published_or_final_version / abstract / toc / Surgery / Master / Master of Philosophy

by Chan Hoi Tak. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 129-137). / Abstracts in English and Chinese. / Acknowledgment --- p.i / Abstract --- p.ii / Abstract (Chinese Version) --- p.iv / Abbreviations --- p.vi / Contents --- p.viii / Chapter CHAPTER ONE --- INTRODUCTION --- p.1 / Chapter 1.1 --- Aflatoxins --- p.1 / Chapter 1.1.1 --- AFB1 Metabolism --- p.5 / Chapter 1.1.2 --- Bioactivation --- p.5 / Chapter 1.1.3 --- Detoxification --- p.8 / Chapter 1.1.4 --- Toxicity of AFB1 --- p.9 / Chapter 1.2 --- Licorice Plants --- p.11 / Chapter 1.2.1 --- Glycyrrhizic Acid (GA) --- p.13 / Chapter 1.2.2 --- Metabolism of GA --- p.16 / Chapter 1.2.3 --- Adverse Effects of GA --- p.19 / Chapter 1.3 --- Aim of Research --- p.19 / Chapter CHAPTER TWO --- MATERIALS AND METHODS --- p.21 / Chapter 2.1 --- Cell cultures --- p.21 / Chapter 2.1.1 --- Isolation of splenocytes --- p.21 / Chapter 2.1.2 --- Culture of cell lines --- p.22 / Chapter 2.1.3 --- Trypsinziation of cells --- p.22 / Chapter 2.2 --- Preparation of drugs --- p.23 / Chapter 2.2.1 --- Preparation of commercially available chemicals for cell culture --- p.23 / Chapter 2.2.2 --- Preparation of Licorice extracts for cell culture --- p.23 / Chapter 2.2.3 --- Preparation of chemicals for enzymatic reaction --- p.24 / Chapter 2.3 --- Cytotoxicity assay Methods --- p.24 / Chapter 2.3.1 --- MTT assay --- p.25 / Chapter 2.3.2 --- Neutral red assay --- p.25 / Chapter 2.4 --- Cytotoxicity Assay --- p.32 / Chapter 2.5 --- Chemoprotection assay --- p.32 / Chapter 2.5.1 --- Direct addition of drugs --- p.33 / Chapter 2.5.2 --- Pretreatment of cells --- p.33 / Chapter 2.5.3 --- Culture of cells with drugs --- p.34 / Chapter 2.6 --- Preparation of enzymes --- p.36 / Chapter 2.6.1 --- Preparation of cells --- p.36 / Chapter 2.6.2 --- Pretreatment of rat microsomes --- p.36 / Chapter 2.7 --- Bradford Assay --- p.37 / Chapter 2.8 --- Alkoxyresorufin O-Dealkylase assay --- p.39 / Chapter 2.8.1 --- Effects of AFB1 on P450 --- p.44 / Chapter 2.8.2 --- Effects of drugs on P450 --- p.44 / Chapter 2.9 --- Glutathione-S-transferase assay --- p.44 / Chapter 2.9.1 --- GST assay in rat microsomal fractions --- p.48 / Chapter 2.9.1.1 --- Effects of AFB1 on GST --- p.48 / Chapter 2.9.1.2 --- Effects of drugs on GST --- p.48 / Chapter 2.9.2 --- GST assay in crude fractions from cells --- p.48 / Chapter 2.9.2.1 --- Direct addition effects of drugs on GST --- p.48 / Chapter 2.9.2.2 --- Effects of drug-containing medium on GST --- p.49 / RESULTS / Chapter CHAPTER THREE --- CELL CULTURES --- p.50 / Chapter 3.1 --- Cytotoxicity assay --- p.51 / Chapter 3.1.1 --- Cytotoxicity of AFB1 --- p.51 / Chapter 3.1.1.1 --- Cytotoxicity of AFB1 to splenocytes --- p.51 / Chapter 3.1.1.2 --- Cytotoxicity of AFB1 to cell lines --- p.57 / Chapter 3.1.2 --- Cytotoxicity of drugs to cell lines --- p.62 / Chapter 3.2 --- Chemoprotection assay --- p.73 / Chapter 3.2.1 --- Direct addition of drugs --- p.73 / Chapter 3.2.2 --- Pretreatment of cells with drugs --- p.78 / Chapter 3.2.3 --- Culture of cells with drugs --- p.83 / Chapter CHAPTER FOUR --- ENZYMATIC ASSAYS --- p.87 / Chapter 4.1 --- Alkoxyresorufin O-dealkylase assay --- p.88 / Chapter 4.1.1 --- Effects of AFB1 on P450s --- p.88 / Chapter 4.1.2 --- Effects of GA on P450s --- p.92 / Chapter 4.1.3 --- Effects of EX on P450s --- p.95 / Chapter 4.2 --- Glutathione -S- transferase assay --- p.98 / Chapter 4.2.1 --- Effects of drugs on GST in cells --- p.100 / Chapter 4.2.2 --- Effects of AFB1 and drugs on GST from rats --- p.108 / Chapter 4.2.2.1 --- Effects of AFB1 on GST from rats --- p.108 / Chapter 4.2.2.2 --- Effects of drugs on GST from rats --- p.112 / Chapter CHAPTER FIVE --- DISCUSSION --- p.115 / Chapter 5.1 --- Cytotoxicity of AFB1 --- p.118 / Chapter 5.2 --- "Cytotoxicity of EX, GA and AA" --- p.119 / Chapter 5.3 --- Chemoprotection of GA and EX on AFB1 cytotoxicity --- p.121 / Chapter 5.4 --- Effects of GA and EX on enzymes involved in AFB1 metabolism --- p.123 / REFERENCES --- p.129

Lee, Ngan Hon. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 120-133). / Abstracts in English and Chinese. / Acknowledgements --- p.IV / Abstract --- p.V / 論文摘要 --- p.VII / Table of Contents --- p.IX / List of Figures --- p.XI / List of Abbreviations --- p.XIII / Chapter 1 Introduction --- p.1 / Chapter 1.1 --- Hepatocellular carcinoma (HCC) --- p.1 / Chapter 1.1.1 --- Risk factors --- p.1 / Chapter 1.1.2 --- Molecular mechanism of HCC --- p.4 / Chapter 1.1.3 --- Treatment of HCC --- p.7 / Chapter 1.2 --- Gambogic acid (GA) - a compound derived from Tradition Chinese Medicine (TCM) --- p.9 / Chapter 1.2.1 --- Traditional Chinese Medicine (TCM) --- p.9 / Chapter 1.2.2 --- Gambogic acid --- p.13 / Chapter 1.3 --- Molecular mechanism of apoptosis --- p.18 / Chapter 1.3.1 --- Overview of apoptosis --- p.18 / Chapter 1.3.2 --- Caspases cascade --- p.18 / Chapter 1.3.3 --- Bcl-2 family --- p.20 / Chapter 1.3.4 --- Mitochondria in apoptosis --- p.23 / Chapter 1.4 --- Apoptosis as a strategy for cancer therapies --- p.26 / Chapter 1.5 --- Aims of study --- p.29 / Chapter Chapter 2 --- Materials and Methods --- p.30 / Chapter 2.1 --- Cell culture and treatment --- p.30 / Chapter 2.1.1 --- Cell lines used --- p.30 / Chapter 2.1.2 --- Gambogic acid (GA) --- p.31 / Chapter 2.1.3 --- Chemicals and reagents --- p.31 / Chapter 2.1.4 --- Preparation of solutions --- p.32 / Chapter 2.1.5 --- Procedures --- p.33 / Chapter 2.2 --- Apoptotic detection --- p.35 / Chapter 2.2.1 --- Chemicals and reagents --- p.35 / Chapter 2.2.2 --- Preparation of solutions --- p.35 / Chapter 2.2.3 --- Procedures --- p.37 / Chapter 2.3 --- Effects of GA on gene expression in HepG2 --- p.41 / Chapter 2.3.1 --- Chemicals and Reagents --- p.41 / Chapter 2.3.2 --- Preparation of solutions --- p.41 / Chapter 2.3.3 --- Procedures --- p.43 / Chapter 2.4 --- Protein expression in GA-induced apoptotic cells --- p.51 / Chapter 2.4.1 --- Chemicals and Reagents --- p.51 / Chapter 2.4.2 --- Preparation of solution --- p.51 / Chapter 2.4.3 --- Procedures --- p.54 / Chapter 2.5 --- Caspase cascade study in GA-induced apoptosis --- p.60 / Chapter 2.5.1 --- Chemicals and reagents --- p.60 / Chapter 2.5.2 --- Procedures --- p.60 / Chapter 2.6 --- Downregulation of mRNA using siRNA vector --- p.62 / Chapter 2.6.1 --- siRNA expression vector --- p.62 / Chapter 2.6.2 --- Chemicals and Reagents --- p.63 / Chapter 2.6.3 --- Preparation of solution --- p.63 / Chapter 2.6.4 --- Procedures --- p.64 / Chapter Chapter 3 --- Results --- p.71 / Chapter 3.1 --- GA induces apoptosis in hepatocellular cells --- p.71 / Chapter 3.2 --- Effects of gene expression in HCC --- p.80 / Chapter 3.3 --- Caspase cascade studies in GA-induced apoptosis --- p.83 / Chapter 3.4 --- Caspase 8 activation in GA-treated cells lead to Bid cleavage --- p.89 / Chapter 3.5 --- GA induces Bax conformational changes and cytochrome c release --- p.95 / Chapter 3.6 --- Levels of protein players involved in apoptosis and cell cycle --- p.101 / Chapter Chapter 4 --- Discussion --- p.106 / References --- p.120

Siu, Yeung Tung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 65-75). / Abstracts in English and Chinese. / Title Page --- p.i / Abstract in English --- p.ii / Abstract in Chinese --- p.iii / Acknowledgement --- p.iv / Table of Contents --- p.v-viii / List of Figures --- p.ix / List of Tables --- p.x / Abbreviations --- p.xi-xii / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Growth factors involved in hepatocytes proliferation --- p.1-6 / Chapter 1.1.1 --- Hepatocyte growth factor (HGF) --- p.1 / Chapter 1.1.2 --- Tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6) --- p.2 / Chapter 1.1.3 --- Epidermal growth factor (EGF) and transforming growth factor-α (TGF-α) --- p.3 / Chapter 1.1.4 --- Other comitogens --- p.4 / Chapter 1.1.5 --- Transforming growth factor-β (TGF-β) --- p.5 / Chapter 1.2 --- Bone marrow stromal cells and hepatocytes proliferation --- p.7-12 / Chapter 1.2.1 --- Role of bone marrow stromal cells in bone marrow --- p.7 / Chapter 1.2.2 --- Bone marrow as a source of hepatic oval cells --- p.8 / Chapter 1.2.3 --- Growth factors secreted by bone marrow stromal cells involved in hepatocytes proliferation --- p.9 / Chapter 1.2.4 --- Endocrine in hepatocytes proliferation --- p.12 / Chapter 1.3 --- Objective of this study --- p.13-15 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1 --- Cell cultures --- p.16 / Chapter 2.2 --- Selection of human hepatic cell line for the detection of mitogenic activity --- p.17-18 / Chapter 2.2.1 --- "Enrichment of human hepatic cell lines, Hep 3B, Hep G2, C3A, SK-Hep-1 and Chang cells at G0-G1 phases by serum deprivation" --- p.17 / Chapter 2.2.2 --- "Incubation of serum deprived Hep 3B, Hep G2, C3A, SK- Hep-1 and Chang cells with mitogenic stimuli" --- p.17 / Chapter 2.2.3 --- Cell cycle analysis by flow cytometry using propidium iodide staining --- p.17 / Chapter 2.3 --- "Detection of mitogenic activity of human bone marrow stromal cells on the selected cell line, SK-Hep-1 cells" --- p.18-20 / Chapter 2.3.1 --- Partially growth arrested human SK-Hep-1 cells --- p.18 / Chapter 2.3.2 --- Human bone marrow stromal cells --- p.19 / Chapter 2.3.2.1 --- Bone marrow stromal cellular extract --- p.19 / Chapter 2.3.2.2 --- Total protein assay --- p.19 / Chapter 2.3.3 --- Incubation of SK-Hep-1 cells with bone marrow stromal cellular extracts --- p.20 / Chapter 2.4 --- Characterization of hepatocyte mitogenic activity of bone marrow stromal cellular extract --- p.21-22 / Chapter 2.4.1 --- Dialysis --- p.21 / Chapter 2.4.2 --- Temperature treatment --- p.21 / Chapter 2.4.3 --- Proteolysis --- p.22 / Chapter 2.5 --- Performing a preliminary test on the difference between bone marrow stromal cellular extract and other growth factors --- p.22-26 / Chapter 2.5.1 --- Incubation of SK-Hep-1 cells with bone marrow stromal cellular extract or other growth factors --- p.22 / Chapter 2.5.2 --- Metabolic labeling of SK-Hep-1 cells with [32P]orthophosphate --- p.23 / Chapter 2.5.3 --- Incubation of labeled SK-Hep-1 cells with bone marrow stromal cellular extract or other growth factors --- p.23 / Chapter 2.5.4 --- SK-Hep-1 cells lysate extraction --- p.23 / Chapter 2.5.5 --- Two-dimensional electrophoresis --- p.24 / Chapter 2.5.5.1 --- First dimension isoelectric focusing --- p.24 / Chapter 2.5.5.2 --- Second dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis --- p.25 / Chapter 2.5.6 --- Amplification of radiolabeled signal by EN3HANCE --- p.25 / Chapter 2.5.7 --- Visualization of autoradiography --- p.26 / Chapter 2.5.8 --- Visualization by silver staining --- p.26 / Chapter Chapter 3 --- Results / Chapter 3.1 --- Selection of human hepatic cell line for the detection of mitogenic activity --- p.27-30 / Chapter 3.1.1 --- "Enrichment of human hepatic cell lines, Hep 3B, Hep G2, C3A, SK-Hep-1 and Chang cells at G0-G1 phases by serum deprivation" --- p.27 / Chapter 3.1.2 --- DNA synthesis of hepatic cell lines in response to 10 % FBS after serum deprivation --- p.29 / Chapter 3.2 --- "Detection of mitogenic activity of human bone marrow stromal cells on the selected cell line, SK-Hep-1 cells" --- p.31-39 / Chapter 3.2.1 --- Cell cycle distribution of partially growth arrested SK-Hep-1 cells in response to mitogens --- p.31 / Chapter 3.2.2 --- Time course on DNA synthesis of partially growth arrested SK-Hep-1 cells in response to FBS and bone marrow stromal cellular extract --- p.36 / Chapter 3.2.3 --- Dose response on DNA synthesis of partially growth arrested SK-Hep-1 cells in response to bone marrow stromal cellular extracts --- p.38 / Chapter 3.3 --- Characterization of hepatocyte mitogenic activity of bone marrow stromal cellular extract --- p.40-44 / Chapter 3.4 --- Performing a preliminary test on the difference between bone marrow stromal cellular extract and other growth factors --- p.45-49 / Chapter 3.4.1 --- Mitogenic response of SK-Hep-1 cells in response to bone marrow stromal cellular extract and other growth factors --- p.45 / Chapter 3.4.2 --- Early intracellular signaling of SK-Hep-1 cells in response to bone marrow stromal cellular extract and other growth factors --- p.47 / Chapter Chapter 4 --- Discussion / Chapter 4.1 --- Selection of human hepatic cell line for the detection of mitogenic activity --- p.50 / Chapter 4.2 --- "Mitogenic activity of human bone marrow stromal cells on the selected cell line, SK-Hep-1 cells" --- p.51 / Chapter 4.3 --- Characterization of hepatocyte mitogenic activity of bone marrow stromal cellular extract --- p.52 / Chapter 4.4 --- Performing a preliminary test on the difference between bone marrow stromal cellular extract and other growth factors --- p.53 / Chapter 4.5 --- Possible directions for future investigation --- p.55 / Chapter 4.6 --- Conclusions --- p.56 / Chapter Chapter 5 --- Appendices / Chapter 5.1 --- Reagents and solutiuons --- p.57-64 / Chapter 5.1.1 --- Selection of human hepatic cell line for the detection of mitogenic activity --- p.57 / Chapter 5.1.2 --- "Detection of mitogenic activity of human bone marrow stromal cells on the selected cell line, SK-Hep-1 cells" --- p.59 / Chapter 5.1.3 --- Characterization of hepatocyte mitogenic activity of bone marrow stromal cellular extract --- p.60 / Chapter 5.1.4 --- Performing a preliminary test on the difference between bone marrow stromal cellular extract and other growth factors --- p.61 / Chapter Chapter 6 --- References --- p.65-75

To, Ka Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (p. 115-120). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Abstract --- p.ii / 中文摘要 --- p.vi / List of abbreviations --- p.ix / List of tables --- p.xii / List of figures --- p.xiii / Contents --- p.xvi / Chapter Chapter One: --- General introduction --- p.1 / Chapter 1.1 --- Background of Hepatocellular carcinoma (HCC) --- p.2 / Chapter 1.2.1 --- ZBP-89 structure and its expression in cancers --- p.3 / Chapter 1.2.2 --- Transcriptional regulation of ZBP-89 --- p.5 / Chapter 1.3.1 --- Apoptosis and necrosis --- p.6 / Chapter 1.3.2 --- Mechanisms of Apoptosis --- p.7 / Chapter 1.4 --- Bcl-2 family --- p.11 / Chapter 1.5 --- Regulation of p53 cancer cells --- p.12 / Chapter 1.6 --- The aim of the study --- p.13 / Chapter Chapter Two: --- Up-regulation of Bak expression by Ad-ZBP-89 induce apoptosis in human liver cancer cells --- p.15 / Chapter 2.1. --- Introduction --- p.16 / Chapter 2.2. --- Materials and methods --- p.18 / Chapter 2.2.1. --- Cell culture --- p.18 / Chapter 2.2.2. --- RT-PCR --- p.19 / Chapter 2.2.3. --- Western blotting --- p.21 / Chapter 2.2.4. --- Adenovirus infection and Cell viability assay --- p.24 / Chapter 2.2.5. --- Detection of apoptosis --- p.26 / Chapter 2.2.6. --- RNA interference --- p.27 / Chapter 2.2.7. --- Statistical analysis --- p.29 / Chapter 2.3. --- Results --- p.30 / Chapter 2.3.1. --- Endogenous expression of ZBP-89 and Bak of human liver cancer cells --- p.30 / Chapter 2.3.2. --- Effects of Ad-ZBP-89 on proliferation in HCC cell lines --- p.31 / Chapter 2.3.3. --- Effects of Ad-ZBP-89 on the expression of Bcl-2 family members --- p.34 / Chapter 2.3.4. --- ZBP-89 induced Bak expression and release of cytochrome c --- p.39 / Chapter 2.3.5. --- Effects of Ad-ZBP-89 on apoptosis rate in HCC cell lines --- p.41 / Chapter 2.3.6. --- Effects of ZBP-89 siRNA on expression of Bcl-2 family members and proliferation in HCC cell lines --- p.43 / Chapter 2.3.7. --- Effects of Bak siRNA and its combined effect with Ad-ZBP-89 on the expression of Bak and reduced apoptosis in HCC cell lines --- p.50 / Chapter 2.4. --- Discussion --- p.55 / Chapter Chapter Three: --- Identification of ZBP-89 protein as an apoptosis activator for a pro-apoptotic Bak gene promoter --- p.60 / Chapter 3.1. --- Introduction --- p.61 / Chapter 3.2. --- Materials and methods --- p.64 / Chapter 3.2.1. --- Cell lines and tissues --- p.64 / Chapter 3.2.2. --- Transient transfection and Luciferase activity assay --- p.64 / Chapter 3.2.3. --- pGL3-Bak-promoter vector construction --- p.67 / Chapter 3.2.4. --- "Preparation of mitochondrial, cytosolic and nuclear fractions" --- p.74 / Chapter 3.2.5. --- Electrophoretic mobility shift assay --- p.75 / Chapter 3.2.6. --- Overexpression of Bak --- p.76 / Chapter 3.2.7. --- RT-PCR and Western blot analysis on HCC tissues samples --- p.80 / Chapter 3.2.8. --- Statistical Analysis --- p.80 / Chapter 3.3. --- Results --- p.81 / Chapter 3.3.1. --- ZBP-89 activates Bak-luciferase promoter genes in HCC cells --- p.81 / Chapter 3.3.2. --- ZBP-89 activates shortened Bak-luc-promoter in PLC/PRF/5 and SK-Hep-1 cells --- p.82 / Chapter 3.3.3. --- ZBP-89 is a potential binding protein to the Bak promoter gene region -457/-407 --- p.85 / Chapter 3.3.4. --- The combined effects of Bak overexpression and Ad-ZBP-89 induce apoptosis in HCC cells --- p.89 / Chapter 3.3.5. --- The combined effects on Bak protein expression --- p.94 / Chapter 3.3.6. --- Bak expression in HCC tissues --- p.98 / Chapter 3.4. --- Discussion --- p.99 / Chapter Chapter Four: --- Conclusion and Future Perspectives --- p.104 / Chapter 4.1. --- Conclusion --- p.104 / Chapter 4.2. --- Future Perspectives --- p.112 / Reference --- p.113

Zhu, Jinyong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 128-139). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Wong, Chi Bun. / Thesis submitted in: Nov 2006. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 116-127). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / 摘要 --- p.v / Abbreviations --- p.vii / List of Table and Figures --- p.ix / Table of Contents --- p.x / Chapter Chapter 1 --- p.1 / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Identification of the proteins regulated by BRE when BRE was over-expressed or silencedin C2C12 and D122 --- p.1 / Chapter 1.1.1 --- What is BRE? --- p.1 / Chapter 1.1.2 --- BRE gene is Highly Conserved --- p.2 / Chapter 1.1.3 --- BRE binds to the Intracellular Domain of TNFR1 and Fas --- p.3 / Chapter 1.1.4 --- BRE Suppresses Apoptosis --- p.4 / Chapter 1.1.5 --- "BRE forms a Holoenzyme Complex with BRCA1, BARD1 and BRCC36" --- p.4 / Chapter 1.16 --- Roles of the Differentially Expressed Proteins Identified in the siRNA knockdown Experiments --- p.5 / Chapter 1.1.6.1 --- Akt3 --- p.5 / Chapter 1.1.6.2 --- Mdm2/4 --- p.6 / Chapter 1.1.6.3 --- Prohibitin --- p.7 / Chapter 1.1.6.4 --- Carbonic Anhydrase III --- p.8 / Chapter 1.1.6.5 --- 26S Proteasome --- p.8 / Chapter 1.2 --- The Role of BRE in Liver: a morphological approach --- p.9 / Chapter 1.2.1 --- The General Structure of the Liver. --- p.9 / Chapter 1.2.2 --- The Essential Functions of the Liver --- p.11 / Chapter 1.2.3 --- Inflammation of the Liver --- p.11 / Chapter 1.2.3.1 --- Hepatitis --- p.11 / Chapter 1.2.3.2 --- Acute Hepatitis --- p.12 / Chapter 1.2.3.3 --- Chronic Hepatitis --- p.12 / Chapter 1.2.4 --- Necrosis and Apoptosis --- p.13 / Chapter 1.2.5 --- The Apoptotic Pathway --- p.14 / Chapter 1.2.6 --- Hepatic Necrosis is Divided into Different Zones --- p.16 / Chapter 1.2.6.1 --- Hepatitis Necrosis is Categorized into 3 Zones --- p.16 / Chapter 1.2.7 --- Carbon Tetrachloride (CCL4) --- p.16 / Chapter 1.2.8 --- TNFa is a Pleiotropic Cytokine --- p.17 / Chapter 1.3 --- The Objectives of This Project --- p.20 / Chapter Chapter 2 --- p.21 / Chapter 2. --- Materials and Methods --- p.21 / Chapter 2.1 --- Animals --- p.21 / Chapter 2.2 --- Adminstration of Carbon Tetrachloride and Corn Oil --- p.21 / Chapter 2.3 --- Cell Cultures --- p.22 / Chapter 2.4 --- Cell Culturing --- p.22 / Chapter 2.5 --- Gene Silencing with Small Interfering RNA (siRNA) --- p.23 / Chapter 2.5.1 --- Transfection with BRE siRNA --- p.24 / Chapter 2.6 --- Cell Proliferation Assays --- p.24 / Chapter 2.7 --- In-Situ Hybridization of BRE Sense and Antisense Probes --- p.25 / Chapter 2.8 --- Immunohistological Staining --- p.26 / Chapter 2.9 --- Semi-Quantitative RT-PCR --- p.28 / Chapter 2.10 --- Comparative Proteomics --- p.29 / Chapter 2.10.1 --- Sample Preparation for Two Dimensional Gel Electrophoresis --- p.29 / Chapter 2.10.2 --- Two Dimensional Polyacrylamide Gel Electrophoresis --- p.30 / Chapter 2.10.3 --- In-Gel Digestion and MALDI-TOF Analysis --- p.31 / Chapter 2.11 --- Western Blotting --- p.32 / Chapter 2.12 --- Flow Cytometry --- p.34 / Chapter 2.13 --- Haematoxylin and Eosin Staining (H&E) --- p.34 / Chapter Chapter 3 --- p.36 / Chapter 3. --- Results --- p.36 / Chapter 3.1 --- BRE expression in C2C12 cells --- p.36 / Chapter 3.2 --- Comparative Proteomic Profile of BRE silenced C2C12 cells --- p.41 / Chapter 3.3 --- Effect of Silencing BRE on C2C12 cell Proliferation --- p.49 / Chapter 3.4 --- Effects of BRE over-expression in D122 cells --- p.54 / Chapter 3.5 --- BRE Expression in the Liver --- p.62 / Chapter 3.5.1 --- Histological Analysis of Liver Sections after 24 hours of CCL4 Insult --- p.62 / Chapter 3.5.2 --- BRE Expression in the Liver --- p.62 / Chapter 3.6 --- Histological Study of Liver Treated with CCL4 --- p.67 / Chapter 3.7 --- BRE Expression in Experimental Liver --- p.76 / Chapter Chapter 4 --- p.92 / Chapter 4. --- Discussion --- p.92 / Chapter 4.1 --- Expression of BRE in C2C12 --- p.92 / Chapter 4.2 --- The Regulatory Function of BRE --- p.96 / Chapter 4.3 --- The Relationship Between BRE and p53 --- p.98 / Chapter 4.4 --- The Relationship Between BRE and NFkB --- p.104 / Chapter 4.5 --- BRE Expression in Normal Control and CCL4 Treated Livers --- p.105 / Chapter 4.6 --- A Possible Explanation for the Necrosis Pattern Observed --- p.107 / Chapter 4.7 --- The Relationship Between BRE and the TNF Receptors --- p.109 / Chapter Chapter 5 --- p.112 / Chapter 5. --- Conclusion and Future Prospects --- p.112 / References --- p.116