HEPATOCELLULAR CARCINOMA – BASIC RESEARCH pot

HEPATOCELLULAR CARCINOMA – BASIC RESEARCH Edited by Wan-Yee Lau Hepatocellular Carcinoma – Basic Research Edited by Wan-Yee Lau Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Vedran Greblo Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Hepatocellular Carcinoma – Basic Research, Edited by Wan-Yee Lau p. cm. ISBN 978-953-51-0023-2 Contents Preface IX Part 1 Biomarker / Therapeutic Target 1 Chapter 1 LAPTM4B: A Novel Diagnostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma 3 Rou Li Zhou Chapter 2 Novel Therapeutic Targets for Hepatocellular Carcinoma Treatment 35 Yangchao Chen and Chi Han Li Chapter 3 Clinical Significance of Serum Ornithine Carbamoyltransferase in Liver Diseases – Is the Ratio of OCT/ALT a New Tumor Marker? 61 Katsutoshi Tokushige, Etsuko Hashimoto, Noriko Matsushita, Nobuyuki Torii, Makiko Taniai, Keiko Shiratori and Hiroshi Maruyama Chapter 4 New Molecular Biomarkers Candidates for the Development of Multiparametric Platforms for Hepatocellular Carcinoma Diagnosis, Prognosis and Personalised Therapy 73 Annalucia Serafino and Pasquale Pierimarchi Part 2 Carcinogenesis / Invasion / Metastasis 101 Chapter 5 Modulation of Cell Proliferation Pathways by the Hepatitis B Virus X Protein: A Potential Contributor to the Development of Hepatocellular Carcinoma 103 Jessica C. Casciano, Sumedha Bagga, Bei Yang and Michael J. Bouchard Chapter 6 Vascular Adhesion Protein-1 and Hepatocellular Cancer 153 Ozgur Kemik, Ahu Sarbay Kemik and A. Cumhur Dulger VI Contents Chapter 7 Tissue Factor Pathway Inhibitor-2 Inhibits the Growth and Invasion of Hepatocellular Carcinoma Cells and is Inactivated in Human Hepatocellular Carcinoma 161 Yong Xu, Xiaolin Qin, Jinjing Zhou, Zhiguang Tu, Xiao Bi, Wuxian Li, Xiaoqing Fan and Yi Zhang Chapter 8 Proteoglycans in Chronic Liver Disease and Hepatocellular Carcinoma: An Update 171 Péter Tátrai and Ilona Kovalszky Chapter 9 Chemically Induced Hepatocellular Carcinoma and Stages of Development with Biochemical and Genetic Modulation: A Special Reference to Insulin-Like-Growth Factor II and Raf Gene Signaling 201 Biswajit Mukherjee, Miltu Kumar Ghosh and Chowdhury Mobaswar Hossain Chapter 10 Hepatocellular Carcinoma: Insights from the Centrosome Abnormalities 219 Ying Chen and Qingzhong Kong Chapter 11 Cytoplasmic Connexin32 and Self-Renewal of Cancer Stem Cells: Implication in Metastasis 235 Yasufumi Omori, Yohei Kawasaki, Qingchang Li, Toshiaki Yoshioka, Yohei Yamamoto and Katsuhiko Enomoto Chapter 12 The Involvement of the ERK-Hypoxia-Angiogenesis Signaling Axis and HIF-1 in Hepatocellular Carcinoma 253 Ilias Mylonis and George Simos Chapter 13 Gap Junction Intercellular Communication and Connexin Expression Profile in Normal Liver Cells and Hepatocarcinoma 275 Glaucia M. Machado-Santelli and Marisa Ionta Chapter 14 Mechanisms of HBx Mediated Liver Cancer: Multiple Pathways and Opportunities 287 Mark A. Feitelson, Alla Arzumanyan, Tiffany Friedman, N. Lale Tufan, Zhaorui Lian, Marcia M. Clayton, Joyce Kang, Helena M. G. P. V. Reis, Jingbo Pan, Jie Liu, Patrick Arbuthnot and Michael Kew Chapter 15 Molecular Mechanism of DNA Damage Response Pathway During Hepatic Carcinogenesis 313 Yasunobu Matsuda and Toshifumi Wakai Part 3 Detection / Prevention / Prevalence 325 Chapter 16 Hepatocellular Carcinoma: Methods of Circulating Tumor Cells (CTC) Measurements 327 Natalia Olaya and Franck Chiappini Contents VII Chapter 17 Use of a Human–Derived Liver Cell Line for the Detection of Protective Effect of Dietary Antioxidants Against Food Mutagens 357 Paloma Morales and A.I. Haza Chapter 18 Reviews on the Epidemiology, Quality of Life, and Management of Chronic Hepatitis B (CHB) 373 Elegance T.P. Lam and Cindy L.K. Lam Preface Hepatocellular Carcinoma represents a leading cause of cancer death and a major health problem in developing countries. It has also become increasingly important with the increase in hepatitis C infection in developed countries. Knowledge of hepatocellular carcinoma has progressed rapidly. This book is a compendium of papers written by experts to present the most up-to-date knowledge of hepatocellular carcinoma. We have decided to divide this book on Hepatocellular Carcinoma into two books because of the overwhelming number of excellent book chapters we received from scientists and clinicians from all parts of the world:- Hepatocellular Carcinoma – Basic Research, and Hepatocellular Carcinoma – Clinical Research. Hepatocellular Carcinoma – Basic Research is divided into three sections: (I) Biomarkers / Therapeutic Target; (II) Carcinogenesis / Invasion / Metastasis; and (III) Detection / Prevention / Prevalence. There are 18 chapters in this book. This book is an important contribution to the field of hepatocellular carcinoma with an emphasis on basic research. The intended readers of this book are scientists and clinicians who are interested in research on hepatocellular carcinoma. Epidemiologists, pathologists, hospital administrators and drug manufacturers will also find this book useful. Dr. Wan-Yee Lau Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China [...]... iv) (c) Positive correlation between LAPTM4B mRNA levels and tumor grades Each spot in the figure represents the ratio of tumor vs paired noncancerous liver tissue (T/N) of the LAPTM4B mRNA expression evaluated by Northern blot These spots derived from 55 HCC patients (Shao et al., 2003) 8 Hepatocellular Carcinoma – Basic Research Fig 5 Expression of LAPTM4B-35 and LAPTM4B-24 protein identified by Western... and open a novel avenue for overcoming multi-drug resistance in chemotherapy by targeting LAPTM4B-35 24 Hepatocellular Carcinoma – Basic Research 3.6 Over-expression of LAPTM4B-35 activates a signaling network associated with carcinogenesis Over-expression of LAPTM4B-35 in liver and hepatocellular carcinoma cell lines enhances a wide range of malignant cellular and molecular phenotypes The mechanism... autophagocytosis, and abolishes carcinogenicity of hepatocellular carcinoma cells LAPTM4B-24 is an isoform encoded by the LAPTM4B gene It is a truncated form of LAPTM4B-35 by lacking a 91 amino acid sequence at the N-terminus (Shao et al., 2003) We have demonstrated that up-regulation of LAPTM4B-24 via transfection with plasmids 26 Hepatocellular Carcinoma – Basic Research pcDNA-BE or infection with replication-deficient... are susceptible to primary hepatocellular carcinoma This may be of importance for the assessment and prevention of developing hepatocellular carcinoma in high risk populations, in particular for the patients with liver cirrhosis of small liver nodule from HBV and HCV chronic infection (Shao et al., LAPTM4B: A Novel Diagnostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma 11 unpublished... for IHC (original magnification 200X) (d) Kaplan–Meier survival curves plotted with SPSS 16.0 (n=6) LAPTM4B-35 up-regulation shortened the live span of mice challenged with L02-Ad-AE cells, as compared to the control group infected by Ad-null, the empty Ad vectors P=0.049 L02-Ad-AE versus L02-Ad-Null (Lily et al., 2011) 14 Hepatocellular Carcinoma – Basic Research Fig 8 LAPTM4B-35 promotes tumor growth... resistance has also been demonstrated in breast cancer (Hu, 2009; Y.Li., 2010) and ovarian cancer (Yin, 2011a) by other research groups Y Li et al (2010) demonstrated that amplification of LAPTM4B and YWHAZ, which was shown by fluorescence in situ 22 Hepatocellular Carcinoma – Basic Research Fig 15 LAPTM4B-35 motivates multi-drug efflux by interaction with P-gp (a) Upper panel: The LAPTM4B-35 over-expressing... cDNA (NM_018407, ID=55353, Figure 1) harboring this fragment was performed by Expressed Sequence Tag (EST) splicing, 5’ rapid amplification 4 Hepatocellular Carcinoma – Basic Research of cDNA ends (FACE) and reverse transcription-polymerase chain reaction (RT–PCR) Based on the lysosome-targeting signal (YXXΦ) found on the encoded protein this gene was originally designated by the HUGO Gene Nomenclature... Biomarker and Therapeutic Target for Hepatocellular Carcinoma 25 or platform of signal molecules which functions at signal network upstream Further investigation of this point will greatly improve our understanding on hepatocarcinogenesis, metastasis and recurrence of hepatocellular carcinoma, and will thus provide novel strategies for targeted chemotherapy of hepatocellular carcinoma Overall our studies... encodes would be pivotal diagnostic biomarkers and therapeutic targets for hepatocellular carcinoma 2 LAPTM4B: A novel gene associated with hepatocellular carcinoma 2.1 Identification and cloning of the LAPTM4B gene To search for genes involved in deregulation of proliferation and aberrant differentiation for hepatocellular carcinoma, fluorescent-differential display was performed using human liver... have potential for hepatocarcinogenesis and metastasis In addition, the HepG2 cell line which originated from human hepatoblastoma and the BEL7402 cell line which originated from human hepatocellular carcinoma were used for generating upregulated and down-regulated cell models to study the effects of LAPTM4B-35 on tumor LAPTM4B: A Novel Diagnostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma . all parts of the world:- Hepatocellular Carcinoma – Basic Research, and Hepatocellular Carcinoma – Clinical Research. Hepatocellular Carcinoma – Basic Research is divided into three sections:. HEPATOCELLULAR CARCINOMA – BASIC RESEARCH Edited by Wan-Yee Lau Hepatocellular Carcinoma – Basic Research Edited by Wan-Yee Lau . field of hepatocellular carcinoma with an emphasis on basic research. The intended readers of this book are scientists and clinicians who are interested in research on hepatocellular carcinoma.