasonography as a screening test for primary liver cancer. Author(s): Zhang B, Yang B. Source: Journal of Medical Screening. 1999; 6(2): 108-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10444731&dopt=Abstract

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Comments on “Hepatic radioembolization with yttrium-90 glass microspheres for treatment of primary liver cancer” by Cao et al, Chin Med J 1999; 112: 430-432. Author(s): Ho S, Lau WY, Leung WT. Source: Chinese Medical Journal. 2001 April; 114(4): 433-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11780473&dopt=Abstract

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Comparison of anamnestic history, alcohol intake and smoking, nutritional status, and liver dysfunction between thorotrast patients who developed primary liver cancer and those who did not. Author(s): Kiyosawa K, Imai H, Sodeyama T, Franca ST, Yousuf M, Furuta S, Fujisawa K, Kido C. Source: Environmental Research. 1989 August; 49(2): 166-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2546755&dopt=Abstract

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Computed tomography and magnetic resonance imaging evaluation of liver cancer. Author(s): Harisinghani MG, Hahn PF. Source: Gastroenterology Clinics of North America. 2002 September; 31(3): 759-76, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481730&dopt=Abstract

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Computer-aided dynamic simulation of microwave-induced thermal distribution in coagulation of liver cancer. Author(s): Liang P, Dong B, Yu X, Yu D, Cheng Z, Su L, Peng J, Nan Q, Wang H. Source: Ieee Transactions on Bio-Medical Engineering. 2001 July; 48(7): 821-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442294&dopt=Abstract

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Critical involvement of the phosphatidylinositol 3-kinase/Akt pathway in anchorageindependent growth and hematogeneous intrahepatic metastasis of liver cancer. Author(s): Nakanishi K, Sakamoto M, Yasuda J, Takamura M, Fujita N, Tsuruo T, Todo S, Hirohashi S. Source: Cancer Research. 2002 May 15; 62(10): 2971-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019180&dopt=Abstract

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CYP enzyme polymorphisms and susceptibility to HCV-related chronic liver disease and liver cancer. Author(s): Silvestri L, Sonzogni L, De Silvestri A, Gritti C, Foti L, Zavaglia C, Leveri M, Cividini A, Mondelli MU, Civardi E, Silini EM. Source: International Journal of Cancer. Journal International Du Cancer. 2003 April 10; 104(3): 310-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569554&dopt=Abstract

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Cytokeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver cancer. Author(s): Uenishi T, Kubo S, Hirohashi K, Tanaka H, Shuto T, Yamamoto T, Nishiguchi S. Source: British Journal of Cancer. 2003 June 16; 88(12): 1894-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799633&dopt=Abstract

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Cytokine, infiltrating macrophage and T cell-mediated response to development of primary and secondary human liver cancer. Author(s): Bortolami M, Venturi C, Giacomelli L, Scalerta R, Bacchetti S, Marino F, Floreani A, Lise M, Naccarato R, Farinati F. Source: Dig Liver Dis. 2002 November; 34(11): 794-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546515&dopt=Abstract

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Dearterialization of colorectal liver cancer: institutional experience. Author(s): Ohlsson B, Lindell G, Lundstedt C, Jeppsson B, Persson B, Bengmark S, Tranberg KG. Source: Digestive Surgery. 1999; 16(3): 229-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436372&dopt=Abstract

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Debulking surgery and arterial embolization for unresectable liver cancer. Author(s): Shimamura Y, Gunven P, Ishii M, Ono M, Abe K. Source: Hepatogastroenterology. 1993 February; 40(1): 10-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8385063&dopt=Abstract

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Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma. Author(s): Ching YP, Wong CM, Chan SF, Leung TH, Ng DC, Jin DY, Ng IO. Source: The Journal of Biological Chemistry. 2003 March 21; 278(12): 10824-30. Epub 2003 January 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531887&dopt=Abstract

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Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients. Author(s): Wong IH, Lo YM, Zhang J, Liew CT, Ng MH, Wong N, Lai PB, Lau WY, Hjelm NM, Johnson PJ. Source: Cancer Research. 1999 January 1; 59(1): 71-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9892188&dopt=Abstract

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Detection of hepatitis B virus DNA by polymerase chain reaction in HBsAg negative Senegalese patients suffering from cirrhosis or primary liver cancer. Author(s): Coursaget P, Le Cann P, Leboulleux D, Diop MT, Bao O, Coll AM. Source: Fems Microbiology Letters. 1991 September 15; 67(1): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1778420&dopt=Abstract

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Detection of microcystins, a blue-green algal hepatotoxin, in drinking water sampled in Haimen and Fusui, endemic areas of primary liver cancer in China, by highly sensitive immunoassay. Author(s): Ueno Y, Nagata S, Tsutsumi T, Hasegawa A, Watanabe MF, Park HD, Chen GC, Chen G, Yu SZ. Source: Carcinogenesis. 1996 June; 17(6): 1317-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8681449&dopt=Abstract

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Determination of plasma urokinase-type plasminogen activator antigen in patients with primary liver cancer: characterization as tumor-associated antigen and comparison with alpha-fetoprotein. Author(s): Huber K, Kirchheimer JC, Ermler D, Bell C, Binder BR. Source: Cancer Research. 1992 April 1; 52(7): 1717-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1372529&dopt=Abstract

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Development of a computer-aided surgery system: three-dimensional graphic reconstruction for treatment of liver cancer. Author(s): Hashimoto D, Dohi T, Tsuzuki M, Horiuchi T, Ohta Y, Chinzei K, Suzuki M, Idezuki Y. Source: Surgery. 1991 May; 109(5): 589-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1850556&dopt=Abstract

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Diabetes mellitus and the risk of primary liver cancer. Author(s): La Vecchia C, Negri E, Decarli A, Franceschi S. Source: International Journal of Cancer. Journal International Du Cancer. 1997 October 9; 73(2): 204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9335443&dopt=Abstract

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Diagnosis of metastatic liver cancer. Author(s): Franco JA, Schwartz MA. Source: Jama : the Journal of the American Medical Association. 1984 September 14; 252(10): 1279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6471241&dopt=Abstract

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Diagnosis of metastatic liver cancer. Author(s): Jewel KL. Source: Jama : the Journal of the American Medical Association. 1984 January 13; 251(2): 216-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6690778&dopt=Abstract

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Diagnosis of metastatic liver cancer. Author(s): Silberstein EB. Source: Jama : the Journal of the American Medical Association. 1983 June 24; 249(24): 3305-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6854865&dopt=Abstract

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Diagnosis of primary liver cancer using lectin affinity chromatography of serum alkaline phosphatase. Author(s): Lu Y, Lu Q, Chen HL. Source: J Exp Clin Cancer Res. 1997 March; 16(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9148865&dopt=Abstract

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Diagnostic accuracy of primary liver cancer: implications for cancer registration. Author(s): Donato F, Rodella S, Chiesa R, Picoco C, Donati LF, Nardi G. Source: Tumori. 1995 March-April; 81(2): 86-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7778224&dopt=Abstract

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Diagnostic and prognostic value of the determination of the aminopropeptide of type III procollagen in patients with primary liver cancer. Author(s): Farinati F, Annoni G, Donato MF, Nardelli P, Bertozzo A, De Maria N, Zotti S, Salvagnini M, Martinez D, Naccarato R. Source: Journal of Gastroenterology and Hepatology. 1990 November-December; 5(6): 633-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1966598&dopt=Abstract

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Discriminant analysis in the clinical and biochemical diagnosis of primary liver cancer. Author(s): Farinati F, Varnier M, Piccoli A, Caldironi MW, Zotti S, Plebani M, Di Mario F, Naccarato R. Source: J Med. 1986; 17(5-6): 347-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2438364&dopt=Abstract

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Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report. Author(s): Lee K, Chan K, Leung WT, Leung NW, Ho S, Chan M, Lau CC, Tao M, Lau WY, Shiu W. Source: Eur J Drug Metab Pharmacokinet. 1992 July-September; 17(3): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1337040&dopt=Abstract

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Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients. Author(s): Marchio A, Pineau P, Meddeb M, Terris B, Tiollais P, Bernheim A, Dejean A. Source: Oncogene. 2000 August 3; 19(33): 3733-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10949927&dopt=Abstract

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Do asymptomatic, long term carriers of hepatitis B virus develop liver cancer? Author(s): Munjal DD. Source: Clinical Biochemistry. 1981 December; 14(6): 316-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6174255&dopt=Abstract

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Does hepatitis B virus play a role in primary liver cancer in children of Western countries? Author(s): Pontisso P, Basso G, Perilongo G, Morsica G, Cecchetto G, Ruvoletto MG, Alberti A. Source: Cancer Detection and Prevention. 1991; 15(5): 363-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1661202&dopt=Abstract

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Effect of arterial administration of a high molecular weight anti-tumor agent, styrene maleic acid neocarzinostatin, for multiple small liver cancer--a pilot study. Author(s): Ikeda K, Saitoh S, Suzuki Y, Tsubota A, Koida I, Kobayashi M, Arase Y, Chayama K, Murashima N, Kumada H. Source: Journal of Gastroenterology. 1997 August; 32(4): 513-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9250900&dopt=Abstract

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Effect of the molar ratio of branched-chain to aromatic amino acids on growth and albumin mRNA expression of human liver cancer cell lines in a serum-free medium. Author(s): Saito Y, Saito H, Nakamura M, Wakabayashi K, Takagi T, Ebinuma H, Ishii H. Source: Nutrition and Cancer. 2001; 39(1): 126-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588894&dopt=Abstract

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Effects of matrix metalloproteinase inhibitor BB-94 on liver cancer growth and metastasis in a patient-like orthotopic model LCI-D20. Author(s): Bu W, Tang ZY, Sun FX, Ye SL, Liu KD, Xue Q, Chen J, Gao DM. Source: Hepatogastroenterology. 1998 July-August; 45(22): 1056-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9756006&dopt=Abstract

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Effects of radiation on incidence of primary liver cancer among atomic bomb survivors. Author(s): Cologne JB, Tokuoka S, Beebe GW, Fukuhara T, Mabuchi K. Source: Radiation Research. 1999 October; 152(4): 364-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10477913&dopt=Abstract

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Energy blocker to treat liver cancer. Author(s): Foubister V. Source: Drug Discovery Today. 2002 September 15; 7(18): 934-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546860&dopt=Abstract

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Epidemiologic study of the relationship between schistosomiasis due to Schistosoma japonicum and liver cancer/cirrhosis. Author(s): Takemura Y, Kikuchi S, Inaba Y. Source: The American Journal of Tropical Medicine and Hygiene. 1998 October; 59(4): 551-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9790429&dopt=Abstract

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Epidemiology of liver cancer in Europe. Author(s): Bosch FX, Ribes J. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 July-August; 14(7): 621-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10978949&dopt=Abstract

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Epidemiology of liver cancer in Indonesia. Author(s): Marwoto W, Diana S, Roostini ES. Source: Southeast Asian J Trop Med Public Health. 1985 December; 16(4): 607-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3012789&dopt=Abstract

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Epidemiology of liver cancer in Italy with special regard to the autopsy studies in Trieste. Author(s): Melato M, Zanconati F. Source: Rev Gastroenterol Peru. 1990; 10(3): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1966610&dopt=Abstract

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Epidemiology of primary liver cancer. Author(s): Bosch FX, Ribes J, Borras J. Source: Seminars in Liver Disease. 1999; 19(3): 271-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10518307&dopt=Abstract

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Estrogens, testosterone and sex hormone binding globulin in relation to liver cancer in men. Author(s): Kuper H, Mantzoros C, Lagiou P, Tzonou A, Tamimi R, Mucci L, Benetou V, Spanos E, Stuver SO, Trichopoulos D. Source: Oncology. 2001; 60(4): 355-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408804&dopt=Abstract

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Evaluation of 3D image registration as applied to MR-guided thermal treatment of liver cancer. Author(s): Wilson DL, Carrillo A, Zheng L, Genc A, Duerk JL, Lewin JS. Source: Journal of Magnetic Resonance Imaging : Jmri. 1998 January-February; 8(1): 7784. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9500264&dopt=Abstract

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Evaluation of prognosis by hepatoscintigraphy in patients with metastatic liver cancer. Author(s): Okazaki N, Yoshino M, Yoshida T, Oyamada H. Source: Clin Oncol. 1980 September; 6(3): 243-51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7428202&dopt=Abstract

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Excess risk of primary liver cancer in patients with diabetes mellitus. Author(s): Adami HO, Chow WH, Nyren O, Berne C, Linet MS, Ekbom A, Wolk A, McLaughlin JK, Fraumeni JF Jr. Source: Journal of the National Cancer Institute. 1996 October 16; 88(20): 1472-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8841022&dopt=Abstract

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Experimental and bioinformatics comparison of gene expression between T cells from TIL of liver cancer and T cells from UniGene. Author(s): Li B, Perabekam S, Liu G, Yin M, Song S, Larson A. Source: Journal of Gastroenterology. 2002; 37(4): 275-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11993511&dopt=Abstract

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Exposure biomarkers in chemoprevention studies of liver cancer. Author(s): Wild CP, Turner PC. Source: Iarc Sci Publ. 2001; 154: 215-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11220661&dopt=Abstract

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Exposure to N-nitroso compounds in a population of high liver cancer regions in Thailand: volatile nitrosamine (VNA) levels in Thai food. Author(s): Mitacek EJ, Brunnemann KD, Suttajit M, Martin N, Limsila T, Ohshima H, Caplan LS. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 1999 April; 37(4): 297-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10418946&dopt=Abstract

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Expression of liver cancer associated gene HCCA3. Author(s): Wang ZX, Hu GF, Wang HY, Wu MC. Source: World Journal of Gastroenterology : Wjg. 2001 December; 7(6): 821-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854909&dopt=Abstract

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Expression of sialyl-Tn, Tn and T antigens in primary liver cancer. Author(s): Sasaki M, Yamato T, Nakanuma Y. Source: Pathology International. 1999 April; 49(4): 325-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10365852&dopt=Abstract

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Extent of pathologic invasion of the inferior vena cava in resected liver cancer compared with possible caval invasion diagnosed by preoperative images. Author(s): Maeba T, Okano K, Mori S, Karasawa Y, Goda F, Wakabayashi H, Usuki H, Maeta H. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2000; 7(3): 299-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982630&dopt=Abstract

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Factors influencing primary liver cancer resection survival rate. Author(s): Tang ZY, Yu YQ, Zhou XD, Chen QM. Source: Chinese Medical Journal. 1981 November; 94(11): 749-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6174276&dopt=Abstract

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Fibrolamellar hepatic carcinoma in an area with a low incidence of primary liver cancer: a retrospective study. Author(s): Kaczynski J, Gustavsson B, Hansson G, Wallerstedt S. Source: The European Journal of Surgery = Acta Chirurgica. 1996 May; 162(5): 367-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8781917&dopt=Abstract

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Follow-up study of HBs Ag-positive blood donors with special reference to effect of drinking and smoking on development of liver cancer. Author(s): Oshima A, Tsukuma H, Hiyama T, Fujimoto I, Yamano H, Tanaka M. Source: International Journal of Cancer. Journal International Du Cancer. 1984 December 15; 34(6): 775-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6511124&dopt=Abstract

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Frequent rearrangements of chromosomes 1, 7, and 8 in primary liver cancer. Author(s): Parada LA, Hallen M, Tranberg KG, Hagerstrand I, Bondeson L, Mitelman F, Johansson B. Source: Genes, Chromosomes & Cancer. 1998 September; 23(1): 26-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713994&dopt=Abstract

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Fumonisins as a possible contributory risk factor for primary liver cancer: a 3-year study of corn harvested in Haimen, China, by HPLC and ELISA. Author(s): Ueno Y, Iijima K, Wang SD, Sugiura Y, Sekijima M, Tanaka T, Chen C, Yu SZ. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 1997 December; 35(12): 1143-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9449219&dopt=Abstract

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Functional inactivation but not structural mutation of p53 causes liver cancer. Author(s): Ueda H, Ullrich SJ, Gangemi JD, Kappel CA, Ngo L, Feitelson MA, Jay G. Source: Nature Genetics. 1995 January; 9(1): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7704023&dopt=Abstract

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GB virus-C/hepatitis G virus infection in an area endemic for viral hepatitis, chronic liver disease, and liver cancer. Author(s): Kao JH, Chen PJ, Lai MY, Chen W, Liu DP, Wang JT, Shen MC, Chen DS. Source: Gastroenterology. 1997 April; 112(4): 1265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9098011&dopt=Abstract

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Gene expression profiling of preneoplastic liver disease and liver cancer: a new era for improved early detection and treatment of these deadly diseases? Author(s): Kim JW, Wang XW. Source: Carcinogenesis. 2003 March; 24(3): 363-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663493&dopt=Abstract

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Gene transfer to liver cancer cells of B7-1 plus interleukin 12 changes immunoeffector mechanisms and suppresses helper T cell type 1 cytokine production induced by interleukin 12 alone. Author(s): Sun Y, Qian C, Peng D, Prieto J. Source: Human Gene Therapy. 2000 January 1; 11(1): 127-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10646645&dopt=Abstract

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Genistein is an effective stimulator of sex hormone-binding globulin production in hepatocarcinoma human liver cancer cells and suppresses proliferation of these cells in culture. Author(s): Mousavi Y, Adlercreutz H. Source: Steroids. 1993 July; 58(7): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8212077&dopt=Abstract

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Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. Author(s): Tseng TL, Shih YP, Huang YC, Wang CK, Chen PH, Chang JG, Yeh KT, Chen YM, Buetow KH. Source: Cancer Research. 2003 February 1; 63(3): 647-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566309&dopt=Abstract

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Glutathione S-transferases in human liver cancer. Author(s): Hayes PC, May L, Hayes JD, Harrison DJ. Source: Gut. 1991 December; 32(12): 1546-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1663474&dopt=Abstract

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Growth inhibition by the farnesyltransferase inhibitor FTI-277 involves Bcl-2 expression and defective association with Raf-1 in liver cancer cell lines. Author(s): Mazzocca A, Giusti S, Hamilton AD, Sebti SM, Pantaleo P, Carloni V. Source: Molecular Pharmacology. 2003 January; 63(1): 159-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488548&dopt=Abstract

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Growth inhibition of human liver cancer cells by alpha-fetoprotein antisense strategy. Author(s): Wang XW, Xie H. Source: In Vitro Cellular & Developmental Biology. Animal. 1999 March; 35(3): 118-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10476906&dopt=Abstract

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Guidelines for treatment of liver cancer. Author(s): Livraghi T. Source: European Journal of Ultrasound : Official Journal of the European Federation of Societies for Ultrasound in Medicine and Biology. 2001 June; 13(2): 167-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11369528&dopt=Abstract

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HCV infection and liver cancer mortality in a Japanese population with HTLV-I. Author(s): Stuver SO, Okayama A, Tachibana N, Tsubouchi H, Mueller NE, Tabor E. Source: International Journal of Cancer. Journal International Du Cancer. 1996 July 3; 67(1): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8690522&dopt=Abstract

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HCV-associated liver cancer. Author(s): Tong CY, Gilmore IT, Hart CA. Source: Lancet. 1995 April 22; 345(8956): 1058-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7723533&dopt=Abstract

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Hepatectomy for huge primary liver cancer: report of 171 patients. Author(s): Chen X, Wu Z, Qiu F. Source: Zhonghua Wai Ke Za Zhi. 2000 January; 38(1): 6-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831974&dopt=Abstract

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Hepatectomy for primary liver cancer in 114 cases. A follow-up study with long-term results. Author(s): Li GC, Wang CE, Zhu SL, Deng ZC, Li GH, Wan DS, Li JQ, Zhan YQ. Source: Chinese Medical Journal. 1985 May; 98(5): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2990825&dopt=Abstract

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Hepatic radioembolization with Yttrium-90 glass microspheres for treatment of primary liver cancer. Author(s): Cao X, He N, Sun J, Tan J, Zhang C, Yang J, Lu T, Li J. Source: Chinese Medical Journal. 1999 May; 112(5): 430-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593513&dopt=Abstract

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Hepatic segmentectomy on primary liver cancer with situs inversus totalis. Author(s): Kamiike W, Itakura T, Tanaka H, Hatanaka N, Nakamuro M, Miyata M, Izumi H. Source: Hpb Surg. 1996; 9(3): 169-72; Discussion 172-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8725459&dopt=Abstract

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Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea. Author(s): Shin HR, Lee CU, Park HJ, Seol SY, Chung JM, Choi HC, Ahn YO, Shigemastu T. Source: International Journal of Epidemiology. 1996 October; 25(5): 933-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8921477&dopt=Abstract

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Hepatitis B and C viruses and primary liver cancer. Author(s): Brechot C. Source: Baillieres Clin Gastroenterol. 1996 July; 10(2): 335-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8864037&dopt=Abstract

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Hepatitis B infection and primary liver cancer. Author(s): Maupas P, Melnick JL. Source: Prog Med Virol. 1981; 27: 1-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6262862&dopt=Abstract

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Hepatitis B vaccination and reduced risk of primary liver cancer among male adults: a cohort study in Korea. Author(s): Lee MS, Kim DH, Kim H, Lee HS, Kim CY, Park TS, Yoo KY, Park BJ, Ahn YO. Source: International Journal of Epidemiology. 1998 April; 27(2): 316-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9602416&dopt=Abstract

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Hepatitis B virus infection and primary liver cancer--an unfolding story. Author(s): Shafritz DA. Source: The Western Journal of Medicine. 1984 May; 140(5): 776-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6328775&dopt=Abstract

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Hepatitis viruses, schistosomal infection and liver cancer in Egypt. Author(s): Bedwani R, El-Khwsky F, El-Shazly M, Seif HA, Zaki A, Renganathan E, La Vecchia C. Source: International Journal of Cancer. Journal International Du Cancer. 1996 November 27; 68(5): 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8938154&dopt=Abstract

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High concentrations of N-terminal peptide of type III procollagen in the sera of patients with various cancers, with special reference to liver cancer. Author(s): Hatahara T, Igarashi S, Funaki N. Source: Gann. 1984 February; 75(2): 130-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6735030&dopt=Abstract

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High mortality rates from liver cancer in the urban area of Campania Region: prevalence of hepatitis and sociodemographic factors. Author(s): Montella M, Bidoli E, De Marco MR, Iannuzzo M, Fusco M, Palombino R, Franceschi S, Monfardini S. Source: Oncol Rep. 1998 January-February; 5(1): 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9458315&dopt=Abstract

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HIP/PAP gene, encoding a C-type lectin overexpressed in primary liver cancer, is expressed in nervous system as well as in intestine and pancreas of the postimplantation mouse embryo. Author(s): Lasserre C, Colnot C, Brechot C, Poirier F. Source: American Journal of Pathology. 1999 May; 154(5): 1601-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10329612&dopt=Abstract

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Human CRYL1, a novel enzyme-crystallin overexpressed in liver and kidney and downregulated in 58% of liver cancer tissues from 60 Chinese patients, and four new homologs from other mammalians. Author(s): Chen J, Yu L, Li D, Gao Q, Wang J, Huang X, Bi G, Wu H, Zhao S. Source: Gene. 2003 January 2; 302(1-2): 103-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527201&dopt=Abstract

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Human fetuin/alpha2HS-glycoprotein level as a novel indicator of liver cell function and short-term mortality in patients with liver cirrhosis and liver cancer. Author(s): Kalabay L, Jakab L, Prohaszka Z, Fust G, Benko Z, Telegdy L, Lorincz Z, Zavodszky P, Arnaud P, Fekete B. Source: European Journal of Gastroenterology & Hepatology. 2002 April; 14(4): 389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11943951&dopt=Abstract

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Human liver cancer cells and endothelial cells incorporate iodised oil. Author(s): Bhattacharya S, Dhillon AP, Winslet MC, Davidson BR, Shukla N, Gupta SD, Al-Mufti R, Hobbs KE. Source: British Journal of Cancer. 1996 April; 73(7): 877-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8611399&dopt=Abstract

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Hunting for tumor suppressor genes in liver cancer. Author(s): Thorgeirsson SS. Source: Hepatology (Baltimore, Md.). 2003 April; 37(4): 739-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668963&dopt=Abstract

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Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites: the Paris Prospective Study. Author(s): Balkau B, Kahn HS, Courbon D, Eschwege E, Ducimetiere P; Paris Prospective Study. Source: Diabetes Care. 2001 May; 24(5): 843-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11347741&dopt=Abstract

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Identification and characterization of nine novel human small GTPases showing variable expressions in liver cancer tissues. Author(s): He H, Dai F, Yu L, She X, Zhao Y, Jiang J, Chen X, Zhao S. Source: Gene Expression. 2002; 10(5-6): 231-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450215&dopt=Abstract

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IHPBA concordant classification of primary liver cancer: working group report. Author(s): Makuuchi M, Belghiti J, Belli G, Fan ST, Lau JW, Ringe B, Strasberg SM, Vauthey JN, Yamaoka Y, Yamasaki S; Working Group of the International Scientific Committee of the International Hepato-Pancreato-Biliary Association. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2003; 10(1): 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918454&dopt=Abstract

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Impacts of chemicals on liver cancer risk. Author(s): Wogan GN. Source: Seminars in Cancer Biology. 2000 June; 10(3): 201-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936069&dopt=Abstract

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In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3. Author(s): Pourgholami MH, Akhter J, Lu Y, Morris DL. Source: Cancer Letters. 2000 April 3; 151(1): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766428&dopt=Abstract

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Increased level of serum hepatocyte growth factor/scatter factor in liver cancer is associated with tumor metastasis. Author(s): Junbo H, Li Q, Zaide W, Yunde H. Source: In Vivo. 1999 March-April; 13(2): 177-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10363175&dopt=Abstract

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Increased morbidity odds ratio of primary liver cancer and cirrhosis of the liver among vinyl chloride monomer workers. Author(s): Du CL, Wang JD. Source: Occupational and Environmental Medicine. 1998 August; 55(8): 528-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849539&dopt=Abstract

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Increased mortality from liver cancer in England and Wales is not related to hepatitis C. Author(s): Taylor-Robinson SD, Thomas HC, Arora S, Hargreaves S. Source: Bmj (Clinical Research Ed.). 1999 September 4; 319(7210): 640. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473489&dopt=Abstract

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Increased mortality odds ratio of male liver cancer in a community contaminated by chlorinated hydrocarbons in groundwater. Author(s): Lee LJ, Chung CW, Ma YC, Wang GS, Chen PC, Hwang YH, Wang JD. Source: Occupational and Environmental Medicine. 2003 May; 60(5): 364-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709523&dopt=Abstract

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Indications and results of liver transplantation for primary and metastatic liver cancer. Author(s): Koffron A, Fryer JP, Abecassis M. Source: Cancer Treat Res. 2001; 109: 77-99. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775446&dopt=Abstract

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Inhibition of proliferation, invasion and adhesion of liver cancer cells by 5azacytidine and butyrate. Author(s): Wang XM, Li J, Evers BM. Source: Anticancer Res. 1999 July-August; 19(4B): 2901-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10652571&dopt=Abstract

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Inhibitory effects of synthetic beta peptide on invasion and metastasis of liver cancer. Author(s): Sun JJ, Zhou XD, Liu YK, Tang ZY, Sun RX, Zhao Y, Uemura T. Source: Journal of Cancer Research and Clinical Oncology. 2000 October; 126(10): 595600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043397&dopt=Abstract

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Insulin-like growth factor 1 in hepatocellular carcinoma and metastatic liver cancer in men. Author(s): Stuver SO, Kuper H, Tzonou A, Lagiou P, Spanos E, Hsieh CC, Mantzoros C, Trichopoulos D. Source: International Journal of Cancer. Journal International Du Cancer. 2000 July 1; 87(1): 118-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10861461&dopt=Abstract

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Interaction of vinyl chloride monomer exposure and hepatitis B viral infection on liver cancer. Author(s): Wong RH, Chen PC, Wang JD, Du CL, Cheng TJ. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2003 April; 45(4): 379-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708141&dopt=Abstract

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Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer. Author(s): Ikeda K, Arase Y, Saitoh S, Kobayashi M, Suzuki Y, Suzuki F, Tsubota A, Chayama K, Murashima N, Kumada H. Source: Hepatology (Baltimore, Md.). 2000 August; 32(2): 228-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10915728&dopt=Abstract

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International trends and patterns of primary liver cancer. Author(s): McGlynn KA, Tsao L, Hsing AW, Devesa SS, Fraumeni JF Jr. Source: International Journal of Cancer. Journal International Du Cancer. 2001 October 15; 94(2): 290-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668511&dopt=Abstract

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Intraoperative ultrasonography in liver cancer. Author(s): Torzilli G, Makuuchi M. Source: Surg Oncol Clin N Am. 2003 January; 12(1): 91-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735132&dopt=Abstract

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Invasion and metastasis of liver cancer: expression of intercellular adhesion molecule 1. Author(s): Sun JJ, Zhou XD, Liu YK, Tang ZY, Feng JX, Zhou G, Xue Q, Chen J. Source: Journal of Cancer Research and Clinical Oncology. 1999; 125(1): 28-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10037274&dopt=Abstract

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IP6 in treatment of liver cancer. I. IP6 inhibits growth and reverses transformed phenotype in HepG2 human liver cancer cell line. Author(s): Vucenik I, Tantivejkul K, Zhang ZS, Cole KE, Saied I, Shamsuddin AM. Source: Anticancer Res. 1998 November-December; 18(6A): 4083-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891449&dopt=Abstract

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IP6 in treatment of liver cancer. II. Intra-tumoral injection of IP6 regresses preexisting human liver cancer xenotransplanted in nude mice. Author(s): Vucenik I, Zhang ZS, Shamsuddin AM. Source: Anticancer Res. 1998 November-December; 18(6A): 4091-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891450&dopt=Abstract

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It could have been something they ate -- functional food and the treatment of liver cancer. Author(s): Bass NM. Source: Journal of Hepatology. 2002 July; 37(1): 147-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076875&dopt=Abstract

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Kidney cancer, leukemia, and liver cancer. Part 3. Author(s): Kemp C. Source: Am J Hosp Palliat Care. 1999 March-April; 16(2): 479-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10232125&dopt=Abstract

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Laparoscopic in situ ablation of liver cancer with cryotherapy and radiofrequency ablation. Author(s): Tait IS, Yong SM, Cuschieri SA. Source: The British Journal of Surgery. 2002 December; 89(12): 1613-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445075&dopt=Abstract

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Large primary liver cancer treated by chemoembolization combined with radiotherapy successfully. Author(s): Guo WJ, Yu EX. Source: Hepatogastroenterology. 2003 March-April; 50(50): 519-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749262&dopt=Abstract

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Limited hepatic resection effective for selected cirrhotic patients with primary liver cancer. Author(s): Kanematsu T, Takenaka K, Matsumata T, Furuta T, Sugimachi K, Inokuchi K. Source: Annals of Surgery. 1984 January; 199(1): 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6318677&dopt=Abstract

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Liver and circulating NK1.1(+)CD3(-) cells are increased in infection with attenuated Salmonella typhimurium and are associated with reduced tumor in murine liver cancer. Author(s): Feltis BA, Miller JS, Sahar DA, Kim AS, Saltzman DA, Leonard AS, Wells CL, Sielaff TD. Source: The Journal of Surgical Research. 2002 September; 107(1): 101-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384070&dopt=Abstract

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Liver cancer among employees in Denmark. Author(s): Dossing M, Petersen KT, Vyberg M, Olsen JH. Source: American Journal of Industrial Medicine. 1997 September; 32(3): 248-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9219654&dopt=Abstract

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Liver cancer imaging: the need for accurate detection of intrahepatic disease spread. Author(s): Solbiati L, Cova L, Ierace T, Marelli P, Dellanoce M. Source: Journal of Computer Assisted Tomography. 1999 November; 23 Suppl 1: S29-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608395&dopt=Abstract

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Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses. Author(s): Fukuhara T, Sharp GB, Mizuno T, Itakura H, Yamamoto M, Tokunaga M, Tokuoka S, Cologne JB, Fujita Y, Soda M, Mabuchi K. Source: Journal of Radiation Research. 2001 June; 42(2): 117-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599879&dopt=Abstract

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Liver cancer in low and middle income countries. Author(s): Hall AJ, Wild CP. Source: Bmj (Clinical Research Ed.). 2003 May 10; 326(7397): 994-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742895&dopt=Abstract

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Liver cancer in Taiwan falls after universal hepatitis B vaccination. Author(s): Mayor S. Source: Bmj (Clinical Research Ed.). 1997 July 5; 315(7099): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9233314&dopt=Abstract

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Liver cancer mortality in Japan. Author(s): Tsukada T. Source: Japanese Journal of Clinical Oncology. 1998 November; 28(11): 713-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9861242&dopt=Abstract

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Liver cancer mortality rates by prefectures in Japan. Author(s): Yamamoto S. Source: Japanese Journal of Clinical Oncology. 2000 November; 30(11): 525. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11155926&dopt=Abstract

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Liver cancer risk is increased in patients with porphyria cutanea tarda in comparison to matched control patients with chronic liver disease. Author(s): Fracanzani AL, Taioli E, Sampietro M, Fatta E, Bertelli C, Fiorelli G, Fargion S. Source: Journal of Hepatology. 2001 October; 35(4): 498-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682034&dopt=Abstract

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Liver cancer toll high in Japan. Author(s): Easton A. Source: Bmj (Clinical Research Ed.). 1999 June 5; 318(7197): 1510. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10356000&dopt=Abstract

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Liver cancer, the prevention and control in Thailand. Author(s): Phornphutkul K. Source: Gan to Kagaku Ryoho. 2002 February; 29 Suppl 1: 209-13. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890107&dopt=Abstract

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Liver cancer. Author(s): Aguayo A, Patt YZ. Source: Clinics in Liver Disease. 2001 May; 5(2): 479-507. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11385973&dopt=Abstract

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Liver cancer. Author(s): Oberfield RA, Steele G Jr, Gollan JL, Sherman D. Source: Ca: a Cancer Journal for Clinicians. 1989 July-August; 39(4): 206-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2547500&dopt=Abstract

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Liver cirrhosis and the risk of primary liver cancer. Author(s): La Vecchia C, Negri E, Cavalieri d'Oro L, Franceschi S. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 1998 August; 7(4): 315-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806120&dopt=Abstract

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Liver transplantation followed by adjuvant nonmyeloablative hemopoietic stem cell transplantation for advanced primary liver cancer in humans. Author(s): Soderdahl G, Barkholt L, Hentschke P, Mattsson J, Uzunel M, Ericzon BG, Ringden O. Source: Transplantation. 2003 April 15; 75(7): 1061-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698103&dopt=Abstract

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Liver transplantation for primary liver cancer. Author(s): Ringe B, Canelo R, Lorf T. Source: Transplantation Proceedings. 1996 June; 28(3): 1174-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8658616&dopt=Abstract

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LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Author(s): Mouta Carreira C, Nasser SM, di Tomaso E, Padera TP, Boucher Y, Tomarev SI, Jain RK. Source: Cancer Research. 2001 November 15; 61(22): 8079-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719431&dopt=Abstract

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M2 alpha-1-antitrypsin phenotype and primary liver cancer. Author(s): Sizaret P, Clerc M, Esteve J, Frants RR, Pillot J. Source: British Journal of Cancer. 1981 February; 43(2): 226-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6970588&dopt=Abstract

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Magnesium in drinking water and liver cancer morbidity--a possible relation? Author(s): Tukiendorf A. Source: Cent Eur J Public Health. 2002 December; 10(4): 157-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528390&dopt=Abstract

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Magnesium in drinking water and the risk of death from liver cancer. Author(s): Yang CY, Chiu HF, Tsai SS, Chang CC, Chuang HY. Source: Magnes Res. 2002 December; 15(3-4): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635876&dopt=Abstract

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Magnetic resonance imaging (MRI) of primary liver cancer--MRI-pathologic correlation. Author(s): Ohtomo K, Itai Y, Furui S, Yoshikawa K, Yashiro N, Iio M. Source: Radiat Med. 1985 January-March; 3(1): 38-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2999880&dopt=Abstract

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Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. Author(s): Lin SY, Liu JD, Chang HC, Yeh SD, Lin CH, Lee WS. Source: Journal of Cellular Biochemistry. 2002; 84(3): 532-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813258&dopt=Abstract

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Massive culture of human liver cancer cells in a newly developed radial flow bioreactor system: ultrafine structure of functionally enhanced hepatocarcinoma cell lines. Author(s): Kawada M, Nagamori S, Aizaki H, Fukaya K, Niiya M, Matsuura T, Sujino H, Hasumura S, Yashida H, Mizutani S, Ikenaga H. Source: In Vitro Cellular & Developmental Biology. Animal. 1998 February; 34(2): 10915. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9542647&dopt=Abstract

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May primary liver cancer induce a graft-versus-tumor effect? Author(s): Sirvent-von Bueltzingsloewen A, Gratecos N, Fuzibet JG, Cassuto JP. Source: Bone Marrow Transplantation. 2003 February; 31(4): 317-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621473&dopt=Abstract

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Membrane fluidity correlates with liver cancer cell proliferation and infiltration potential. Author(s): Funaki NO, Tanaka J, Kohmoto M, Sugiyama T, Ohshio G, Nonaka A, Yotsumoto F, Takeda Y, Imamura M. Source: Oncol Rep. 2001 May-June; 8(3): 527-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295074&dopt=Abstract

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Metastatic models of human liver cancer in nude mice orthotopically constructed by using histologically intact patient specimens. Author(s): Sun FX, Tang ZY, Liu KD, Xue Q, Gao DM, Yu YQ, Zhou XD, Ma ZC. Source: Journal of Cancer Research and Clinical Oncology. 1996; 122(7): 397-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8690749&dopt=Abstract

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Microwave coagulation therapy for liver cancer: laparoscopic microwave coagulation. Author(s): Ido K, Isoda N, Sugano K. Source: Journal of Gastroenterology. 2001 March; 36(3): 145-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11291876&dopt=Abstract

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Minute liver cancer and concomitant esophageal varices: detection and successful surgical treatment. Author(s): Kanematsu T, Sugimachi K, Kohno H, Matsumata T, Kobayashi M, Inokuchi K. Source: World Journal of Surgery. 1981 September; 5(5): 707-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6277091&dopt=Abstract

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Molecular biomarkers for aflatoxins: from adducts to gene mutations to human liver cancer. Author(s): Groopman JD, Wang JS, Scholl P. Source: Canadian Journal of Physiology and Pharmacology. 1996 February; 74(2): 203-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8723033&dopt=Abstract

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Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum. Author(s): Chang YC, Ho CL, Chen HH, Chang TT, Lai WW, Dai YC, Lee WY, Chow NH. Source: British Journal of Cancer. 2002 December 2; 87(12): 1449-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454776&dopt=Abstract

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Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells. Author(s): Lin SY, Chang YT, Liu JD, Yu CH, Ho YS, Lee YH, Lee WS. Source: Molecular Carcinogenesis. 2001 October; 32(2): 73-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746819&dopt=Abstract

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Molecular mechanisms of hepatitis B virus-associated liver cancer. Author(s): Rabe C, Cheng B, Caselmann WH. Source: Digestive Diseases (Basel, Switzerland). 2001; 19(4): 279-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11935087&dopt=Abstract

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Mortality associated with oral contraceptive use. Relative risk of liver cancer remains high. Author(s): Horowitz J. Source: Bmj (Clinical Research Ed.). 1999 August 7; 319(7206): 386. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10490326&dopt=Abstract

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Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C. UK Haemophilia Centre Directors' Organisation. Author(s): Darby SC, Ewart DW, Giangrande PL, Spooner RJ, Rizza CR, Dusheiko GM, Lee CA, Ludlam CA, Preston FE. Source: Lancet. 1997 November 15; 350(9089): 1425-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9371165&dopt=Abstract

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Mortality trend of liver cancer in Japan: 1960-2000. Author(s): Yoshimi I, Sobue T. Source: Japanese Journal of Clinical Oncology. 2003 April; 33(4): 202-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816081&dopt=Abstract

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Multifactoral etiology of human liver cancer. Author(s): Harris CC, Sun T. Source: Carcinogenesis. 1984 June; 5(6): 697-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6327110&dopt=Abstract

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Multistage theory of carcinogenesis: the epidemiological evidence for liver cancer. Author(s): Kaldor JM, Bosch FX. Source: Bulletin Du Cancer. 1990; 77(5): 515-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2400827&dopt=Abstract

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Natural history of liver cancer. Author(s): Domellof L. Source: Ann Chir Gynaecol Suppl. 1986; 200: 19-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3014986&dopt=Abstract

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New treatments with curative intent for metastatic colorectal liver cancer. Author(s): Kadry Z, Clavien PA. Source: Expert Opinion on Pharmacotherapy. 2002 August; 3(8): 1191-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150696&dopt=Abstract

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Nonassociation of aflatoxin with primary liver cancer in a cross-sectional ecological survey in the People's Republic of China. Author(s): Campbell TC, Chen JS, Liu CB, Li JY, Parpia B. Source: Cancer Research. 1990 November 1; 50(21): 6882-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2208157&dopt=Abstract

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Novel drug delivery device may improve liver cancer outcomes. Author(s): Reidenbach F. Source: The Lancet Oncology. 2002 August; 3(8): 450. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147418&dopt=Abstract

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Novel treatments for liver cancer and other solid tumors show early promise. Author(s): Skolnick AA. Source: Jama : the Journal of the American Medical Association. 1994 June 15; 271(23): 1813-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8196128&dopt=Abstract

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Nutritional pharmacotherapy of chronic liver disease: from support of liver failure to prevention of liver cancer. Author(s): Moriwaki H, Tajika M, Miwa Y, Kato M, Yasuda I, Shiratori Y, Okuno M, Kato T, Ohnishi H, Muto Y. Source: Journal of Gastroenterology. 2000; 35 Suppl 12: 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10779208&dopt=Abstract

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Observation of changes in peripheral T-lymphocyte subsets by flow cytometry in patients with liver cancer treated with radioimmunotherapy. Author(s): Zeng ZC, Tang ZY, Liu KD, Yu YQ, Yang BH, Cai XJ, Xie H, Cao SL. Source: Nuclear Medicine Communications. 1995 May; 16(5): 378-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7659390&dopt=Abstract

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Occupational and non-occupational risk factors in relation to an excess of primary liver cancer observed among residents of Brooklyn, New York. Author(s): Fleisher JM. Source: Cancer. 1990 January 1; 65(1): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2293864&dopt=Abstract

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Occupational exposure and liver cancer in women: results of the Multicentre International Liver Tumour Study (MILTS). Author(s): Heinemann K, Willich SN, Heinemann LA, DoMinh T, Mohner M, Heuchert GE. Source: Occupational Medicine (Oxford, England). 2000 August; 50(6): 422-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994245&dopt=Abstract

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Occupational risk factors and liver cancer. A retrospective case-control study of primary liver cancer in New Jersey. Author(s): Stemhagen A, Slade J, Altman R, Bill J. Source: American Journal of Epidemiology. 1983 April; 117(4): 443-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6837558&dopt=Abstract

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Occupational risks for primary liver cancer in Shanghai, China. Author(s): Chow WH, McLaughlin JK, Zheng W, Blot WJ, Gao YT. Source: American Journal of Industrial Medicine. 1993 July; 24(1): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8352295&dopt=Abstract

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Occurrence of an atypical alkaline phosphatase fraction (“biliary”) in primary liver cancer. Author(s): Burlina A, Plebani M, Dechecchi C, Zaninotto M, Farinati F, Naccarato R. Source: Clinical Biochemistry. 1983 December; 16(6): 346-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6198108&dopt=Abstract

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Oral contraceptive use and liver cancer. Author(s): Palmer JR, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, Shapiro S. Source: American Journal of Epidemiology. 1989 November; 130(5): 878-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2554724&dopt=Abstract

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Oral contraceptives and primary liver cancer among young women. Author(s): Hsing AW, Hoover RN, McLaughlin JK, Co-Chien HT, Wacholder S, Blot WJ, Fraumeni JF Jr. Source: Cancer Causes & Control : Ccc. 1992 January; 3(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1536912&dopt=Abstract

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Oral contraceptives and primary liver cancer. Author(s): La Vecchia C, Negri E, Parazzini F. Source: British Journal of Cancer. 1989 March; 59(3): 460-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2930715&dopt=Abstract

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Oral contraceptives and primary liver cancer: temporal trends in three countries. Author(s): Waetjen LE, Grimes DA. Source: Obstetrics and Gynecology. 1996 December; 88(6): 945-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8942832&dopt=Abstract

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Overexpression of glutamine synthetase in human primary liver cancer. Author(s): Christa L, Simon MT, Flinois JP, Gebhardt R, Brechot C, Lasserre C. Source: Gastroenterology. 1994 May; 106(5): 1312-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7909780&dopt=Abstract

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Paclitaxel promotes liver graft survival in rats and inhibits hepatocellular carcinoma growth in vitro and is a potentially useful drug for transplant patients with liver cancer. Author(s): Iesalnieks I, Tange S, Scherer MN, Graeb C, Frank E, Jauch KW, Geissler EK. Source: Transplantation Proceedings. 2002 September; 34(6): 2316-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270414&dopt=Abstract

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Palliative biliary drainage in metastatic liver cancer: know when to hold 'em, when to fold 'em? Author(s): Baillie J. Source: The American Journal of Gastroenterology. 2003 June; 98(6): 1221-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818260&dopt=Abstract

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Patterns of familial transmission of HBV and the risk of developing liver cancer: a case-control study in the Philippines. Author(s): Munoz N, Lingao A, Lao J, Esteve J, Viterbo G, Domingo EO, Lansang MA. Source: International Journal of Cancer. Journal International Du Cancer. 1989 December 15; 44(6): 981-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2606583&dopt=Abstract

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Peroxisome proliferator-activated receptor alpha: role in rodent liver cancer and species differences. Author(s): Holden PR, Tugwood JD. Source: Journal of Molecular Endocrinology. 1999 February; 22(1): 1-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9924174&dopt=Abstract

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Peroxisome proliferator-activated receptor gamma ligands inhibit cell growth and induce apoptosis in human liver cancer BEL-7402 cells. Author(s): Li MY, Deng H, Zhao JM, Dai D, Tan XY. Source: World Journal of Gastroenterology : Wjg. 2003 August; 9(8): 1683-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918101&dopt=Abstract

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Policy forum: public health. Reducing liver cancer--global control of aflatoxin. Author(s): Henry SH, Bosch FX, Troxell TC, Bolger PM. Source: Science. 1999 December 24; 286(5449): 2453-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10636808&dopt=Abstract

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Prevention of liver cancer and cirrhosis by vaccines. Author(s): Prince AM. Source: Clin Lab Med. 1996 June; 16(2): 493-505. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8792084&dopt=Abstract

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Prevention of liver cancer. Author(s): Guyton KZ, Kensler TW. Source: Current Oncology Reports. 2002 November; 4(6): 464-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354357&dopt=Abstract

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Prevention of liver cancer: basic and clinical aspects. Author(s): Moriwaki H. Source: Experimental & Molecular Medicine. 2002 November 30; 34(5): 319-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526094&dopt=Abstract

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Primary liver cancer and aflatoxin intake in Transkei. Author(s): van Rensburg SJ, van Schalkwyk GC, van Schalkwyk DJ. Source: Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer. 1990 JanuaryApril; 10(1-2): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2231312&dopt=Abstract

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Primary liver cancer and its relationship to chronic infection with the hepatitis B virus. Author(s): Hadziyannis SJ. Source: Springer Seminars in Immunopathology. 1981 April; 3(4): 473-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6267725&dopt=Abstract

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Primary liver cancer and occupation in men: a case-control study in a high-incidence area in Northern Italy. Author(s): Porru S, Placidi D, Carta A, Gelatti U, Ribero ML, Tagger A, Boffetta P, Donato F. Source: International Journal of Cancer. Journal International Du Cancer. 2001 December 15; 94(6): 878-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745492&dopt=Abstract

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Primary liver cancer in the Transvaal. Author(s): van der Merwe CF. Source: Hepatogastroenterology. 1981 October; 28(5): 233-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6178670&dopt=Abstract

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Primary liver cancer with dual expression of hepatocyte and bile duct epithelial markers. Author(s): Uenishi T, Hirohashi K, Shuto T, Tsukamoto T, Yamamoto T, Ogawa M, Kubo S, Tanaka H, Kinoshita H. Source: Hepatogastroenterology. 2002 July-August; 49(46): 1092-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143210&dopt=Abstract

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Primary liver cancer, other malignancies, and mortality risks following porphyria: a cohort study in Denmark and Sweden. Author(s): Linet MS, Gridley G, Nyren O, Mellemkjaer L, Olsen JH, Keehn S, Adami HO, Fraumeni JF Jr. Source: American Journal of Epidemiology. 1999 June 1; 149(11): 1010-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10355376&dopt=Abstract

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Prioritization of patients with liver cancer within the MELD system. Author(s): Roberts JP. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 April; 8(4): 329-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965575&dopt=Abstract

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Prolonged stability and sustained prodrug cell killing activity using receptormediated delivery of malarial circumsporozoite-cytosine deaminase fusion protein into liver cancer cells. Author(s): Lin-Lee YC, Nakamura S, Gandhi V, Curley SA, Stuber D, Burkot TR, Kuo MT. Source: Molecular Cancer Therapeutics. 2002 May; 1(7): 461-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479264&dopt=Abstract

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Prospective study of diabetes mellitus and liver cancer in Japan. Author(s): Fujino Y, Mizoue T, Tokui N, Yoshimura T. Source: Diabetes/Metabolism Research and Reviews. 2001 September-October; 17(5): 374-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747142&dopt=Abstract

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Pulmonary complications after hepatic artery chemoembolization or infusion via the inferior phrenic artery for primary liver cancer. Author(s): Tajima T, Honda H, Kuroiwa T, Yabuuchi H, Okafuji T, Yosimitsu K, Irie H, Aibe H, Masuda K. Source: Journal of Vascular and Interventional Radiology : Jvir. 2002 September; 13(9 Pt 1): 893-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354823&dopt=Abstract

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Radiofrequency ablation of unresectable primary liver cancer. Author(s): Seidenfeld J, Korn A, Aronson N. Source: Journal of the American College of Surgeons. 2002 June; 194(6): 813-28; Discussion 828. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081073&dopt=Abstract

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Re: Excess risk of primary liver cancer in patients with diabetes mellitus. Author(s): Nelson R, Persky V, Davis F, Becker E. Source: Journal of the National Cancer Institute. 1997 February 19; 89(4): 327-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9048838&dopt=Abstract

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Real-time ultrasonography in detection of primary liver cancer in intertropical Africa. Author(s): Tortey E, Coursaget P, Cotty P, Diop T, Barres JL, Sow MT, Yvonnet B, Chiron JP, Pourcelot L. Source: Lancet. 1985 March 2; 1(8427): 514-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2857873&dopt=Abstract

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Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells. Author(s): Ebinuma H, Saito H, Kosuga M, Wakabayashi K, Saito Y, Takagi T, Nakamoto N, Okuyama T, Ishii H. Source: Journal of Cellular Physiology. 2001 July; 188(1): 56-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382922&dopt=Abstract

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Reduction of telomerase activity in human liver cancer cells by a histone deacetylase inhibitor. Author(s): Nakamura M, Saito H, Ebinuma H, Wakabayashi K, Saito Y, Takagi T, Nakamoto N, Ishii H. Source: Journal of Cellular Physiology. 2001 June; 187(3): 392-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11319763&dopt=Abstract

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Regional intra-arterial chemotherapy of metastatic liver cancer. Author(s): Santi L, Civalleri D, Conte PF, Fraschini G, Sertoli MR. Source: Chemioterapia. 1985 October; 4(5): 359-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4075432&dopt=Abstract

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Registries in Japan: current status of hepatocellular carcinoma in Japan. Liver Cancer Study Group of Japan. Author(s): Arii S, Okamoto E, Imamura M. Source: Seminars in Surgical Oncology. 1996 May-June; 12(3): 204-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8727612&dopt=Abstract

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Relationship between cirrhosis, liver cancer, and hepatic metastases. An autopsy study. Author(s): Melato M, Laurino L, Mucli E, Valente M, Okuda K. Source: Cancer. 1989 July 15; 64(2): 455-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2736492&dopt=Abstract

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Relative incidence of primary liver cancer in cirrhosis in Austria. Etiological considerations. Author(s): Ferenci P, Dragosics B, Marosi L, Kiss F. Source: Liver. 1984 February; 4(1): 7-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6321878&dopt=Abstract

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Repeated liver resection for recurrent liver cancer. Author(s): Neeleman N, Andersson R. Source: The British Journal of Surgery. 1996 July; 83(7): 893-901. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8813771&dopt=Abstract

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Resection of metastatic liver cancer in a patient with an anomalous intrahepatic portal system: a case report. Author(s): Hiei K, Nimura Y, Nagino M, Kamiya J, Kondo S, Toyoda S, Sibata Y. Source: Hepatogastroenterology. 1995 November-December; 42(6): 1002-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8847010&dopt=Abstract

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Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Author(s): Arii S, Yamaoka Y, Futagawa S, Inoue K, Kobayashi K, Kojiro M, Makuuchi M, Nakamura Y, Okita K, Yamada R. Source: Hepatology (Baltimore, Md.). 2000 December; 32(6): 1224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11093728&dopt=Abstract

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Right trisectionectomy for primary liver cancer. Author(s): Rui JA, Wang SB, Chen SG, Zhou L. Source: World Journal of Gastroenterology : Wjg. 2003 April; 9(4): 706-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679915&dopt=Abstract

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Risk estimates of liver cancer due to aflatoxin exposure from peanuts and peanut products. Author(s): Dichter CR. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 1984 June; 22(6): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6539733&dopt=Abstract

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Risk factors for the rising rates of primary liver cancer in the United States. Author(s): El-Serag HB, Mason AC. Source: Archives of Internal Medicine. 2000 November 27; 160(21): 3227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11088082&dopt=Abstract

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Risk of HBV reinfection after liver transplantation in HBsAg-positive cirrhosis. Primary hepatocellular carcinoma is not a predictor for HBV recurrence. The European Cooperative Study Group on Liver Cancer and Transplantation. Author(s): Mazzaferro V, Regalia E, Montalto F, Pulvirenti A, Brunetto MR, Bonino F, Lerut J, Gennari L. Source: Liver. 1996 April; 16(2): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8740845&dopt=Abstract

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Role and limitations of magnetic resonance imaging in the diagnostic work-up of patients with liver cancer. Author(s): Sharma R, Saini S. Source: Journal of Computer Assisted Tomography. 1999 November; 23 Suppl 1: S39-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608396&dopt=Abstract

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Role of promoter methylation in increased methionine adenosyltransferase 2A expression in human liver cancer. Author(s): Yang H, Huang ZZ, Zeng Z, Chen C, Selby RR, Lu SC. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2001 February; 280(2): G184-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208539&dopt=Abstract

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Semiautomatic 3-D image registration as applied to interventional MRI liver cancer treatment. Author(s): Carrillo A, Duerk JL, Lewin JS, Wilson DL. Source: Ieee Transactions on Medical Imaging. 2000 March; 19(3): 175-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875702&dopt=Abstract

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Seroprevalences of hepatitis B and C viruses and Helicobacter pylori infection in a small, isolated population at high risk of gastric and liver cancer. Author(s): Chen SY, Liu TY, Chen MJ, Lin JT, Sheu JC, Chen CJ. Source: International Journal of Cancer. Journal International Du Cancer. 1997 May 29; 71(5): 776-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9180145&dopt=Abstract

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Serum transforming growth factor-alpha level can be a parameter for evaluating liver regeneration after partial hepatectomy in patients with liver cancer. Author(s): Tomiya T, Hayashi S, Yanase M, Umeda N, Tani M, Yamada S, Masaki N, Ogata I, Fujiwara K. Source: Seminars in Oncology. 1997 April; 24(2 Suppl 6): S6-14-S6-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9151911&dopt=Abstract

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Sex hormones and liver cancer. Author(s): De Maria N, Manno M, Villa E. Source: Molecular and Cellular Endocrinology. 2002 July 31; 193(1-2): 59-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161002&dopt=Abstract

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Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths. Author(s): Chen ZM, Liu BQ, Boreham J, Wu YP, Chen JS, Peto R. Source: International Journal of Cancer. Journal International Du Cancer. 2003 October 20; 107(1): 106-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925964&dopt=Abstract

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Sonographically guided microwave coagulation treatment of liver cancer: an experimental and clinical study. Author(s): Dong BW, Liang P, Yu XL, Zeng XQ, Wang PJ, Su L, Wang XD, Xin H, Li S. Source: Ajr. American Journal of Roentgenology. 1998 August; 171(2): 449-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9694473&dopt=Abstract

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Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer. Author(s): Louha M, Poussin K, Ganne N, Zylberberg H, Nalpas B, Nicolet J, Capron F, Soubrane O, Vons C, Pol S, Beaugrand M, Berthelot P, Franco D, Trinchet JC, Brechot C, Paterlini P. Source: Hepatology (Baltimore, Md.). 1997 October; 26(4): 998-1005. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9328326&dopt=Abstract

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Spontaneous necrosis of liver cancer: one more possible cause. Author(s): Tarazov PG. Source: The American Journal of Gastroenterology. 1996 September; 91(9): 1872-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8792728&dopt=Abstract

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Squamous cell liver cancer arising from an epidermoid cyst. Author(s): Caratozzolo E, Massani M, Recordare A, Ciardo L, Antoniutti M, Jelmoni A, Bassi N. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2001; 8(5): 490-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11702262&dopt=Abstract

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Status of hyperthermia in the treatment of advanced liver cancer. Author(s): Moroz P, Jones SK, Gray BN. Source: Journal of Surgical Oncology. 2001 August; 77(4): 259-69. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11473375&dopt=Abstract

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Strategies for chemoprevention of liver cancer. Author(s): Kensler TW, Egner PA, Wang JB, Zhu YR, Zhang BC, Qian GS, Kuang SY, Gange SJ, Jacobson LP, Munoz A, Groopman JD. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2002 August; 11 Suppl 2: S58-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570336&dopt=Abstract

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Stromal expression of urokinase-type plasminogen activator receptor (uPAR) is associated with invasive growth in primary liver cancer. Author(s): Akahane T, Ishii M, Ohtani H, Nagura H, Toyota T. Source: Liver. 1998 December; 18(6): 414-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9869396&dopt=Abstract

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Studies on hyperthermia combined with arterial therapeutic blockade for treatment of tumors: (Part III) effectiveness of hyperthermia combined with arterial chemoembolization using degradable starch microspheres on advanced liver cancer. Author(s): Murata T, Akagi K, Imamura M, Nasu R, Kimura H, Nagata K, Tanaka Y. Source: Oncol Rep. 1998 May-June; 5(3): 709-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9538181&dopt=Abstract

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Subclinical course of cholesteryl ester storage disease in an adult with hypercholesterolemia, accelerated atherosclerosis, and liver cancer. Author(s): Elleder M, Chlumska A, Hyanek J, Poupetova H, Ledvinova J, Maas S, Lohse P. Source: Journal of Hepatology. 2000 March; 32(3): 528-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735626&dopt=Abstract

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Surgery for biliary obstruction by tumour thrombus in primary liver cancer. Author(s): Leow CK, Lau WY. Source: The British Journal of Surgery. 1997 June; 84(6): 890. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9189120&dopt=Abstract

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Surgery for biliary obstruction by tumour thrombus in primary liver cancer. Author(s): Tantawi B, Cherqui D, Tran van Nhieu J, Kracht M, Fagniez PL. Source: The British Journal of Surgery. 1996 November; 83(11): 1522-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014665&dopt=Abstract

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Survival and distribution pattern of childhood liver cancer in Taiwan. Author(s): Lee CL, Ko YC. Source: European Journal of Cancer (Oxford, England : 1990). 1998 December; 34(13): 2064-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10070312&dopt=Abstract

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Survival of patients with primary liver cancer, pancreatic cancer and biliary tract cancer in Europe. EUROCARE Working Group. Author(s): Faivre J, Forman D, Esteve J, Obradovic M, Sant M. Source: European Journal of Cancer (Oxford, England : 1990). 1998 December; 34(14 Spec No): 2184-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10070285&dopt=Abstract

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Survival rate for liver cancer in Taiwan. Author(s): Lee CL, Ko YC, Choong CS. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 January; 63(1): 16-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10645046&dopt=Abstract

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Synthesis of 188 Re-labelled long chain alkyl diaminedithiol for therapy of liver cancer. Author(s): Lee YS, Jeong JM, Kim YJ, Chung JW, Park JH, Suh YG, Lee DS, Chung JK, Lee MC. Source: Nuclear Medicine Communications. 2002 March; 23(3): 237-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891481&dopt=Abstract

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Temporal changes in liver cancer incidence rates in Japan: accounting for death certificate inaccuracies and improving diagnostic techniques. Author(s): Sharp GB, Cologne JB, Fukuhara T, Itakura H, Yamamoto M, Tokuoka S. Source: International Journal of Cancer. Journal International Du Cancer. 2001 September 1; 93(5): 751-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477591&dopt=Abstract

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The MEK1-ERK map kinase pathway and the PI 3-kinase-Akt pathway independently mediate anti-apoptotic signals in HepG2 liver cancer cells. Author(s): Mitsui H, Takuwa N, Maruyama T, Maekawa H, Hirayama M, Sawatari T, Hashimoto N, Takuwa Y, Kimura S. Source: International Journal of Cancer. Journal International Du Cancer. 2001 April 1; 92(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279606&dopt=Abstract

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The microcell mediated transfer of human chromosome 8 into highly metastatic rat liver cancer cell line C5F. Author(s): Liu H, Ye SL, Yang J, Tang ZY, Liu YK, Qin LX, Qiu SJ, Sun RX. Source: World Journal of Gastroenterology : Wjg. 2003 March; 9(3): 449-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632495&dopt=Abstract

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The relationship between internally deposited alpha-particle radiation and subsitespecific liver cancer and liver cirrhosis: an analysis of published data. Author(s): Sharp GB. Source: Journal of Radiation Research. 2002 December; 43(4): 371-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674201&dopt=Abstract

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The rise and fall in primary liver cancer mortality in Italy. Author(s): Capocaccia L, Capocaccia R. Source: Dig Liver Dis. 2002 August; 34(8): 606-7; Author Reply 607-8. No Abstract Available. Erratum In: Dig Liver Dis. 2002 October; 34(10): 761. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502219&dopt=Abstract

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The rise and fall in primary liver cancer mortality in Italy. Author(s): Muller-Lissner S. Source: Dig Liver Dis. 2002 August; 34(8): 606; Author Reply 607-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502218&dopt=Abstract

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The rise and fall in primary liver cancer mortality in Italy. Author(s): La Vecchia C, Negri E, Pelucchi C. Source: Dig Liver Dis. 2002 March; 34(3): 169-71. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990386&dopt=Abstract

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The role of cigarette smoking and drinking in the development of liver cancer: 28 years of observations on male cohort members in a farming and fishing area. Author(s): Shibata A, Fukuda K, Toshima H, Tashiro H, Hirohata T. Source: Cancer Detection and Prevention. 1990; 14(6): 617-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2257559&dopt=Abstract

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The thermal activity of normal and malignant tissues. Microcalorimetric response of liver cancer to hepatic artery ligation, cryosurgery, adriamycin and norcantharidin. Author(s): Mack P, Cheng LY. Source: Hpb Surg. 1998; 11(2): 75-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9893237&dopt=Abstract

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Time trends and age-period-cohort effects on the incidence of primary liver cancer in a well-defined French population: 1976-1995. Author(s): Benhamiche AM, Faivre C, Minello A, Clinard F, Mitry E, Hillon P, Faivre J. Source: Journal of Hepatology. 1998 November; 29(5): 802-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9833919&dopt=Abstract

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Time trends of primary liver cancer: indication of increased incidence in selected cancer registry populations. Author(s): Saracci R, Repetto F. Source: Journal of the National Cancer Institute. 1980 August; 65(2): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6931246&dopt=Abstract

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Towards global control of liver cancer? Author(s): Stuver SO. Source: Seminars in Cancer Biology. 1998 August; 8(4): 299-306. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9870036&dopt=Abstract

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Transplantation of autologous and allogeneic bone marrow with liver from a cadaveric donor for primary liver cancer. Author(s): Ringden O, Soderdahl G, Mattsson J, Uzunel M, Remberger M, Hentschke P, Hagglund H, Sparrelid E, Elmhorn-Rosenborg A, Duraj F, Zetterquist H, Ericzon BG. Source: Transplantation. 2000 May 27; 69(10): 2043-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852594&dopt=Abstract

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Transplants for liver cancer show promise, not proof. Author(s): Randal J. Source: Journal of the National Cancer Institute. 1996 May 15; 88(10): 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8627636&dopt=Abstract

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Treatment of pain according to syndrome differentiation in 169 cases of liver cancer. Author(s): Liu LM, Yu EX. Source: J Tradit Chin Med. 1989 December; 9(4): 277-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2561000&dopt=Abstract

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Treatment of primary liver cancer. Author(s): Hafstrom L, Naredi P, Lindner P, Holmberg S, Schersten T. Source: The European Journal of Surgery = Acta Chirurgica. 1998 August; 164(8): 569-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9720932&dopt=Abstract

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Trends in mortality from primary liver cancer in Europe. Author(s): La Vecchia C, Lucchini F, Franceschi S, Negri E, Levi F. Source: European Journal of Cancer (Oxford, England : 1990). 2000 May; 36(7): 909-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10785597&dopt=Abstract

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Trends in primary liver cancer. Author(s): De Vos Irvine H, Goldberg D, Hole DJ, McMenamin J. Source: Lancet. 1998 January 17; 351(9097): 215-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9449895&dopt=Abstract

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Truncated form of beta-catenin and reduced expression of wild-type catenins feature HepG2 human liver cancer cells. Author(s): Carruba G, Cervello M, Miceli MD, Farruggio R, Notarbartolo M, Virruso L, Giannitrapani L, Gambino R, Montalto G, Castagnetta L. Source: Annals of the New York Academy of Sciences. 1999; 886: 212-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667222&dopt=Abstract

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Tumor-derived epigenetic changes in the plasma and serum of liver cancer patients. Implications for cancer detection and monitoring. Author(s): Wong IH, Johnson PJ, Lai PB, Lau WY, Lo YM. Source: Annals of the New York Academy of Sciences. 2000 April; 906: 102-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10818604&dopt=Abstract

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Ultrasonographic differentiation of hepatocellular carcinoma from metastatic liver cancer. Author(s): Yoshida T, Matsue H, Okazaki N, Yoshino M. Source: Journal of Clinical Ultrasound : Jcu. 1987 September; 15(7): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2839556&dopt=Abstract

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Ultrastructural aspects of the human primary liver cancer. Author(s): Lapis K. Source: Appl Pathol. 1988; 6(2): 117-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2839214&dopt=Abstract

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Urinary excretion of aflatoxin and liver cancer in Karachi. Author(s): Nizami F, Nizami HM, Ahmad M. Source: J Pak Med Assoc. 1986 May; 36(5): 112-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3093719&dopt=Abstract

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Vasoconstrictors to improve localization of radioactive microspheres in the treatment of liver cancer. Author(s): Grady ED, Auda SP, Cheek WV. Source: J Med Assoc Ga. 1981 November; 70(11): 791-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7334287&dopt=Abstract

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Viral co-factors in liver cancer: lessons from hepatitis B virus. Author(s): Butel JS, Lee TH, Slagle BL. Source: Princess Takamatsu Symp. 1995; 25: 185-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8875624&dopt=Abstract

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Viral hepatitis and liver cancer: new opportunities for prevention. Author(s): Bosch FX. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 1996 October; 5(5): 408-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8972279&dopt=Abstract

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Viral role in cervical and liver cancer. Author(s): Lancaster WD. Source: Cancer. 1992 September 15; 70(6 Suppl): 1794-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1325282&dopt=Abstract

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Vital factors in liver cancer. Author(s): Rumsby PC. Source: Human & Experimental Toxicology. 1996 June; 15(6): 539-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793539&dopt=Abstract

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Volatile nitrosamines and tobacco-specific nitrosamines in the smoke of Thai cigarettes: a risk factor for lung cancer and a suspected risk factor for liver cancer in Thailand. Author(s): Mitacek EJ, Brunnemann KD, Hoffmann D, Limsila T, Suttajit M, Martin N, Caplan LS. Source: Carcinogenesis. 1999 January; 20(1): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9934860&dopt=Abstract

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Why can't we cure primary liver cancer? Author(s): Johnson PJ. Source: European Journal of Cancer (Oxford, England : 1990). 1995 September; 31A(10): 1562-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7488400&dopt=Abstract

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Worldwide immunization program targets hepatitis B and liver cancer. Author(s): Newman ME. Source: Journal of the National Cancer Institute. 1991 May 15; 83(10): 666-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2023266&dopt=Abstract

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

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

7

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

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

Anticarcinogenic effect of red ginseng on the development of liver cancer induced by diethylnitrosamine in rats. Author(s): Department of Pathology, Tongji Medical University, Wuhan, China. [email protected] Source: Wu, X G Zhu, da H Li, X J-Korean-Med-Sci. 2001 December; 16 Suppl: S61-5 1011-8934

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Antitumor and antivascular effects of AC-7700, a combretastatin A-4 derivative, against rat liver cancer. Author(s): First Department of Surgery, Oita Medical University, Japan. [email protected] Source: Ohno, T Kawano, K Sasaki, A Aramaki, M Tahara, K Etoh, T Kitano, S Int-J-ClinOncol. 2002 June; 7(3): 171-6 1341-9625

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Chemoembolization for primary liver cancer. Author(s): Klinik fur Radiologie, Johannes Gutenberg-Universitat, Mainz, Germany. Source: Achenbach, T Seifert, J K Pitton, M B Schunk, K Junginger, T Eur-J-Surg-Oncol. 2002 February; 28(1): 37-41 0748-7983

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Cumulative exposure to tamoxifen: DNA adducts and liver cancer in the rat. Author(s): SEAC Toxicology Unit, Unilever Research, Sharnbrook, Bedfordshire, UK. [email protected] Source: Carthew, P Lee, P N Edwards, R E Heydon, R T Nolan, B M Martin, E A ArchToxicol. 2001 August; 75(6): 375-80 0340-5761

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Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study. Author(s): Department of Pediatrics and Surgery, Northwestern University and Children's Memorial Hospital, Chicago, IL, USA. [email protected] Source: Katzenstein, Howard M Krailo, Mark D Malogolowkin, Marcio H Ortega, Jorge A Liu Mares, Wen Douglass, Edwin C Feusner, James H Reynolds, Marleta Quinn, John J Newman, Kurt Finegold, Milton J Haas, Joel E Sensel, Martha G Castleberry, Robert P Bowman, Laura C J-Clin-Oncol. 2002 June 15; 20(12): 2789-97 0732-183X

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Liver myofibroblasts: physiology, role in liver fibrosis and liver cancer, and pharmacological modulation. Source: Ledinghen, V. de Godichaud, S. Krisa, S. Faouzi, S. Monvoisin, A. Neaud, V. Rosenbaum, J. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. December 1998. volume 36 (Suppl.) page 69-74. 1388-0209

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Management of chronic hepatitis C and prevention of hepatocellular carcinoma. Author(s): Department of Gastroenterology, Toranomon Hospital, Okinaka, Memorial Institute for Medical Research, Tokyo, Japan. Source: Chayama, K J-Gastroenterol. 2002; 37 Suppl 13: 69-73 0944-1174

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Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells. Author(s): Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan. Source: Lin, S Y Chang, Y T Liu, J D Yu, C H Ho, Y S Lee, Y H Lee, W S Mol-Carcinog. 2001 October; 32(2): 73-83 0899-1987

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Pulmonary complications after hepatic artery chemoembolization or infusion via the inferior phrenic artery for primary liver cancer. Author(s): Department of Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. [email protected] Source: Tajima, T Honda, H Kuroiwa, T Yabuuchi, H Okafuji, T Yosimitsu, K Irie, H Aibe, H Masuda, K J-Vasc-Interv-Radiol. 2002 September; 13(9 Pt 1): 893-900 1051-0443

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Synthesis of 188 Re-labelled long chain alkyl diaminedithiol for therapy of liver cancer. Author(s): Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea. Source: Lee, Y S Jeong, J M Kim, Y J Chung, J W Park, J H Suh, Y G Lee, D S Chung, J K Lee, M C Nucl-Med-Commun. 2002 March; 23(3): 237-42 0143-3636

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The natural history of hepatocellular carcinoma. Author(s): Department of Internal Medicine, University of Milan, IRCCS Maggiore Hospital, Via Pace, 9, 20122 Milan, Italy. [email protected] Source: Romeo, R Colombo, M Toxicology. 2002 December 27; 181-182: 39-42 0300-483X

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Transcatheter arterial chemoembolization of hepatocellular carcinoma: a Japanese experience. Author(s): Department of Radiology, Fukuoka University Hospital, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. [email protected] Source: Higashihara, H Okazaki, M Hepatogastroenterology. 2002 Jan-February; 49(43): 72-8 0172-6390

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Vitamins Vitamin K Alternative names: Menadione, Menaphthone, Menaquinone, Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com

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Minerals Selenium Source: Prima Communications, Inc.www.personalhealthzone.com

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

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

Anticarcinogenic effect of red ginseng on the development of liver cancer induced by diethylnitrosamine in rats. Author(s): Wu XG, Zhu DH, Li X. Source: Journal of Korean Medical Science. 2001 December; 16 Suppl: S61-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748378&dopt=Abstract

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Antiproliferative effects of Ceratonia siliqua L. on mouse hepatocellular carcinoma cell line. Author(s): Corsi L, Avallone R, Cosenza F, Farina F, Baraldi C, Baraldi M. Source: Fitoterapia. 2002 December; 73(7-8): 674-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490228&dopt=Abstract

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Combating hepatocellular carcinoma with an integrated approach. Author(s): Ho S, Johnson PJ, Leung WT, Lau WY.

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Source: Chinese Medical Journal. 1999 January; 112(1): 80-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593648&dopt=Abstract •

Combined electro-acupuncture with liver artery intubation in treatment of massive liver cancer. Author(s): Xin YL, Liu DR, Meng X. Source: Hepatobiliary Pancreat Dis Int. 2002 August; 1(3): 397-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607714&dopt=Abstract

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Combined interventional therapies of hepatocellular carcinoma. Author(s): Qian J, Feng GS, Vogl T. Source: World Journal of Gastroenterology : Wjg. 2003 September; 9(9): 1885-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970869&dopt=Abstract

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Current strategies for chemoprevention of hepatocellular carcinoma. Author(s): Okita K, Sakaida I, Hino K. Source: Oncology. 2002; 62 Suppl 1: 24-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868781&dopt=Abstract

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Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line. Author(s): Ruffa MJ, Ferraro G, Wagner ML, Calcagno ML, Campos RH, Cavallaro L. Source: Journal of Ethnopharmacology. 2002 March; 79(3): 335-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849838&dopt=Abstract

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Docetaxel inhibits SMMC-7721 human hepatocellular carcinoma cells growth and induces apoptosis. Author(s): Geng CX, Zeng ZC, Wang JY. Source: World Journal of Gastroenterology : Wjg. 2003 April; 9(4): 696-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679913&dopt=Abstract

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Downregulation of hepatitis B surface antigen expression in human hepatocellular carcinoma cell lines by HD-03, a polyherbal formulation. Author(s): Yeh SF, Gupta M, Sarma DN, Mitra SK. Source: Phytotherapy Research : Ptr. 2003 January; 17(1): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557256&dopt=Abstract

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Effect of arsenic trioxide on human hepatocellular carcinoma HepG2 cells: inhibition of proliferation and induction of apoptosis. Author(s): Siu KP, Chan JY, Fung KP.

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Source: Life Sciences. 2002 June 7; 71(3): 275-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034346&dopt=Abstract •

Effects of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of spontaneous liver cancer. Author(s): Watanabe S, Kitade Y, Masaki T, Nishioka M, Satoh K, Nishino H. Source: Nutrition and Cancer. 2001; 39(1): 96-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588908&dopt=Abstract

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Efficacy and toxicity of intra-arterial cisplatin and etoposide for advanced hepatocellular carcinoma. Author(s): Sangro B, Rios R, Bilbao I, Beloqui O, Herrero JI, Quiroga J, Prieto J. Source: Oncology. 2002; 62(4): 293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138235&dopt=Abstract

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Elicitation of prior distributions for a phase III randomized controlled trial of adjuvant therapy with surgery for hepatocellular carcinoma. Author(s): Tan SB, Chung YF, Tai BC, Cheung YB, Machin D. Source: Controlled Clinical Trials. 2003 April; 24(2): 110-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689733&dopt=Abstract

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Etoposide upregulates Bax-enhancing tumour necrosis factor-related apoptosis inducing ligand-mediated apoptosis in the human hepatocellular carcinoma cell line QGY-7703. Author(s): Miao L, Yi P, Wang Y, Wu M. Source: European Journal of Biochemistry / Febs. 2003 July; 270(13): 2721-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823542&dopt=Abstract

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Experimental study on ultrasound-guided intratumoral injection of “Star-99” in treatment of hepatocellular carcinoma of nude mice. Author(s): Lin LW, Lin XD, He YM, Gao SD, Xue ES. Source: World Journal of Gastroenterology : Wjg. 2003 April; 9(4): 701-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679914&dopt=Abstract

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Fibrolamellar hepatocellular carcinoma in children and adolescents. Author(s): Katzenstein HM, Krailo MD, Malogolowkin MH, Ortega JA, Qu W, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Newman K, Finegold MJ, Haas JE, Sensel MG, Castleberry RP, Bowman LC. Source: Cancer. 2003 April 15; 97(8): 2006-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673731&dopt=Abstract

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Following a trial that stopped early: what next for adjuvant hepatic intra-arterial iodine-131 lipiodol in resectable hepatocellular carcinoma? Author(s): Tan SB, Machin D, Cheung YB, Chung YF, Tai BC, Machin D. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 March 15; 20(6): 1709. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896125&dopt=Abstract

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gamma-Carboxyglutamic acid content of hepatocellular carcinoma-associated desgamma-carboxy prothrombin. Author(s): Naraki T, Kohno N, Saito H, Fujimoto Y, Ohhira M, Morita T, Kohgo Y. Source: Biochimica Et Biophysica Acta. 2002 April 24; 1586(3): 287-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997080&dopt=Abstract

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Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. Author(s): Ho CK, Huang YL, Chen CC. Source: Planta Medica. 2002 November; 68(11): 975-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451486&dopt=Abstract

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Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Author(s): Yoshizawa H. Source: Oncology. 2002; 62 Suppl 1: 8-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868791&dopt=Abstract

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Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study. Author(s): Katzenstein HM, Krailo MD, Malogolowkin MH, Ortega JA, Liu-Mares W, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Newman K, Finegold MJ, Haas JE, Sensel MG, Castleberry RP, Bowman LC. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 June 15; 20(12): 2789-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065555&dopt=Abstract

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Hepatocellular carcinoma: a case of extrahepatic seeding after percutaneous radiofrequency ablation using an expandable needle electrode. Author(s): Shirato K, Morimoto M, Tomita N, Kokawa A, Sugimori K, Saito T, Tanaka K. Source: Hepatogastroenterology. 2002 July-August; 49(46): 897-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143236&dopt=Abstract

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Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. Author(s): Matsui Y, Uhara J, Satoi S, Kaibori M, Yamada H, Kitade H, Imamura A, Takai S, Kawaguchi Y, Kwon AH, Kamiyama Y.

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Source: Journal of Hepatology. 2002 July; 37(1): 78-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076865&dopt=Abstract •

Inhibition of DES-induced DNA adducts by diallyl sulfide: Implications in liver cancer prevention. Author(s): Green M, Thomas R, Gued L, Sadrud-Din S. Source: Oncol Rep. 2003 May-June; 10(3): 767-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684656&dopt=Abstract

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Inhibitory effects of luteolin isolated from Ixeris sonchifolia Hance on the proliferation of HepG2 human hepatocellular carcinoma cells. Author(s): Yee SB, Lee JH, Chung HY, Im KS, Bae SJ, Choi JS, Kim ND. Source: Arch Pharm Res. 2003 February; 26(2): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643593&dopt=Abstract

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It could have been something they ate -- functional food and the treatment of liver cancer. Author(s): Bass NM. Source: Journal of Hepatology. 2002 July; 37(1): 147-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076875&dopt=Abstract

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Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. Author(s): Lin SY, Liu JD, Chang HC, Yeh SD, Lin CH, Lee WS. Source: Journal of Cellular Biochemistry. 2002; 84(3): 532-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813258&dopt=Abstract

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Mechanical properties of hepatocellular carcinoma cells. Author(s): Zhang G, Long M, Wu ZZ, Yu WQ. Source: World Journal of Gastroenterology : Wjg. 2002 April; 8(2): 243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11925600&dopt=Abstract

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Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells. Author(s): Lin SY, Chang YT, Liu JD, Yu CH, Ho YS, Lee YH, Lee WS. Source: Molecular Carcinogenesis. 2001 October; 32(2): 73-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746819&dopt=Abstract

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Paclitaxel promotes liver graft survival in rats and inhibits hepatocellular carcinoma growth in vitro and is a potentially useful drug for transplant patients with liver cancer. Author(s): Iesalnieks I, Tange S, Scherer MN, Graeb C, Frank E, Jauch KW, Geissler EK.

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Source: Transplantation Proceedings. 2002 September; 34(6): 2316-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270414&dopt=Abstract •

Pegylated liposomal doxorubicin in combination with hyperthermia in the treatment of a case of advanced hepatocellular carcinoma. Author(s): Dvorak J, Zoul Z, Melichar B, Jandik P, Mergancova J, Motyckova I, Kalousova D, Petera J. Source: Journal of Clinical Gastroenterology. 2002 January; 34(1): 96-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743256&dopt=Abstract

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Percutaneous radiofrequency ablation of small hepatocellular carcinoma: long-term results. Author(s): Buscarini L, Buscarini E, Di Stasi M, Vallisa D, Quaretti P, Rocca A. Source: European Radiology. 2001; 11(6): 914-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419162&dopt=Abstract

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Preliminary investigation on regulating effects of different TCM treatments on transcription of the correlated genes of liver cancer in rats. Author(s): Guan D, Fang Z, Lu H, Li H. Source: J Tradit Chin Med. 2003 March; 23(1): 62-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747207&dopt=Abstract

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Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced versus mangafodipir trisodium-enhanced MR imaging. Author(s): Kim SK, Kim SH, Lee WJ, Kim H, Seo JW, Choi D, Lim HK, Lee SJ, Lim JH. Source: Ajr. American Journal of Roentgenology. 2002 September; 179(3): 741-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185056&dopt=Abstract

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Preoperative predictors of survival after resection of small hepatocellular carcinomas. Author(s): Wayne JD, Lauwers GY, Ikai I, Doherty DA, Belghiti J, Yamaoka Y, Regimbeau JM, Nagorney DM, Do KA, Ellis LM, Curley SA, Pollock RE, Vauthey JN. Source: Annals of Surgery. 2002 May; 235(5): 722-30; Discussion 730-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981219&dopt=Abstract

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Prevention of liver cancer. Author(s): Guyton KZ, Kensler TW. Source: Current Oncology Reports. 2002 November; 4(6): 464-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354357&dopt=Abstract

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Psycho-neuro-immunological treatment of hepatocellular carcinoma with major depression--a single case report. Author(s): Jozuka H, Jozuka E, Suzuki M, Takeuchi S, Takatsu Y.

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Source: Current Medical Research and Opinion. 2003; 19(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661782&dopt=Abstract •

Radiofrequency ablation for treatment of hepatocellular carcinoma with cirrhosis. Author(s): Lo HW, Tsai YJ, Chen PH, Chen HY, Ker CG, Juan CC. Source: Hepatogastroenterology. 2003 May-June; 50(51): 645-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828052&dopt=Abstract

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Review article: percutaneous treatment of hepatocellular carcinoma. Author(s): Gaiani S, Celli N, Cecilioni L, Piscaglia F, Bolondi L. Source: Alimentary Pharmacology & Therapeutics. 2003 June; 17 Suppl 2: 103-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786621&dopt=Abstract

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Study of apoptosis in human liver cancers. Author(s): Shan CM, Li J. Source: World Journal of Gastroenterology : Wjg. 2002 April; 8(2): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11925601&dopt=Abstract

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Study on chemoprevention of hepatocellular carcinoma by ginseng: an introduction to the protocol. Author(s): Ginseng-HCC Chemopreventive Study Osaka Group. Source: Journal of Korean Medical Science. 2001 December; 16 Suppl: S70-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748380&dopt=Abstract

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The role of [18F]fluorodeoxyglucose positron emission tomography imaging in the evaluation of hepatocellular carcinoma. Author(s): Wudel LJ Jr, Delbeke D, Morris D, Rice M, Washington MK, Shyr Y, Pinson CW, Chapman WC. Source: The American Surgeon. 2003 February; 69(2): 117-24; Discussion 124-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641351&dopt=Abstract

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Thermal ablation therapy for hepatocellular carcinoma. Author(s): Ahmed M, Goldberg SN. Source: Journal of Vascular and Interventional Radiology : Jvir. 2002 September; 13(9 Pt 2): S231-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354841&dopt=Abstract

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Traditional Chinese medicine for primary liver cancer. Author(s): Li ZQ,.

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Source: World Journal of Gastroenterology : Wjg. 1998 August; 4(4): 360-364. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11819321&dopt=Abstract •

Trans-resveratrol, a grapevine-derived polyphenol, blocks hepatocyte growth factorinduced invasion of hepatocellular carcinoma cells. Author(s): De Ledinghen V, Monvoisin A, Neaud V, Krisa S, Payrastre B, Bedin C, Desmouliere A, Bioulac-Sage P, Rosenbaum J. Source: International Journal of Oncology. 2001 July; 19(1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408926&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to liver 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 Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com

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Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Liver Cancer Source: Integrative Medicine Communications; www.drkoop.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Viral Hepatitis Source: Prima Communications, Inc.www.personalhealthzone.com •

Herbs and Supplements Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Androstenedione Source: Prima Communications, Inc.www.personalhealthzone.com Asian Ginseng Alternative names: Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Bupleurum Alternative names: Bupleurum chinense, Bupleurum falcatum Source: Healthnotes, Inc.; www.healthnotes.com DHEA Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10022,00.html DHEA (dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Echinacea Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Echinacea Alternative names: Echinacea angustifolia, Echinacea pallida, Echinacea purpurea, Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Echinacea Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Echinacea Pallida Source: Integrative Medicine Communications; www.drkoop.com Echinacea Purpurea Source: Integrative Medicine Communications; www.drkoop.com Glutathione Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ip-6 Source: Healthnotes, Inc.; www.healthnotes.com Lavandula Alternative names: Lavender; Lavandula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Menadione Source: Integrative Medicine Communications; www.drkoop.com Menaphthone Source: Integrative Medicine Communications; www.drkoop.com Menaquinone Source: Integrative Medicine Communications; www.drkoop.com Panax Ginseng Source: Integrative Medicine Communications; www.drkoop.com Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the

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MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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

Dissertations on Liver 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 liver 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: •

Glutathione S-transferase PI Regulation in Hepatocellular Carcinoma by Bakker, Jila; PhD from The Johns Hopkins University, 2003, 177 pages http://wwwlib.umi.com/dissertations/fullcit/3068115

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Profiling Gene Expression Changes in Hepatocellular Carcinomas and the Identification of Novel Tumor Markers by Graveel, Carrie Renee; PhD from The University of Wisconsin - Madison, 2002, 217 pages http://wwwlib.umi.com/dissertations/fullcit/3060502

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

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

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

A phase II multicenter uncontrolled trial of BAY 43-9006 in patients with advanced hepatocellular carcinoma Condition(s): Carcinoma, Hepatocellular Study Status: This study is currently recruiting patients. Sponsor(s): Bayer Corporation Purpose - Excerpt: The primary objective of the study is to evaluate the anti-cancer activity (e.g. proportion of patients with confirmed complete responses and partial responses as per the WHO criteria) in patients with advanced inoperable biopsy-proven hepatocellular carcinoma. The secondary objectives are as follows: * To determine duration of response, time Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048919

•

A Study to Estimate Safety and Efficacy of Bay 43-9006 in the Treatment of Hepatocellular Carcinoma Condition(s): Carcinoma, Hepatocellular Study Status: This study is currently recruiting patients.

8

These are listed at www.ClinicalTrials.gov.

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Sponsor(s): Bayer Corporation Purpose - Excerpt: The study's primary objective is to evaluate anti-cancer activity (e.g. proportion of patients with confirmed complete response or partial response) in patients with advanced, inoperable biopsy-proven hepatocellular carcinoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044512 •

An Evaluation of Chronic Thalidomide Administration in Patients Undergoing Chemoembolization for Unresectable Hepatocellular Cancer Condition(s): Liver Cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: This is a clinical trial to test the safety and efficacy of the drug thalidomide in combination with a procedure called chemoembolization in patients with inoperable liver cancer. Chemoembolization is the process by which chemotherapy is instilled directly into the blood vessels feeding the tumor, so that the blood vessels feeding the tumor may be blocked. Chemoembolization consists of two separate procedures. It will be done by infusing chemotherapy with the drug doxorubicin through the hepatic artery into the liver and then by infusing collagen to cut off the blood supply to the tumor. A catheter will be inserted at various times to allow for these infusions. The objectives are to investigate the feasibility and potential activity of chronic administration of thalidomide in patients with unresectable hepatocellular cancer who receive chemoembolization to predominant tumor masses. The toxicity of thalidomide in these patients will be evaluated. Overall safety will also be assessed. Serum levels of angiogenic cytokines such as VEGF, bFGF, and TNF-a, that are believed to have a role in hepatocellular carcinoma, will be collected. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006198

•

Antineoplaston Therapy in Treating Children With Hepatoblastoma Condition(s): recurrent childhood liver cancer; childhood hepatoblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating children with hepatoblastoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00003488 •

Antineoplaston Therapy in Treating Patients With Primary Liver Cancer Condition(s): stage IV childhood liver cancer; recurrent childhood liver cancer; advanced adult primary liver cancer; recurrent adult primary liver cancer Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients who have primary liver cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003530

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Arsenic Trioxide in Treating Patients With Liver Cancer Condition(s): advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of arsenic trioxide in treating patients who have hepatocellular (liver) cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049270

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BAY 43-9006 in Treating Patients With Advanced Inoperable Liver Cancer Condition(s): adult primary hepatocellular carcinoma; advanced adult primary liver cancer; localized unresectable adult primary liver cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: BAY 43-9006 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of BAY 43-9006 in treating patients who have advanced inoperable hepatocellular carcinoma (liver cancer). Phase(s): Phase II Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058383 •

Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer Condition(s): adult primary hepatocellular carcinoma; recurrent adult primary liver cancer; localized unresectable adult primary liver cancer Study Status: This study is currently recruiting patients. Sponsor(s): New York Presbyterian Hospital; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies such as bevacizumab 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 bevacizumab in treating patients who have unresectable nonmetastatic liver cancer that has not spread to the main portal vein. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055692

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BMS-247550 in Treating Patients With Liver or Gallbladder Cancer Condition(s): adult primary liver cancer; extrahepatic bile duct cancer; Gallbladder Cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of Chicago Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of BMS-247550 in treating patients who have liver or gallbladder cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023946

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Chemoembolization and Bevacizumab in Treating Patients With Liver Cancer That Cannot Be Removed With Surgery Condition(s): localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma 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. Chemoembolization kills tumor cells by delivering drugs directly into the tumor and then blocking the blood flow to the tumor. Monoclonal antibodies such as bevacizumab can locate tumor cells and

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may kill any cells that are left after chemoembolization. PURPOSE: Randomized phase II trial to compare the effectiveness of chemoembolization followed by bevacizumab to that of chemoembolization alone in treating patients who have liver cancer that cannot be removed with surgery. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049322 •

Chemoembolization in Treating Patients With Primary Liver Cancer or Metastases to the Liver Condition(s): localized unresectable adult primary liver cancer; advanced adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma; liver metastases Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Chemoembolization kills tumor cells by delivering drugs directly into the tumor and then blocking the blood flow to the tumor. PURPOSE: Phase II trial to study the effectiveness of chemoembolization in treating patients who have primary liver cancer or metastases to the liver that cannot be surgically removed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003907

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Chemotherapy in Treating Children With Liver Cancer Condition(s): childhood childhood liver cancer

hepatoblastoma;

childhood

hepatocellular

carcinoma;

Study Status: This study is currently recruiting patients. Sponsor(s): Societe Internationale d'Oncologie Pediatrique Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which chemotherapy regimen is more effective in treating children with liver cancer. PURPOSE: Randomized phase III trial to study the effectiveness of cisplatin with or without doxorubicin and the effectiveness of combining cisplatin, carboplatin, and doxorubicin in treating children who have liver cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003912

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Combination Chemotherapy With or Without Amifostine in Treating Young Patients With Liver Cancer Condition(s): childhood hepatoblastoma; childhood liver cancer; Drug Toxicity Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy. It is not yet known which chemotherapy regimen is most effective for children and young adults with liver cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without amifostine in treating patients who have liver cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003994

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Epirubicin and Celecoxib in Treating Patients With Hepatocellular Carcinoma Cancer Condition(s): advanced adult primary liver cancer; localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Celecoxib may stop the growth of tumor cells 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 celecoxib with epirubicin may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining celecoxib with epirubicin in treating patients who have hepatocellular carcinoma (liver cancer). Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057980

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Epirubicin and Thalidomide in Treating Patients With Liver Cancer Condition(s): adult primary hepatocellular carcinoma; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer Study Status: This study is currently recruiting patients. Sponsor(s): Dana-Farber/Harvard Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as epirubicin use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of hepatocellular (liver) cancer by stopping blood flow to the tumor. Combining epirubicin with thalidomide may kill more tumor cells.

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PURPOSE: Phase II trial to study the effectiveness of combining epirubicin with thalidomide in treating patients who have unresectable or metastatic liver cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058487 •

Erlotinib in Treating Patients With Liver Cancer That Cannot be Surgically Removed Condition(s): adult primary hepatocellular carcinoma; advanced adult primary liver cancer; localized unresectable adult primary liver cancer Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of erlotinib in treating patients who have liver cancer that cannot be surgically removed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047333

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Erlotinib in Treating Patients With Unresectable Liver Cancer and Liver Dysfunction Condition(s): recurrent adult primary liver cancer; localized unresectable adult primary liver cancer; advanced adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. PURPOSE: Phase I trial to study the effectiveness of erlotinib in treating patients who have unresectable liver cancer and liver dysfunction. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047346

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Gemcitabine Plus Docetaxel in Treating Patients With Unresectable or Metastatic Liver Cancer Condition(s): localized unresectable adult primary liver cancer; advanced adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI)

112 Liver Cancer

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 tumor cells. PURPOSE: Phase II trial to study the effectiveness of gemcitabine plus docetaxel in treating patients who have unresectable or metastatic liver cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006010 •

Hepatic Arterial Infusion Plus Internal Radiation Therapy in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery Condition(s): localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): University of Pittsburgh Cancer Institute Purpose - Excerpt: RATIONALE: Hepatic arterial infusion uses a catheter to deliver anticancer substances directly into the liver. Internal radiation uses radioactive material placed directly into the tumor to kill tumor cells and cause less damage to normal tissue. PURPOSE: Phase II trial to study the effectiveness of combining hepatic arterial infusion with internal radiation therapy in treating patients who have liver cancer that can not be removed by surgery. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039078

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Liver Perfusion for Patients with Inoperable Liver Cancer Condition(s): Liver Cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will determine the maximum safe dose and side effects of the drug melphalan given through the DelCath system to treat liver cancer. In this system, the chemotherapy is delivered to the liver through special catheters (flexible plastic tubes) inserted through small puncture holes in the groin area into the blood vessels going into and out of the liver. This allows the drug to be administered directly to the liver in amounts that would not be safe if it circulated throughout the body. Patients 14 years of age or older with cancer that has arisen in or spread mainly to the liver and cannot be removed surgically may be eligible for this study. Candidates will be screened with a physical examination, blood tests, electrocardiogram (EKG), chest X-ray, and imaging studies, such as X-ray studies, CT scan of the chest, abdomen and pelvis and MRI scan of the liver, to evaluate the tumor. Other tests may be done if medically indicated. Participants will be admitted to the hospital for treatment under sedation. The groin area is numbed and catheters are placed into the large artery and vein that supply blood to and from the liver, creating a separate circulation for the liver, similar to the

Clinical Trials 113

heart-lung bypass in open-heart surgery. Once the catheters are in place, melphalan is perfused into the liver for 30 minutes. The circulation to the liver remains separate and the blood is filtered through the DelCath system for another 30 minutes after the drug is given to remove as much of it as possible from the blood coming out of the liver. Following the procedure, patients stay in the intensive care unit for 24 hours for observation. Patients who enter the study early receive lower doses of melphalan. The dose is increased as the study progresses to determine the highest safe and effective dose. Patients will be informed of the progress of the study at the point they enter. Lower doses may be less effective against the tumor, and higher doses may have a greater risk of side effects. Patients stay in the hospital for 3 to 5 days during the perfusion part of the study and return to the outpatient clinic after 3 weeks to evaluate recovery. If recovery is satisfactory, a second treatment will be scheduled. About 4 weeks after the second treatment, the tumor will be evaluated to assess the response to therapy. Patients whose tumor has shrunk or stayed the same will be offered another two treatments. When the treatments are finished, patients will return for evaluation every 3 months for 2 years and then every 4 months for a third year. During these visits they will have a physical examination, imaging scans, X-rays and blood tests to evaluate disease status. If the liver tumor grows or spreads beyond the liver during this time, the patient will be taken off the study and other alternatives for care will be discussed. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021606 •

Liver Perfusion of Melphalan in Inoperable Liver Cancer Condition(s): Liver Neoplasm; Neoplasm Metastasis Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study is testing whether administration of a drug called melphalan directly into the liver (isolated hepatic perfusion) can shrink tumors in patients with inoperable cancer whose tumor is confined to the liver. Blood tests and special X-ray studies will be done before treatment and over a period of several months after treatment to evaluate the treatment's effectiveness. Similar perfusion studies with melphalan have been done in patients with cancer (who received another drug together with melphalan) and perfusion of the extremity has been performed in patients with a serious type of skin cancer called melanoma. In both studies tumors shrank, some up to less than half the original size. In some patients, tumors went away completely. Isolated liver perfusion is a major operation, done under general anesthesia. In this procedure, catheters (plastic tubes) are placed into the large blood vessels that deliver blood to and remove blood from the liver, creating a circulation to the liver separate from the rest of the body. During the operation, the liver receives oxygen from an external pump similar to the heart-lung machine used in open-heart surgery. For one hour, melphalan is administered through the pump in large doses that would not be safe if it reached all parts of the body in the normal blood circulation. The entire operation lasts between six and eight hours. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

114 Liver Cancer

Web Site: http://clinicaltrials.gov/ct/show/NCT00001820 •

Megestrol in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery Condition(s): localized unresectable adult primary liver cancer; advanced adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): NMRC Asia-Pacific Hepatocellular Carcinoma Trials Group Purpose - Excerpt: RATIONALE: Estrogen can stimulate the growth of cancer cells. Hormone therapy using megestrol may fight liver cancer by blocking the uptake of estrogen. It is not yet known if megestrol is an effective treatment for liver cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of megestrol in treating patients who have liver cancer that cannot be removed by surgery. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041275

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Nolatrexed Dihydrochloride Compared With Doxorubicin in Treating Patients With Recurrent or Unresectable Liver Cancer Condition(s): localized unresectable adult primary liver cancer; advanced adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Eximias Pharmaceutical Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which chemotherapy regimen is more effective for liver cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two different chemotherapy regimens in treating patients who have recurrent or unresectable liver cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012324

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Oblimersen and Doxorubicin in Treating Patients With Advanced Liver Cancer or Other Solid Tumor Condition(s): adult primary hepatocellular carcinoma; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; unspecified adult solid tumor, protocol specific Study Status: This study is currently recruiting patients. Sponsor(s): Princess Margaret Hospital; 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. Oblimersen may increase

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the effectiveness of doxorubicin by making tumor cells more sensitive to the drug. PURPOSE: Phase I/II trial to study the effectiveness of combining oblimersen with doxorubicin in treating patients who have locally advanced, recurrent, or metastatic liver cancer or other solid tumor. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047229 •

Oxaliplatin in Treating Patients With Liver Cancer Condition(s): advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Beckman Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of oxaliplatin in treating patients who have unresectable, recurrent or metastatic liver cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052364

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Prevention of Recurrent Hepatitis B after Liver Transplantation Condition(s): Hepatitis B; Cirrhosis; Acute Liver Failure; Hepatocellular Carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Hepatitis B accounts for approximately 5000 deaths per year in the United States. Liver transplantation offers the only hope for patients who develop endstage liver disease. Early results of liver transplantation for hepatitis B were poor with recurrence rate of 80% and 1-year survival of only 50%. Recent studies found that preventive therapy using hepatitis B immune globulin (HBIG) or antiviral medications such as lamivudine can reduce the recurrence rate to roughly 30% with accompanying improvement in survival. However, HBIG when given as intravenous infusion in high doses is very expensive, while long-term use of lamivudine is associated with drug resistance. Some studies found that preventive therapy using both HBIG and lamivudine may decrease recurrence rate to less than 10% but the dose and duration of HBIG needed when used in combination with lamivudine is not clear. Adefovir, a new antiviral medication, is effective against lamivudine resistant hepatitis B but its role in liver transplantation is uncertain because of the risk of kidney damage. Many studies showed that the risk of recurrent hepatitis B is related to the viral load before transplant. Thus, it may be possible to tailor the preventive therapy according to the risk. The aim of this study is to establish the most cost-effective preventive therapy for recurrent hepatitis B after liver transplantation.

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Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059267 •

Radioactive Iodine in Treating Patients Who Have Undergone Surgery for Liver Cancer Condition(s): localized resectable hepatocellular carcinoma

adult primary

liver

cancer;

adult primary

Study Status: This study is currently recruiting patients. Sponsor(s): NMRC Asia-Pacific Hepatocellular Carcinoma Trials Group Purpose - Excerpt: RATIONALE: Radioactive iodine may be effective in reducing the rate of recurrence of liver cancer after surgery to remove the tumor. It is not yet known if radioactive iodine is more effective than no further treatment after surgery. PURPOSE: Randomized phase III trial to determine the effectiveness of radioactive iodine in treating patients who have undergone surgery for liver cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027768 •

Rebeccamycin Analogue in Treating Patients With Advanced Liver and/or Biliary Cancer Condition(s): adult primary liver cancer; cholangiocarcinoma of the extrahepatic bile duct; cholangiocarcinoma of the gallbladder; unresectable extrahepatic bile duct cancer; unresectable gallbladder cancer Study Status: This study is currently recruiting patients. Sponsor(s): Ireland Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of rebeccamycin analogue in treating patients who have advanced liver and/or biliary cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005997

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Safety and Efficacy of Doxorubicin Adsorbed to Magnetic Beads vs. IV Doxorubicin in Treating Liver Cancer Condition(s): Carcinoma, Hepatocellular Study Status: This study is currently recruiting patients. Sponsor(s): FeRx Purpose - Excerpt: MTC-DOX is Doxorubicin or DOX, a chemotherapy drug, that is adsorbed, or made to "stick", to magnetic beads (MTCs). MTCs are tiny, microscopic

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particles of iron and carbon. When DOX is added to MTCs, DOX attaches to the carbon part of the MTCs. MTC-DOX is directed to and deposited in the area of a tumor, where it is thought that it then "leaks" through the blood vessel walls. Once in the surrounding tissues, it is thought that Doxorubicin becomes "free from" the magnetic beads and will then be able to act against the tumor cells. The iron component of the particle has magnetic properties, making it possible to direct MTC-DOX to specific tumor sites in the liver by placing a magnet on the body surface. It is hoped that MTC-DOX used with the magnet may target the chemotherapy directly to liver tumors and provide a treatment to patients with liver cancer. To be sure of the effect of MTC-DOX on liver cancer, it will be compared to the effect of Doxorubicin given through the vein. The study treatments will be administered every three weeks, (which is considered a study treatment cycle), until you complete six treatment cycles, the tumor grows, disappears, or you experience a side effect, which may cause you to leave the study. Follow-up visits will occur on Days 3, 10, and 21 following treatment in the first cycle and Days 7 and 21 for the remaining cycles, and also 60 days after you receive your last treatment cycle. Therefore, the purpose of this Phase 2/3 study is to evaluate safety, tolerance, and efficacy (survival time) of an MTC-DOX dosing strategy where the DOX dose is determined by tumor size Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034333 •

Seocalcitol in Treating Patients With Hepatocellular Carcinoma Condition(s): localized resectable hepatocellular carcinoma

adult primary

liver

cancer;

adult primary

Study Status: This study is currently recruiting patients. Sponsor(s): LEO Pharma Purpose - Excerpt: RATIONALE: Seocalcitol may help hepatocellular carcinoma (liver cancer) cells develop into normal liver cells. It is not yet known whether seocalcitol is more effective than no further therapy in treating liver cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of seocalcitol in treating patients who have undergone surgery or received injections for liver cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058162 •

Seocalcitol Versus Placebo in Advanced Hepatocellular Carcinoma Condition(s): Liver Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): LEO Pharma Purpose - Excerpt: The purpose of the study is to determine whether Seocalcitol is effective in the treatment of advanced primary liver cancer (hepatocellular carcinoma). Phase(s): Phase III Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051532 •

Seocalcitol Versus Placebo in the Adjuvant Treatment of Hepatocellular Carcinoma. Condition(s): Liver Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): LEO Pharma Purpose - Excerpt: To evaluate the efficacy of Seocalcitol in prolonging time to relapse following intended curative resection or percutaneous ablative treatment, i.e. percutaneous ethanol injection(s), percutaneous acetic acid injection(s), percutaneous microwave coagulation therapy, or percutaneous radiofrequency ablation for hepatocellular carcinoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051545

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Study of T900607-sodium in chemotherapy naive patients with hepatocellular carcinoma. Condition(s): Hepatocellular Carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Tularik Purpose - Excerpt: The purpose of the study is to determine whether T900607-sodium is effective and safe in treating hepatocellular carcinoma, a type of liver cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00043433

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T138067-sodium versus doxorubicin hepatocellular carcinoma patients

in

chemotherapy-naive,

unresectable,

Condition(s): Hepatocellular Carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Tularik Purpose - Excerpt: This is an international, multicenter, randomized study of intravenous T138067-sodium versus intravenous doxorubicin in hepatocellular carcinoma (liver cancer). Patients can not have been treated before with chemotherapy and surgery is not recommended for their cancer. A total of 750 subjects will be enrolled in this study. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00057382 •

T900607 in Treating Patients With Unresectable Liver Cancer Condition(s): localized unresectable adult primary liver cancer; advanced adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Ireland Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of T900607 in treating patients who have unresectable liver cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054262

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Testing of ADI-PEG in Hepatocellular Carcinoma Condition(s): Carcinoma, Hepatocellular Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: Amino acid deprivation therapy is an effective means for the treatment of some forms of cancer. Recently it has been found that human hepatocellular carcinomas (HCC) cell lines appear to require arginine for growth. Arginine is not an essential amino acid for human adults or infants as it can be synthesized from citrulline (for review see Rogers 1994). Therefore, selective elimination of arginine from the circulation may be a means of treating patients with metastatic melanoma or non resectable HCC. The enzyme arginine deiminase (ADI) metabolizes arginine into citrulline (Cunin 1986). However, ADI is only found in microbes and not in humans. ADI is therefore, highly immunogenic and has a short serum half-life following injection. These potential drawbacks (microbial source and thus viewed as foreign by the human immune system, and a short serum half-life) can be overcome by covalent attachment of polyethylene glycol (PEG) to argininedeiminase and termed this drug ADI-PEG 20. ADI-PEG 20 appears to be an effective anti-cancer treatment for human HCC. Pharmacokinetic and pharmacodynamic data indicates a once a week injection of 160 IU/m2 of ADI-PEG 20 eliminates all detectable arginine from the circulation for at least 7 days. This treatment appears to be well tolerated. The purpose of this study is to determine the efficacy of this treatment in patients with HCC. Efficacy is a primary end point of this study. No patients will recieve placebo. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056992

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Thalidomide and Chemoembolization With Doxorubicin in Treating Patients With Liver Cancer That Cannot be Removed by Surgery Condition(s): localized unresectable adult primary liver cancer; advanced adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Kaplan Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Thalidomide may stop the growth of liver cancer by stopping blood flow to the tumor. Chemoembolization kills tumor cells by delivering drugs directly into the tumor and then blocking the blood flow to the tumor. Combining thalidomide with chemoembolization may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining thalidomide and chemoembolization in treating patients who have liver 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/NCT00006016

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Treatment of hepatocellular carcinoma with Tetrathiomolybdate Condition(s): Carcinoma, Hepatocellular Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Hepatocellular carcinoma (HCC) is a deadly tumor for which the incidence is increasing in the United States, primarily due to prevalence of hepatitis C infection. An important aspect of the development of HCC is that it occurs in patients who have underlying cirrhosis of the liver, thereby limiting the therapeutic options. There is potential curative treatment for these patients, such as resection of the tumor lesion and liver transplantation, but these treatments are feasible in a small percent of patients only. Furthermore, the majority of the patients with HCC are also not candidates for palliative treatments such as percutaneous ablation of the tumor, chemotherapy or radiation. Additionally, it has been shown that these palliative treatment modalities do not alter survival, and are associated with significant risks. Therefore, there are no treatment options for most patients with HCC. A new theory has emerged in the fight against cancer through inhibition of angiogenesis (development of new blood vessels). The hypothesis being that if there is no blood supply "feeding" the tumor cells cannot divide or survive. One such approach, pioneered in this institution by Drs. George Brewer and Sofia Merajver, is the anticopper approach using the medication tetrathiomolybdate (TM). By creating a mild copper deficiency state, several pathways required for angiogenesis are inhibited. They performed a Phase I trial in which patients with metastatic cancer were treated with TM resulting in decrease tumor vascularity. TM had excellent safety profile in this patient population. HCC is well known to be a hypervascular tumor. An antiangiogenesis approach might provide a novel treatment for this HCC. This is a pilot study of 10 patients with HCC who are not candidates for curative surgical therapy with resection or liver transplantation, nor for ablative techniques. Patients seen in the General Liver clinic and Liver Transplant clinic who have an overall good performance status, with an expected survival of more than 6 months will be enrolled. After an initial evaluation, they will be given 120 mg/day of TM in divided doses for one year. The size and vascularity of the tumor will be

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evaluated by magnetic resonance imaging (MRI). The primary outcome of this study is to prevent tumor progression. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006332 •

Vaccine Therapy in Treating Patients With Liver Cancer Condition(s): localized resectable adult primary liver cancer; localized unresectable adult primary liver cancer; advanced adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have liver cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022334

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Gefitinib in Treating Patients With Advanced Unresectable Hepatocellular Carcinoma (Liver Cancer) Condition(s): advanced adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma; localized unresectable adult primary liver cancer Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have advanced unresectable hepatocellular carcinoma (liver cancer ). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071994

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Gemcitabine Plus Pemetrexed Disodium in Treating Patients With Unresectable or Metastatic Biliary Tract or Gallbladder Cancer Condition(s): advanced adult primary liver cancer; unresectable gallbladder cancer; unresectable extrahepatic bile duct cancer; adult primary cholangiocellular carcinoma Study Status: This study is not yet open for patient recruitment.

122 Liver Cancer

Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as gemcitabine use different ways to stop tumor cells from dividing so they stop growing or die. Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining gemcitabine with pemetrexed disodium may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining gemcitabine with pemetrexed disodium in treating patients who have unresectable or metastatic biliary tract or gallbladder cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059865

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 “liver cancer” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Bicistronic DNA construct comprising X-myc transgene for use in production of transgenic animal model systems for human hepatocellular carcinoma and transgenic animal model systems so produced Inventor(s): Anand; Rajesh (New Delhi, IN), Kumar; Vjay (New Delhi, IN), Singh; Mahavir (New Delhi, IN), Totey; Satish (New Delhi, IN) Assignee(s): International Centre for Genetic Engineering and Biotechnology (New Delhi, IN), National Institute of Immunology (New Delhi, IN) Patent Number: 6,274,788 Date filed: February 2, 1999 Excerpt(s): The present invention relates to a bicistronic DNA construct comprising Xmyc transgene. In particular, the present invention relates to a bicistronic X15-myc

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transgene capable of expressing truncated X protein and a full-length murine c-myc protein. More particularly, the present invention relates to a bicistronic DNA construct being an X15-myc transgene for use in the production of transgenic animal model systems for human hepatocellular carcinoma and transgenic animal model systems so produced. The invention is based partially on the discovery that in susceptible transgenic mice that carry a bicistronic X-myc transgene there is an accelerated formation of liver tumors involving all lobes. Hepatocellular carcinoma (HCC) is one of the ten most common human cancers with over 250,000 new cases worldwide each year. Evidence gathered over decades of epidemiological studies clearly indicate that there is an indisputable association between infection due to hepatitis B virus (HBV) and HCC. The incidence of HCC is directly proportional to that of HBV. At least 50% of individuals chronically infected by HBV develop HCC. At present more than 200 million people worldwide are chronically infected. Every year one to two million die as a result of the infection, approximately 700,000 of such deaths being due to HBV associated HCC (Szmuness, 1978, Prog. Med. Virol. 24:40-69). Although an HBV vaccine exists, the WHO estimates that 400 million people will be chronically infected by HBV by the year 2000. Since, the incubation period for the development of HBV-associated HCC is as long as 30 years or even more, the danger posed by HBV related HCC will continue to remain a major threat for decades. Therefore, there is an urgent need for better therapies to supplement existing ones such as liver resection, transplantation and ethanol injection. Otherwise, the situation is not likely to improve. However, it has been difficult to examine the pathogenic mechanism in great detail because of the limited host range of HBV and the lack of in vitro culture systems to propagate it. In view of this, most of the studies of HCC were, until recently, limited to the analysis of HBV-infected patients and chimpanzees or HBV-related hepadnavirus infections in woodchucks. Web site: http://www.delphion.com/details?pn=US06274788__ •

Cancer-related antigen-specific human immunoglobulins and human/human hybridomas having the ability to produce said human immunoglobulins Inventor(s): Hagiwara; Hideaki (1556, Kou, Befu-cho, Kasai-shi, Hyogo-ken, JP), Nagao; Junzo (Kasai, JP) Assignee(s): Hagiwara; Hideaki (Kasai, JP), Hagiwara; Yoshihide (Kasai, JP) Patent Number: 5,093,261 Date filed: May 20, 1988 Abstract: A new human/human fused cell clone derived from human B cells having the ability to produce immunoglobulins and human B cells substantially lacking the ability to produce immunoglobulins, antigen-specific human immunoglobulins produced by the human/human fused cell clone, and a method of producing the human immunoglobulins. More specifically, a human/human hybridoma having the ability to produce antigen-specific human immunoglobulins, which is a human/human fused cell strain derived from human B cells of a human patient with liver cancer and a subclone of a human lymphoblast cell strain; and antigen-specific human immunoglobulins produced by the human/human fused cell strain. Excerpt(s): This invention relates to a new human/human fused cell clone derived from human B cells having the ability to produce immunoglobulins and human B cells substantially lacking the ability to produce immunoglobulins, antigen-specific human immunoglobulins produced by the human/human fused cell clone, and to a method of producing the human immunoglobulins. More specifically, this invention relates to a

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human/human hybridoma having the ability to produce antigen-specific human immunoglobulins, which is a human/human fused cell strain derived from human B cells of a human patient with liver cancer and a subclone of a human lymphoblast cell strain. The invention also relates to antigen-specific human immunoglobulins produced by the human/human fused cell strain. The invention also pertains to a method of producing antigen-specific human immunoglobulins which comprises cultivating the human/human fused cell strain in a culture medium, and isolating the antigen-specific human immunoglobulins from the culture broth. The antigen-specific immunoglobulins are useful in medical, pharmaceutical and biochemical fields, for example for prevention, treatment and diagnosis of human liver cancer, the preparation of biochemical reagents and biopolymers, and purification of cancer antigens. Web site: http://www.delphion.com/details?pn=US05093261__ •

Cell cultivation method and floating animal cell culture unit for the same Inventor(s): Hayano; Fusakazu (Chigasaki, JP), Yoshida; Koichi (Fuji, JP) Assignee(s): Asahi Kasei Kogyo Kabushiki Kaisha (Osaka, JP) Patent Number: 4,391,912 Date filed: September 18, 1980 Abstract: A method of cultivating floating animal cells, such as lymphocytic cells, medullary tumor cells, medullary tumor cells obtained by the cell fusion with other cells, lymphoma cells, leukemic cells, leukocytic cells, mastocarcinoma cells, liver cancer cells, etc., which comprises introducing a culture medium in a cell culture unit comprising a shell and a plurality of hollow fibers enclosed in the shell, said hollow fiber being open at either end outside of the shell and having a pore diameter of from about 20 A to 10.sup.5 A, wherein the culture medium passes through the interior of the hollow fibers and the floating animal cells are cultivated in the space between the shell and the hollow fibers is disclosed. A floating animal cell culture unit for the method is also disclosed. Excerpt(s): This invention relates to a method for cultivating floating animal cells in a cell culture unit composed of hollow fibers. More particularly it is concerned with a method for cultivating floating animal cells in a cell culture unit composed of a shell and open ended hollow fibers enclosed in the shell, comprising introducing a culture medium through the hollow fibers and cultivating the floating animal cells in the space between the shell and the hollow fibers. The present invention also relates to a floating animal cell culture unit used for the method. Various methods for cultivating animal cells have been known. Animal cells include those which grow and proliferate while attached to a growth surface (referred to as "attaching cells") and those which grow and proliferate in a floating state (referred to as "floating cells"). Significant advances have been made in the study of cultivation of attaching cells. Such attaching cells can generally grow and proliferate only in a single layer on the attached surface. Richard A. Knazek, et al., however, have succeeded in three-dimensionally growing and proliferating attaching cells by employing a method in which the attaching cells are grown on the exterior surface of semipermeable hollow fibers or capillaries and a culture medium is passed through the hollow fibers or capillaries (see Journal of Medicine, Vol. 296, No. 3, pp. 154-159 (1977)). Additionally, U.S. Pat. No. 3,997,396 discloses a method of three-dimensionally growing and proliferating attaching cells in which the attaching cells are grown on one surface of a hollow fiber membrane and oxygen is supplied to the other surface.

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Web site: http://www.delphion.com/details?pn=US04391912__ •

Diphenylhexene composition for use in treating liver carcinoma and psoriasis Inventor(s): Metzler; Manfred (Im Speitel 23, D-76229 Karlsruhe, DE), Pechan; Reinhard (Elektrastr 36, D-81925 Munchen, DE) Assignee(s): none reported Patent Number: 5,650,445 Date filed: February 27, 1996 Abstract: The new compound 3,4-diphenyl-3-hexene has valuable pharmaceutical properties and is suitable for the treatment of diseases that are associated with degenerate cell growth in particular for the treatment of liver cancer and psoriasis. Excerpt(s): This application is a continuation of PCT/EP94/02837, filed Aug. 26, 1994, and designating the United States. The present invention concerns the new chemical compound diphenyl-3-hexene, a process for its production and its use as a therapeutic agent. Numerous diseases in humans are due to an uncontrolled growth of body cells. This disorder in proliferation can lead to a benign degeneration such as psoriasis vulgaris in the case of keratinocytes or.beta.-thalassaemia in the case of erythrocytes or even to a malignant degeneration such as in all forms of cancer. Web site: http://www.delphion.com/details?pn=US05650445__

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Inhibition of liver cancer by the use of GnRH and GnRH analogs Inventor(s): Habibi; Hamid R. (Calgary, CA) Assignee(s): University Technologies International,Inc. (Calgary, CA) Patent Number: 5,760,000 Date filed: May 13, 1994 Abstract: The invention provides a method for treating liver cancer in a mammal comprising administering to the mammal an inhibitory effective amount of at least one GnRH-related compound. Pharmaceutical preparations useful for the treatment of liver cancer comprising an inhibitory effective amount of at least one GnRH-related compound and a pharmaceutically acceptable carrier are also provided. A further aspect of the invention provides a method for diagnosing liver cancer by determining the presence of receptors for GnRH on a biological sample. Excerpt(s): This invention relates to the use of GnRH and GnRH analogs to inhibit liver cancer by the suppression of cell growth. The following references are cited in the application as numbers in brackets (› !) at the relevant portion of the application. 1. T. Yano, et al., Breast Cancer Research and Treatment, 21:35-45 (1992). Web site: http://www.delphion.com/details?pn=US05760000__

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Method and apparatus for surgical operation using microwaves Inventor(s): Tabuse; Katsuyoshi (831-54, Otani, Wakayama-shi, Wakayama-ken, JP), Zenitani; Toshio (1-23-603, Nigawa-kita 1-chome, Takarazuka-shi, Hyogo-ken, JP) Assignee(s): none reported Patent Number: 4,494,539 Date filed: May 4, 1982 Abstract: The present application discloses an invention of a surgical operation method using microwave characterized in that microwaves are radiated to bio-tissue from a monopolar type operating electrode attached to the tip of a coaxial cable for transmitting microwaves, and an operation of coagulation, hemostasis or transection is performed on the bio-tissue with the use of thermal energy generated from the reaction of the microwaves on the bio-tissue. The bio-tissue can be operated in an easy, safe and bloodless manner. Therefore, the present method can be utilized for an operation on a parenchymatous organ having a great blood content or for coagulation or transection on a parenchymatous tumor.According to the present method, there can be performed an operation on liver cancer which has been conventionally regarded as very difficult.Apparatus for embodying the present method can be economically manufactured in a small size. Excerpt(s): The present invention relates to a surgical operation method using microwave according to which an operation of coagulation, hemostasis or transection is performed on bio-tissue with the use of thermal energy generated from the reaction of microwaves on the bio-tissue and an operation, for example, on a parenchymatous organ having a great blood content can be performed in an easy, safe and bloodless manner. As an operation device, there are conventionally known an electrocautery (high frequency knife) and a laser operation device (laser knife). The electrocautery uses a power supply with frequency of 0.3 to 10 MHz, wavelength of 1000 to 30 m and output of 200 to 500 W, and includes a high frequency operating electrode of the knife or tweezers type and a nonactive electrode. Web site: http://www.delphion.com/details?pn=US04494539__

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Method for the production of in vivo model of hepatocellular carcinoma without lung metastasis Inventor(s): Futakuchi; Mitsuru (Aichi, JP), Shirai; Tomoyuki (Aichi, JP) Assignee(s): Kabushiki Kaisha Daiyu-Kai Institute of Medical Science (Ichinomiya, JP) Patent Number: 6,632,975 Date filed: October 10, 2000 Abstract: The present invention provides a method for producing an in vivo model of hepatocellular carcinoma without lung metastasis in an animal by injecting diethylnitrosamine and administering nitrosomorpholine in the drinking water of the animal, as well as, methods of identifying an antimetstatic agent using the in vivo model. Excerpt(s): The present invention relates to a method for the production of an in vivo lung metastatic hepatoma model, which may be useful in the search for and evaluation of antimetastatic agents. Metastasis is one of the most malignant phenotypic expressions of carcinoma, and the inhibition of metastasis is the ultimate goal of anticancer therapy.

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However, current antimetastatic studies using in vivo models, that is, animal models, have metastasis produced through an extremely artificial process. For example, tumor tissue itself or tumor cells have been administered by subcutaneous or intraperitoneal injection, or via direct intravenous injection to nude mice, i.e., animals whose rejection immunity is artificially removed or weakened. It is clear, however, that individual defense mechanism such as immunopotency or drug pharmacokinetics change according to the developmental stage of primary lesion or degree of systemic distribution of tumor tissue in individuals. Thus, the establishment of an animal model which represents the natural course of carcinoma in the human body, that is, an animal model where metastasis would be formed after development of carcinoma, has been highly desired. Web site: http://www.delphion.com/details?pn=US06632975__ •

Method for treating liver cancer Inventor(s): Bogden; Arthur E. (Hopedale, MA), Coy; David H. (New Orleans, LA), Kim; Sun Hyuk (Chestnut Hill, MA), Moreau; Jacques-Pierre (Upton, MA) Assignee(s): Biomeasure, Inc. (Milford, MA), The Administration of the Tulane Educational Fund (New Orleans, LA) Patent Number: 6,083,915 Date filed: May 10, 1991 Abstract: A method of treating liver cancer involving administration to the subject a therapeutically effective amount of a bombesin analog. Excerpt(s): This invention relates to the treatment of hepatoma, i.e., liver cancer. The amphibian peptide bombesin, pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-HisLeu-Met-NH.sub.2 [Anastasi et al., Experientia 27:166-167 (1971)], is closely related to the mammalian gastrin-releasing peptides (GRP), e.g., the porcine GRP, Ala-Pro-ValSer-Val-Gly-Gly-Gly-Thr-Val-Leu-Ala-Lys-Met-Tyr-Pro-Arg-Gly-As n-His-Trp-Ala-ValGly-His-Leu-Met-NH.sub.2 [McDonald et al., Biochem. Biophys. Res. Commun. 90:227233 (1979)] and human GRP, Val-Pro-Leu-Pro-Ala-Gly-Gly-Gly-Thr-Val-Leu-Thr-LysMet-Tyr-Pro-Arg-Gly-As n-His-Trp-Ala-Val-Gly-His-Leu-Met-NH.sub.2. Bombesin has been found to be a growth factor for a number of human cancer cell lines, including small-cell lung carcinoma (SCLC), and has been detected in human breast and prostate cancer [Haveman et al., eds. Recent Results in Cancer Research-Peptide Hormones in Lung Cancer, Springer-Verlag, New York (1986)]. A number of these cancers are known to secrete peptide hormones related to GRP or bombesin. Consequently, antagonists to bombesin have been proposed as agents for the treatment of these cancers. Web site: http://www.delphion.com/details?pn=US06083915__

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Radioactive chitosan complex for radiation therapy Inventor(s): Kim; Jae-Rock (Seoul, KR), Kim; Young-Mi (Seoul, KR), Park; Kyoung Bae (Seoul, KR) Assignee(s): Korea Atomic Energy Research Institute (Daejeon-Si, KR) Patent Number: 5,762,903 Date filed: March 8, 1996

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Abstract: The present invention relates to the radioactive chitosan complex formed by labelling a chitosan, a biocompatible and biodegradable natural polymer, with radionuclide, a radioactive chitosan macroaggregate formed by making chitosan complex into particles, and a kit for preparing radioactive chitosan complex, process for preparation thereof and the use thereof for an internal radiation therapeutic agent. The radioactive chitosan complex and its macroaggregate can be used as an internal radiation therapy for rheumatoid arthritis or cystic cancer such as liver cancer, brain cancer, breast cancer, ovary cancer and the like by administering them directly to the lesion. Excerpt(s): The present invention relates to a radioactive chitosan complex, its macroaggregate and a kit for preparing radioactive chitosan complex, process for preparation thereof, and the use thereof for radiation therapy. In particular, the present invention relates to a radioactive chitosan complex formed by labelling chitosan with radionuclides, and radioactive chitosan macroaggregate formed by making chitosan complex into particles, and a kit for preparing radioactive chitosan complex. The present invention relates to the process for preparation of radioactive chitosan complex by reacting radionuclide solution with chitosan solution, and the process for preparation of radioactive chitosan macroaggregate by adding alkaline solution to radioactive chitosan complex. Web site: http://www.delphion.com/details?pn=US05762903__ •

Steroid/thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma Inventor(s): Blaudin de THE; Hugues (Paris, FR), Dejean; Anne (Paris, FR), Marchio; Agnes (Paris, FR), Tiollais; Pierre (Paris, FR) Assignee(s): Institut Pasteur () Patent Number: 5,149,781 Date filed: June 20, 1988 Abstract: A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all non-hepatic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences. Excerpt(s): Primary hepatocellular carcinoma (HCC) represents the most common cancer, especially in young men, in many parts of the world (as in China and in much of Asia and Africa) (reviewed in Tiollais et al., 1985). Its etiology was investigated mostly by epidemiological studies, which revealed that, beyond some minor potential agents such as aflatoxin and sex steriod hormones, hepatitis B virus (HBV) chronic infection could account for a large fraction of liver cancers (Beasley and Hwang, 1984). A single HBV integration in a HCC sample in a short liver cell sequence has been reported recently. The sequence was found to be homologous to steroid receptor genes and to the

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cellular proto-oncogene c-erbA (Dejean et al., 1986). Ligand-dependent transcriptional activators, such as steroid or thyroid hormone receptors, have recently been cloned allowing rapid progress in the understanding of their mechanism of action Nevertheless, there exists a need in the art for the identification of transcripts that may encode for activational elements, such as nuclear surface receptors, that may play a role in hepatocellular carcinoma. Such findings would aid in identifying corresponding transcripts in susceptible individuals. In addition, identification of transcripts could aid in elucidating the mechanisms by which HCC occurs. Web site: http://www.delphion.com/details?pn=US05149781__ •

Therapeutic agents for liver regeneration Inventor(s): Doi; Hideyuki (Miyagi-ken, JP), Komatsu; Hiromichi (Nagano-ken, JP), Nishihira; Tetsuro (Miyagi-ken, JP) Assignee(s): Chugai Seiyaku Kabushiki Kaisha (Tokyo, JP) Patent Number: 5,916,921 Date filed: December 18, 1996 Abstract: A therapeutic agent for liver regeneration which contains valine as an active ingredient is disclosed that is effective against hepatopathy in hepatitis, fatty liver and drug-induced liver disorders. The agent promotes liver regeneration and recovery to normal liver function. It is also capable of inducing rapid-operative recovery of patients who were hepatectomized due to gallbladder cancer, liver cancer and metastatic liver cancer. Excerpt(s): This invention relates to therapeutic agents for liver regeneration containing valine, which is a branched-chain amino acid, as an active ingredient. To be more precise, the invention relates to valine-containing preparations that are capable of regenerating hepatocytes in cases such as after the removal of the liver due, for example, to hepatopathy, hepatitis and cirrhosis. Some factors and drugs are known to have a hepatocyte regenerating action. For example, Archive of Pathology, 16, 226-231 (1993) teaches that when a diet containing 1 wt % of a dried thyroid gland powder was continuously fed after partial hepatectomy, the liver weight increased significantly over the control from the seventh day of the partial hepatectomy. Journal of Biological Chemistry, 247, 1757-1766 (1972) reports that a liquid mixture of triiodothyronine (T3), mixed amino acids in solution, glucagon and heparin caused DNA synthesis in the liver. Web site: http://www.delphion.com/details?pn=US05916921__

Patent Applications on Liver 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 liver cancer:

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

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Cancer treatment with Go6976 and its related compounds Inventor(s): Lu, Zhimin; (San Diego, CA), Wang, Keming; (Suzhuu, CN) Correspondence: John R. Ross; Ross Patent Law Office; P.O. Box 2138; Del Mar; CA; 92014; US Patent Application Number: 20020016352 Date filed: July 24, 2001 Abstract: A chemotheraputic cancer treatment in which Go6976 or a compound chemically similar to Go6976 is administered to a mammal for the treatment of the cancer. The chemical compound is targeted to PKC.alpha. activity. Experiments have shown Go6976 and similar compounds to be effective for the treatment of breast cancer, leukemia, lung cancer, bone cancer, skin cancer, prostate cancer, liver cancer, brain tumor, cervical cancer, and cancers located in the digestive tract including gastric cancer and colorectal cancers. These treatments may be accomplished utilizing Go6976 and compounds similar to it alone or in combination with prior art chemotherapy agents or with radiation therapy. In a preferred embodiment Go6976 is used for the treatment of cancer as a preventative drug by preventing cancer cell formation. Excerpt(s): This application is a continuation-in-part application of Ser. No. 09/370,190 filed Aug. 9, 1999. This invention relates to cancer treatments and especially to cancer treatments directed to protein kinase C.alpha. enzyme. Researchers have recognized that a family of enzymes known as protein kinase C enzymes is associated with a large number of cancers. This family includes at least eleven isoenzymes. A particular member of this family is identified as the protein kinase C alpha enzyme, abbreviated: PKC.alpha. Researches have reported increases in PKC.alpha. activity in human breast tumors (NG et al., Science. 283:2085-2089) and significant increases in PKC.alpha.: expression in prostate cancers (Cornford et al., Am. J. Pathol. 154: 137 -144). Researchers have reported that PKC.alpha. is required for the metastasis of human melanoma (Dennis et al., Cancer Lett. 128:65-70) and that PKC.alpha. is related to the progression of brain tumors (Shen et al., Mol. Pharmacol. 55:396-402). Recently, Muller et al were granted a patent, U.S. Pat. No. 5,744,460, which discloses a cancer treatment utilizing an antisense oligonuclotide targeted to PKC.alpha. combined with a chemotherapeutic agent. U.S. Pat. Nos. 5,882,927 and 5,885,970 issued to Bennett et al also disclose antisense oligonuclotides targeted to PKC. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Combined preparations comprising morpholine anthracyclines and anticancer agent Inventor(s): Caruso, Michele; (Milan, IT), Geroni, Maria Christina; (Milan, IT), Ripamonti, Marina; (Milan, IT), Suarato, Antonino; (Milan, IT) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030087839 Date filed: October 31, 2002 Abstract: The present invention relates to combined preparations comprising a morpholinyl anthracycline administered in combination anticancer agents chosen from an allylating agent, an antimetabolite, a topoisomerase II inihbitor, a topoisomerase I

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inhibitor, an antimitotic drug and a platinum derivative, which are useful anticancer therapy, particularly in the treatment of a primary or metastatic liver cancer. Excerpt(s): The present invention pertains to the field of neoplastic diseases theraphy. In particular, the present invention refers to the synergic anticancer effect displayed by an anthracycline derivative administered in combination with at least another pharmaceutical substance effective in anticancer theraphy. Cancers are a leading cause of death in animals and humans; surgery, radiation and chemotherapy are the useful means to fight cancers. In particular, combined chemotheraphy, designed to treat cancer by using more than one drug in combination or association, is a well accepted modality of treatment of neoplastic diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for the targeted delivery of agents to treat liver cancer Inventor(s): Tsang, Shui Ying; (Sunshine City, HK), Wong, Jeffrey Tze Fei; (Mid-levels, HK) Correspondence: John Flaim; Baker & Mckenzie; 2001 Ross Avenue; Suite 2300; Dallas; TX; 75201; US Patent Application Number: 20020146449 Date filed: April 5, 2001 Abstract: The invention provides compositions containing an effective amount of a therapeutic agent encapsulated in a liposome coupled to a desialyated glycoprotein, e.g., desialyated glycoprotein-.alpha.1. This invention further provides methods for the targeted delivery of a therapeutic agent to a tissue expressing asialoglycoprotein receptors by delivery to the tissue an effective amount of a composition containing an effective amount of the agent encapsulated in a liposome coupled to a desialyated glycoprotein, e.g., desialyated glycoprotein-.alpha.1. Also provided by this invention is a method for inhibiting the proliferation of liver cancer by administering to a subject in need of such therapy an effective amount of a composition containing doxorubicin encapsulated in desialyated glycoprotein-.alpha.1 coupled to a liposome. Excerpt(s): The present invention relates to the field of drug delivery, pharmacology and cancer chemotherapy. Throughout this disclosure, various publications are referenced by a number within parenthesis. The full bibliographic citation for each reference can be found at the end of this application, immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into this disclosure to more fully describe the state of the art to which this invention pertains. Most of the cytotoxic drugs used in cancer chemotherapy have a narrow chemotherapeutic utility and serious side effects at high dosages. As a result, drug delivery systems have been developed to modify the biodistribution of cytotoxic drugs, improving their selectivity for tumors or reducing the damage to normal tissues. Liposomes have been used extensively in this regard. The use of liposomes as a drug delivery system has provided a means to improve the therapeutic utility of some conventional drugs [7, 19]. Since many liposomes are rapidly taken up by the cells of the mononuclear phagocyte system or reticuloendothelial system (RES) [12, 20], they have been effective in delivering drugs to organs of the RES. However, their rapid clearance from the bloodstream has also limited their utility for transporting drugs to disease sites beside the RES. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Diagnostic means useful for predictive assessment of human hepatocellular carcinoma disease (HCC), as well as diagnostic methods using the same Inventor(s): Buendia, Marie-Annick; (Le-Perreux, FR), Dejean, Anne; (Paris, FR), Nagai, Hisaki; (Kawasaki, JP), Pineau, Pascal; (Paris, FR), Tiollais, Pierre; (Paris, FR) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20020042073 Date filed: July 6, 2001 Abstract: The present invention pertains to new polynucleotides or new combinations of polynucleotides useful as diagnostic tools for predicting the occurrence of a human hepatocellular carcinoma disease. The invention is also directed to polynucleotides that consist in candidate tumor suppressor genes the alteration of which is involved in the occurrence of hepatocellular carcinoma in a patient, as well as to polynucleotides derived from such new candidate tumor suppressor genes and to the corresponding expressed polypeptides. The invention also concerns diagnostic methods using said polynucleotides as diagnostic tools. Excerpt(s): Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world, with 251,000 new cases each year (Bosh et al., 1991) and, to date, this pathology carries a very poor prognosis. Epidemiological evidence has shown the predominant role of hepatitis B virus (HBV) as a major causal agent of liver cancer. Other risk factors include chronic infection with hepatitis C virus (HCV), alcohol abuse, environmental exposure to hepatocarcinogens such as aflatoxin B1, and several genetic diseases (Reviewed in Buendia et al., 1995, and described also in Bosch et al., 1991; Wogan, 1992). More particularly, epidemiologic studies indicate that more than 50% of HCCs are attributable to chronic hepatitis B virus (HBV) infection (Bosch et al., 1991). However, the role of hepatotropic viral agents and the molecular events leading to liver carcinogenesis remain unknown. A mutagenic role of HBV DNA integration in the host genome, that occurs frequently at early stages of HBV-associated tumorigenesis, was conclusively established only in rare cases (Dejean et al., 1986; De The et al., 1987; Wang et al., 1990). suggesting more indirect transformation pathways (Matsubara, 1991). Viral DNA integrated into hepatocyte DNA can be detected in about 80% of chronic HBV carriers (Chen et al., 1986). A common feature in chronic viral hepatitis and liver cirrhosis is long lasting inflammation of the liver associated with chronic regenerative conditions, which might enhance the susceptibility of liver cells to genetic changes. HCC usually develops after a 20-50 year period of HBV chronic infection, often subsequent to cirrhosis (Lok et al., 1991). The long latent period before the establishment of carcinomas indicates that they are the result of a multistep process, and several studies have been directed toward the identification of common genetic alterations (Sugimura et al., 1992). Both activation of cellular oncogenes and inactivation of tumor suppressor genes have been implicated (Okuda et al., 1992; Sugimura et al., 1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 137

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Enzyme activated chemotherapy of liver cancer Inventor(s): Chung, Sum Man Stephen; (Hong Kong, CN) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030212147 Date filed: January 22, 2003 Abstract: The present invention provides methods of screening for anti-cancer drugs based on the activities of overexpressed enzymes by the cancer cells to convert non-toxic compounds to cytotoxic drugs which can specifically kill these cancer cells. In particular, the present invention provides methods of screening for anti-cancer drugs which can be used to treat liver cancer, especially hepatocellular carcinoma. The present invention also provides methods of treating cancers, in particular liver cancer, especially hepatocellular carcinoma, by administering to a subject the drugs selected by the screning methods of the present invention. In a particular embodiment, naphthalene or a derivative thereof is administered to a subject. The present invention further provides pharmaceutical compositions for treating or ameliorating cancers as well as kits containing such compositions. Excerpt(s): The present invention relates to methods of screening for anti-cancer drugs based on the activities of overexpressed enzymes by the cancer cells to convert non-toxic chemicals or compounds to cytotoxic drugs which can specifically kill these cancer cells. In particular, the present invention relates to methods of screening for anti-cancer drugs which can be used to treat liver cancer, especially hepatocellular carcinoma (HCC). The present invention also relates to methods of treating or ameliorating cancers, in particular, liver cancer, especially hepatocellular carcinoma, by administering the drugs selected by the screening methods of the present invention. The present invention further relates to pharmaceutical compositions for treating or ameliorating cancers, as well as kits containing such compositions. Liver cancer, especially hepatocellular carcinoma (HCC), is one of the leading causes of cancer related death in Hong Kong and China. It is also a significant health problem in many other countries, including the United States and European countries. Currently the only effective treatment is by surgical removal of the cancerous tissues, if the cancer is discovered at early stages, its size remains small, and is not metastasized to other sites. However, most cases of HCC are asymptomatic at early stages and, when the patients are diagnosed as having HCC, it is usually too late for surgical intervention. Various chemotherapy regimen, including hepatic intraarterial chemotherapy (HIA) and chemoembolization using conventional chemotherapeutic agents, have shown limited success (Venook, A. P., 2000, Regional strategies for managing hepatocellular carcinoma. Oncology (Huntingt) 14:347-54). Aldose reductase (AR) is a nicotinamide adenine dinucleotide phosphate (NADPH)dependent enzyme that was originally identified by its ability to reduce glucose to sorbitol and is present in kidney and testes as well as in many other tissues. AR is also efficient in reducing various aromatic and aliphatic aldehydes, e.g., glyceraldehyde, benzaldehyde and pyridine aldehyde (Inazu, N., et al., 1994, J. Biochem. (Tokyo) 115:991-999) and it has been suggested that AR may be responsible for detoxifying toxic lipid aldehydes produced during oxidative stress and other harmful aldehydes produced as a result of cellular metabolism (V. Jagt et al., 1992, J. Biol. Chem., 267:43644369; V. Jagt et al., 1995, Biochem. Biophs. Acta 35 1249:117-126). On the other hand, it was also reported that AR is overexpressed in stomach carcinoma cell lines (Ax, et al., 2000, Biochem. Pharmacol. 59:293-300) and colon-cancer cell lines (Akashi, et al., 2000, Int. J. Cancer 88:873-80). In addition, it was previously shown that about 29% of HCC

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overexpressed AR, and about 54% overexpressed ARL-1, an aldose reductase-like protein that is 71% identical to AR in amino acid sequence, with similar enzymatic activity as AR (Cao, D. L. Fan, S. T., and Chung, S. S. M., 1998, Identification and characterization of a novel human aldose reductase-like gene. J. Biol. Clem. 273a:1142935). As described above, AR and ARL-1 have broad substrate specificity and these two enzymes can reduce a broad range of aliphatic and aromatic aldehydes. Accordingly, they are generally considered to be enzymes that detoxify anti-cancer drugs (Hyndman, et al., 1999, Enzymol. Molec. Biol. Carbonyl Metab 7:427-434, Weiner et al. ed., Kluwer Academic/Plenum Pub. New York). Furthermore, there is evidence that these enzymes can indeed make cancer cells more resistant to some anti-cancer drugs (Lee, et al., 2001, Anti-cancer Drugs 12:129-132). However, the potential of these enzymes to be utilized to convert non-toxic chemicals to cytotoxic drugs so as to specifically kill cancer cells that overexpress the enzymes, has not been actively explored. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Galectin expression is induced in cirrhotic liver and hepatocellular carcinoma Inventor(s): Dowling, Christopher; (Freeport, ME), Hsu, Daniel K.; (Davis, CA), Liu, FuTong; (Davis, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020155513 Date filed: October 10, 2001 Abstract: The present invention relates to the discovery of a marker for liver disease. Novel diagnostics, prognostics, therapeutics and methods of use of the foregoing for the treatment and prevention of hepatocellular carcinoma are also disclosed. Excerpt(s): This application is a continuation of international application number PCT/US00/08561, and claims the benefit of priority of international application number PCT/US00/08561 having international filing date of Mar. 29, 2000, designating the United States of America and published in English, which claims the benefit of priority of U.S. provisional patent application No. 60/129,111, filed Apr. 13, 1999; both of which are hereby expressly incorporated by reference in their entireties. Hepatocellular carcinoma is a major type of cancer causing a quarter of a million deaths worldwide each year (Kew, M. C., Tumors of the liver. In: D. Zakim and T. D. Boyer (eds.), Hepatology. A Textbook of Liver Disease, pp. 1206-1240, W. B. Saunders, Philadelphia (1990)). While various factors have been identified as causes for HCC, the major established factors are infections of hepatitis viruses B (HBV) and C (HCV). Various potential mechanisms exist whereby infection by HBV can result in HCC. These include both chronic liver injury caused by cytotoxic T cell responses to infected hepatocytes and intracellular occlusion resulting from expression of viral protein (Chisari, F. V., Analysis of hepadnavirus gene expression, biology, and pathogenesis in the transgenic mouse. In: Current Topics in Microbiology and Immunology, pp. 85-99, SpringerVerlag, Berlin (1991)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 139

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Gene expression profiles in liver cancer Inventor(s): Horne, Darci T.; (Gaithersburg, MD), Scherf, Uwe; (Gaithersburg, MD), Vockley, Joseph; (Damascus, MD) Correspondence: Morgan Lewis & Bockius Llp; 1111 Pennsylvania Avenue NW; Washington; DC; 20004; US Patent Application Number: 20020142981 Date filed: June 14, 2001 Abstract: The present invention identifies the global changes in gene expression associated with liver cancer by examining gene expression in tissue from normal liver, metastatic malignant liver and hepatocellular carcinoma. The present invention also identifies expression profiles which serve as useful diagnostic markers as well as markers that can be used to monitor disease states, disease progression, drug toxicity, drug efficacy and drug metabolism. Excerpt(s): This application is related to U.S. Provisional Application 60/211,379, filed on Jun. 14, 2000, and U.S. Provisional Application 60/237,054, filed Oct. 2, 2000, which are herein incorporated by reference in their entirety. Primary hepatocellular carcinoma (HCC) is a widespread cancer throughout the world, especially prevalent where the incidence of chronic hepatitis B (HBV) and hepatitis C (HCV) viral infections are endemic (Groen, (1999) Semin. Oncol. Nurs. 15, 48-57; Idilman et al., (1998) J. Viral. Hepat. 5, 110-117; Di Bisceglie et al., (1998) Hepatol. 28, 1161-1165; Johnson, (1997) Hepatogastroenerology 44, 307-312; Sheu, (1997) J. Gastroeneterol. Hepatol. 12, S309313). Hepatocellular carcinomas are very malignant tumors that generally offer a poor prognosis, dependent on the size of the tumor, the effect on normal liver functions, and the involvement of metastases. They are best treated by surgical resection, when the tumors are diagnosed at a stage where this is a viable possibility, but the recurrence rate for these cancers remains high (Johnson, (1997) Hepatogastroenterology 44, 307-312; Schafer & Sorrell, (1999) Lancet 353, 1253-1257; Groen, (1999) Semin. Oncol. Nurs. 15, 4857; Sitzman, (1995) World. J. Surg. 19, 790-794; DiCarlo, (1995) Hepato-Gastroenterol. 42, 222-259; Tanaka et al., (1996) Hepato-Gastroenterol. 43, 1172-1181; El-Assal et al., (1997) Surgery 122, 571-577). Numerous risk factors for the development of HCC have been identified: cirrhosis, HBV or HCV infection, being male, alcohol-related liver disease, exposure to aflatoxins, vinyl chloride and radioactive thorium dioxide, cigarette smoking, ingestion of inorganic arsenic, the use of oral contraceptives and anabolic steroids, iron accumulation, and various inherited metabolic disorders (hemochromatosis, glycogen storage disease, porphyria, tyrosinemia,.alpha.-1antitrypsin deficiency) (Di Bisceglie et al., (1998) Hepatol. 28, 1161-1165; Chen et al., (1997) J. Gastroenterol. Hepatol. 12, S294-308; Schafer & Sorrell (1999) Lancet 353, 12531257; Groen, (1999) Semin. Oncol. Nurs. 15, 48-57; Idilman et al., (1998) J. Viral. Hepat. 5, 110-117; Johnson, (1997) Hepato-Gastroenterol. 44, 307-312). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Homozygous deletion of chromosome 8p23 in hepatocellular carcinoma Inventor(s): DeJean, Anne; (Paris, FR), Marchio, Agnes; (Sevran, FR), Pineau, Pascal; (Paris, FR) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030027155 Date filed: September 13, 2001 Abstract: A method for detecting human hepatocellular carcinoma (HCC), wherein the method comprises detecting a homozygous deletion in human chromosome 8p23. Excerpt(s): This application is based on and claims the benefit of U.S. Provisional Application Ser. No. 60/234,308, filed Sep. 21, 2000 (Attorney Docket No. 03495.6050). The entire disclosure of this Provisional application is relied upon and incorporated by reference herein. The identification of several major tumor suppressor genes (TSG) in the last decade has brought substantial gains in the fundamental understanding of two common human malignant tumors: breast and colorectal cancers. Notably, advances in molecular genetics lead to a better characterization of biological behaviors of tumors associated with specific TSG mutations (Kinzler and Vogelstein, 1997, Dillon et al., 1998). Ultimately, such progress would benefit patients at high risk of recurrence or metastasis and lead to the definition of appropriate treatments. However, such a propitious situation is not found in the field of primary liver cancer. Actually, major TSG involved in hepatocellular carcinoma (HCC) development and located on chromosomes 8p, 4q, 13q and 6q still remain to be identified. Hepatocellular carcinoma (HCC), the most frequent histological form of primary liver cancer, is one of the most prevalent human tumors with more than 400,000 new cases diagnosed each year worldwide (Parkin et al., 1999). The natural history of HCC, generally diagnosed in an advanced form, is characterized by very poor survival rates (Markovic et al., 1998). Several studies have recently demonstrated a significant increase in its incidence in the past twenty years in Japan, USA, and Europe (Taylor-Robinson et al., 1997, Deuffic et al., 1998, El-Serag and Mason, 1999, Makimoto and Higuchi, 1999). This increased incidence is thought to reflect the strong impact of some infectious or environmental factors on the pathogenesis of the tumor. The importance of chronic infection with hepatitis B and C viruses (HBV/HCV) in HCC has been well documented all over the world and, taken together, these viral infections are present in more than 80% of new primary liver cancer cases (Tsukuma et al., 1993, Brechot et al., 1998). In addition, at least in some geographical areas, chemical carcinogenic compounds (essentially alcohol and aflatoxin B1) represent major risk factors of primary liver cancer (Grisham, 1996). The available data in Europe suggests a further important rise in HCC incidence. This, as well as the major role of hepatitis viruses in this cancer, put forward this tumor as a major health care problem. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 141

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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; 30309-3400; 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 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

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Liver-caring medicine containing antrodia camphorata Inventor(s): Chen, Chin-Nung; (Taoyuan City, TW), Chen, Jinn-Chu; (Hsinchu, TW), Chuang, Cheng-Hung; (Changhua City, TW), Dai, Yu-Yun; (Taipei, TW), Hu, Miao-Lin; (Miaoli City, TW), Sheu, Sen-Je; (Taiping City, TW), Sio, Hok-man; (Taichung, TW), Tsai, Chin-Chuan; (Taichung, TW) Correspondence: Rosenberg, Klein & Lee; 3458 Ellicott Center Drive-suite 101; Ellicott City; MD; 21043; US Patent Application Number: 20030113297 Date filed: September 28, 2001 Abstract: The present invention relates to a liver-caring medicine that cures alcoholinduced liver cancer and contains active ingredients from the fruiting body and the mycelium of Antrodia Camphorata or Antrodia Cinnamomea, which is a kind of mushroom that only grows inside a unique plant in Taiwan, a Cinnamomum kanehirae tree. Excerpt(s): Antrodia Camphorata is also called Cinnamomum kanehirae mushroom, camphor mushroom, camphor chamber mushroom and yin-yang mushroom in Taiwan. The fruitbody of Antrodia Camphorata is perennial and has a strong smell. It differs a lot from general reishi mushroom in its plate-shaped or bell-shaped appearance. The plate-shaped one is orange red (yellow) with ostioles all over its surface and has light yellow white phellem in bottom layer. It grows by adhering phellem to the inner wall inside a hollow Cinnamomum kanehirae. The bell-shaped one also shows orange (yellow) color in fruitbody layer (bell surface) that is completely filled with ostioles (4.about.5 ostioles/mm), inside which are spores of bitter taste in orange red for fresh state and in orange brown or brown afterward. Bell body is a shell that appears in dark green brown color. The spores look smooth and transparent in slightly curved column shape under the investigation by microscope. The culture of Antrodia Camphorata still needs to be improved. So far, it is still collected from mountain field. However, the collection is a tough job. The first thing is to find where the Cinnamomum kanehirae trees are. The problem lies in the difficulty in distinguishing Cinnamomum kanehirae tree from Micranthum hayata. The most direct method presently was proposed by Fujita Yasuji Micranthum hayata tree oil is mainly composed of safrole and pentadecaldehyde, so it contains safrole smell in root beer. Cinnamomum kanehirae tree oil is mainly dterpinenol, which smells like camphor oil. Hence the different smells are used to distinguish them. The second problem is to find the hollow trees in a large forest. This is very difficult. If Antrodia Camphorata is found in the hollow Cinnamomum kanehirae tree, regular collection becomes possible. Because it is hard to find hollow Cinnamomum kanehirae trees, unworthy businessmen cut down the trees for Antrodia Camphorata to grow and collect it for sale. Therefore, under the consideration of environmental protection and economics, it is necessary to develop culturing technology for antrodia camphorat. But there is never a technical breakthrough. Antrodia Camphorata on Cinnamomum kanehirae wood chips grows slowly and even stops growth. Hence, using modem biotechnology to grow Antrodia Camphorata mycelium will be the most economical and environmental protection compliant artificial culture. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 143

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Method and activated lymphocyte preparations for preventing recurrence of carcinoma Inventor(s): Sekine, Teruaki; (Koto-ku, JP), Takayama, Tadatoshi; (Suginami-ku, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030044387 Date filed: September 4, 2001 Abstract: Activated lymphocytes are administered to a cancer patient at least five or more times within eight months after performing surgical and chemotherapeutic treatment or radiotherapy for treating cancer particularly liver cancer, so that recurrence of the cancer can be prevented over a long period of five or more years. The activated lymphocytes to be administered while performing treatment of cancer may be autologously derived from a cancer patient or collected from the other cancer patient at need. The activated lymphocytes can be cultivated for proliferating or activating lymphocyte cells collected in the presence of solid-phase anti-CD3 antigen and interleukin 2. Excerpt(s): This invention relates to a method for preventing recurrence of carcinoma and cancer over a long term and preparations containing activated lymphocytes for preventing recurrence of carcinoma and cancer over a long term, and more particularly to a long-term prophylactic method and longterm prophylactic preparations capable of preventing recurrence of carcinoma and cancer over a span of at least five years or more. The report makes it clear that the lymphocytes have the effectiveness of preventing recurrence of cancer and improving antitumor activation within about one to two years. However, even if the lymphocytes are solely used, recurrence of cancer cannot substantially be prevented with clinical significance over a long term of five years or more, on the basis of which an assessment of the therapeutic value of the lymphocytes is made. Further, the report-indicates that use of the activated lymphocytes enables prevention of recurrence of cancer. However, a long-term prevention of recurrence of carcinoma cannot be guaranteed in the report. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of producing primary hepatocellular carcinoma-bearing model animals Inventor(s): Ishii, Shun-Ichiro; (Hyogo, JP) Correspondence: Sughrue, Mion, Zinn, Macpeak & Seas, Pllc; Suite 800; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037-3213; US Patent Application Number: 20020062491 Date filed: September 19, 2001 Abstract: A method for producing primary hepatocellular carcinoma-bearing model animals is provided and is made easily and surely in a large scale. The model animals are effectively utilized for a method of diagnosis and therapy of primary hepatocellular carcinoma. Excerpt(s): The present invention relates to a production of primary hepatocellular carcinoma-bearing model animals and to the model animals produced thereby. More particularly, the present invention relates to a production of primary hepatocellular carcinoma-bearing model animals, characterized by being selected and subjected to

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administrating diethylnitrosoamine, breeding with a choline-deficient amino acid diet, and a normal diet, in a combined manner under a predetermined condition and also relates to the model animals produced as such. It has been known that, in advance of a occurrence of hepatocellular carcinoma, many progressive steps and processes are existed in carcinoma and occurrence thereof is resulted after a period of time for showing preneoplastic lesions. With regard to a method for producing carcinomabearing model animals, it is a conventional method where known carcinogen is mixed with drinking water or with feed, and is administered for a long period of time but said method is hardly adopted as for producing the primary hepatocellular carcinomahearing model animals as an object of hepatocellular carcinoma, because of too heavy labor needed, and many risks caused. When a carcinogen screening system, such as a medium-term carcinogenesis bioassay system (Exp. Toxic Pathol., 48, p. 113-119, 1996) on the basis of a two-step carcinogenesis theory (a theory that carcinogenesis comprises two steps, i.e. initiation and promotion) [Hosp. Pract. (Off Ed.), 18(7), p. 101-113, 1983] is utilized, it is possible to produce preneoplastic lesions within a short period of time (e.g., about eight weeks) by a combination of administration of carcinogen and partial hepatectomy (PH), and soon, although hepatocellular carcinoma is not produced thereby. Therefore, the above method is unable to be adopted as a method for producing a primary hepatocellular carcinoma-bearing model animals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nucleic acids, proteins, and antibodies Inventor(s): Barash, Steven C.; (Rockville, MD), Rosen, Craig A.; (Laytonsville, MD), Ruben, Steven M.; (Olney, MD) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20020042096 Date filed: January 17, 2001 Abstract: The present invention relates to novel liver related polynucleotides and the polypeptides encoded by these polynucleotides herein collectively known as "liver antigens," and the use of such liver antigens for detecting disorders of the liver, particularly the presence of cancer of liver and cancer metastases. More specifically, isolated liver associated nucleic acid molecules are provided encoding novel liver associated polypeptides. Novel liver polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human liver associated polynucleotides and/or polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to the liver, including cancer of liver tissues, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and/or compositions for inhibiting the production and function of the polypeptides of the present invention. Excerpt(s): The Sequence Listing may be viewed on an IBM-PC machine running the MS-Windows operating system by using the V viewer software, licensed by HGS, Inc., included on the compact discs (see World Wide Web URL: http://www.fileviewer.com). The present invention relates to novel liver related polynucleotides, the polypeptides encoded by these polynucleotides herein collectively

Patents 145

referred to as "liver antigens," and antibodies that immunospecifically bind these polypeptides, and the use of such liver polynucleotides, antigens, and antibodies for detecting, treating, preventing and/or prognosing disorders of the liver, including, but not limited to, the presence of liver cancer and liver cancer metastases. More specifically, isolated liver nucleic acid molecules are provided encoding novel liver polypeptides. Novel liver polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human liver polynucleotides, polypeptides, and/or antibodies. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to the liver, including liver cancer, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The invention further relates to methods and/or compositions for inhibiting or promoting the production and/or function of the polypeptides of the invention. A variety of agents, including viruses, drugs, environmental pollutants, genetic disorders, and systemic diseases, can affect the liver. The resulting disorders usually affect one of the three functional components of the liver: the hepatocyte (liver cell) itself, the bile secretory (cholangiolar) apparatus, or the blood vascular system. Most acute liver diseases are self-limited, and liver functioning returns to normal once the causes are removed or eliminated. In some cases, however, the acute disease process destroys massive areas of liver tissue in a short time, leading to extensive death (necrosis) of hepatic cells and often to death of the patient. Hepatitis may result from viral infections or toxic damage from drugs or poisons. When acute hepatitis lasts for six months or more, a slow but progressive destruction of the surrounding liver cells and bile ducts occurs, a stage called chronic active hepatitis. If hepatocellular damage is severe enough to destroy entire acini (clusters of lobules), they are often replaced with fibrous scar tissue. Bile canaliculi and hepatocytes regenerate in an irregular fashion adjacent to the scar tissue and result in a chronic condition called cirrhosis of the liver. Where inflammatory activity continues after the onset of cirrhosis, the disorderly regeneration of hepatocytes and cholangioles may lead to the development of hepatocellular or cholangiolar cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical composition for the treatment of hepatocellular carcinoma Inventor(s): Chang, Jang-Yang; (Taipei, TW), Chen, Li-Tzong; (Kaohsiung City, TW), Hsu, Ming-Chu; (Taipei, TW), Huang, Chun-Ying; (Taipei, TW), Liu, Tsang-Wu; (Taipei, TW), Whang-Peng, Jia-Kang; (Taipei, TW) Correspondence: Ladas & Parry; 26 West 61st Street; New York; NY; 10023; US Patent Application Number: 20010018445 Date filed: January 24, 2001 Abstract: The invention mainly discloses a pharmaceutical composition for use in the treatment of hepatocellular carcinoma, which comprises thalidomide and a pharmaceutically acceptable carrier. Excerpt(s): Thalidomide was first synthesized in 1953, and it was widely used as a sedative and for the prevention of vomiting during pregnancy. In 1963, it was found that women who took thalidomide in the first trimester of pregnancy would deliver terata, such as phocomelia. Therefore, thalidomide was prohibited in Europe and the USA. In view of studies in recent years, thalidomide has the efficacy on adjustment of

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the immune system which may treat immune system related diseases. For instance, Arch Dermatol. 1993, vol. 129, p. 1548-1550 described the use of thalidomide in the treatment of cutaneous lupus erythematosus; the Journal of Rheumatology, 1989, 16, p. 159-163 described the use of thalidomide in the treatment of refractory rheumatoid arthritis; Arch Dermatol. 1990, vol. 126, p. 923-927 described the use of thalidomide in the treatment of Behcet's syndrome; Journal of Pediatr. Gastroenerol. Nurt. 1999, vol. 28, p. 214-216 described the use of thalidomide in the treatment of Cornh's disease; and Journal of Rheumatology, 1998, vol. 25, p.964-969 described the use of thalidomide in the treatment of rheumatoid arthritis. In addition, U.S. Pat. Nos. 5,593,990 and 5,629,327 disclose that thalidomide could effectively inhibit angiogenesis; U.S. Pat. No. 5,654,312 discloses the methods of treatment for inflammatory and autoimmune dermatoses. In addition, the Journal of Infectious Diseases, 1993, 168, p. 408-414 taught that thalidomide could effectively inhibit tumor necrotic factor-alpha (TNF-I). Anti-Cancer Drugs, 1996, 7, p.339-343 demonstrated that thalidomide could effectively inhibit basic fibroblast growth factor-induced angiogenesis. Thalidomide is widely applied in the clinical treatment of malignant tumors which are highly vascular and cannot be effectively treated by chemical therapy. For instance, U.S. Pat. No. 5,696,092 discloses the use of thalidomide in the inhibition of metastases of cancers of epithelial cell origin, especially human prostate cancers. Among the above prior art references, none of the references or patents teaches that thalidomide could be specifically used in the treatment of hepatocellular carcinoma. Up to the present time, there are not any drugs that can effectively treat hepatocellular carcinoma. Patients with metastatic hepatocellular carcinoma or hepatocellular carcinoma, where local treatment has failed, normally survive for only three to four months. Metastatic hepatocellular carcinoma or hepatocellular carcinoma, where local treatment has failed, is mainly subjected to systemic therapy. The use of Doxorubicin, a high dosage of Tamoxifen in combination Doxorubicin or EA-PFL (etopoxide, adrimycin, cisplatin, fluorouracil and leucovorin), is an effective example. The remission rate of those drugs can achieve levels between 15 and 30%. However, because the patients of hepatocellular carcinoma usually develop complication of liver cirrhosis and other complications (such as leukopenia, thrombopenia or liver function impairment), they cannot be subject to systemic chemotherapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Plant drug for treatment of liver disease Inventor(s): Zhao, Xinxian; (Shenzhen, CN) Correspondence: Xinxian Zhao; 67-08 168th Street; Flushing; NY; 11365; US Patent Application Number: 20030026854 Date filed: April 4, 2001 Abstract: The present invention related to safe plant drug for treatment of liver disease, specifically, this invention proves a safe plant drug Schisandrin and its preparation. Schisandrin has the following pharmaceutical functions: increasing tumor suppresson genes express activity, decreasing activity of oncogenes, increasing immune function, increasing liver DNA synthesis, decreasing serum alamine aminotransferase activity, increasing glutathione level, increasing glutathione reductase activity, decreasing lipid peroxidation of liver, increasing hepatic microsomal monooxygenases activity, increasing ATP content in liver, increasing energy metabolism activity, decreasing density lipoprotein oxidation, protecting gastrointestinal function, increasing killer cell

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activity, increasing complement activity, decreasing induced liver cancer activity and decreasing grown of cancer cells. Excerpt(s): The present invention related to safe plant drug for treatment of liver disease, specifically, this invention proves a safe plant drug Schisandrin and its preparation. The most common types of liver disease are hepatitis and cirrhosis. So far, no one drug has been succeeded to treat for hepatitis and cirrhosis. The hepatitis victim is always short on appetite and finds it is difficult. Therefore, it is important that to eat the suitable food to supply liver for self-repair. The traditional medical book described that a good treatment for hepatitis is high protein diet, Brewer's yeast, wheat germ, egg yolks, and other high quality protein, which combats the stress damage. Some drugs have been used for treatment of liver disease, but clinical results are not successful. For the reasons given above, to discover an effect safe drug for treating patients with liver disease is necessary and important. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Prevention of liver cancer by administration of simvastatin Inventor(s): Weinberg, Assa; (Los Angeles, CA) Correspondence: Dave B. Koo, ESQ.; Squire, Sanders & Dempsey L.L.P.; 801 S. Figueroa Street, 14th Floor; Los Angeles; CA; 90017-5554; US Patent Application Number: 20020151583 Date filed: April 11, 2001 Abstract: A method for preventing liver cancer is disclosed. In one embodiment, the method comprises administrating an effective amount of simvastatin to patients showing elevated alphafetoprotein levels. In another embodiment, the method comprises administrating simvastatin to patients upon detection of a liver condition, i.e viral Hepatitis B, Hepatitis C and liver cirrhosis. Excerpt(s): In spite of substantial advances in the understanding of the mechanism of oncogenesis (transformation of a normal cell into a malignant one), a method to prevent and reverse such oncogenic process has not been put into practice. Many environmental, dietary and genetic factors play a significant role in the formation of a malignant tumor, but no drug is known to prevent the formation of a malignant tumor. In many cases, patients affected with a malignant tumor are deemed to be terminal. Cancer of the liver or hepatocellular carcinoma is a particular case in point. It is an aggressive and rapidly spreading disease. Even with the combined use of the four classic treatment modalities, surgery, radiation, chemotherapy and immunotherapy--little has been changed to alter the grim prospect. The only methods capable of eradicating liver cancer at the present time are partial resection of the liver in the case where the malignancy is localized or complete extirpation of the malignant liver and a replacement by transplantation. In liver transplantation cases, the cost of the procedure is substantial, followed by a lifelong administration of anti-rejection drugs, and medical follow-up involving doctor visits, blood tests, and imaging studies. Patients with advanced liver diseases, and in particular, patients with viral hepatitis B and C are known to be at a high risk of developing liver cancer. In the United States, there are 70,000 new hepatitis B cases and more than 250,000 newly diagnosed hepatitis C cases each year. Around the world and especially in Southeast Asia and China, Hepatitis B and C are at epidemic proportion without a cure in sight. The case is particularly serious as the Hepatitis virus can be transmitted during delivery to the newborn baby. This was demonstrated in recent

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studies from Taiwan in which 40% of babies born to Hepatitis B or C carrier mothers were found to be positive for the same, a few days after delivery or a month later. In the same token hepatocellular carcinoma is at epidemic proportions in this region and represents a major public health issue for these countries. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Radioimmunoassay testing kit for detecting aflatoxin-albumin adduct Inventor(s): Huang, Henton; (Tau Yen, TW), Lee, Te-Wei; (Taipei, TW), Ting, Gann; (Taipei, TW), Wang, Mei-Hui; (Hsin Chu, TW), Wu, Chang-Yi; (Taipei, TW) Correspondence: Rosenberg, Klein & Lee; Suite 105; 3444 Ellicott Center Drive; Ellicott City; MD; 21043; US Patent Application Number: 20020115125 Date filed: January 10, 2002 Abstract: The invention discloses one radioimmunoassay testing kit and method for detecting aflatoxin-albumin adducts. The radioimmunoassay testing kit combining with competitive inhibition radioimmunometric assay, could be used to quantitate the aflatoxin-albumin adducts in serum. The invention also discloses their clinical uses in rapid mass detection of the doses of aflatoxin exposure, which is one of risk factors of liver cancer. Excerpt(s): The present invention relates to a radioimmunoassay testing kit and a method, which is used to quantitate the aflatoxin-albumin adduct. In particular the present invention relates to routine uses in serum. The present invention also relates to a method to determine if there is aflatoxin exposure or not. The normal cutoff value is also discloses. Aflatoxins are toxic metabolites produced by the fungal species Aspergillus flavus and Aspergillus parasiticus. Aflatoxin B1 (AFB 1) is the most toxic group. Experimental normal evidence that aflatoxin is carcinogenic, especially in hepatotoxicity. Using the TD50 values for rats developed by Gold et al (Cancer Res. 1993, 53: 9-11). AFB1, which TD50-9.3.times.10.sup.-4 mg/kg per day, is 1000 times more potent a carcinogen than benzo(a)pyrene. Recently, the International Agency for Research on Cancer (IARC) reported that there is sufficient evidence to classify aflatoxin B1 and mixtures of aflatoxins as Group 1 carcinogens in humans. AFB1 requires microsomal oxidation to the reactive AFB1-8,9-epoxide (AFBO) to exert its hepatocarcinogenic effects, and the extent of covalent binding of AFBO to cellular RNA, DNA, protein or other macromolecules (IARC 1993;56:303). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Theobromine with an anti-carcinogenic activity Inventor(s): Kang, Kyung Sun; (Kyunggi-do, KR), Kim, Dong Young; (Kyunggi-do, KR), Kim, Han Soo; (Kyunggi-do, KR), Kwon, Ik Boo; (Seoul, KR), Lee, Hyong Joo; (Seoul, KR), Lee, Ki Won; (Kyunggi-do, KR), Lee, Man Jong; (Kyunggi-do, KR), Park, Hyung Hwan; (Kyunggi-do, KR) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030099686 Date filed: August 15, 2002 Abstract: Disclosed is theobromine with an anti-carcinogenic activity which inhibits the suppression of GJIC (gap junctional intercellular communication), a pathological phenomenon occurring during development of various kinds of cancers including liver cancer, as well as DNA synthesis of cancer cells thereby inhibiting proliferation of liver, gastric and colon cancer cells. Excerpt(s): The present invention relates to theobromine with an anti-carcinogenic activity, and more particularly, to theobromine which inhibits the suppression of gap junctional intercellular communication (GJIC), a pathological phenomenon occurring during development of various kinds of cancers including liver cancer, as well as DNA synthesis of cancer cells thereby inhibiting proliferation of cancer cells. Although a wide range of attempts has been made to treat cancer over the last three decades, incidence and death rates of cancer have not decreased. (Sporn, M. B., Lancet, 347:1377-1381, 1996) This appears mainly due to the fact that the approaches on cancers for the past thirty years have been mostly focused on from the therapeutic point rather than preventive point. As is already known, intake of certain food or a drug that contains components which can effectively inhibit or delay the multi-step progress of cancer will help to reduce the risk of cancer and the subsequent mortalities resulted thereof and many researches have been carried out (Kang et al., Chemoprevention of cancer, Korea Medicine, 2000; Surh, Y. J., Mutat. Res, 428:305-327, 1999; Sporn, M. B., Lancet, 347:13771381, 1996; Caragay, A. B., Food Technol., 65-68, 1992). Carcinogenesis is a multi-step process comprising stages of initiation, promotion and progression. In searching of agents which may be effective in prevention or inhibition of cancer, the recent researches have been more concerned with identifying substances that can inhibit promotion and promotion stages rather than those of initiation stage, which is a relatively short and irreversible stage (Kang et al., Chemoprevention of cancer, Korea Medicine, 2000; Surh, Y. J., Mutat. Res, 428: 305-327, 1999; Sporn, M. B., Lancet, 347: 1377-1381, 1996). In particular, unlike pharmaceutical drugs, the prevention and inhibition of cancer by means of food extract and fraction will become more effective if they target on the promotion stage of carcinogenesis, which is generally progressed for more than 20 years and is also reversible (Kang et al., Chemoprevention of cancer, Korea Medicine, 135-136, 2000; Yamasaki, H. et al, Carcinogenesis 11: 1051-1058, 1999; Kelloff. G. J. et al., Eur. J. Cancer, 35: 1755-1762, 1999; Surh, Y. J., Mutat. Res, 428: 305-327, 1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Transgenic animals expressing androgen receptor complex-associated protein Inventor(s): Chang, Tai-Jay; (Taipei, TW) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030082721 Date filed: July 25, 2002 Abstract: Transgenic animals expressing an androgen receptor complex-associated protein gene. These animals serve as models for developing drugs to treat cancer, e.g., liver cancer. Excerpt(s): This application is a continuation-in-part of and claims priority to U.S. application Ser. No. 09/781,693, filed Feb. 12, 2001 and U.S. Provisional Application Serial No. 60/262,312, filed Jan. 17, 2001, the contents of which are incorporated herein by reference. A variety of genes that are overexpressed in tumor cells relative to healthy cells have been identified. It is expected that the identification of such genes will provide drug targets for anti-cancer drug development and for cancer diagnostics. The number of steroid receptors (e.g., androgen receptors) in liver tumor cells appears to be increased relative to their adjacent healthy liver cells. Steroid hormones generally exert their physiological effects by binding to their specific nuclear receptors to form complexes that in turn act as transcription factors. The complexes bind to specific nucleotide sequences (steroid responsive elements) in the promoters of steroidresponsive genes to facilitate transcription of those genes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of cancers Inventor(s): Moehler, Hanns; (Meilen, CH), Pfirrmann, Rolf W.; (Lucerne, CH), Redmond, H. Paul; (Wilton, IE), Stendel, Ruediger; (Berlin, DE) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.; 1425 K Street, N.W.; Suite 800; Washington; DC; 20005; US Patent Application Number: 20030027818 Date filed: March 29, 2002 Abstract: A method of inducing apoptotic death of a neoplastic cell, whereby the neoplastic cell is contacted with an apoptosis-inducing amount of a methylol-containing compound. This method is useful for treating both primary and metastatic cancers. A preferred embodiment includes administering a :4 methylol transfer agent to the mammal, at a total daily dose of from about 2 g to about 60 g, the administration including at least two dosing cycles, each dosing cycle including an infusion phase of about 1 to 8 days, and a non-administration phase of about 1 to 14 days. Another embodiment includes treating liver cancer by administration of a solution of a methylol transfer agent directly to the liver via a hepatic vessel. Excerpt(s): This application claims the benefit of U.S. provisional applications 60/280748, filed Apr. 3, 2001, 60/281710, filed Apr. 6, 2001, 60/281711, filed Apr. 6, 2001, 60/281712, filed Apr. 6, 2001, 60/281713, filed Apr. 6, 2001, and 60/284933, filed Apr. 20, 2001, and 60/284934, filed Apr. 20, 2001. The invention relates to the use of methylolcontaining compounds, such as taurolidine and taurultam, for the treatment of cancer. Methylol transfer agents, such as the antibacterial and anti-toxin drug taurolidine and the related product taurultam, have been shown to exert a modifying effect on the

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toxicity of tumor necrosis factor (TNF) which is used, inter alia, in the treatment of tumors. Furthermore, the action of methylol transfer agents has been shown to be selective in that the growth of normal cell-lines was not significantly inhibited. 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 liver 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 “liver 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 liver cancer. You can also use this procedure to view pending patent applications concerning liver cancer. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON LIVER CANCER Overview This chapter provides bibliographic book references relating to liver cancer. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on liver 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 “liver 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 liver cancer: •

Living with Hepatitis C: A Survivor's Guide Source: New York, NY: Hatherleigh Press. 1999. 255 p. Contact: Available from Hatherleigh Company, Ltd. 1114 First Avenue, Suite 500, New York, NY 10021. (800) 367-2550 or (212) 832-1039. Website: hatherleigh.com. PRICE: $14.95 plus shipping and handling. ISBN: 1578260345. Summary: This book offers information and guidance for people living with hepatitis C. The authors explain in nontechnical language the causes of the disease, how to understand blood tests and biopsies, the major and minor symptoms, how to avoid infecting others, and the importance of good nutrition in long term management of the disease. Readers will learn how to deal with the emotional rollercoaster and the cycle of grief and how to protect themselves and their families financially. The book also details the latest treatments (including Ribavirin), what to expect if a liver transplant is chosen as the appropriate means of therapy, and current medical research activities regarding

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hepatitis C. Other topics covered in the 13 chapters are risk factors for liver cancer, coinfection with hepatitis C and HIV, and children with hepatitis C. The book includes lengthy quotes from patients with hepatitis, a technique that offers the patient's perspectives, insights, and experiences to the reader. The book concludes with a lengthy list of resources, a bibliography, and a subject index. •

Management of Hepatitis C: NIH Consensus Development Conference Program and Abstracts Source: Bethesda, MD: National Institutes of Health. 1997. 139 p. Contact: Available from NIH Consensus Program Information Center. P.O. Box 2577, Kensington, MD 20891. (888) 644-2667. Fax (301) 816-2494. PRICE: Single copy free. Summary: This document presents abstracts of the NIH Consensus Development Conference on the Management of Hepatitis C, held in March 1997 in Bethesda, Maryland. It notes the conference's agenda, panel, speakers, and planning committee members. The document was designed for the use of panelists and participants in the conference and as a pertinent reference document for anyone interested in the conference deliberations. The abstracts are presented in four sections: the natural history of hepatitis C, diagnostic considerations, the epidemiology and spread of hepatitis C, and therapeutic issues. Specific topics covered include the clinical spectrum of disease, blood donors with hepatitis C, hepatitis C and hepatocellular carcinoma (liver cancer), hepatitis C and alcohol, diagnostic tests for hepatitis C, the role of liver biopsy, the epidemiology of hepatitis C, the sexual and perinatal spread of hepatitis C virus infection, the use of interferon alfa-2b, ribavirin treatment, drug side effects, predictive factors for a beneficial response to drug therapy in hepatitis C, the treatment of patients with liver cirrhosis, retreatment with interferon, and cost effectiveness considerations. Each abstract includes brief references.

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Living With Hepatitis B: A Survivor's Guide Contact: Hatherleigh Press, 5-22 46 Ave Ste 200, Long Island City, NY, 11101, (800) 3672550, http://www.hatherleigh.com. Summary: This monograph provides medical, emotional, financial, and nutritional information to help anyone diagnosed with chronic hepatitis B to understand and cope with the disease. It explains the disease hepatitis B, its diagnosis, tests and biopsies, transmission, prevention, and its effect on the liver. The monograph also discusses healthy nutrition for an individual with hepatitis B, emotional effects of the disease, and financial concerns due to disability and the cost of lifelong medical care. Other topics covered include types of treatment; when a liver transplant becomes necessary; liver cancer; coinfection with HIV/AIDS, hepatitis C, and hepatitis D; hepatitis B in children; and research trends.

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Liver Disorders Sourcebook Source: Detroit, MI: Omnigraphics. 2000. 591 p. Contact: Available from Omnigraphics, Inc. 615 Griswold, Detroit, MI 48226. (800) 2341340. Fax (800) 875-1340. PRICE: $78.00 plus shipping and handling. ISBN: 0780802403. Summary: This Sourcebook provides basic health care information about liver functions, guidelines for liver health, and tests that assess liver distress. The book also presents the symptoms, treatments, and preventive measures available for liver cancer; hepatitis A, B, C, D and E; genetically based liver diseases; and other liver diseases. The liver

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transplantation process is explained. Specific topics include strategies for protecting the liver, risk factors, common laboratory tests in liver disease, liver biopsy, cancer tumor markers, cirrhosis (scarring of the liver), infectious agents and parasites, pregnancy and the liver, jaundice in the healthy newborn, the liver's response to drugs, alcohol and the liver, acetaminophen, herbs and alternative medicine, galactosemia, Gaucher disease, hereditary hemochromatosis, Niemann-Pick disease, Wilson's disease, biliary atresia, cystic disease of the liver, fatty liver, gallstones, primary biliary cirrhosis, primary sclerosing cholangitis, organ donation, and the bioartificial liver. A glossary, a directory of organizations and support groups with up to date contact information (including websites and email addresses), a listing of transplant centers, and a subject index conclude the volume. •

Hepatobiliary Diseases: Pathophysiology and Imaging Source: Malden, MA: Blackwell Science, Inc. 2001. 764 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $275.00. ISBN: 0632055421. Summary: This textbook aims to familiarize the reader with various imaging modalities, the information they provide, and with the merits of each, in order to facilitate the combined use of different imaging techniques in the diagnosis and management of hepatobiliary (liver and bile tract) diseases. The book includes 47 chapters in seven sections: progress in imaging, anatomy and gross changes in the liver, diffuse liver diseases, vascular disease, space-occupying lesions, other liver diseases, and biliary tract disease. Specific topics include computed tomography (CT scan) and magnetic resonance imaging (MRI); harmonic ultrasound; anatomy of the liver; acute hepatitis and acute hepatic failure; chronic hepatitis; cirrhosis (liver scarring); fatty liver (steatosis); alcoholic liver disease; iron overload; Wilson's disease; amyloidosis, metabolic diseases, drug-induced and chemical-induced liver injuries; vascular anatomy of the liver and vascular anomalies; portal hypertension (high blood pressure); thrombosis (clotting) affecting the liver; Budd-Chiari syndrome; primary malignant tumors of the liver (liver cancer); benign liver lesions; cysts of the liver; liver abscess; blunt hepatic trauma; parasitic diseases; infections and the liver; transplantation; anatomy of the biliary tract; congenital anomalies and dilatation; Caroli's disease; stone disease (gallstones); biliary tract stenosis; primary sclerosing cholangitis; cholecystitis and Mirizzi syndrome; tumors of the gallbladder; adenomyomatosis and cholesterolosis; Hilar carcinoma; and tumors of the common bile duct and papilla of Vater. Each chapter includes black and white reproductions of imaging techniques and a list of references. The book includes a color plate section and a detailed subject index.

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Viral Hepatitis: An Epidemic in the Making? New Approaches to the Prevention, Diagnosis, and Treatment of Viral Hepatitis Source: Bethesda, MD: American Gastroenterological Association. 200x. 36 p. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, Seventh Floor, Bethesda, MD 20814. (301) 654-2055. Fax (301) 652-3890. E-mail: [email protected]. PRICE: Single copy free. Also available at http://www.gastro.org/phys-sci/viral-hep.html. Summary: Viral hepatitis is a major public health concern and the most common cause of chronic liver disease, cirrhosis (scarring), and hepatocellular carcinoma (liver cancer).

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This monograph explores current strategies used to prevent, diagnose, and manage the major forms of viral hepatitis seen in the United States. All cases of hepatitis A and hepatitis B infection are potentially preventable, and new therapies have proven to be beneficial for many patients with hepatitis C; however, research for a vaccine to prevent hepatitis C is still underway. The costs associated with viral hepatitis are significant, particularly for hepatitis B and C. When quality of life is factored into the equation, the costs are even greater. However, there has been significant progress in recent years in the understanding of the diagnosis, epidemiology, natural history, prevention, and treatment of viral hepatitis. The monograph enables readers to identify the critical elements of screening, prevention, and treatment protocols for hepatitis A, E, B, and C; to recognize the signs and symptoms of the several forms of viral hepatitis; to explain to patients the importance of preventing viral hepatitis; and to improve quality of care and the clinical outcomes of patients with viral hepatitis. Tables and figures illustrate the monograph. 14 figures. 4 tables. 79 references.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “liver cancer” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “liver cancer” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “liver cancer” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

21st Century Complete Medical Guide to Liver Cancer - Authoritative Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment Options by PM Medical Health News; ISBN: 1592480144; http://www.amazon.com/exec/obidos/ASIN/1592480144/icongroupinterna

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Diagnosis and Treatment of Hepatocellular Carcinoma by Tito Livraghi (Editor), et al; ISBN: 1900151308; http://www.amazon.com/exec/obidos/ASIN/1900151308/icongroupinterna

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Early Detection and Treatment of Hepatocellular Carcinoma by Kyuichi Tanikawa; ISBN: 0849359228; http://www.amazon.com/exec/obidos/ASIN/0849359228/icongroupinterna

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Early Detection and Treatment of Liver Cancer; ISBN: 4762246662; http://www.amazon.com/exec/obidos/ASIN/4762246662/icongroupinterna

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Early Detection and Treatment of Liver Cancer (Gann Monographs on Cancer Research, No 38) by Kunio Okuda, et al; ISBN: 0748400362; http://www.amazon.com/exec/obidos/ASIN/0748400362/icongroupinterna

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Etiology, Pathology, and Treatment of Hepatocellular Carcinoma in North America (Advances in Applied Biotechnology Series, Vol 13) by Edward Tabor, et al (1991); ISBN: 0943255171; http://www.amazon.com/exec/obidos/ASIN/0943255171/icongroupinterna

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Hepatitis B Virus and Primary Liver Cancer by P. Maupas (Editor), Joseph L. Melnick (Editor) (1981); ISBN: 380551784X; http://www.amazon.com/exec/obidos/ASIN/380551784X/icongroupinterna

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Hepatitis Viruses and Hepatocellular Carcinoma: Approaches Through Molecular Biology and Ecology by Kusuya Nishioka, et al; ISBN: 0125199309; http://www.amazon.com/exec/obidos/ASIN/0125199309/icongroupinterna

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Hepatocellular carcinoma; ISBN: 9290180749; http://www.amazon.com/exec/obidos/ASIN/9290180749/icongroupinterna

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Hepatocellular Carcinoma (An Atlas of Its Pathology) by M. Kojiro Nakashima, T. Nakashima; ISBN: 0387700188; http://www.amazon.com/exec/obidos/ASIN/0387700188/icongroupinterna

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Hepatocellular Carcinoma and Liver Metastases: Diagnosis and Treatment by H. -M Hoogewoud; ISBN: 0387562729; http://www.amazon.com/exec/obidos/ASIN/0387562729/icongroupinterna

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Hepatocellular Carcinoma: Diagnosis, Investigation and Management by Anthony S.Y. Leong (Editor), et al; ISBN: 0340740965; http://www.amazon.com/exec/obidos/ASIN/0340740965/icongroupinterna

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Hepatocellular Carcinoma: Methods and Protocols (Methods in Molecular Medicine, Vol 45) by Nagy A. Habib (Editor) (2000); ISBN: 0896037851; http://www.amazon.com/exec/obidos/ASIN/0896037851/icongroupinterna

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Liver Cancer by Kunio Okuda (1997); ISBN: 0443054819; http://www.amazon.com/exec/obidos/ASIN/0443054819/icongroupinterna

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Liver Cancer by Iarc; ISBN: 0197230008; http://www.amazon.com/exec/obidos/ASIN/0197230008/icongroupinterna

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Liver Cancer (Developments in Oncology) by Joseph C. Bottino, et al (1985); ISBN: 0898387132; http://www.amazon.com/exec/obidos/ASIN/0898387132/icongroupinterna

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Liver Cancer (M.D. Anderson Solid Tumor Oncology Series) by Steven A. Curley (Editor), Raphael E. Pollock (Editor) (1998); ISBN: 0387983708; http://www.amazon.com/exec/obidos/ASIN/0387983708/icongroupinterna

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Liver Cancer Risk from Internally-Deposited Radionuclides: Recommendations of the National Council on Radiation Protection and Measurements (Ncrp Report, No. 135) (2001); ISBN: 0929600681; http://www.amazon.com/exec/obidos/ASIN/0929600681/icongroupinterna

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Liver cancer: proceedings of a working conference held at the Chester Beatty Research Institute, London, England, 30 June to 3 July 1969; ISBN: 0119503492; http://www.amazon.com/exec/obidos/ASIN/0119503492/icongroupinterna

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Prevention of Liver Cancer: Report. (WHO Technical Report Series); ISBN: 9241206918; http://www.amazon.com/exec/obidos/ASIN/9241206918/icongroupinterna

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Primary Liver Cancer (1989); ISBN: 7800030156; http://www.amazon.com/exec/obidos/ASIN/7800030156/icongroupinterna

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Primary Liver Cancer by Tang Zhao-You, et al; ISBN: 0387502289; http://www.amazon.com/exec/obidos/ASIN/0387502289/icongroupinterna

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Primary Liver Cancer in Japan by Takaoshi, K.D. Tobe (Editor), Takayoshi Tobe; ISBN: 0387700897; http://www.amazon.com/exec/obidos/ASIN/0387700897/icongroupinterna

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Primary Liver CancerEtiological and Progression Factors by Christian Brechot (Editor), et al; ISBN: 0849349133; http://www.amazon.com/exec/obidos/ASIN/0849349133/icongroupinterna

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Progress in Hepatocellular Carcinoma Treatment by Kiwamu Okita (Editor) (1999); ISBN: 4431702571; http://www.amazon.com/exec/obidos/ASIN/4431702571/icongroupinterna

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Progress in Hepatology 3 - Hepatocellular Carcinoma by Takahashi Memorial Forum, et al; ISBN: 0444826785; http://www.amazon.com/exec/obidos/ASIN/0444826785/icongroupinterna

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Researching Hepatocellular Carcinoma in Japan: A Message to the World: Tokyo, July 29, 2000 (Supplement Issue: Oncology 2001, 3) by O. Hino (Editor), et al (2001); ISBN: 3805573286; http://www.amazon.com/exec/obidos/ASIN/3805573286/icongroupinterna

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Subclinical Hepatocellular Carcinoma by Zhao-You Tang (Editor) (1984); ISBN: 0387126643; http://www.amazon.com/exec/obidos/ASIN/0387126643/icongroupinterna

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The LEC Rat: a New Model for Hepatitis and Liver Cancer; ISBN: 443170079X; http://www.amazon.com/exec/obidos/ASIN/443170079X/icongroupinterna

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The LEC Rat: A New Model for Hepatitis and Liver Cancer by M. Mori (Editor), et al; ISBN: 354070079X; http://www.amazon.com/exec/obidos/ASIN/354070079X/icongroupinterna

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The Lec Rat: A New Model for Hepatitis and Liver Cancer by Taniguchi, et al; ISBN: 038770079X; http://www.amazon.com/exec/obidos/ASIN/038770079X/icongroupinterna

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The Official Patient's Sourcebook on Adult Primary Liver Cancer: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597834571; http://www.amazon.com/exec/obidos/ASIN/0597834571/icongroupinterna

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Therapeutic Strategies in Primary and Metastatic Liver Cancer; ISBN: 3540160116; http://www.amazon.com/exec/obidos/ASIN/3540160116/icongroupinterna

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Therapeutic Strategies in Primary and Metastatic Liver Cancer (Recent Results in Cancer Research, Vol 100) by Ch. Herfarth, et al (1986); ISBN: 0387160116; http://www.amazon.com/exec/obidos/ASIN/0387160116/icongroupinterna

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Therapy for Viral Hepatitis and Prevention of Hepatocellular Carcinoma by Masao Omata (Editor), et al (2003); ISBN: 4431402802; http://www.amazon.com/exec/obidos/ASIN/4431402802/icongroupinterna

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Viruses and Liver Cancer by Edward Tabor (Editor), E. Tabor; ISBN: 0444505806; http://www.amazon.com/exec/obidos/ASIN/0444505806/icongroupinterna

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What you need to know about liver cancer (SuDoc HE 20.3152:L 75) by U.S. Dept of Health and Human Services; ISBN: B000115VUC; http://www.amazon.com/exec/obidos/ASIN/B000115VUC/icongroupinterna

Books

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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 “liver 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 •

An Update on regional treatment of liver cancer: the role of vascular occlusion Author: Kemeny, N. (Nancy); Year: 1994; Kent: Wells Medical Ltd., c1992; ISBN: 1869969634

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Liver cancer: proceedings of a working conference: held at the Chester Beatty Research Institute, London, England, 30 June to 3 July 1969. Author: Chester Beatty Research Institute.; Year: 1982; Lyon: International Agency for Research on

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Selected abstracts on diagnosis and treatment of hepatocellular carcinoma Author: Korinek, Josef Karel.; Year: 1994; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health; Springfield, Va.: National Technical Information Service [distributor, 1982]

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The synthesis of a research on liver cancer in Thailand Author: Suriyawongpaisal, Paibul.; Year: 1977; [Bangkok?]: Thailand Research Fund, [2000?]

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Towards the aggressive surgery of liver cancer based on the redox theory Author: Ozawa, Kazue,; Year: 1992; [Japan]: Nakayama Institute of; ISBN: 4906225225

Chapters on Liver Cancer In order to find chapters that specifically relate to liver cancer, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and liver 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 “liver cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on liver cancer: •

Liver Cancer: Are You at Risk? Source: in Everson, G.T.; Weinberg, H. Living with Hepatitis B: A Survivor's Guide. Long Island, NY: Hatherleigh Press. 2002. p.198- 209. Contact: Available from Hatherleigh Press. 5-22 46th Avenue Suite 200, Long Island City, NY 11101. (800) 528-2550. E-mail: [email protected]. Website:

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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http://store.yahoo.com/hatherleighpress/index.html. PRICE: $15.95 plus shipping and handling. ISBN: 1578260841. Summary: Chronic hepatitis B can lead to cirrhosis (liver scarring), liver cancer, and the need for liver transplantation. This chapter on liver cancer is from a book that helps readers diagnosed with hepatitis B virus (HBV) infection educate themselves about the disease and its treatment. Primary liver cancer is an extremely serious, life threatening complication of chronic hepatitis B. The authors discuss risk factors, warning signs, screening and diagnostic tests for liver cancer, and results of current treatment. Specific topics include primary liver cancer, secondary liver cancer, stage of hepatitis B as a risk factor, duration of infection as a risk factor, other liver disease, warning signs (asymptomatic but with underlying cirrhosis, deterioration in liver function, pain, sudden development of portal hypertension), testing, early screening guidelines, diagnostic tests, treatment options, cancer staging, hepatic (liver) resection, transplantation, chemoembolization, high frequency radio waves (radiofrequency tumor ablation), alcohol injection, cryosurgery, and chemotherapy. Throughout the chapter the authors include quotes from real people who are living with hepatitis.

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CHAPTER 8. MULTIMEDIA ON LIVER CANCER Overview In this chapter, we show you how to keep current on multimedia sources of information on liver 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 liver cancer is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “liver 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 “liver cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on liver cancer: •

Hepatitis 101: Basic Tools for Teaching Liver Wellness and Hepatitis Prevention Source: Silver Spring, MD: Hepatitis Foundation International. 2002. (videorecording). Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904. (800) 891-0707. Fax: (301) 622-4702. E-mail: [email protected]. Website: www.hepfi.org. PRICE: $37.00; plus shipping and handling. Summary: This tutorial videotape was developed to help teachers, counselors, outreach workers, and health professionals offer effective and easy to communicate messages about liver wellness, and the prevention of viral hepatitis and substance abuse. Viral hepatitis is a disease caused by viruses that damage the liver. Serious cases can lead to life-threatening liver cirrhosis (or scarring), liver failure and eventually liver cancer. The most common forms of viral hepatitis include hepatitis A, hepatitis B and hepatitis C. This program focuses on hepatitis C and the risk factors that increase one's likelihood of contracting the disease, notably substance abuse. The program uses memorable

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analogies that everyone can relate to in their daily lives to motivate individuals to avoid liver damaging activities and to adopt healthier lifestyle behaviors. •

Hepatitis B: A Discovery Channel Program Source: Cedar Grove, NJ: Hepatitis Foundation International. 199x. (videocassette). Contact: Available from Hepatitis Foundation International. 30 Sunrise Terrace, Cedar Grove, NJ 07009. (800) 891-0707 or (201) 239-1035. Fax (201) 857-5044. PRICE: Free with membership; contact directly for current price for nonmembers. Summary: This video presents a health update on hepatitis B. After an introduction that reviews the anatomy and physiology of the liver, various health care providers (including two epidemiologists from the CDC) describe how all types of hepatitis affect the liver. The program continues with a discussion of hepatitis A, B, and C, and how each is transmitted and treated. The program then focuses on hepatitis B, covering details of transmission, symptoms, risk factors and behaviors, complications of hepatitis B virus (HBV) infection, including an increased risk of liver cancer, epidemiology, fulminant hepatitis, and the progression of HBV to chronic, carrier state. Additional sections describe the use of liver transplantation for people with hepatitis B and the psychosocial impact of chronic HBV infection. The program concludes with an interview with Thelma King Thiel, the founder and CEO of the Hepatitis Foundation International, an educational and support organization.

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Basics of Alpha 1-Antitrypsin Liver Disease Source: Washington, DC: Alpha-1 Association. 200x. (videorecording). Contact: Available from Alpha-1 Association. 1225 Eye Street NW, Suite 1225, Washington, DC 20005-5918. (800) 521-3025 or (202) 887-1900. Fax: (202) 887-1964. Website: www.alpha1.org. E-mail: [email protected]. PRICE: Contact organization for copies. Summary: This videocassette depicts a slide lecture program given by Dr. Jeffrey Teckman at an Alpha-1 Association conference. Dr. Teckman describes the physiology and chemistry of the alpha-antitrypsin system, then the pathophysiology of alpha1antitrypsin deficiency. Dr. Teckman uses highly technical language, but then defines his terms and uses graphics to explain how the pathophysiology works (not all slides to which he refers are included in this videotape). Dr. Teckman also discusses the complications that are seen with this common, but underdiagnosed, genetic liver disease, including chronic hepatitis (liver inflammation), cirrhosis (scarring of the liver), liver cancer, and emphysema. Other topics include the Swedish research study that provided a great deal of basic information about this disease, the genetics, screening, diagnosis, the role of liver biopsy in diagnosis, and treatment options. The program concludes with a section of questions from the lecture audience, along with Dr. Teckman's answers.

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Hepatitis B: Patient information Source: Cedar Grove, NJ: American Liver Foundation. n.d. 1 videotape (10 minutes, 1/2 inch VHS). Contact: Available from American Liver Foundation, 2021 A Pontius Avenue, Los Angeles, CA 90025. Telephone: (310) 477-4615 / fax: (310) 478- 4685 / e-mail: [email protected] / Web site: www.liver411.com.

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Summary: This videotape portrays a physician talking with a young Asian woman about liver cancer and its primary cause, hepatitis B: how hepatitis B spread, symptoms and the usual course of liver cancer, the body's ability to fight hepatitis B, carriers, effectiveness and safety of vaccinations, and populations at higher risk of contracting hepatitis B. •

Hepatitis B: A Family's Story. Our Family, Our Strength Source: St. Paul, MN: Hepatitis B Coalition. 1995. (videorecording). Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $10.00. Summary: This videotape program educates viewers about hepatitis B and its potential impact. The first part of the program, presented in the Cambodian language, features a narrator who introduces Dr. Hie-Won Hann, a physician helping Asian families fighting hepatitis B. The program shows Dr. Hann interviewing a pregnant Cambodian woman; a second scenario features Dr. Hann and the woman's family, who have all come in to learn more about hepatitis B. Topics covered include the complications of hepatitis B (acute disease, liver cancer), chronic infection with hepatitis B, how to protect a baby from getting hepatitis B, testing family members, protecting uninfected family members, treating the chronic carrier, how the disease is transmitted (perinatal, sexual transmission, and close familial contact, i.e., sharing toothbrushes, razors, etc.), why the disease is common among Asian people, and the importance of achieving widespread vaccination. The videorecording comes with an English and a Cambodian copy of the script. The second part of the tape, presented in English, features Dr. Haing S. Ngor introducing the history of Indo-Chinese people in the U.S. and stressing the important place that family serves in these cultures. The remainder of the tape is the same as the Cambodian language part, but in English.

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Your Liver Source: Bronx, NY: Latin Organization for Liver Awareness. 199x. (videocassette). Contact: Available from Latino Organization for Liver Awareness (LOLA). 1560 Mayflower Avenue, Bronx, New York, NY 10465. (718) 892-8697. Fax (718) 918-0527. (888) 367-LOLA. PRICE: $10.00; plus shipping and handling. Summary: This videotape program reviews the physiology of the liver, and describes different types of liver disease, focusing on hepatitis. Narrated by Debbie Delgado-Vega, a liver transplant recipient and advocate and educator in the field, the program first summarizes the functions of the liver. The liver stores vitamins and minerals, makes bsoleilwelile to help digestion, detoxifies chemicals, stores energy, removes poisons and pollutants that may be ingested from the air, makes clotting factors, and defends against germs that cause disease. The program then lists the types of liver disease, including liver disorders in children, alcohol related liver disease, liver cancer, cirrhosis (scarring), and viral hepatitis (inflammation of the liver due to viral infection). The program discusses hepatitis in depth, explaining the differences between acute disease (less than 6 months in duration) and chronic disease; the numbers of people in the United States with hepatitis B (1.2 million) and hepatitis C (4.8 million); the complications of chronic hepatitis that can lead to cirrhosis (inflammation, scarring and nodules); symptoms, notably fatigue; how hepatitis B and C are transmitted in blood and other body fluids; other risk factors, including the use of intranasal cocaine, intravenous drugs, tattoos or body piercing, pre 1992 blood transfusion, unprotected sex, and having served time in jail; treatment options, including interferons and ribavirin; and why it is important to

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get tested and treated, even if there are no apparent symptoms. The narrator stresses that more Latinos die from liver disease than any other minority group and chronic liver disease is the third leading cause of death among Latinos. The conclusion of the program shows clips and materials from educational programs and public health and advocacy activities conducted by LOLA (Latino Organization for Liver Awareness). The program is narrated in English, with some clips at the end in Spanish. •

Diagnosing Alpha 1 Antitrypsin Deficiency Source: Minneapolis, MN: Alpha 1 Association. 199x. (videocassette). Contact: Available from Alpha 1 Association. 8120 Penn Avenue, South, Suite 549, Minneapolis, MN 55431-1326. (800) 521-3025 or (612) 703-9979. Fax (612) 703-9977. Email: [email protected]. Website: www.alpha1.org. PRICE: $3.00 plus shipping and handling. Summary: This videotape program, narrated by Sandra Brandley, the Executive Director of the Alpha 1 National Association, reminds physicians of the symptoms and differential diagnosis of alpha 1 antitrypsin deficiency (A1AD or Alpha 1). The program features Dr. James Stoller, who describes the typical underdiagnosis of A1AD which is typical: the mean time until diagnosis is 7 years (from onset of symptoms) and the mean number of doctors consulted before diagnosis is 3.5. Alpha 1 is a relatively common genetic disorder that affects infants, children, and adults. It is the most common metabolic disorder that causes liver disease in infants and children; the disorder also causes cirrhosis and cancer of the liver in adults. Symptoms of A1AD deficiency in children include prolonged obstructive jaundice, low birth weight, mildly elevated liver enzymes, cholestasis, enlarged liver, abnormal bleeding, feeding difficulties, poor growth (or failure to thrive), and ascites (abnormal accumulation of fluids). In adults, the spectrum of liver disease associated with A1AD deficiency varies from mild to severe. Symptoms include chronic active hepatitis, cryptogenic cirrhosis (liver scarring of unknown cause), portal hypertension (high blood pressure in the portal vein of the liver), and hepatocellular carcinoma (liver cancer). A rare but telling symptom is panniculitis, a chronic inflammation of subcutaneous fat featuring ulcerated skin lesions on the torso. Dr. Stoller reminds viewers of the indications for A1AD screening: premature onset of moderate to severe chronic obstructive pulmonary disease (COPD) before age 50; predominant basilar emphysema; chronic bronchitis with airflow obstruction in a nonsmoker; bronchiectasis (irreversible dilation and destruction of the bronchial walls) without clear risk factors; development of unremitting asthma; family history of A1AD; cirrhosis without apparent risk factors; and family history of panniculitis. The program includes a chart of laboratory values and the risk of development of A1AD, and a series of interviews with patients about the interplay of early diagnosis and good quality of life. The program concludes with the contact information for the Alpha 1 National Association (800-521-3025).

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Viral Hepatitis and Blood Borne Pathogens: The Invisible Threat Source: Silver Spring, MD: Hepatitis Foundation International. 2002. (videorecording). Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904. (800) 891-0707. Fax: (301) 622-4702. E-mail: [email protected]. Website: www.hepfi.org. PRICE: $45.00; plus shipping and handling. Summary: Viral hepatitis is a disease caused by viruses that damage the liver. Serious cases can lead to life-threatening liver cirrhosis (or scarring), liver failure and eventually liver cancer. The most common forms of viral hepatitis include hepatitis A, hepatitis B

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and hepatitis C. This program focuses on hepatitis B and C and the risk factors that increase one's likelihood of contracting the disease, notably substance abuse. The video is designed for an adult audience. Topics include prevention of hepatitis B and C, AIDS, substance abuse, cirrhosis, and transmission of hepatitis. •

Update on Management of Hepatitis C Source: Kansas City, MO: American Academy of Family Physicians. 2000. (videocassette). Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237. PRICE: $17.95 for members; $25.00 for nonmembers, plus shipping and handling. Summary: Viral hepatitis remains the most common cause of liver disease worldwide and infection with the hepatitis C virus (HCV) has become a serious health problem in the United States. This continuing education program assists family physicians in this new challenge of the identification and diagnosis of patients at greatest risk of HCV infection. While there is, as yet, no known cure for HCV, early medical intervention and lifestyle changes can significantly improve the prognosis. Infection with HCV can lead to chronic hepatitis, cirrhosis (liver scarring), and hepatocellular carcinoma (HCC, liver cancer). Unlike hepatitis A and B, there is no vaccination available to prevent hepatitis C, nor are there any preexposure or postexposure prophylaxis (prevention) options. This program reviews the epidemiology of HCV, identification of patients at risk, diagnosis, HCV related liver disease, and management approaches, including interferon monotherapy, combination therapy, side effects, contraindications, and ongoing medical monitoring. The program includes a video tape and a study guide; the latter includes references and a patient education handout, as well as a posttest with which viewers can qualify for continuing education credit. 6 figures. 13 tables. 31 references.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio 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 “Sound Recordings.” Type “liver cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on liver cancer: •

Keynote Speaker: 3rd National Forum on AIDS and Hepatitis B, Washington, D.C., November 21-23, 1988 Contact: Sound Solution, PO Box 566074, Dallas, TX, 75356, (214) 258-6144. Summary: In this sound recording, Dr. Ralph Reed, Deputy Assistant Secretary of the U.S. Department of Health and Human Services, delivers the keynote address at the Third National Forum on AIDS and Hepatitis B, presented by the National Foundation for Infectious Diseases, Nov. 23, 1988. He compliments the group on the topic of the conference: Protecting America's health-care system. He says that sometimes it seems that the Public Health Service worries more about the health of doctors and nurses than they do themselves. However, the epidemic of Acquired immunodeficiency syndrome (AIDS), caused by the Human immunodeficiency virus (HIV), is changing many physicians' attitudes. He says that people who were nonchalant about the dangers of

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Hepatitis B are becoming more cautious about AIDS, although only 12 health-care workers worldwide have ever died of AIDS; while 10,000 to 12,000 health care workers each year are infected by Hepatitis B in the United States. Of these, 200 to 300 die. He then describes the program begun by the Indian Health Service to combat Hepatitis B in Alaska. A screening program of blood tests in the Native Alaskan villages identified the geographic hot spots where Hepatitis B was most prevalent. People in these villages were immunized first; then the remainder of the population of 75,000 Native Alaskans, including all newborn babies. Fifteen hundred chronic carriers were identified, and these are now being checked twice a year in their villages. He says that without this program, 40 per cent of male chronic carriers and 20 per cent of female chronic carriers would die of liver cancer. He adds that this is the first Hepatitis B program in the world to screen pregnant females and immunize newborn babies. Dr. Reed says that the success of the program is due to the availability of several good vaccines. This, unfortunately, is not the case with AIDS. There is no vaccine and no cure. The only thing that the PHS can do is to tell people how to avoid AIDS, and a booklet about AIDS was mailed to every family in the United States, 107 million booklets in all. Also, he says, 13 regional centers for AIDS education and training have been set up across the country. These centers provide consultation and training for the primary-care providers who will deal dire. •

Fear of the Unknown: Anxiety & Stress in Caring for Patients With AIDS & Hepatitis B: 3rd National Forum on AIDS and Hepatitis B, Washington, D.C., November 21 - 23, 1988 Contact: Sound Solution, PO Box 566074, Dallas, TX, 75356, (214) 258-6144. Summary: This sound recording covers a workshop on fear of the unknown, especially as it relates to Acquired immunodeficiency syndrome (AIDS). The moderator opens the session with a discussion of Hepatitis B. He says that 25,000 cases are reported to the Centers for Disease Control and Prevention (CDC) each year, primarily among young adults, but it is estimated that 300,000 persons become infected each year. Approximately 4,000 deaths each year result from cirrhosis of the liver following Hepatitis B infection, and 800 deaths each year from liver cancer. He says that Hepatitis B among health-care workers is decreasing since recombinant vaccines were developed, but the infection among Intravenous drug users (IVDU's) continues to rise. Next, Dr. Hassib Aoun, a former holder of a fellowship in cardiology at Johns Hopkins Hospital, describes his experiences following his infection with Human immunodeficiency virus (HIV) after a laboratory accident in 1983. A capillary tube of blood that he was planning to test shattered and cut his finger. Three years later, he developed AIDS. Although the original accident was documented, and the patient's blood was later tested for AIDS, (there were no antibody tests in 1983) the hospital accepted no responsibility for his illness and provided no compensation or insurance coverage. He says he still believes that health-care workers should never deny care to AIDS patients, but if they are expected to risk their lives providing this care, they should be protected economically with appropriate insurance. Dr. Jeff Hackman, Assistant Professor of Psychiatry and Behavioral Medicine at George Washington University Medical Center, then discusses a project to train health-care workers in the medical and mental health aspects of AIDS. A battery of attitude questionnaires given to second-year medical students revealed that 75 per cent were worried about contracting AIDS, and 80 per cent felt that in the future, AIDS would prove to be more infectious than it is considered today. Fifty percent of the medical students believed that they could contract AIDS from the routine care of an AIDS patient. They also said that their families were more frightened and less supportive of AIDS patients than the medical students themselves.

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Bibliography: Multimedia on Liver 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 liver 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 liver cancer: •

International symposium [sound recording]: liver cancer, a global problem Source: ASCO 36th Annual Meeting, May 2000; Year: 2000; Format: Sound recording; [Alexandria, Va.]: American Society of Clinical Oncology, c2000

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

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

Transplant extends survival in liver cancer patients Source: Reuters Health eLine Date: October 31, 2003

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Smoking contributes to HBV-related liver cancer deaths in China Source: Reuters Medical News Date: October 31, 2003

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Liver transplant extends survival in patients with liver cancer Source: Reuters Medical News Date: October 31, 2003

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Steatosis identified as risk factor for liver cancer in HCV-infected patients Source: Reuters Medical News Date: July 02, 2003

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Asian Americans at high risk for hep C liver cancer Source: Reuters Health eLine Date: May 19, 2003

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Oligonucleotide IGF2 inhibitor enhances survival in hepatocellular carcinoma Source: Reuters Medical News Date: February 05, 2003

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Phase III liver cancer drug trial passes safety board review Source: Reuters Medical News Date: January 16, 2003

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Eximias' phase III liver cancer drug trial passes safety board review Source: Reuters Industry Breifing Date: January 16, 2003

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Hepatitis C-associated liver cancer risk increased in AIDS patients Source: Reuters Medical News Date: January 02, 2003

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Gene amplifications tied to poor prognosis of liver cancer Source: Reuters Medical News Date: December 25, 2002

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IGF-1 levels predict liver cancer in patients with HCV-related cirrhosis Source: Reuters Medical News Date: December 20, 2002

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Device extends liver cancer patients' lives-study Source: Reuters Health eLine Date: October 10, 2002

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FeRx liver cancer drug gains US fast-track status Source: Reuters Industry Breifing Date: August 26, 2002

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EU grants FeRx drug orphan status for liver cancer Source: Reuters Industry Breifing Date: August 01, 2002

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Cell proliferation marker predicts liver cancer recurrence after resection Source: Reuters Medical News Date: July 25, 2002

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Presence of HBeAg associated with increased risk of liver cancer Source: Reuters Medical News Date: July 17, 2002

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Youngsters with advanced liver cancer have poor prognosis Source: Reuters Medical News Date: July 05, 2002

Periodicals and News

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Procedure may up survival of liver cancer patients Source: Reuters Health eLine Date: May 27, 2002

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Chemoembolization can prolong life in patients with unresectable liver cancer Source: Reuters Industry Breifing Date: May 17, 2002

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FDA clears radiotherapy microspheres for liver cancer Source: Reuters Medical News Date: March 07, 2002

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Honso USA botanical to be studied in Sloan-Kettering liver cancer trial Source: Reuters Industry Breifing Date: February 25, 2002

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Decreased level of TIMP-2 enzyme predicts metastasis of liver cancer Source: Reuters Medical News Date: February 25, 2002

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Heavy drinking raises hepatocellular carcinoma risk Source: Reuters Medical News Date: February 22, 2002

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Heavy drinking raises risk of liver cancer: study Source: Reuters Health eLine Date: February 21, 2002

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Adjuvant therapy cost effective for liver cancer patients awaiting transplant Source: Reuters Industry Breifing Date: January 23, 2002

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Tamoxifen does not prolong survival in liver cancer patients Source: Reuters Industry Breifing Date: November 30, 2001

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Chlorophyll derivative may cut liver cancer risk Source: Reuters Health eLine Date: November 29, 2001

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Electrolysis seen as helpful in the management of liver cancer Source: Reuters Industry Breifing Date: November 08, 2001

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Radioactive microspheres treat liver cancer Source: Reuters Industry Breifing Date: October 25, 2001

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Diabetes not a significant risk factor for primary liver cancer Source: Reuters Medical News Date: August 27, 2001

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Matrix begins new phase II study of IntraDose for liver cancer Source: Reuters Industry Breifing Date: June 28, 2001

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Radioactive beads show promise for liver cancer Source: Reuters Health eLine Date: June 04, 2001

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Tegafur/uracil prolongs survival in patients with advanced liver cancer Source: Reuters Medical News Date: May 31, 2001

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Hyperinsulinemia a risk factor for fatal liver cancer in nondiabetic me Source: Reuters Medical News Date: May 24, 2001

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Rare liver cancer on the rise in UK Source: Reuters Medical News Date: May 21, 2001

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SciClone begins phase II study of Zadaxin plus chemo in liver cancer Source: Reuters Industry Breifing Date: May 14, 2001

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Titan begins phase I/II trial of liver cancer candidate Source: Reuters Industry Breifing Date: March 28, 2001

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Transarterial lipiodol benefits patients with unresectable liver cancer Source: Reuters Medical News Date: March 01, 2001

•

Zarix to begin Canadian phase IIII study of Thymitaq for liver cancer Source: Reuters Industry Breifing Date: February 05, 2001

•

FeRx receives orphan drug status for liver cancer treatment Source: Reuters Industry Breifing Date: January 29, 2001

•

Histologic grade of liver cancer affects survival after transplantation Source: Reuters Medical News Date: January 22, 2001

•

Two-stage hepatectomy may benefit select liver cancer patients Source: Reuters Medical News Date: January 02, 2001

•

Enzo Biochem to begin study HCV, liver cancer drug Source: Reuters Industry Breifing Date: November 30, 2000

•

Surge in liver cancer linked to hepatitis C Source: Reuters Health eLine Date: November 29, 2000

•

Lipiodol hepatic angiography may help identify early liver cancer Source: Reuters Medical News Date: November 28, 2000

•

Hepatitis C infection primary cause of increase in liver cancer in US veterans Source: Reuters Medical News Date: November 27, 2000

•

Portal vein embolization safe in injured livers before liver cancer resection Source: Reuters Medical News Date: November 06, 2000

Periodicals and News

•

Enzo product effective against human liver cancer in animal studies Source: Reuters Industry Breifing Date: October 30, 2000

•

Center offers new liver cancer treatment Source: Reuters Health eLine Date: October 30, 2000

•

Chromosomal aberrations distinguish recurrent from second primary liver cancer Source: Reuters Industry Breifing Date: September 04, 2000

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “liver 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 “liver cancer” (or synonyms). If you know the name of a company that is relevant to liver 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/.

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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 “liver cancer” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “liver cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on liver cancer: •

Liver Tests: Simple Blood Tests Can Reveal a Lot Source: Mayo Clinic Health Letter. 18(5): 1-3. May 2000. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This article, from a health newsletter, reviews the liver function tests that are used to monitor liver health and disease. The author begins by reviewing the healthy functions of the liver, including regulating the composition of the blood, manufacturing vital nutrients (such as cholesterol, vitamin A, certain proteins, bile), and neutralizing toxic substances. Sometimes there is an obvious sign of a problem, such as jaundice, which is a buildup of bilirubin in the blood, resulting in a yellow appearance of the skin and eyes. The various liver tests basically screen for three types of abnormalities: liver cell damage, reduced protein levels in the blood, and failure to eliminate certain substances from the blood. Information from the blood tests, combined with a thorough physical exam and sometimes diagnostic imaging, may be enough to reach a specific diagnosis; sometimes a liver biopsy is added to the list of diagnostic tests. Some of the more common liver disorders that are detected with these tests are viral hepatitis, alcohol or drug related liver disease, liver cancer, nonalcoholic steatohepatitis (a form of fatty liver), and hemochromatosis (high amounts of iron stored in the body). One sidebar reviews the drugs that can lead to liver toxicity. The author concludes that mild liver test abnormalities are normal; however, significantly abnormal test results should never be ignored. 1 figure.

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

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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for liver cancer. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with liver cancer. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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

Systemic - U.S. Brands: Platinol; Platinol-AQ http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202143.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

Fluorouracil •

Systemic - U.S. Brands: Adrucil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202245.html

Hepatitis B Vaccine Recombinant •

Systemic - U.S. Brands: Engerix-B http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202281.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

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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 liver 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 “liver 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 liver cancer: •

Thymalfasin (trade name: Zadaxin) http://www.rarediseases.org/nord/search/nodd_full?code=1033

•

MTC-DOX for Injection http://www.rarediseases.org/nord/search/nodd_full?code=1092

•

MTC-DOX for Injection (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1181

•

nolatrexed (trade name: THYMITAQ) http://www.rarediseases.org/nord/search/nodd_full?code=1186

•

tri-antennary glcotripeptide derivative of 5-fluor (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1205

•

Nolatrexed (trade name: THYMITAQ) http://www.rarediseases.org/nord/search/nodd_full?code=1227

•

tri-antennary glycotripeptide derivative of 5-fluo (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1231

•

Iodine I 131 murine monoclonal antibody to alpha-f http://www.rarediseases.org/nord/search/nodd_full?code=149

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•

Technetium Tc-99m murine monoclonal antibody to hu (trade name: Immuraid, AFPTc99m) http://www.rarediseases.org/nord/search/nodd_full?code=324

•

Iodine I 123 murine monoclonal antibody to alph-fe http://www.rarediseases.org/nord/search/nodd_full?code=633

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

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

•

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

•

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

•

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

•

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

•

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

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

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

•

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

•

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

•

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

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “liver cancer” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “liver cancer” (or synonyms) into the “For these words:” box. The following is a sample result: •

Chronic Hepatitis B Virus Infection in Asian Countries Source: Journal of Gastroenterology and Hepatology. 15(12): 1356-1361. December 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5 to 10 percent of adults and up to 90 percent of infants will become chronically infected. Of those who become chronically infected, 75 percent are in Asia where hepatitis B is the leading cause of chronic hepatitis (liver infection), cirrhosis (liver scarring), and hepatocellular carcinoma (liver cancer). This article offers detailed statistics on chronic HBV infection in Asian countries, including Indonesia, the Phillipines, Thailand, China, Taiwan, and Malaysia. In the highly endemic countries in Asia (places where HBV is found on a routine basis in the population), the majority of infections are contracted postnatally or perinatally (during birth). Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum (blood) and minimal hepatic (liver) inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg positive for prolonged periods of time. The outcome after anti HBe seroconversion depends on the degree of preexisting liver damage and any subsequent HBV reactivation. Without preexisting cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with preexisting cirrhosis, further complications may happen. The annual incidence of hepatic decompensation (reduction in liver function) in HBV related cirrhosis varies from 2 to 10 percent and in these patients, the 5 year survival rate drops dramatically to 14 to 35 percent. The annual risk of developing HCC (liver cancer) in patients with cirrhosis varies between 1 and 6 percent. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. The authors conclude that prevention of HBV infection through vaccination is still therefore the best strategy for

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decreasing the incidence of hepatitis B associated cirrhosis and HCC. 1 table. 32 references.

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 “liver 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 73363 547 1017 23 0 74950

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

15

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

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

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

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Liver Cancer In the following section, we will discuss databases and references which relate to the Genome Project and liver cancer. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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

Deleted in Liver Cancer 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604258

•

Hepatocellular Carcinoma Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?114550

•

Hepatocellular Carcinoma-associated Protein 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607860

•

Liver Cancer Oncogene Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?165320 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

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•

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

•

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

Physician Resources

•

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

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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 “liver cancer” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “liver cancer” (or synonyms) into the search box, and

24

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

192 Liver Cancer

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).

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on liver 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 liver 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 liver 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 “liver cancer”:

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•

Guides on liver cancer Liver Cancer http://www.nlm.nih.gov/medlineplus/livercancer.html

•

Other guides Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Colorectal Cancer http://www.nlm.nih.gov/medlineplus/colorectalcancer.html Gallbladder and Bile Duct Diseases http://www.nlm.nih.gov/medlineplus/gallbladderandbileductdiseases.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 Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html Pancreatic Cancer http://www.nlm.nih.gov/medlineplus/pancreaticcancer.html Thyroid Cancer http://www.nlm.nih.gov/medlineplus/thyroidcancer.html

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

General/Overviews What Is Liver Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_1x_what_is_liver_cancer_25. asp

•

Diagnosis/Symptoms After the Tests: Staging Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_3x_after_the_tests_staging_2 5.asp How Is Liver Cancer Found? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_3x_how_is_liver_cancer_fou nd_25.asp

Patient Resources

195

If Liver Cancer Is Suspected Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_3x_if_liver_cancer_is_suspec ted_25.asp Liver Biopsy Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/liverbiopsy/index.htm Ultrasound-Abdomen Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/ultrasound-abdomen.htm •

Treatment Adult Primary Liver Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/adult-primary-liver/patient/ Cryosurgery in Cancer Treatment: Questions and Answers Source: National Cancer Institute http://cis.nci.nih.gov/fact/7_34.htm How Is Liver Cancer Treated? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_4x_how_is_liver_cancer_trea ted_25.asp Radiofrequency Ablation Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/drd/rfa/frame-patient.html Radiofrequency Catheter Ablation (RFA) Source: Society of Interventional Radiology http://www.sirweb.org/patPub/radiofrequencyAblation.shtml Treatments: Chemoembolization, Tumor Ablation, and More Source: Society of Interventional Radiology http://www.sirweb.org/patPub/cancerTreatments.shtml

•

Specific Conditions/Aspects Oral Contraceptives and Cancer Risk Source: National Cancer Institute http://cis.nci.nih.gov/fact/3_13.htm What Causes Liver Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_2x_what_causes_liver_cance r_25.asp What Should You Ask Your Doctor About Liver Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_5x_what_should_you_ask_y our_physician_about_liver_cancer_25.asp

196 Liver Cancer

•

Children Childhood Liver Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/childliver/patient/

•

From the National Institutes of Health What You Need to Know about Liver Cancer Source: National Cancer Institute http://www.cancer.gov/cancerinfo/wyntk/liver

•

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

•

Prevention/Screening ALT (Alanine Aminotransferase) Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/alt/test.html Can Liver Cancer Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_2x_can_liver_cancer_be_pre vented_25.asp Hepatocellular Cancer (PDQ): Screening Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/screening/hepatocellular/patient/ Liver Panel Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/liver_panel/glance.html

•

Research Chemoembolization May Help Some Patients with Inoperable Liver Cancer Source: National Cancer Institute http://www.cancer.gov/clinicaltrials/results/chemoembolization0602 Increasing Rates of Primary Liver Cancer in the United States Source: American College of Physicians http://www.annals.org/cgi/content/full/139/10/I-28 Interferon Therapy Improves Survival in Patients with Liver Cancer and Hepatitis C Virus Infection Source: American College of Physicians http://www.annals.org/cgi/content/full/138/4/I-52

Patient Resources

197

Ritalin and Liver Cancer Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00132 What's New in Liver Cancer Research? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_7x_whats_new_in_liver_can cer_research_25.asp •

Statistics How Many People Get Liver Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_1x_how_many_people_get_l iver_cancer_25.asp

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. 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 liver 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: •

Silent Killers in the Asian and Pacific Islander American Communities: What Every Asian and Pacific Islander American Should Know About Hepatitis B and Liver Cancer Source: Stanford, CA: Asian Liver Center. 200x. 8p. Contact: Available from Asian Liver Center. The Asian Liver Center at Stanford University, 300 Pasteur Drive, H3680, Stanford, CA 94305. (650) 725-4837. Fax: (650) 7230006. Website: http://liver.stanford.edu/. PRICE: Full-text available online at no charge. Summary: Although hepatitis B is uncommon in the majority of the United States population, Asian and Pacific Islander Americans have a disproportionately high incidence of the disease. Hepatitis B is a virus that is transmitted mainly by blood; the virus causes liver damage and can cause liver cancer. This brochure, written in English and Korean, reviews the risk factors for hepatitis B, then discusses the role of vaccination, transmission, silent progression of the disease (lack of symptoms), chronic hepatitis, liver cancer, and the role of screening. The brochure also describes the Jade Ribbon Campaign, a program designed to help fight hepatitis B and liver cancer. The

198 Liver Cancer

brochure includes the contact (http://liver.Stanford.edu). •

information

for

the

Asian

Liver

Center

Liver Cancer Source: Toronto, Ontario: Canadian Liver Foundation. 200x. 4 p. Contact: Available from Canadian Liver Foundation. Suite 1500, 2235 Sheppard Avenue East, Toronto Ontario, M2J 5B5. (416) 491-3353 or (800) 563-5483. Fax (416) 491-4952. Email: [email protected]. Website: [email protected]. PRICE: Full-text available online at no charge; Contact organization for print copies. Summary: The liver filters blood from all parts of the body, thus cancer cells can easily lodge in the liver and develop into metastatic nodules. The immense regenerative capacity of the liver may also be linked to the development of liver cancers. This fact sheet, from the Canadian Liver Foundation, reviews liver cancer. Written in questionand-answer format, the fact sheet covers the function and anatomy of the liver, why cancers often form in the liver, the causes of liver cancer, classification of liver cancer, the incidence of primary and secondary tumors, common symptoms associated with liver cancer, risk factors associated with benign primary liver tumors, therapy for benign primary tumors, risk factors associated with malignant primary tumors, diagnostic tests used to detect malignant tumors, treatment and prognostic considerations, general information about secondary liver treatment, and research for future liver cancer treatment. The fact sheet concludes with the contact information for the Canadian Liver Foundation (www.liver.ca or 800-563-5483).

•

Could There Be A Hepatitis Carrier In This Family?: Is Liver Cancer In Their Future? Source: St. Paul, MN: Hepatitis B Coalition. 199x. 2 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. PRICE: $1 per copy. Summary: This patient education brochure reviews hepatitis B and how hepatitis B carrier status is related to an increased risk for developing liver failure or liver cancer. Topics include transmission of hepatitis B, symptoms, why hepatitis B is common among Asian people, the vaccine against hepatitis B, and the Hepatitis B Coalition of Minnesota. The brochure includes the mission statement of the Coalition and information about how to join the Coalition, including contact information. Ethnicallyappropriate line drawings illustrate the brochure. This brochure is also available in Hmong and Vietnamese. 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

•

199

Adult Primary Liver Cancer (PDQ®): Treatment Summary: General overview and treatment options for adult primary liver cancer are discussed in this brochure. Treatment choice depends on the stage of the cancer and the patient's general state of health. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6135

•

Adult Primary Liver Cancer (PDQ®): Treatment Information for Professionals Summary: Treatment information for liver cancer form NCI's PDQ® database, intended for use by doctors and other health care professionals. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4355

•

Hepatitis B Immunization Coverage Among Vietnamese-American Children 3 to 18 Years Old Summary: Persons with chronic hepatitis B virus (HBV) infection are at increased risk of chronic hepatitis, cirrhosis, and liver cancer. Source: American Academy of Pediatrics http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7366

•

Questions and Answers About Liver Cancer Summary: Basic consumer health information about liver cancer -- symptoms, diagnosis, treatment -- and availability of treatment studies (clinical trials) for patients with liver cancer. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4353

•

What You Need To Know About™ Liver Cancer Summary: This National Cancer Institute (NCI) booklet has important information about cancer that begins in the liver. It discusses possible causes, symptoms, diagnosis, and treatment of liver cancer. Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7134 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 liver 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

200 Liver Cancer

specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

•

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

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to liver cancer. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with liver 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 liver cancer. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “liver cancer” (or a synonym), and you will receive information on all relevant organizations listed in the database.

Patient Resources

201

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 “liver 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 “liver 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 “liver cancer” (or a synonym) into the search box, and click “Submit Query.”

203

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.

204 Liver 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

205

•

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/

206 Liver 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

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

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/

208 Liver 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

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on liver cancer: •

Basic Guidelines for Liver Cancer Hepatocellular carcinoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000280.htm

•

Signs & Symptoms for Liver Cancer Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm

•

Diagnostics and Tests for Liver Cancer 5'-N'Tase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003575.htm

210 Liver Cancer

Abdominal CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003789.htm Alpha-1 antitrypsin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003715.htm ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm AST Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003472.htm Bilirubin; urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003595.htm Delta-ALA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003457.htm Gall bladder radionuclide scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003826.htm Gamma-glutamyl transpeptidase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003458.htm Leucine aminopeptidase - serum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003559.htm Leucine aminopeptidase - urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003617.htm Liver biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003895.htm Liver function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003436.htm Liver scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003825.htm PBG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003596.htm Porphyrins; urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003614.htm Serum alpha-fetoprotein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003573.htm •

Background Topics for Liver Cancer Cancer - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002166.htm

Online Glossaries 211

Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Hepatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002378.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Liver disease - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002182.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm Toxins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002331.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

213

LIVER CANCER DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 2-Acetylaminofluorene: A hepatic carcinogen whose mechanism of activation involves Nhydroxylation to the arylhydroxamic acid followed by enzymatic sulfonation to sulfoxyfluorenylacetamide. It is used to study the carcinogenicity and mutagenicity of aromatic amines. [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] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [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] Acute Disease: Disease having a short and relatively severe course. [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] 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] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

214 Liver Cancer

Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Aflatoxins: A group of closely related toxic metabolites that are designated mycotoxins. They are produced by Aspergillus flavus and A. parasiticus. Members of the group include aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, aflatoxin M1, and aflatoxin M2. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low

Dictionary 215

serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [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] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkaptonuria: An inborn error of amino acid metabolism resulting from a defect in the enzyme homogentisate 1,2-dioxygenase and causing an accumulation of homogentisic acid in the urine. The condition is characterized by ochronosis in various tissues and arthritis. [NIH]

Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Allogeneic: Taken from different individuals of the same species. [NIH] 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-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [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, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH]

216 Liver Cancer

Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [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] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [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] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [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] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of

Dictionary 217

hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antiangiogenesis: Prevention of the growth of new blood vessels. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidote: A remedy for counteracting a poison. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage

218 Liver Cancer

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] Antimetastatic: Having to do with reducing inflammation. [NIH] Antimitotic: Inhibiting or preventing mitosis. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arsenic trioxide: An anticancer drug that induces programmed cell death (apoptosis) in certain cancer cells. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arterial embolization: The blocking of an artery by a clot of foreign material. This can be done as treatment to block the flow of blood to a tumor. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH]

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Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Avian: A plasmodial infection in birds. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] 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] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and

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polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Beer: An alcoholic beverage usually made from malted cereal grain (as barley), flavored with hops, and brewed by slow fermentation. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzaldehyde: A colorless oily liquid used as a flavoring agent and to make dyes, perfumes, and pharmaceuticals. Benzaldehyde is chemically related to benzene. [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] Bevacizumab: A monoclonal antibody that may prevent the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]

Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioassay: 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] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [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

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include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any living organism. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] 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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone 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]

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Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [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] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] Camphor: A bicyclic monoterpene ketone found widely in plant (primarily the camphor tree, Cinnamomum camphora). Natural camphor is used topically as a skin antipruritic and as an anti-infective agent. [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] 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] Carboxy: Cannabinoid. [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]

Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH]

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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] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] 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] Celiac Artery: The arterial trunk that arises from the abdominal aorta and after a short course divides into the left gastric, common hepatic and splenic arteries. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [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,

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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 Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [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] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chemoembolization: A procedure in which the blood supply to the tumor is blocked surgically or mechanically, and anticancer drugs are administered directly into the tumor. This permits a higher concentration of drug to be in contact with the tumor for a longer period of time. [NIH]

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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] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlormethiazole: A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate gaba receptors response and it may also affect glycine receptors. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [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] 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] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from

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the small intestines to the tissues. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical 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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Effect: Variation in health status arising from different causal factors to which each birth cohort in a population is exposed as environment and society change. [NIH]

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Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon Polyps: Small, fleshy, mushroom-shaped growths in the colon. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU]

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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] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with

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some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] 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] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] 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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] 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] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Coumarin: A fluorescent dye. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other

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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] Cryosurgery: The use of freezing as a special surgical technique to destroy or excise tissue. [NIH]

Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [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] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources,

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including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] 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] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]

Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] 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 Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The

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dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathermy: The induction of local hyperthermia by either short radio waves or highfrequency sound waves. [NIH] Diethylnitrosamine: A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] 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] 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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] 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] Diuretic: A drug that increases the production of urine. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the

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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] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] 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] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH]

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Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] 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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [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] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of

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the failed kidneys. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]

for

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [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] 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] Epigastralgia: Pain in the epigastrium. [EU] 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]

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Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Varices: Stretched veins in the esophagus that occur when the liver is not working properly. If the veins burst, the bleeding can cause death. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Ethoxyquin: Antioxidant; also a post-harvest dip to prevent scald on apples and pears. [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] 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] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [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]

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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] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] 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] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [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] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [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

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chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [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] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [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] Forearm: The part between the elbow and the wrist. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [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] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH]

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Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [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]

Gastrin-Releasing Peptide: Neuropeptide and gut hormone that helps regulate gastric acid secretion and motor function. Once released from nerves in the antrum of the stomach, the neuropeptide stimulates release of gastrin from the G cells. [NIH] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic 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,

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transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [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] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [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 (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] Glucosinolates: Substituted thioglucosides. They are found in rapeseed (Brassica campestris) products and related Cruciferae. They are metabolized to a variety of toxic products which are most likely the cause of hepatocytic necrosis in animals and humans. [NIH]

Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH]

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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]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [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] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] 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] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Graft-versus-tumor: An immune response to a person's tumor cells by immune cells present in a donor's transplanted tissue, such as bone marrow or peripheral blood. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH]

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Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] 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-Lung Machine: A mechanical device that temporarily takes over the functions of the heart and lungs; called also a pump-oxygenator. It is used as an aid to surgery. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhaging: A copious discharge of blood from the blood vessels. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH]

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Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis Viruses: Any of the viruses that cause inflammation of the liver. They include both DNA and RNA viruses as well viruses from humans and animals. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatoblastoma: A type of liver tumor that occurs in infants and children. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]

Hepatoma: A liver tumor. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [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] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH]

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Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] 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] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH]

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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] Hypervascular: Having a large number of blood vessels. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large

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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] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [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] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [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] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inferior vena cava: A large vein that empties into the heart. It carries blood from the legs

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and feet, and from organs in the abdomen and pelvis. [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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [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] 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] 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]

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 Alfa-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent. [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] 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]

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Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [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] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invasive cervical cancer: Cancer that has spread from the surface of the cervix to tissue deeper in the cervix or to other parts of the body. [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 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] 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] 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] Isocyanates: Organic compounds that contain the -NCO radical. [NIH] Isolated hepatic perfusion: A procedure in which a catheter is placed into the artery that provides blood to the liver; another catheter is placed into the vein that takes blood away from the liver. This temporarily separates the liver's blood supply from blood circulating throughout the rest of the body and allows high doses of anticancer drugs to be directed to the liver only. [NIH]

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Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [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] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Latent period: A seemingly inactive period, as that between exposure of tissue to an injurious agent and the manifestation of response, or that between the instant of stimulation and the beginning of response. [EU] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH]

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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] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

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] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] 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]

Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver 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 metastases: Cancer that has spread from the original (primary) tumor to the liver.

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[NIH]

Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver Regeneration: Repair or renewal of hepatic tissue. [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] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lycopene: A red pigment found in tomatoes and some fruits. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] 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

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diseases. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [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] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megestrol: 17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone

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used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] 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] 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] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] 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] 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] Methionine Adenosyltransferase: An enzyme that catalyzes the synthesis of Sadenosylmethionine from methionine and ATP. EC 2.5.1.6. [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

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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] 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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]

Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH]

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Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] 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 Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [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] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] 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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]

Myalgia: Pain in a muscle or muscles. [EU] Mycotoxins: Toxins derived from bacteria or fungi. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [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]

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NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] 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] 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] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH]

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Nolatrexed: An anticancer drug that belongs to the family of drugs called thymidylate synthase inhibitors. Also called AG337. [NIH] Nonmetastatic: Cancer that has not spread from the primary (original) site to other sites in the body. [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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Ochronosis: Deposition of polymerized homogentisic acid as a brown-black pigment in the connective tissue. It occurs in alkaptonuria, but has also been observed in connection with exposure to certain chemicals (e.g., phenol, trinitrophenol, benzene derivatives). [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] Oltipraz: A drug used in cancer prevention. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots,

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beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is

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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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. [NIH] Papilla: A small nipple-shaped elevation. [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] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU]

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Penicillin: An antibiotic drug used to treat infection. [NIH] 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 proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [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] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions

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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] Phocomelia: Congenital deformity that leaves the child without legs. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Planning Techniques: Procedures, strategies, and theories of planning. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators.

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It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]

Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH]

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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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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

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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] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] 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] 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 Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [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] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [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

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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] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] 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] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein 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] 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

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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] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] 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] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH]

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Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] 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] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] 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] 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] 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]

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Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] 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] Reishi: A mushroom, Ganoderma lucidum, of the aphyllophorales order of basidomycetous fungi. It has long been used in traditional Chinese medicine in various forms. Contains sterols, coumarin, mannitol, polysaccharides, and triterpenoids. [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 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 tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Support: Financial support of research activities. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH]

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Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [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] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [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] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] 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] 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] Sebaceous: Gland that secretes sebum. [NIH]

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Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] 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] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] 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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH]

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Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures.

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It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] 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] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [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]

Steatosis: Fatty degeneration. [EU] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

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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] Stringency: Experimental conditions (e. g. temperature, salt concentration) used during the hybridization of nucleic acids. [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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [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] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] 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

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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] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] 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 therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] 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] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] 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] Thermal ablation: A procedure using heat to remove tissue or a part of the body, or destroy

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its function. For example, to remove the lining of the uterus, a catheter is inserted through the cervix into the uterus, a balloon at the end of the catheter is inflated, and fluid inside the balloon is heated to destroy the lining of the uterus. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thioacetamide: A crystalline compound used as a laboratory reagent in place of hydrogen sulfide. It is a potent hepatocarcinogen. [NIH] Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Thorium Dioxide: Thorium oxide (ThO2). A radiographic contrast agent that was used in the early 1930s through about 1954. High rates of mortality have been linked to its use and it has been shown to cause liver cancer. [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]

Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] 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] 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] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH]

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Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [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] Toremifene: A first generation selective estrogen receptor modulator (SERM). Like tamoxifen, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] 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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The

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blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [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] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [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]

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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] Unresectable gallbladder cancer: Cancer that has spread to the tissues around the gallbladder (such as the liver, stomach, pancreas, intestine, or lymph nodes in the area) and cannot be surgically removed. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

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] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is

Dictionary 279

used. [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] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of 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] Vincristine: 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 Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viremia: The presence of viruses in the blood. [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] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Weight Gain: Increase in body weight over existing weight. [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]

280 Liver Cancer

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] 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] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [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]

281

INDEX 2 2-Acetylaminofluorene, 11, 31, 213 A Abdomen, 30, 112, 195, 213, 221, 235, 241, 247, 248, 249, 250, 257, 259, 260, 272, 273, 275 Abdominal, 209, 210, 213, 223, 248, 258, 259, 260 Aberrant, 42, 49, 213 Ablation, 33, 62, 63, 120, 160, 195, 213 Abscess, 155, 213 Acceptor, 17, 213, 250, 258, 275, 276 Acetaminophen, 155, 213 Acetylcholine, 213, 225 Acute Disease, 145, 163, 213 Adduct, 15, 26, 39, 148, 213 Adenine, 137, 213 Adenocarcinoma, 213, 243 Adenovirus, 42, 44, 213 Adipose Tissue, 213, 259 Adjustment, 145, 213 Adjuvant, 23, 65, 93, 94, 118, 171, 213 Adjuvant Therapy, 23, 93, 213 Adrenal Glands, 214, 216 Adverse Effect, 214, 233, 271, 279 Aerobic, 214, 258 Aerobic Metabolism, 214, 258 Aerobic Respiration, 214, 258 Aerosol, 214, 279 Affinity, 50, 214, 271 Affinity Chromatography, 50, 214 Aflatoxins, 10, 13, 24, 33, 36, 68, 139, 148, 214 Age Groups, 4, 214 Age of Onset, 214, 277 Age-Adjusted, 14, 214 Aged, 80 and Over, 214 Agonist, 214, 233, 274, 276 Albumin, 9, 14, 52, 148, 214, 261 Aldehydes, 137, 215 Algorithms, 215, 221 Alimentary, 97, 215, 260 Alkaline, 50, 70, 132, 215, 216, 222 Alkaline Phosphatase, 50, 70, 215 Alkaloid, 215, 226, 227 Alkaptonuria, 27, 215, 257 Alkylating Agents, 215, 278 Allogeneic, 82, 215, 241

Alpha Particles, 215, 266 Alpha-1, 66, 162, 210, 215 Alpha-fetoprotein, 7, 43, 44, 50, 57, 210, 215, 237 Alternative medicine, 155, 173, 215 Aluminum, 215, 280 Ameliorating, 137, 215 Amifostine, 110, 215 Amino Acid Sequence, 138, 215, 216, 217, 239, 264, 271 Amino Acids, 52, 133, 215, 216, 239, 256, 260, 263, 265, 273, 278 Amino-terminal, 216, 264 Ammonia, 216, 240 Amphetamines, 216, 226 Amplification, 17, 27, 216 Ampulla, 216, 225, 234 Amyloidosis, 155, 216 Anabolic, 139, 216, 232 Anabolic Steroids, 139, 216 Anaesthesia, 216, 246 Anal, 13, 216, 235, 251 Analgesic, 213, 216, 250 Analog, 131, 216, 238, 249 Analytes, 196, 216 Anaphylatoxins, 216, 227 Anatomical, 216, 246, 269 Androgen-Binding Protein, 216, 271 Anemia, 190, 216, 238 Anesthesia, 113, 217 Angiogenesis, 120, 146, 217, 252 Angiography, 172, 217 Animal model, 9, 11, 23, 25, 27, 28, 33, 36, 126, 127, 131, 217, 277 Anions, 214, 217, 248, 270 Annealing, 217, 262 Anomalies, 155, 217, 255 Anthracycline, 134, 135, 217, 231, 235 Antiangiogenesis, 120, 217 Antibacterial, 150, 217, 272 Antibiotic, 217, 231, 233, 235, 260, 272 Antibodies, 108, 144, 145, 217, 242, 245, 246, 251, 261, 267, 270 Antibody, 37, 126, 166, 179, 180, 214, 217, 220, 227, 235, 242, 244, 245, 246, 248, 254, 266, 267, 272 Anticarcinogenic, 26, 88, 91, 217 Anticoagulant, 217, 265

282 Liver Cancer

Anticonvulsant, 217, 225 Antidote, 217, 249 Antigen, 5, 6, 50, 92, 127, 143, 214, 217, 218, 227, 231, 235, 244, 245, 246, 267 Antigen-Antibody Complex, 217, 227 Antigen-presenting cell, 218, 231 Anti-infective, 218, 222, 244, 248 Anti-inflammatory, 213, 218, 223, 240 Anti-Inflammatory Agents, 218, 223 Antimetabolite, 134, 218, 238, 269 Antimetastatic, 130, 218 Antimitotic, 135, 218 Antineoplastic, 215, 218, 222, 233, 238, 247, 253, 262, 275 Antioxidant, 20, 30, 218, 236, 258 Antipruritic, 218, 222 Antipyretic, 213, 218 Antiviral, 4, 18, 115, 218, 246, 247, 269 Anus, 216, 218, 221, 267 Apolipoproteins, 218, 250 Apoptosis, 37, 41, 66, 68, 72, 75, 88, 92, 93, 95, 97, 126, 150, 218 Applicability, 32, 218 Aqueous, 218, 219, 230, 244, 250 Arginine, 15, 119, 216, 218, 247 Aromatic, 25, 52, 137, 213, 218, 261, 273 Arsenic trioxide, 92, 107, 218 Arterial, 7, 49, 51, 52, 75, 79, 89, 93, 94, 112, 218, 223, 225, 245, 265, 274 Arterial embolization, 7, 49, 218 Arteries, 218, 221, 223, 229, 251, 254 Arterioles, 218, 221, 222, 254 Ascites, 164, 219 Aspiration, 45, 219, 237 Assay, 9, 14, 18, 38, 148, 219, 245, 267, 277 Astrocytoma, 219, 240 Asymptomatic, 16, 51, 137, 160, 219, 259 Ataxia, 190, 219, 274 Atrophy, 189, 190, 219 Attenuated, 63, 219 Atypical, 70, 219 Autodigestion, 219, 259 Autologous, 41, 82, 219 Autonomic, 213, 215, 219 Autopsy, 53, 76, 219 Autosuggestion, 219, 245 Avian, 17, 219 B Bacteria, 11, 217, 219, 220, 228, 230, 234, 237, 239, 241, 254, 255, 261, 267, 272, 278 Bactericidal, 219, 236 Barbiturate, 219, 274

Basal Ganglia, 219, 240 Basal Ganglia Diseases, 219 Base, 12, 23, 213, 219, 230, 231, 238, 239, 249, 274, 277, 278 Base Sequence, 219, 230, 238, 239 Beer, 142, 220 Benign, 16, 129, 155, 198, 220, 242, 256, 267 Benzaldehyde, 137, 220 Benzene, 220, 257 Benzo(a)pyrene, 148, 220 Bevacizumab, 108, 220 Bile, 4, 73, 108, 116, 121, 145, 155, 174, 194, 220, 225, 230, 239, 243, 249, 250, 264, 272 Bile Acids, 220, 272 Bile Acids and Salts, 220 Bile Ducts, 4, 145, 220, 239, 264 Bile Pigments, 220, 249 Biliary, 4, 55, 60, 70, 71, 79, 80, 116, 121, 122, 155, 220, 225, 227, 243, 259 Biliary Atresia, 155, 220 Biliary Tract, 80, 121, 122, 155, 220, 259 Bilirubin, 174, 210, 214, 220, 239, 244 Bioassay, 144, 220 Biochemical, 8, 11, 26, 45, 47, 51, 128, 218, 220, 238, 240, 249, 270 Bioengineering, 21, 184, 220 Biological response modifier, 220, 247 Biomarkers, 9, 12, 15, 24, 25, 36, 54, 68, 220 Biopolymers, 128, 221 Biopsy, 105, 106, 154, 155, 162, 174, 195, 210, 221, 260 Biosynthesis, 221, 251, 271, 278 Biotechnology, 36, 40, 126, 142, 156, 159, 173, 185, 188, 189, 190, 191, 221 Biotransformation, 33, 221 Bladder, 8, 126, 210, 221, 256, 265, 278 Blood pressure, 7, 155, 164, 221, 223, 245, 254, 271 Blood transfusion, 42, 45, 163, 221 Blood vessel, 106, 112, 113, 117, 120, 217, 220, 221, 222, 223, 224, 234, 242, 245, 248, 251, 260, 261, 271, 273, 274, 275, 278 Blot, 35, 70, 71, 221 Body Fluids, 36, 163, 220, 221, 222, 233, 271, 277 Bone Marrow, 67, 82, 141, 220, 221, 241, 245, 251, 253, 254, 271, 272, 273, 275 Bone scan, 221, 269 Bowel, 216, 221, 232, 248, 249, 256, 273 Bowel Movement, 221, 232, 273 Brachytherapy, 221, 247, 248, 266

Index 283

Branch, 207, 222, 243, 251, 259, 266, 272, 274 Breakdown, 222, 224, 232, 239, 271 Breeding, 27, 144, 222 Bronchi, 222, 235, 276 Bronchial, 164, 222 Bronchiectasis, 164, 222 Bronchitis, 164, 222, 225 Buccal, 222, 251 Bypass, 113, 222 C Calcium, 222, 227, 249, 252, 265 Camphor, 142, 222 Capillary, 166, 222, 263, 279 Carbohydrate, 222, 241, 263, 270 Carbon Dioxide, 222, 230, 268 Carboplatin, 109, 222 Carboxy, 94, 222 Carcinogen, 11, 24, 26, 31, 33, 144, 148, 213, 220, 222, 253, 275 Carcinogenesis, 4, 9, 15, 25, 26, 28, 33, 38, 42, 49, 56, 68, 69, 84, 95, 136, 144, 149, 222, 225 Carcinogenic, 31, 33, 36, 140, 148, 149, 215, 220, 222, 232, 247, 256, 257, 265, 272 Cardiac, 222, 231, 234, 235, 239, 241, 255, 272 Cardiology, 166, 222 Cardiotoxicity, 222, 235 Cardiovascular, 8, 222, 223, 270 Cardiovascular disease, 8, 223 Carrier Proteins, 223, 261, 267 Carrier State, 162, 223 Case report, 6, 40, 76, 96, 223, 226 Case series, 5, 223, 226 Catabolism, 27, 223 Catecholamine, 223, 232, 260 Catheterization, 223, 248 Catheters, 112, 113, 223, 246, 247 Causal, 136, 223, 226, 235 Cause of Death, 4, 126, 135, 164, 223, 231 Celecoxib, 110, 223 Celiac Artery, 223, 243 Cell, 9, 14, 18, 20, 21, 23, 24, 31, 32, 35, 39, 41, 44, 46, 48, 52, 56, 59, 62, 67, 72, 74, 79, 81, 91, 92, 93, 94, 107, 111, 119, 121, 122, 126, 127, 128, 129, 131, 132, 134, 137, 138, 141, 145, 146, 147, 150, 151, 170, 174, 189, 190, 213, 214, 215, 216, 218, 219, 221, 223, 224, 225, 226, 227, 228, 230, 231, 234, 235, 236, 238, 240, 241, 243, 244, 245, 246, 247, 248, 249,

250, 252, 254, 255, 256, 257, 258, 260, 261, 262, 263, 264, 267, 268, 273, 274, 275, 276, 277, 278, 279 Cell Cycle, 223, 226, 230, 236 Cell Death, 218, 223, 236, 256 Cell Division, 189, 219, 223, 224, 236, 254, 261 Cell Fusion, 128, 223 Cell membrane, 223, 261 Cell motility, 224, 243 Cell proliferation, 24, 46, 67, 170, 224 Cell Respiration, 214, 224, 258, 268 Cell Size, 224, 238 Cell Transplantation, 224 Cellular metabolism, 137, 224 Cellulose, 224, 261 Central Nervous System, 213, 216, 220, 224, 226, 238, 239, 240, 242, 270 Centrifugation, 224, 254 Cerebellar, 219, 224, 268 Cerebral, 219, 224, 235, 240 Cerebral hemispheres, 219, 224, 240 Cerebrospinal, 224, 271 Cerebrospinal fluid, 224, 271 Cerebrovascular, 219, 223, 224, 274 Cerebrum, 224, 277 Cervical, 10, 13, 84, 126, 134, 224 Cervix, 10, 224, 248, 275 Chemoprevention, 9, 15, 26, 30, 54, 79, 92, 97, 149, 225 Chemopreventive, 9, 26, 27, 30, 97, 225 Chemoprotective, 26, 110, 225 Chemotactic Factors, 225, 227 Chlormethiazole, 225 Chlorophyll, 171, 225, 230 Chloroplasts, 225, 230 Cholangitis, 4, 155, 225 Cholecystitis, 155, 225 Cholestasis, 164, 225 Cholesterol, 174, 220, 225, 229, 239, 244, 250, 251, 271, 272, 274, 276 Cholesterol Esters, 225, 250 Choline, 32, 144, 225 Chromatin, 9, 31, 218, 225 Chromosomal, 51, 173, 216, 225, 240, 261 Chromosome, 37, 81, 140, 225, 228, 242 Chronic Disease, 163, 225 Chronic Obstructive Pulmonary Disease, 164, 225 Chronic renal, 225, 262, 278 Chylomicrons, 225, 250 CIS, 32, 195, 226

284 Liver Cancer

Cisplatin, 41, 47, 93, 109, 146, 178, 226 Clear cell carcinoma, 226, 231 Clinical Medicine, 226, 264 Clinical study, 78, 226 Clinical trial, 8, 12, 22, 29, 30, 105, 106, 122, 185, 199, 226, 229, 255, 259, 265, 267 Clone, 127, 132, 226 Cloning, 5, 27, 47, 221, 226 Coagulation, 48, 67, 78, 118, 130, 222, 226, 242, 261, 275 Coca, 226 Cocaine, 163, 226 Coenzyme, 226, 251, 271 Cofactor, 226, 265, 275 Cohort Effect, 82, 226 Cohort Studies, 4, 227, 235 Colchicine, 227, 277 Collagen, 106, 227, 237, 252, 264, 265 Colloidal, 214, 227, 270 Colon Polyps, 25, 227 Colorectal, 28, 32, 49, 69, 134, 140, 194, 227 Colorectal Cancer, 28, 32, 134, 140, 194, 227 Combination chemotherapy, 110, 227 Combination Therapy, 165, 227 Common Bile Duct, 4, 155, 227, 230 Complement, 147, 216, 227, 228, 239, 261 Complementary and alternative medicine, 91, 100, 228 Complementary medicine, 91, 228 Complete remission, 228, 268 Complete response, 105, 106, 228 Computational Biology, 185, 188, 228 Computed tomography, 48, 155, 228, 269 Computerized axial tomography, 228, 269 Computerized tomography, 228 Conception, 228, 229, 237 Concomitant, 67, 228 Confounding, 24, 228 Conjugated, 126, 220, 228, 230 Conjugation, 221, 228 Conjunctiva, 229, 247 Connective Tissue, 221, 227, 229, 238, 239, 251, 257, 269 Consultation, 166, 229 Consumption, 4, 5, 9, 17, 25, 43, 229, 257, 268 Contamination, 25, 229, 243 Continuum, 12, 229 Contraceptive, 68, 71, 229 Contraindications, ii, 165, 229 Contralateral, 24, 229, 268

Control group, 20, 229 Conventional therapy, 229 Conventional treatment, 30, 229 Coronary, 223, 229, 253 Coronary heart disease, 223, 229 Coronary Thrombosis, 229, 254 Cortex, 219, 229, 236, 264, 268 Corticosteroids, 229, 240 Cortisol, 214, 229 Coumarin, 229, 268 Cross-Sectional Studies, 229, 235 Cryosurgery, 82, 160, 195, 230 Cryotherapy, 63, 230 Cultured cells, 31, 230 Curative, 23, 69, 118, 120, 230, 274 Cutaneous, 146, 230, 251, 261 Cyanobacteria, 36, 230 Cyclic, 141, 230, 263 Cyclin, 35, 41, 230 Cyst, 79, 230 Cysteine, 230, 273 Cystic Duct, 227, 230 Cytochrome, 24, 26, 230 Cytokine, 48, 56, 230, 274 Cytoplasm, 218, 223, 230, 233, 236, 241, 254 Cytosine, 74, 230 Cytotoxic, 8, 92, 94, 135, 137, 138, 230, 267 Cytotoxicity, 226, 230 D Data Collection, 230, 238 Databases, Bibliographic, 185, 231 Daunorubicin, 231, 233 Death Certificates, 5, 231 Decompensation, 12, 186, 231 Degenerative, 231, 243 Dehydroepiandrosterone, 99, 231 Deletion, 11, 140, 218, 231 Denaturation, 231, 262 Dendrites, 231, 256 Dendritic, 41, 231, 253 Dendritic cell, 41, 231 Density, 146, 224, 231, 238, 250, 257, 262 Deoxyguanosine, 10, 20, 231 Deprivation, 119, 231 DES, 94, 95, 216, 231 Detoxification, 24, 33, 39, 231 Deuterium, 231, 244 Diabetes Mellitus, 4, 5, 54, 74, 75, 231, 240, 242, 247 Diagnostic Imaging, 174, 231 Diagnostic procedure, 125, 173, 231

Index 285

Dialyzer, 231, 242 Diastolic, 232, 245 Diathermy, 232, 254 Diethylnitrosamine, 88, 91, 130, 232 Diffusion, 232, 247 Digestion, 163, 215, 220, 221, 232, 248, 250, 260, 273, 278 Digestive system, 123, 232, 239, 255 Digestive tract, 134, 232, 271 Dihydrotestosterone, 232, 268, 271 Dilatation, 155, 222, 232, 264, 278 Dilation, 164, 232, 278 Diploid, 232, 261 Direct, iii, 8, 23, 35, 117, 131, 142, 177, 226, 232, 233, 259, 268 Disease Progression, 12, 17, 19, 139, 232, 279 Disinfectant, 232, 236 Dissociation, 214, 232 Distal, 232, 234 Diuretic, 232, 252, 271 Docetaxel, 92, 111, 112, 232 Dopamine, 226, 232, 261 Dosimetry, 30, 233 Doxorubicin, 21, 96, 106, 109, 114, 115, 116, 118, 120, 135, 146, 178, 233, 235 Drug Delivery Systems, 21, 135, 233 Drug Interactions, 178, 233 Drug Resistance, 29, 31, 115, 233 Drug Tolerance, 233, 276 Drug Toxicity, 110, 139, 233 Duct, 73, 108, 116, 121, 194, 216, 223, 225, 227, 233, 236, 269 Duodenum, 220, 233, 234, 243, 273 Dyes, 220, 233, 238 Dysplasia, 37, 190, 233 Dyspnea, 231, 233 Dystrophy, 189, 233 E Edema, 231, 233, 278 Effector, 213, 227, 233 Efficacy, 7, 9, 21, 26, 33, 34, 93, 105, 106, 116, 117, 118, 119, 139, 145, 233 Egg Yolk, 147, 233 Elastin, 227, 233, 237 Electrocardiogram, 112, 234 Electrocoagulation, 226, 234 Electrode, 32, 94, 130, 234 Electrolyte, 234, 271, 278 Electrons, 218, 219, 234, 248, 258, 266, 267 Emboli, 24, 172, 234 Embolization, 24, 172, 234

Embryo, 59, 233, 234, 246 Emphysema, 162, 164, 225, 234 Empirical, 44, 234 Encapsulated, 135, 234, 250 Endemic, 16, 42, 49, 56, 139, 186, 234, 272 Endocytosis, 21, 234 Endometrial, 15, 234 Endometriosis, 141, 234 Endometrium, 234 Endoscope, 234 Endoscopic, 6, 234 Endothelial cell, 59, 234, 238, 275 Endotoxic, 234, 250 Endotoxin, 234, 277 End-stage renal, 225, 234, 262 Environmental Exposure, 136, 235, 257 Environmental Health, 26, 33, 184, 186, 235 Environmental Pollutants, 145, 235 Enzymatic, 39, 138, 213, 222, 227, 235, 262 Enzyme-Linked Immunosorbent Assay, 36, 235 Epidemic, 13, 147, 155, 165, 235, 272 Epidemiologic Studies, 136, 235 Epidemiological, 5, 15, 25, 28, 33, 36, 69, 127, 132, 136, 235 Epidermal, 235, 249, 253 Epidermis, 235, 249, 264 Epigastralgia, 4, 235 Epigastric, 235, 258 Epinephrine, 232, 235, 277 Epirubicin, 51, 110, 235 Epithelial, 73, 146, 213, 235, 243 Epithelial Cells, 235, 243 Erythrocytes, 129, 216, 221, 236, 267 Esophageal, 7, 13, 35, 67, 141, 236 Esophageal Varices, 67, 236 Esophagus, 28, 232, 236, 239, 260, 273, 278 Essential Tremor, 190, 236 Estradiol, 236, 271 Estrogen, 15, 28, 114, 236, 270, 274, 276 Estrogen receptor, 28, 236 Ethanol, 20, 118, 127, 236, 237 Ethnic Groups, 4, 236 Ethoxyquin, 33, 236 Etoposide, 93, 178, 236 Excitation, 216, 236, 238 Excrete, 236, 268 Exocrine, 236, 258 Exogenous, 221, 236, 277 Exons, 27, 236 Extensor, 236, 266

286 Liver Cancer

External-beam radiation, 236, 248, 266 Extracellular, 32, 229, 234, 236, 237, 252, 271 Extracellular Matrix, 229, 236, 237, 252 Extracellular Matrix Proteins, 237, 252 Extracellular Space, 32, 236, 237 Extravasation, 7, 237 Extremity, 113, 237 Eye Infections, 213, 237 F Failure to Thrive, 164, 237 Family Planning, 185, 237 Fat, 25, 164, 213, 220, 221, 229, 234, 237, 250, 269, 271 Fatigue, 163, 237 Fatty acids, 214, 237, 241, 250 Fatty Liver, 133, 155, 174, 237 Feces, 237, 273 Fermentation, 220, 237 Fetoprotein, 47, 237 Fetus, 215, 237, 264, 278 Fibrin, 237, 262, 275 Fibrinogen, 237, 261, 262, 275 Fibroblast Growth Factor, 40, 146, 237 Fibrosis, 3, 88, 186, 190, 238, 269 Flow Cytometry, 70, 238 Fluorescence, 238 Fluorescent Dyes, 238 Fluorouracil, 146, 178, 238 Focus Groups, 22, 238 Fold, 13, 14, 16, 35, 71, 238, 253, 257 Folic Acid, 238, 249 Follicles, 238 Forearm, 221, 238 Frameshift, 37, 238, 277 Frameshift Mutation, 238, 277 Fungi, 35, 228, 237, 238, 254, 255, 268, 272, 280 G GABA, 225, 238 Galactosemia, 155, 239 Gallbladder, 108, 116, 121, 122, 133, 155, 194, 213, 220, 225, 230, 232, 239, 243, 278 Gallstones, 155, 220, 239 Gamma Rays, 239, 255, 266, 267 Ganglia, 213, 215, 219, 239, 256 Gas, 216, 222, 232, 239, 244, 255, 256, 279 Gastric, 7, 40, 78, 134, 149, 219, 223, 235, 239, 260 Gastric Acid, 239 Gastric Juices, 239, 260 Gastric Mucosa, 239, 260

Gastrin, 131, 239, 244 Gastrin-Releasing Peptide, 131, 239 Gastroenterologist, 13, 239 Gastrointestinal, 20, 25, 28, 44, 77, 146, 235, 236, 239, 270, 273, 275, 277 Gastrointestinal tract, 25, 236, 239, 270, 277 Gemcitabine, 111, 112, 121, 122, 239 Gene Expression, 31, 38, 54, 60, 103, 138, 139, 190, 239 Genetic Code, 239, 257 Genetic Engineering, 126, 221, 226, 239 Genetic Techniques, 9, 240 Genetic testing, 240, 262 Genetics, 23, 27, 35, 44, 55, 140, 162, 228, 240, 259 Genotype, 240, 261 Germ Cells, 240, 258 Gestation, 240, 260 Ginseng, 88, 91, 97, 99, 100, 240 Gland, 240, 251, 258, 259, 261, 265, 269, 270, 273, 275 Glioblastoma, 40, 126, 240 Glucocorticoid, 8, 240 Glucose, 137, 189, 224, 231, 239, 240, 241, 242, 247, 269, 271 Glucose Intolerance, 231, 240 Glucosinolates, 33, 240 Glucuronic Acid, 240, 242 Glutamic Acid, 238, 240, 265 Glutamine, 71, 240 Glutathione Peroxidase, 20, 241, 270 Glycerol, 241, 261 Glycerophospholipids, 241, 261 Glycine, 220, 225, 241 Glycogen, 139, 241 Glycogen Storage Disease, 139, 241 Glycoprotein, 59, 135, 237, 241, 271, 275, 277 Gonadal, 241, 272 Governing Board, 241, 263 Grade, 30, 172, 241 Graft, 67, 71, 95, 241, 244, 246 Graft Rejection, 241, 246 Graft Survival, 71, 95, 241 Graft-versus-tumor, 67, 241 Gram-negative, 230, 234, 241 Gram-Negative Bacteria, 230, 234, 241 Granulocytes, 241, 249, 279 Groin, 112, 241 H Hair follicles, 141, 241, 279

Index 287

Half-Life, 119, 242 Haploid, 242, 261 Haptens, 214, 242, 267 Headache, 242, 247 Health Status, 226, 242 Heart attack, 223, 242 Heart-Lung Machine, 113, 242 Heme, 220, 230, 242, 263, 278 Hemochromatosis, 13, 139, 155, 174, 242 Hemodialysis, 38, 231, 242 Hemoglobin, 217, 236, 242, 263 Hemoglobinuria, 189, 242 Hemorrhage, 234, 242, 273 Hemorrhaging, 6, 242 Hemostasis, 130, 242, 270 Heparin, 133, 242 Hepatic Artery, 4, 43, 74, 82, 89, 106, 243 Hepatitis A, 43, 59, 84, 133, 147, 155, 156, 162, 243 Hepatitis Viruses, 138, 140, 157, 243 Hepatobiliary, 92, 155, 243 Hepatoblastoma, 106, 109, 110, 243 Hepatocyte, 9, 14, 18, 24, 38, 60, 73, 98, 133, 136, 145, 225, 243 Hepatocyte Growth Factor, 38, 60, 98, 243 Hepatology, 3, 4, 6, 7, 28, 42, 51, 59, 60, 62, 63, 65, 76, 78, 79, 82, 95, 138, 158, 186, 243 Hepatoma, 4, 14, 31, 44, 130, 131, 132, 243 Hepatotoxic, 8, 243 Hepatotoxicity, 20, 148, 243 Hepatovirus, 243 Hereditary, 155, 243, 268 Heredity, 239, 240, 243 Herpes, 39, 243 Herpes Zoster, 243 Heterogeneity, 38, 214, 243 Heterotrophic, 238, 243 Histidine, 243, 247 Histology, 21, 243 Histone Deacetylase, 45, 75, 243 Homeostasis, 30, 243 Homogeneous, 21, 229, 244 Homologous, 31, 32, 132, 244 Hormonal, 219, 244 Hormone therapy, 114, 213, 244 Horseradish Peroxidase, 235, 244 Host, 16, 18, 20, 127, 136, 144, 145, 186, 223, 241, 244, 245, 246, 278, 279 Hybrid, 226, 244 Hybridization, 132, 223, 244, 273 Hybridoma, 127, 128, 244

Hydrogen, 141, 213, 219, 222, 231, 237, 241, 244, 250, 254, 256, 257, 258, 266, 275, 280 Hydrogen Peroxide, 241, 244, 250 Hydrolysis, 221, 226, 244, 263, 265 Hydrophobic, 14, 241, 244, 250 Hydroxylation, 213, 244 Hydroxylysine, 227, 244 Hydroxyproline, 227, 244 Hyperbilirubinemia, 244, 249 Hypercholesterolemia, 79, 244 Hypersensitivity, 244, 269 Hypertension, 7, 155, 160, 164, 223, 242, 245, 278 Hyperthermia, 79, 96, 232, 245 Hypertrophy, 24, 245 Hypervascular, 120, 245 Hypnotic, 219, 245, 274 I Iatrogenic, 78, 245 Id, 90, 98, 197, 200, 206, 208, 245 Ileal, 6, 7, 245 Ileum, 7, 245 Immune function, 146, 245 Immune response, 14, 16, 121, 213, 217, 218, 241, 242, 245, 246, 273, 278, 279 Immune Sera, 245 Immune system, 119, 146, 218, 245, 246, 251, 252, 255, 260, 278, 279 Immunity, 131, 245, 276 Immunization, 6, 85, 199, 245, 246, 264, 270 Immunoassay, 49, 235, 245 Immunodeficiency, 165, 166, 189, 245 Immunodeficiency syndrome, 165, 166, 245 Immunogenic, 119, 245, 250, 267 Immunoglobulin, 217, 236, 245, 254 Immunohistochemistry, 27, 245 Immunologic, 225, 245, 267 Immunology, 23, 41, 126, 138, 213, 214, 238, 244, 246 Immunosuppressant, 215, 238, 246 Immunosuppressive, 240, 246 Immunosuppressive therapy, 246 Immunotherapy, 41, 43, 147, 246 Immunotoxins, 246, 267 Impairment, 146, 219, 225, 237, 246, 253 Implant radiation, 246, 247, 248, 266 In situ, 17, 63, 246 In vitro, 15, 31, 33, 60, 71, 95, 127, 141, 223, 246, 262, 276

288 Liver Cancer

In vivo, 15, 18, 21, 24, 26, 27, 31, 32, 42, 60, 130, 223, 242, 246, 250, 258 Incision, 246, 248, 249 Incubation, 127, 246 Incubation period, 127, 246 Indicative, 156, 246, 259, 278 Induction, 26, 33, 37, 92, 232, 246, 271 Infant, Newborn, 214, 246 Infarction, 229, 246, 253 Inferior vena cava, 55, 246 Infiltration, 67, 247 Influenza, 11, 247 Infusion, 74, 89, 112, 115, 150, 247, 276 Ingestion, 9, 25, 139, 247, 262 Initiation, 17, 19, 28, 144, 149, 247, 276 Inlay, 247, 268 Inoperable, 105, 106, 107, 112, 113, 196, 247 Inorganic, 139, 226, 247, 261, 262 Insight, 13, 15, 25, 31, 38, 247 Insulin, 61, 247, 277 Intensive Care, 113, 247 Interferon, 62, 154, 165, 196, 247 Interferon Alfa-2b, 154, 247 Interferon-alpha, 247 Intermittent, 4, 186, 247, 263 Internal Medicine, 77, 89, 239, 247 Internal radiation, 112, 132, 247, 248, 266 Interstitial, 221, 237, 247, 248 Intestinal, 248, 252 Intestine, 59, 220, 221, 227, 248, 249, 278 Intracellular, 9, 32, 138, 240, 246, 248, 270 Intrahepatic, 4, 29, 48, 64, 76, 248 Intraperitoneal, 131, 248 Intravenous, 21, 51, 115, 118, 131, 163, 166, 247, 248 Intrinsic, 24, 214, 248 Intubation, 92, 223, 248 Invasive, 10, 21, 24, 79, 245, 248, 252 Invasive cervical cancer, 10, 248 Involuntary, 219, 236, 248, 255 Iodine, 94, 116, 179, 180, 248 Iodine-131, 94, 248 Ionizing, 215, 235, 248, 267 Ions, 219, 232, 234, 244, 248, 265 Irradiation, 248, 268 Ischemia, 219, 248 Isocyanates, 33, 248 Isolated hepatic perfusion, 113, 248 J Jaundice, 4, 155, 164, 174, 244, 249

K Kb, 132, 184, 249 Keratin, 249 Keratinocytes, 129, 249 Kidney Disease, 115, 123, 184, 190, 249 Kinetics, 19, 21, 25, 249 L Labile, 227, 249 Lamivudine, 115, 249 Laparotomy, 7, 249 Large Intestine, 227, 232, 248, 249, 267, 271 Latent, 136, 249, 264 Latent period, 136, 249 Laxative, 249, 271 Lectin, 50, 59, 249 Lesion, 15, 120, 131, 132, 249, 251 Lethal, 14, 219, 249 Leucocyte, 215, 249 Leucovorin, 146, 249 Leukemia, 44, 63, 126, 134, 141, 189, 233, 235, 250 Leukocytes, 221, 225, 241, 247, 250, 254, 277 Leukopenia, 146, 250 Levo, 250, 253 Library Services, 206, 250 Life cycle, 19, 238, 250 Ligament, 250, 265 Ligands, 72, 250 Ligation, 4, 82, 250 Lipid, 20, 137, 146, 218, 225, 241, 247, 250, 258 Lipid A, 137, 250 Lipid Peroxidation, 20, 146, 250, 258 Lipid Peroxides, 20, 250 Lipopolysaccharides, 250 Lipoprotein, 146, 241, 250, 251 Liposomal, 96, 250 Liposome, 135, 250 Liver Cirrhosis, 4, 20, 42, 59, 81, 99, 136, 146, 147, 154, 161, 164, 250 Liver metastases, 109, 250 Liver Neoplasms, 117, 118, 251, 279 Liver Regeneration, 23, 32, 78, 133, 251 Liver scan, 210, 251, 269 Liver Transplantation, 61, 74, 77, 115, 120, 147, 155, 160, 162, 251 Localization, 84, 245, 251 Locomotion, 251, 261 Longitudinal study, 14, 251 Lovastatin, 251, 271 Low-density lipoprotein, 250, 251

Index 289

Lupus, 146, 251 Lycopene, 93, 251 Lymph, 66, 224, 234, 251, 278 Lymph node, 224, 251, 278 Lymphatic, 246, 251, 271, 272, 275 Lymphatic system, 251, 271, 272, 275 Lymphocyte, 14, 70, 143, 217, 251, 252 Lymphocyte Subsets, 70, 252 Lymphocytic, 128, 252 Lymphoid, 217, 229, 249, 252 Lymphoma, 128, 189, 252 Lysine, 244, 252, 264 Lytic, 252, 270 M Macrophage, 48, 252 Magnetic Resonance Imaging, 47, 48, 53, 77, 121, 155, 252, 269 Malabsorption, 189, 252 Malignancy, 13, 147, 252 Malignant tumor, 139, 140, 146, 147, 155, 198, 252 Malnutrition, 20, 215, 219, 252, 255 Mammary, 252, 274, 276 Mannitol, 252, 268 Matrix metalloproteinase, 52, 252 Meat, 25, 252 Mediate, 32, 81, 233, 252 Medical Records, 252, 269 MEDLINE, 7, 185, 188, 190, 252 Medullary, 128, 252 Megestrol, 114, 252 Melanin, 253, 261, 277 Melanocytes, 253 Melanoma, 30, 113, 119, 126, 134, 189, 253 Melphalan, 112, 113, 253 Mental Disorders, 123, 253, 264 Mental Health, iv, 7, 123, 166, 184, 187, 253, 264, 266 Mercury, 238, 253 Mesenteric, 253, 263 Metabolic disorder, 139, 164, 241, 253 Metabolite, 25, 221, 249, 251, 253, 264 Metastasis, 4, 32, 48, 52, 60, 61, 62, 113, 130, 134, 140, 171, 211, 252, 253 Metastasize, 253, 270 Metastatic cancer, 120, 150, 253 Methionine, 31, 77, 253, 273 Methionine Adenosyltransferase, 77, 253 Methyltransferase, 39, 253 MI, 38, 43, 154, 211, 253 Microbe, 254, 276 Microbiology, 49, 138, 219, 254

Microcirculation, 250, 254, 262 Microorganism, 226, 254, 259, 279 Microscopy, 23, 28, 244, 254 Microsomal, 146, 148, 254 Microspheres, 47, 57, 79, 84, 171, 254 Microwaves, 130, 254, 267 Mitochondrial Swelling, 254, 256 Mitosis, 218, 254 Mitotic, 232, 236, 254, 279 Mitotic inhibitors, 232, 254 Modification, 12, 239, 254, 266, 280 Monitor, 139, 174, 254, 257 Monoclonal, 108, 179, 180, 220, 246, 248, 254, 266 Monocytes, 250, 254, 274 Mononuclear, 135, 254, 277 Monotherapy, 165, 255 Morphological, 19, 234, 253, 255 Motion Sickness, 255 Mucosa, 239, 251, 255 Mucositis, 255, 275 Multicenter Studies, 47, 255 Multicenter study, 255 Multidrug resistance, 31, 255 Muscle Fibers, 255 Muscular Atrophy, 189, 255 Muscular Dystrophies, 233, 255 Mutagen, 220, 255 Mutagenesis, 9, 18, 26, 255 Mutagenic, 15, 18, 136, 215, 232, 255, 256 Mutagenicity, 213, 255 Myalgia, 247, 255 Mycotoxins, 33, 214, 255 Mydriatic, 232, 255 Myeloma, 244, 255 Myocardium, 253, 255 Myotonic Dystrophy, 189, 255 N Naive, 118, 255 Nasal Mucosa, 247, 255 Nausea, 141, 255, 278 Necrosis, 79, 93, 145, 218, 240, 246, 253, 256 Neonatal, 27, 256 Neoplasia, 189, 256 Neoplasm, 113, 256, 277 Neoplastic, 18, 135, 141, 150, 252, 256, 257 Nephropathy, 249, 256 Nerve, 217, 219, 231, 256, 269, 273 Nervous System, 59, 190, 224, 256, 273 Neural, 237, 256 Neural tube defects, 237, 256

290 Liver Cancer

Neuroblastoma, 126, 256 Neurologic, 240, 256 Neurons, 226, 231, 239, 256 Neuropeptide, 239, 256 Neutrons, 215, 248, 256, 266 Nitrogen, 141, 215, 230, 237, 240, 253, 256, 277 Nitrosamines, 84, 256 Nolatrexed, 114, 179, 257 Nonmetastatic, 108, 257 Nuclear, 70, 80, 89, 133, 150, 219, 228, 234, 239, 240, 256, 257 Nuclei, 215, 228, 234, 236, 240, 252, 254, 256, 257, 266 Nucleic acid, 144, 145, 219, 230, 239, 244, 256, 257, 269, 273, 280 Nucleic Acid Hybridization, 244, 257 Nucleus, 9, 218, 219, 225, 230, 231, 239, 254, 256, 257, 266, 273, 274 Nutritional Status, 24, 47, 257 O Ochronosis, 215, 257 Odds Ratio, 61, 257, 268 Odour, 218, 257, 278 Oltipraz, 9, 26, 33, 257 Omentum, 243, 257 Oncogene, 30, 35, 37, 51, 133, 189, 243, 257 Oncogenic, 147, 257 Oncolysis, 257 Oncolytic, 23, 257 Opacity, 231, 257 Operon, 257, 268 Organ Culture, 257, 276 Osmotic, 214, 254, 258, 270 Outpatient, 4, 113, 258 Ovary, 132, 236, 258 Overexpress, 30, 138, 258 Ovulation, 253, 258 Ovum, 240, 250, 258, 264 Oxaliplatin, 115, 258 Oxidants, 30, 258 Oxidation, 146, 148, 213, 218, 221, 230, 241, 250, 258 Oxidation-Reduction, 221, 258 Oxidative metabolism, 12, 214, 258 Oxidative Stress, 20, 26, 137, 258 Oxygenator, 242, 258 P P53 gene, 11, 27, 258 Palliative, 71, 120, 253, 258, 274 Pancreas, 13, 25, 59, 213, 221, 232, 239, 242, 243, 247, 258, 259, 272, 277, 278

Pancreatic, 55, 60, 79, 80, 126, 141, 189, 194, 235, 259 Pancreatic cancer, 80, 141, 189, 235, 259 Pancreatitis, 4, 259 Panniculitis, 164, 259 Papilla, 155, 259 Parasite, 259 Parasitic, 155, 259 Parasitic Diseases, 155, 259 Paroxysmal, 189, 259 Partial remission, 259, 268 Partial response, 105, 106, 259 Particle, 81, 117, 250, 259 Pathogen, 246, 259 Pathogenesis, 5, 16, 138, 140, 259 Pathologic, 55, 66, 218, 221, 229, 244, 259, 266, 278 Pathologic Processes, 218, 259 Pathophysiology, 8, 27, 155, 162, 259 Patient Education, 165, 197, 198, 204, 206, 211, 259 PDQ, 195, 196, 199, 259 Pelvic, 234, 259, 265 Penicillin, 260, 278 Pepsin, 260 Pepsin A, 260 Peptic, 141, 260 Peptic Ulcer, 141, 260 Peptide, 14, 59, 61, 131, 237, 249, 260, 263, 264, 265 Percutaneous, 8, 33, 94, 96, 97, 118, 120, 260 Perennial, 142, 260, 277 Performance status, 120, 260 Perfusion, 112, 113, 260 Perinatal, 34, 154, 163, 260 Periodontitis, 141, 260 Peripheral blood, 78, 241, 247, 260 Peritoneal, 219, 248, 260 Peritoneal Cavity, 219, 248, 260 Phagocyte, 135, 258, 260 Pharmacodynamic, 13, 119, 260 Pharmacokinetic, 13, 21, 119, 260 Pharmacologic, 217, 242, 260, 276 Pharmacotherapy, 69, 70, 260 Pharynx, 247, 260 Phenotype, 15, 27, 62, 66, 260 Phenylalanine, 260, 261, 277 Phocomelia, 145, 261 Phosphates, 24, 261 Phospholipids, 24, 237, 250, 261 Photocoagulation, 226, 261

Index 291

Photosensitivity, 261, 263 Physical Examination, 112, 261 Physiologic, 18, 214, 221, 231, 242, 261, 267 Physiology, 8, 68, 75, 77, 88, 162, 163, 222, 239, 261 Pigment, 220, 225, 251, 253, 257, 261 Pilot study, 52, 120, 261 Pituitary Gland, 237, 261 Planning Techniques, 29, 261 Plants, 11, 215, 222, 225, 226, 240, 249, 261, 269, 272, 276, 277 Plasma, 49, 50, 83, 214, 217, 223, 225, 237, 240, 242, 255, 261, 262, 265, 270, 271, 279 Plasma cells, 217, 255, 261 Plasma protein, 214, 261, 265, 270 Plasmid, 27, 261, 279 Plasmin, 261, 262 Plasminogen, 50, 79, 261, 262 Plasminogen Activators, 261, 262 Platelets, 262, 270, 275 Platinum, 135, 226, 258, 262 Platinum Compounds, 258, 262 Podophyllotoxin, 236, 262 Poisoning, 233, 253, 255, 262 Polycystic, 190, 262 Polyethylene, 119, 262 Polymerase, 5, 49, 262, 268 Polymerase Chain Reaction, 5, 49, 262 Polymers, 221, 262, 265, 273 Polymorphism, 25, 263 Polyp, 25, 263 Polypeptide, 215, 216, 227, 237, 244, 260, 262, 263, 264, 265, 280 Polyposis, 227, 263 Polysaccharide, 217, 224, 263 Porphyria, 65, 74, 139, 263 Porphyria Cutanea Tarda, 65, 263 Porphyria, Hepatic, 263 Porphyrins, 210, 263 Portal System, 76, 263 Portal Vein, 4, 24, 108, 164, 263 Posterior, 216, 219, 258, 263 Postnatal, 263, 272 Postoperative, 4, 94, 263 Postprandial, 4, 263 Post-translational, 216, 263, 271 Potentiate, 225, 263 Practice Guidelines, 187, 263 Precancerous, 28, 225, 264 Preclinical, 34, 264 Precursor, 28, 225, 232, 233, 235, 261, 262, 264, 265, 277, 278

Predictive factor, 154, 264 Predisposition, 11, 264 Premalignant, 264 Prenatal, 234, 264 Prevalence, 4, 5, 6, 12, 14, 20, 28, 35, 38, 59, 120, 257, 264 Prickle, 249, 264 Primary Biliary Cirrhosis, 155, 264 Primary Prevention, 25, 264 Primary tumor, 62, 198, 264 Probe, 132, 264 Procollagen, 51, 59, 264 Prodrug, 22, 74, 264 Progesterone, 253, 264, 272 Prognostic factor, 35, 264 Progression, 12, 16, 19, 28, 37, 121, 134, 149, 158, 162, 197, 217, 264, 277 Progressive, 29, 144, 145, 225, 233, 241, 255, 256, 264, 277 Projection, 94, 265, 268 Proline, 227, 244, 264, 265 Promoter, 28, 32, 35, 37, 77, 265 Prone, 11, 27, 265 Prophylaxis, 165, 265, 278 Proportional, 127, 235, 265 Prospective Studies, 13, 265 Prospective study, 42, 74, 251, 265 Prostate, 30, 99, 126, 131, 134, 146, 189, 221, 265, 277 Protease, 227, 265 Protective Agents, 26, 265 Protein C, 16, 214, 215, 218, 249, 250, 265 Protein Conformation, 215, 249, 265 Protein S, 159, 190, 221, 239, 265 Proteins, 29, 45, 121, 144, 174, 215, 216, 217, 218, 221, 223, 224, 225, 227, 233, 237, 244, 249, 252, 254, 256, 260, 261, 262, 265, 267, 270, 276 Proteolytic, 215, 227, 237, 262, 265 Prothrombin, 94, 265, 275 Protocol, 97, 114, 265 Protons, 215, 244, 248, 266 Protozoa, 228, 254, 266, 272 Psoriasis, 129, 141, 266 Public Health, 5, 9, 12, 16, 33, 53, 66, 72, 148, 155, 159, 164, 165, 187, 220, 266 Public Policy, 185, 266 Publishing, 36, 266 Pulmonary, 74, 89, 221, 229, 266 Pulmonary Artery, 221, 266 Pulse, 254, 266 Pupil, 232, 255, 266

292 Liver Cancer

Purulent, 213, 266 Q Quality of Life, 156, 164, 266, 274 R Race, 10, 253, 266 Radiation therapy, 19, 29, 34, 112, 131, 132, 134, 213, 236, 247, 248, 266 Radio Waves, 160, 232, 254, 267 Radioactive, 34, 84, 112, 116, 131, 132, 139, 171, 221, 242, 244, 246, 247, 248, 251, 257, 266, 267, 269 Radiofrequency ablation, 32, 63, 74, 75, 94, 96, 97, 118, 267 Radioimmunoassay, 148, 267 Radioimmunotherapy, 70, 267 Radiolabeled, 248, 266, 267 Radiological, 195, 260, 267 Radiotherapy, 63, 143, 171, 221, 248, 266, 267 Randomized, 10, 22, 62, 93, 109, 110, 114, 116, 117, 118, 233, 267 Reactivation, 186, 267 Reactive Oxygen Species, 20, 267 Reagent, 267, 275 Receptor, 9, 21, 41, 72, 74, 79, 132, 150, 217, 233, 243, 267, 270 Recombinant, 31, 44, 144, 145, 166, 178, 247, 267, 279 Rectal, 141, 267 Rectum, 218, 221, 227, 232, 239, 249, 265, 267 Recurrence, 62, 77, 115, 116, 139, 140, 143, 170, 225, 267 Red blood cells, 236, 263, 267, 269 Red Nucleus, 219, 268 Reductase, 137, 146, 251, 268, 271 Refer, 1, 222, 227, 238, 243, 251, 255, 256, 267, 268 Refraction, 268, 272 Refractory, 4, 146, 234, 268 Regeneration, 18, 23, 133, 145, 238, 268 Regimen, 109, 110, 114, 137, 233, 260, 268, 269 Reishi, 142, 268 Relapse, 118, 268 Relative risk, 6, 68, 268 Remission, 146, 267, 268 Renal tubular, 27, 268 Repopulation, 27, 39, 268 Repressor, 11, 257, 268 Research Support, 13, 23, 28, 268 Resected, 55, 268

Resection, 4, 23, 32, 55, 62, 63, 76, 96, 118, 120, 127, 139, 147, 160, 170, 172, 268 Respiration, 222, 254, 268 Restoration, 267, 268, 280 Retinoblastoma, 189, 268 Retinoid, 126, 269 Retreatment, 154, 269 Retrospective, 55, 70, 76, 269 Retrospective study, 55, 269 Reversion, 269, 277 Rheumatism, 269 Rheumatoid, 132, 146, 258, 269 Rheumatoid arthritis, 132, 146, 269 Ribavirin, 153, 154, 163, 269 Rigidity, 261, 269 S Saline, 32, 269 Salivary, 232, 259, 269 Salivary glands, 232, 269 Saponins, 269, 272 Scans, 30, 113, 269 Scatter, 60, 269 Sclerosis, 190, 269 Screening, 6, 7, 16, 43, 47, 137, 144, 145, 156, 160, 162, 164, 166, 196, 197, 226, 259, 269 Sebaceous, 269, 279 Secondary tumor, 198, 253, 270 Secretion, 239, 270, 278 Secretory, 145, 270 Sedative, 145, 219, 225, 270 Seizures, 240, 259, 270 Selective estrogen receptor modulator, 270, 274, 276 Selenium, 20, 30, 90, 270 Semen, 265, 270 Semisynthetic, 236, 246, 270 Sequence Analysis, 37, 132, 270 Sequencing, 12, 27, 35, 262, 270 Seroconversion, 186, 270 Serologic, 17, 245, 270 Serotonin, 260, 270, 277 Serum Albumin, 25, 267, 270 Sex Characteristics, 270, 274 Sex Determination, 190, 271 Sex Hormone-Binding Globulin, 56, 271 Shock, 271, 277 Shunt, 7, 271 Side effect, 110, 112, 117, 135, 141, 154, 165, 177, 179, 214, 271, 274, 276, 280 Signs and Symptoms, 156, 268, 271, 278 Simvastatin, 147, 271

Index 293

Skull, 256, 271, 274 Small intestine, 220, 226, 230, 233, 244, 245, 248, 271 Social Environment, 266, 271 Sodium, 118, 271 Soft tissue, 221, 271 Solid tumor, 34, 69, 114, 115, 126, 217, 220, 233, 271 Solvent, 220, 236, 241, 258, 271 Somatic, 39, 223, 254, 271, 274 Somatic cells, 223, 254, 271 Sorbitol, 137, 252, 271 Specialist, 200, 232, 272 Specificity, 7, 16, 17, 141, 214, 272 Spectrum, 19, 154, 164, 254, 267, 272 Sperm, 225, 272, 277 Spinal cord, 219, 224, 225, 256, 272 Spinous, 235, 249, 272 Spleen, 216, 244, 251, 272 Splenic Vein, 263, 272 Sporadic, 263, 268, 272 Spores, 142, 272 Staging, 160, 194, 269, 272 Steatosis, 155, 170, 237, 272 Stem cell transplantation, 65, 272 Stem Cells, 18, 272 Steroid, 9, 132, 150, 220, 229, 269, 271, 272 Stimulant, 272, 278 Stimulus, 234, 236, 273, 275 Stool, 4, 249, 273 Strand, 17, 18, 262, 273 Stress, 20, 147, 166, 209, 223, 229, 255, 258, 264, 269, 273 Stringency, 132, 273 Stroke, 123, 184, 223, 273 Stromal, 79, 234, 273 Structure-Activity Relationship, 26, 273 Styrene, 52, 273 Subacute, 246, 273 Subclinical, 79, 158, 246, 270, 273 Subcutaneous, 131, 164, 233, 259, 273 Subspecies, 272, 273 Substance P, 253, 270, 273 Substrate, 138, 235, 273 Substrate Specificity, 138, 273 Sulfur, 141, 237, 249, 253, 273 Supplementation, 30, 273 Support group, 155, 210, 211, 273 Supportive care, 259, 273 Suppression, 129, 141, 149, 274 Survival Rate, 29, 55, 140, 186, 274 Symphysis, 265, 274

Symptomatic, 259, 274 Synergistic, 5, 11, 20, 36, 274 Systemic, 131, 145, 146, 178, 216, 221, 235, 246, 248, 263, 266, 274, 276 Systemic disease, 145, 274 Systemic therapy, 146, 274 Systolic, 245, 274 T Tamoxifen, 15, 88, 146, 171, 270, 274, 276 Telangiectasia, 190, 274 Telomerase, 75, 274 Temporal, 24, 71, 80, 274 Testosterone, 53, 216, 268, 271, 274 Thalamic, 219, 274 Thalamic Diseases, 219, 274 Thalidomide, 106, 110, 120, 145, 274 Therapeutics, 74, 97, 138, 179, 274 Thermal, 32, 48, 53, 82, 97, 130, 232, 256, 262, 274 Thermal ablation, 32, 97, 274 Thigh, 241, 275 Thioacetamide, 32, 275 Thiotepa, 41, 275 Thorax, 30, 213, 275 Thorium Dioxide, 139, 275 Threshold, 245, 275 Thrombin, 237, 265, 275 Thrombolytic, 262, 275 Thrombomodulin, 265, 275 Thrombopenia, 146, 275 Thrombosis, 4, 155, 265, 273, 275 Thrombus, 80, 229, 246, 275 Thymidine, 39, 41, 275 Thymidine Kinase, 39, 275 Thymidylate Synthase, 257, 275 Thymus, 245, 251, 275 Thyroid, 132, 133, 194, 248, 275, 276, 277 Thyroid Gland, 133, 275, 276 Thyroid Hormones, 275, 277 Thyroxine, 214, 261, 276 Tin, 262, 276 Tissue Culture, 11, 276 Tolerance, 117, 240, 276 Tomography, 16, 23, 47, 64, 77, 97, 276 Topical, 236, 244, 276 Toremifene, 15, 276 Toxicity, 22, 24, 26, 93, 106, 151, 174, 222, 233, 253, 276, 279 Toxicology, 54, 55, 73, 77, 84, 88, 89, 186, 276 Toxins, 36, 211, 217, 240, 246, 255, 267, 276 Trace element, 30, 276

294 Liver Cancer

Trachea, 222, 260, 275, 276 Transcriptase, 249, 274, 276, 280 Transcription Factors, 9, 32, 150, 276 Transfection, 221, 276 Transfer Factor, 245, 276 Transferases, 34, 56, 276 Transfusion, 3, 42, 276 Translational, 12, 15, 23, 28, 277 Translocation, 17, 277 Transplantation, 65, 66, 67, 71, 74, 77, 82, 96, 115, 120, 127, 147, 155, 160, 172, 225, 245, 277 Trauma, 155, 219, 242, 256, 259, 274, 277 Trees, 142, 277 Tryptophan, 227, 270, 277 Tuberculosis, 229, 251, 277 Tuberous Sclerosis, 190, 277 Tubulin, 29, 277 Tumor marker, 155, 221, 277 Tumor model, 31, 277 Tumor Necrosis Factor, 151, 274, 277 Tumor suppressor gene, 26, 35, 60, 136, 140, 258, 277 Tumour, 70, 80, 93, 257, 277 Type 2 diabetes, 8, 277 Typhimurium, 63, 277 Tyrosine, 27, 232, 277 U Ultrasonography, 43, 47, 62, 75, 278 Unconscious, 245, 278 Unresectable gallbladder cancer, 116, 121, 278 Uracil, 172, 278 Uraemia, 259, 278 Urethra, 265, 278 Urinary, 25, 84, 278 Urine, 4, 9, 36, 106, 107, 210, 215, 221, 232, 242, 278 Urokinase, 50, 79, 278 Uroporphyrinogen Decarboxylase, 263, 278 Uterus, 224, 234, 264, 275, 278 V Vaccination, 5, 10, 22, 24, 58, 64, 163, 165, 186, 197, 278

Vaccine, 6, 24, 121, 127, 156, 166, 178, 198, 213, 266, 278 Vacuoles, 234, 278 Vagina, 224, 231, 278 Valine, 133, 278 Varices, 6, 7, 278 Vascular, 8, 74, 97, 145, 146, 155, 159, 246, 250, 254, 262, 275, 278 Vasculitis, 259, 278 Vasodilation, 215, 278 VE, 172, 279 Vector, 31, 259, 279 Vein, 7, 24, 112, 117, 172, 246, 248, 257, 263, 272, 279 Vena, 279 Venous, 231, 265, 279 Venules, 221, 222, 254, 279 Vesicular, 243, 254, 279 Veterinary Medicine, 185, 279 Vinblastine, 277, 279 Vincristine, 277, 279 Vinyl Chloride, 61, 62, 139, 279 Viral Hepatitis, 4, 11, 13, 16, 56, 99, 136, 147, 155, 156, 158, 161, 163, 164, 174, 279 Viral Load, 14, 20, 115, 279 Viremia, 14, 279 Virulence, 219, 276, 279 Vitro, 15, 57, 67, 242, 279 Vivo, 19, 27, 31, 32, 60, 130, 131, 279 Vulgaris, 129, 279 W Weight Gain, 237, 279 White blood cell, 121, 217, 250, 251, 252, 255, 261, 279 Windpipe, 260, 275, 279 Withdrawal, 225, 280 Wound Healing, 238, 252, 280 X Xenograft, 217, 277, 280 X-ray, 112, 113, 228, 238, 239, 248, 255, 257, 266, 267, 269, 280 Y Yeasts, 238, 261, 280 Yttrium, 47, 57, 280 Z Zalcitabine, 249, 280 Zymogen, 265, 280

Index 295

296 Liver Cancer