Chan Chun-pong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 171-176). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / 摘要 --- p.iii / Abbreviation --- p.iv / Table of contents --- p.v / List of figures --- p.xi / List of tables --- p.xvi / Chapter Chapter 1 --- introduction / Chapter 1.1 --- Traditional Chinese medicines (TCMs) --- p.2 / Chapter 1.2 --- Liver disorders in Asia Pacific region --- p.3 / Chapter 1.3 --- Classification of liver disorders --- p.7 / Chapter 1.3.1 --- Hepatitis --- p.8 / Chapter 1.3.1.1 --- Hepatitis A virus infection --- p.8 / Chapter 1.3.1.2 --- Hepatitis B virus infection --- p.9 / Chapter 1.3.1.3 --- Hepatitis C virus infection --- p.11 / Chapter 1.3.1.4 --- Hepatitis D virus infection --- p.12 / Chapter 1.3.1.5 --- Hepatitis E virus infection --- p.12 / Chapter 1.3.2 --- Cancer of the liver --- p.13 / Chapter 1.3.2.1 --- Hepatocellular carcinoma --- p.13 / Chapter 1.3.2.2 --- Cholangiocarcinoma --- p.14 / Chapter 1.3.2.3 --- Metastatic liver cancer --- p.14 / Chapter 1.4 --- Conventional treatment of liver disorders --- p.14 / Chapter 1.5 --- Role of traditional Chinese medicines in hepatoprotective functions --- p.16 / Chapter 1.5.1 --- Abri Herba (Abrus Cantoniensis Hance) --- p.17 / Chapter 1.5.2 --- Rhizoma Coptidis (Coptidis chinensis Franch) --- p.18 / Chapter 1.5.3 --- Fructus Forsythia (Forsythia suspense (Thunb) Vahl) --- p.22 / Chapter 1.6 --- Molecular studies of hepatoprotective effects of TCMs --- p.26 / Chapter 1.6.1 --- Roles of detoxofication enzymes in hepatoprotection --- p.27 / Chapter 1.6.2 --- Studies of growth-related genes in cell cycle control --- p.29 / Chapter 1.7 --- Aims of project --- p.32 / Chapter 1.8 --- Application of the project --- p.33 / Chapter Chapter 2 --- Methods and materials --- p.34 / Chapter 2.1 --- Screening of traditional Chinese medicines --- p.35 / Chapter 2.2 --- Preparation of TCMs --- p.35 / Chapter 2.2.1 --- Preparation of aqueous extracts of TCMs --- p.35 / Chapter 2.2.2 --- Preparation of active components of TCMs --- p.36 / Chapter 2.3 --- In vitro assays --- p.40 / Chapter 2.3.1 --- Cell culture --- p.40 / Chapter 2.3.2 --- Cytotoxicity test --- p.40 / Chapter 2.4 --- Screening of expressed gene induced by TCMs --- p.41 / Chapter 2.4.1 --- RNA preparation --- p.41 / Chapter 2.4.2 --- cDNA array hybridization --- p.42 / Chapter 2.4.3 --- Reverse Transcription --- p.43 / Chapter 2.5 --- Confirmation of expressed genes induced by TCMs --- p.44 / Chapter 2.5.1 --- Semi-quantitative PCR analysis --- p.44 / Chapter 2.5.2 --- Northern blot analysis --- p.46 / Chapter 2.6 --- Studies of effects of TCMs in gene expression --- p.47 / Chapter 2.6.1 --- Dosage-course study --- p.47 / Chapter 2.6.2 --- Time-course study --- p.48 / Chapter Chapter 3 --- Results --- p.50 / Chapter 3.1 --- "Cytotoxicity test of A.H., R.C. and F.F" --- p.51 / Chapter 3.2 --- "Molecular screening of expressed gene induced by A.H., R.C., F.F" --- p.58 / Chapter 3.3 --- Confirmation of expressed gene using semi-quantitative RT- PCR --- p.70 / Chapter 3.3.1 --- Dosage-course and time-course studies of A.H. using RT- PCR --- p.70 / Chapter 3.3.2 --- Dosage-course and time-course studies of R.C. using RT- PCR --- p.94 / Chapter 3.3.3 --- Dosage-course and time-course studies of A.H. using RT- PCR --- p.113 / Chapter 3.4 --- Confirmation of expressed gene using northern blot anaylsis --- p.118 / Chapter 3.4.1 --- Dosage-course and time-course studies of effects of A.H. and L- abrine in Northern blot analysis --- p.118 / Chapter 3.4.2 --- Dosage-course and time-course studies of effects of R.C. and berberine in Northern blot analysis --- p.129 / Chapter 3.4.3 --- Dosage-course and time-course studies of effects of F.Fin Northern blot analysis --- p.147 / Chapter Chapter 4 --- Discussion --- p.152 / Chapter 4.1 --- "Roles of A.H., R.C. and F.F. in treatment and prevention of liver disorders" --- p.153 / Chapter 4.2 --- "Cytotoxicity effect A.H., R.C., and F.F. in liver cells" --- p.153 / Chapter 4.3 --- Effects of herbal medicines on the transcription of mRNA in liver cells --- p.155 / Chapter 4.3.1 --- Effects of treatment of A.H. in liver at transcriptional level … --- p.155 / Chapter 4.3.2 --- Effects of treatment of R.C. in liver at transcriptional level … --- p.156 / Chapter 4.3.3 --- Effects of treatment of R.C. in liver at transcriptional level --- p.157 / Chapter 4.4 --- Comparison of results of RT-PCR and Northern blot analysis --- p.157 / Chapter 4.4.1 --- Comparison of the effects of time and dosage-course studies of DTD expression induced by A.H. and L-abrine --- p.157 / Chapter 4.4.2 --- Comparison of the effects of time and dosage-course studies of p21;cip;waf1 expression induced by A.H. and L-abrine --- p.158 / Chapter 4.4.3 --- Comparison of the effects of time and dosage-course studies of c-myc responsive protein; rcl expression induced by R.C. and berberine --- p.159 / Chapter 4.4.4 --- Comparison of the effects of time and dosage-course studies of GST Ya expression induced by R.C. and berberine --- p.160 / Chapter 4.4.5 --- Comparison of the effects of time and dosage-course studies of GST 7-7 expression induced by F.F --- p.160 / Chapter 4.5 --- Biochemical significance of genes induced by hepatoprotective TCMs --- p.161 / Chapter 4.5.1 --- Roles of significant expression of detoxifying enzymes induced by TCMs in liver cells --- p.161 / Chapter 4.5.2 --- Roles of induction of growth-related c-myc responsive protein; rcl in R.C. treated liver cells --- p.167 / Chapter 4.5.3 --- Roles of increased p21;cip;waf1 expression in A.H. treated liver cells --- p.168 / Chapter 4.6 --- Conclusion --- p.169

Hu, Baoguang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 121-143). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Both mRNA and protein expression levels of P-glycoprotein, one of the major factors involved in drug resistance, was decreased in Pa-treated R-HepG2 cells. The chemo-sensitivity of these MDR cells towards doxorubicin would be enhanced by pretreatment of Pa. / In the study, 35 TCMs with historical background in treating liver diseases were screened. S. barbata was chosen for intensive studies based on its significant anti-hepatoma activity. Using bioassay-guided purification approach, an active component, pheophorbide a (Pa) - a chlorophyll derivative, was isolated from Scutellaria barbata. / Motivated by the severe health hazards worldwide caused by liver cancer, and the pronounced side effects of some recent anti-hepatoma agents in clinical treatment, we have initiated a research project in screening safe and effective agents from Traditional Chinese Medicine (TCM) for the treatment of hepatoma. The main objective of this research is to define the in vitro and in vivo anti-proliferative activities and to identify the action mechanisms of a TCM, the aerial part of Scutellaria barbata , in human hepatoma cells (HepG2 and Hep3B cells). / Pa exhibited anti-proliferative effects on HepG2 and Hep3B cells, through cell-cycle arrest and apoptosis, with IC50 values being 12.5 and 25.7 muM respectively. However, Pa produced insignificant cytotoxic effect on WRL-68 cells, a normal hepatic cell line. Pa also caused cell death in R-HepG2 cells, a multi-drug resistant (MDR) cell line developed from HepG2 cells. Microarray analysis indicated that a hypothetical protein FLJ10803 was found to be down-regulated upon the treatment of Pa on HepG2 cells. The sub-cellular localization of FLJ10803 was demonstrated by over-expression of the GFP fusion protein in HepG2 cells. / The anti-tumor effects of Pa could be enhanced by photodynamic therapy (PDT) approach, presumably due to the rapid generation of reactive oxygen species in the drug-binding site. Pa-PDT showed potent cytotoxicity on hepatoma cell lines, HepG2 and Hep3B, with IC50 values being 0.4 and 1.5 muM, respectively. The antitumor effects were confirmed by studies using animal model, where Pa treatment (300mug/kg/day, s.c.) could significantly inhibit the growth of Hep3B cells in nude mice after PDT treatment in vivo. Fluorescent imaging showed that Pa was located at the mitochondria, and the induction of cell death was found to be initiated by the mitochondrial dependent apoptotic pathway. Results of 2D-gel analysis suggested that Pa-PDT activated an immune-marker expression pathway that results in an over expression of HLA class I proteinsin Pa-PDT treated HepG2 cells. / To conclude, Pa may be a candidate for further development into an anti-hepatomic agent for clinical application. / Tang, Ming Kuen. / "September 2007." / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4742. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 227-243). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Wu Xiujuan. / "May 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 294-314). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Leung, Jackie. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 117-131). / Abstract also in Chinese. / Abstract --- p.i / 論文摘要 --- p.iii / Acknowledgement --- p.iv / List of publications --- p.vi / List of Tables --- p.vi / List of Figures --- p.vi / Table of Contents --- p.ix / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1. --- Liver cancer --- p.1 / Chapter 1.1.1. --- Hepatocellular Carcinoma (HCC) --- p.2 / Chapter 1.2. --- Lung Cancer --- p.5 / Chapter 1.3. --- Pteris semipinnata L --- p.8 / Chapter 1.4. --- Extract of PsL: 5F --- p.10 / Chapter 1.5. --- Animal models in chemotherapy researches --- p.13 / Chapter 1.5.1. --- Model of HCC --- p.13 / Chapter 1.5.2. --- Model of lung cancer --- p.15 / Chapter 1.6. --- Apoptosis: Significance of programmed cell death --- p.17 / Chapter 1.6.1. --- The extrinsic pathway --- p.18 / Chapter 1.6.2. --- The intrinsic pathway --- p.19 / Chapter 1.7. --- Apoptotic molecules related to this study --- p.22 / Chapter 1.7.1. --- Bcl-2 family --- p.22 / Chapter 1.7.1.1. --- Bax --- p.22 / Chapter 1.7.1.2. --- Bcl-2 --- p.23 / Chapter 1.7.2. --- Nuclear factor kappa B --- p.25 / Chapter 1.7.3. --- Inducible nitric oxide synthase --- p.27 / Chapter 1.8. --- Side-effects of chemotherapy --- p.29 / Chapter 1.8.1. --- Chemotherapy and liver dysfunction --- p.30 / Chapter 1.8.2. --- Nephrotoxicity of chemotherapeutic agents --- p.31 / Chapter 1.9. --- Aim of study --- p.33 / Chapter Chapter 2: --- Materials and Methodology --- p.34 / Chapter 2.1. --- Animals --- p.34 / Chapter 2.1.1. --- HCC model --- p.34 / Chapter 2.1.2. --- Lung cancer model --- p.35 / Chapter 2.2. --- Tumors induction --- p.36 / Chapter 2.2.1. --- HCC induction in C3H/HeJ mice --- p.36 / Chapter 2.2.2. --- Lung cancer induction in A/J mice --- p.37 / Chapter 2.3. --- 5F preparation --- p.38 / Chapter 2.4. --- 5F treatment --- p.39 / Chapter 2.5. --- Harvest of samples and tissues --- p.41 / Chapter 2.6. --- Tumor assessment --- p.43 / Chapter 2.7. --- Investigation of apoptosis and cell proliferation --- p.44 / Chapter 2.8. --- Immunohistochemistry --- p.47 / Chapter 2.9. --- Biochemical test --- p.51 / Chapter 2.9.1. --- Liver Function Tests (LFT) --- p.52 / Chapter 2.9.1.1. --- Aspartate aminotransferase (AST) & Alanine aminotransferase (ALT) --- p.52 / Chapter 2.9.2. --- Renal Function Test (RFT) --- p.53 / Chapter 2.9.2.1. --- Serum creatinine level (CRE) --- p.53 / Chapter 2.9.2.2. --- Blood Urea Nitrogen index (BUN) --- p.54 / Chapter 2.10. --- Statistical analysis --- p.55 / Chapter Chapter 3: --- Results --- p.56 / Chapter 3.1. --- Anti-tumor effect of 5F is dose- dependent --- p.56 / Chapter 3.2. --- 5F reduces cell proliferation and induces apoptosis in-vivo --- p.60 / Chapter 3.3. --- Effects of 5F on apoptotic signaling molecules --- p.68 / Chapter 3.3.1. --- 5F up-regulates pro-apoptotic Bax and Bak --- p.68 / Chapter 3.3.2. --- 5F down-regulates anti-apoptotic NF-kappa B and Bcl-2 --- p.76 / Chapter 3.3.3. --- 5F up-regulated iNOS in HCC but not in lung cancer --- p.88 / Chapter 3.3.4. --- Regulation on Erk1/2 was associated with treatment of 5F --- p.93 / Chapter 3.4. --- Side-effect studies of 5F --- p.97 / Chapter Chapter 4: --- Discussion --- p.105 / Chapter Chapter 5: --- Conclusion --- p.116 / Bibliography --- p.117

Cheung Sao Fong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves xxiv-xxxvii). / Abstracts in English and Chinese. / Examination Committee List --- p.i / Declaration --- p.ii / Acknowledgements --- p.iii / Abstract --- p.v / Abstract in Chinese --- p.viii / List of Figures and Tables --- p.x / List of Abbreviations --- p.xix / Table of Content --- p.xxiii / Chapter Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Human Liver Cancer --- p.1 / Chapter 1.1.1 --- Incidence of Hepatocellular Carcinoma --- p.1 / Chapter 1.1.2 --- Causes and Symptoms of Hepatocellular Carcinoma --- p.4 / Chapter 1.1.3 --- Treatment Options for Hepatocellular Carcinoma --- p.4 / Chapter 1.1.4 --- Multi-drug Resistance --- p.5 / Chapter 1.1.4.1 --- Mechanisms of Multi-drug Resistance --- p.5 / Chapter 1.2 --- Traditional Chinese Medicine --- p.10 / Chapter 1.2.1 --- Sophora flavescens and Radix Sophorae --- p.10 / Chapter 1.2.2 --- Flavonoid and its Sub-classification --- p.13 / Chapter 1.2.3 --- Flavonoid and Human Health --- p.15 / Chapter 1.3 --- Cell Death --- p.17 / Chapter 1.3.1 --- Necrosis --- p.17 / Chapter 1.3.2 --- Apoptosis --- p.17 / Chapter 1.3.3 --- Signaling Pathways in Apoptosis --- p.18 / Chapter 1.3.3.1 --- Extrinsic (Death Receptor-mediated) Pathway --- p.20 / Chapter 1.3.3.2 --- Intrinsic (Mitochondrial) Pathway --- p.21 / Chapter 1.3.3.3 --- Cysteine Aspartatic Acid Proteases --- p.21 / Chapter 1.4 --- Research Objective (s) --- p.22 / Chapter Chapter 2 --- MATERIALS AND METHODS --- p.23 / Chapter 2.1 --- Materials --- p.23 / Chapter 2.1.1 --- Cell Lines --- p.23 / Chapter 2.1.1.1 --- HepG2 --- p.24 / Chapter 2.1.1.2 --- RHepG2 --- p.24 / Chapter 2.1.1.3 --- WRL-68 --- p.25 / Chapter 2.1.2 --- Culture Media --- p.26 / Chapter 2.1.2.1 --- Rosewell Park Memorial Institute( RPMl) 1640 Medium --- p.26 / Chapter 2.1.2.2 --- Dulbecco's Modified Eagle's Medium (DMEM) --- p.26 / Chapter 2.1.3 --- Animals --- p.27 / Chapter 2.2 --- Traditional Chinese Medicines and Conventional Anti-cancer Drugs --- p.27 / Chapter 2.3 --- Antibodies --- p.29 / Chapter 2.4 --- Chemicals --- p.30 / Chapter 2.5 --- Reagents and Buffers --- p.34 / Chapter 2.5.1 --- Reagents for Silica Gel Column Chromatography --- p.34 / Chapter 2.5.2 --- Buffers for Common Use --- p.34 / Chapter 2.5.3 --- Reagents for Cell Viability Assay --- p.35 / Chapter 2.5.4 --- Reagents and Buffers for Typical Apoptosis Experiments --- p.35 / Chapter 2.5.4.1 --- Cell Cycle Analysis --- p.35 / Chapter 2.5.4.2 --- Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.35 / Chapter 2.5.4.3 --- DNA Fragmentation Detection --- p.35 / Chapter 2.5.5 --- Reagents and Buffers for Western Blot Study --- p.36 / Chapter 2.5.5.1 --- Whole-cell Protein Extraction --- p.38 / Chapter 2.5.5.2 --- Mitochondrial and Cytosolic Fraction Protein Extraction --- p.38 / Chapter 2.5.6 --- Reagents and Buffers for Mitochondrial Transmembrane Potential Depolarization Measurement --- p.39 / Chapter 2.5.7 --- Reagents and Buffers for in vivo Animal Study --- p.39 / Chapter 2.5.8 --- Reagents and Buffers for Two-Dimensional Gel Electrophoresis --- p.40 / Chapter 2.5.8.1 --- Sample Preparation --- p.40 / Chapter 2.5.8.2 --- First Dimension Gel Electrophoresis - Isoelectric Focusing (IEF) --- p.40 / Chapter 2.5.8.3 --- Second Dimension Gel 日ectrophoresis - SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.40 / Chapter 2.5.8.4 --- Silver Staining --- p.41 / Chapter 2.5.9 --- Reagents for Mass Spectrometry Preparation --- p.42 / Chapter 2.5.9.1 --- Destaining --- p.42 / Chapter 2.5.9.2 --- Trypsin Digestion --- p.42 / Chapter 2.5.9.3 --- Desalting of Peptide Mixture --- p.43 / Chapter 2.5.10 --- Reagents and Buffers for Real-Time PCR --- p.43 / Chapter 2.6 --- Methods --- p.44 / Chapter 2.6.1 --- Isolation of Bioactive Constituents by Silica Gel Column Chromatography --- p.44 / Chapter 2.6.2 --- Cell Viability Assay --- p.45 / Chapter 2.6.3 --- Typical Apoptosis Experiments --- p.45 / Chapter 2.6.3.1 --- Cell Cycle Analysis --- p.46 / Chapter 2.6.3.2 --- Annexin V-FITC/ PI Staining Experiment --- p.47 / Chapter 2.6.3.3 --- Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.48 / Chapter 2.6.3.4 --- DNA Fragmentation Reaction --- p.48 / Chapter 2.6.4 --- Western Blot Study --- p.49 / Chapter 2.6.4.1 --- Whole-cell Protein Extraction --- p.49 / Chapter 2.6.4.2 --- Mitochondrial and Cytosolic Fraction Protein Extraction --- p.50 / Chapter 2.6.5 --- Caspase Activity Determination --- p.54 / Chapter 2.6.6 --- Mitochondrial Transmembrane Potential Depolarization Measurement --- p.55 / Chapter 2.6.7 --- in vivo Animal Study --- p.56 / Chapter 2.6.8 --- Two-Dimensional Gel Electrophoresis --- p.58 / Chapter 2.6.8.1 --- Sample Preparation --- p.58 / Chapter 2.6.8.2 --- First Dimension Electrophoresis - Isoelectric Focusing (IEF) --- p.59 / Chapter 2.6.8.3 --- Second Dimension Electrophoresis - SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.60 / Chapter 2.6.8.4 --- Silver Staining --- p.61 / Chapter 2.6.9 --- Mass Spectrometry Preparation --- p.63 / Chapter 2.6.9.1 --- Destaining and Trypsin Digestion --- p.63 / Chapter 2.6.9.2 --- Peptide Extraction --- p.63 / Chapter 2.6.9.3 --- Desalting of Peptide Mixture --- p.64 / Chapter 2.6.10 --- Real-Time PCR --- p.65 / Chapter 2.6.11 --- Cellular Glutathione Level Detection --- p.69 / Chapter 2.7 --- Statistical Analysis --- p.70 / Chapter Chapter 3 --- RESULTS AND DISCUSSIONS - CYTOTOXICITY OF FLAVONOIDS ISOLATED FROM RADIX SOPHORAE --- p.72 / Chapter 3.1 --- Screening of Cytotoxic Flavonoids from Radix Sophorae --- p.72 / Chapter 3.2 --- Cytotoxicity of Leachianone A on Human Hepatoma Cell Lines --- p.74 / Chapter 3.3 --- Cytotoxicity of Leachianone A on Human Normal Liver Cell Line --- p.77 / Chapter 3.4 --- Cytotoxicity of Sophoraflavone J on Human Hepatoma Cell Line --- p.79 / Chapter 3.5 --- Cytotoxicity of Sophoraflavone J on Human Normal Liver Cell Line --- p.79 / Chapter 3.6 --- Cytotoxicities of Cisplatin and Taxol on Human Hepatoma as well as Normal Liver Cell Lines --- p.81 / Chapter 3.7 --- Conclusion --- p.86 / Chapter Chapter 4 --- "RESULTS AND DISCUSSIONS - MECHANISTIC STUDY OF LEACHIANONE A-INDUCED CELL DEATH IN HEPATOMA CELLS, HepG2 and RHepG2" --- p.88 / Chapter 4.1 --- Promotion of Cell Cycle Arrest --- p.88 / Chapter 4.2 --- Induction of Apoptosis as Evidenced by Phosphatidylserine Externalization and DNA Fragmentation --- p.93 / Chapter 4.2.1 --- Occurrence of Phosphatidylserine Externalization --- p.94 / Chapter 4.2.2 --- DNA Fragmentation Detection --- p.99 / Chapter 4.2.2.1 --- Terminal Deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.99 / Chapter 4.2.2.2 --- DNA Laddering Pattern in Agarose Gel Electrophoresis --- p.103 / Chapter 4.3 --- Recruitment of Multiple Signaling Pathways in Leachianone A-induced Apoptosis --- p.105 / Chapter 4.3.1 --- "Activation of Caspases-3, -8, and -9" --- p.105 / Chapter 4.3.2 --- Altered Expressions of Bcl-2 Family Proteins --- p.112 / Chapter 4.3.3 --- Loss of Mitochondrial Membrane Potential --- p.115 / Chapter 4.4 --- in vivo Tumor Growth Inhibition in HepG2-bearing Nude Mice --- p.121 / Chapter 4.5 --- Conclusion --- p.127 / Chapter Chapter 5 --- RESULTS AND DISCUSSIONS - MECHANISTIC STUDY OF SOPHORAFLAVONE J-INDUCED CELL DEATH IN HEPATOMA CELLS HepG2 --- p.132 / Chapter 5.1 --- Execution of Cellular Apoptosis --- p.133 / Chapter 5.2 --- Involvement of Multiple Signaling Pathways in Sophoraflavone J-induced Apoptosis --- p.138 / Chapter 5.3 --- Differential Proteomes of Control and Sophoraflavone J-treated HepG2 Cells --- p.148 / Chapter 5.4 --- Conclusion --- p.167 / Chapter Chapter 6 --- OVERALL CONCLUSION AND FUTURE PERSPECTIVES --- p.169 / References --- p.xxiv

Yau Mei-sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 96-112). / Abstracts in English and Chinese. / Abstract / Abstract (Chinese Version) / Acknowledgements / List of Abbreviations / Table of Contents / List of Tables / List of Figures / Chapter Chapter 1 --- Introduction / Chapter Chapter 2 --- Literature Review / Chapter 2.1 --- Hepatocellular Carcinoma / Chapter 2.2 --- Epidermal Growth Factor Receptor / Chapter 2.2.1 --- Activation of Epidermal Growth Factor Receptor / Chapter 2.2.2 --- Epidermal Growth Factor Receptor Signaling Pathways / Chapter 2.2.3 --- Expression Level and Patient Survival / Chapter 2.2.4 --- Epidermal Growth Factor Receptor Activity and Tumor Cell Growth / Chapter 2.2.5 --- Epidermal Growth Factor Receptor Activity and Radiation / Chapter 2.3 --- "Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, ZD1839" / Chapter 2.3.1 --- Tumor Cell Growth Control Activities of ZD1839 / Chapter 2.3.2 --- Factors Affecting the Tumor Cell Growth Control Activities of ZD1839 / Chapter 2.3.3 --- Radiosensitization Activities of ZD1839 / Chapter 2.3.4 --- Factors Affecting the Radiosensitization Activities of ZD1839 / Chapter 2.4 --- Study Objectives / Chapter Chapter 3 --- Materials and Methods / Chapter 3.1 --- ZD1839 / Chapter 3.2 --- Cell lines and Cell Culture / Chapter 3.3 --- Immunoblot Analysis / Chapter 3.3.1 --- Total Protein Extraction / Chapter 3.3.2 --- Protein Amount Determination / Chapter 3.3.3 --- Protein Separation / Chapter 3.3.4 --- Blotting / Chapter 3.3.5 --- Antibody Labeling / Chapter 3.3.6 --- Detection of Antibody Binding / Chapter 3.4 --- Cytotoxicity Assay / Chapter 3.5 --- Nucleotide sequence analysis / Chapter 3.5.1 --- Total RNA Extraction / Chapter 3.5.2 --- RNA Amount Determination / Chapter 3.5.3 --- Reverse Transcription - Polymerase Chain Reaction (RT-PCR) / Chapter 3.5.3.1 --- Reverse Transcription / Chapter 3.5.3.2 --- High Fidelity Polymerase Chain Reaction / Chapter 3.5.4 --- Purification of PCR Product / Chapter 3.5.5 --- Cycle Sequencing Reaction / Chapter 3.5.6 --- DNA Precipitation and Sequencing / Chapter 3.6 --- Clonogenic Assay / Chapter 3.7 --- Immunohistochemical Analysis / Chapter Chapter 4 --- Results / Chapter 4.1 --- Immunoblot Analysis / Chapter 4.2 --- Cytotoxicity Assay / Chapter 4.2.1 --- Effect of ZD 1839 on cell morphology / Chapter 4.2.2 --- Effect of ZD 1839 on cell growth / Chapter 4.3 --- Nucleotide sequence analysis / Chapter 4.3.1 --- RNA Concentration of HCC cells / Chapter 4.3.2 --- Sequencing of TK domain within EGFR / Chapter 4.3.3 --- Sequencing of TK domain within HER2 / Chapter 4.4 --- Clonogenic assay / Chapter 4.4.1 --- Effects of ZD 1839 pre-treatment on radiation response / Chapter 4.4.2 --- Effects of ZD 1839 continuous treatment on radiation response / Chapter 4.5 --- Immunohistochemical Analysis / Chapter Chapter 5 --- Discussion / Chapter 5.1 --- Important Findings / Chapter 5.2 --- EGFR Expression of HCC Cells / Chapter 5.3 --- Cytotoxicity of ZD1839 on HCC Cell Lines / Chapter 5.4 --- Factors Affecting the Cytotoxicity of ZD1839 / Chapter 5.4.1 --- Effect of EGFR Expression on ZD1839 Cytotoxicity / Chapter 5.4.2 --- Effect of EGFR Mutations on ZD 1839 Cytotoxicity / Chapter 5.4.3 --- Effect of HER2 Expression on ZD1839 Cytotoxicity / Chapter 5.4.4 --- Effect of HER2 Mutations on ZD 1839 Cytotoxicity / Chapter 5.5 --- Radiation Response ofHCC Cell Lines upon ZD1839 Treatment / Chapter 5.6 --- Factors Affecting Radiation Response of ZD1839-treated HCC Cell Lines / Chapter 5.6.1 --- Effect of Growth Arrest on Radiation Response of HCC Cell Lines / Chapter 5.6.2 --- Other Factors Affecting Radiation Response of HCC Cell Lines / Chapter Chapter 6 --- Conclusion / References

Yu, Wai Lam. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 79-88). / Abstracts in English and Chinese. / Acknowledgements --- p.IV / Abstract --- p.V / 論文摘要 --- p.VII / Table of Contents --- p.IX / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Cancer --- p.1 / Chapter 1.2 --- Hepatocellular Carcinoma (HCC) --- p.2 / Chapter 1.2.1 --- Risk factors causing HCC --- p.3 / Chapter 1.2.2 --- Molecular mechanism of HCC --- p.7 / Chapter 1.2.3 --- Treatment of HCC --- p.8 / Chapter 1.3 --- Tetrandrine (Tet) - A Natural Compound Derived from Traditional Chinese Medicine (TCM) --- p.10 / Chapter 1.3.1 --- Traditional Chinese Medicine (TCM) --- p.10 / Chapter 1.3.2 --- Tetrandrine (Tet) --- p.12 / Chapter 1.4 --- Molecular View of Apoptosis --- p.14 / Chapter 1.4.1 --- Overview of apoptosis --- p.14 / Chapter 1.4.2 --- Caspase cascade --- p.15 / Chapter 1.4.3 --- Bcl-2 protein family --- p.18 / Chapter 1.4.4 --- The role of mitochondria in apoptosis --- p.20 / Chapter 1.5 --- Anti-cancer Agents Inducing Apoptosis Are New Targets --- p.22 / Chapter 1.6 --- Aim of Study --- p.26 / Chapter Chapter 2 --- Materials and Methods --- p.27 / Chapter 2.1 --- Cell Culture And Treatment --- p.27 / Chapter 2.1.1 --- Cell lines used --- p.27 / Chapter 2.1.2 --- Tetrandrine (Tet) --- p.28 / Chapter 2.1.3 --- Chemicals and reagents 2 --- p.83 / Chapter 2.1.4 --- Solution preparation --- p.29 / Chapter 2.1.5 --- Procedures --- p.30 / Chapter 2.2 --- Cell viability --- p.32 / Chapter 2.2.1 --- Chemicals and reagents . --- p.32 / Chapter 2.2.2 --- Solution preparation --- p.32 / Chapter 2.2.3 --- Procedures --- p.32 / Chapter 2.3 --- Apoptosis detection --- p.34 / Chapter 2.3.1 --- Chemicals and reagents --- p.34 / Chapter 2.3.2 --- Solution preparation --- p.35 / Chapter 2.3.3 --- Procedures --- p.36 / Chapter 2.4 --- Gene expression in tet-induced apoptotic cells --- p.39 / Chapter 2.4.1 --- Chemicals and reagents --- p.39 / Chapter 2.4.2 --- Solution preparation --- p.40 / Chapter 2.4.3 --- Procedures --- p.40 / Chapter 2.5 --- Protein expression in tet-induced apoptotic cells --- p.44 / Chapter 2.5.1 --- Chemicals and reagents --- p.44 / Chapter 2.5.2 --- Solution preparation --- p.45 / Chapter 2.5.3 --- Procedures --- p.48 / Chapter 2.6 --- Cell cycle analysis of tet-treated cells --- p.54 / Chapter 2.5.1 --- Chemicals and reagents --- p.54 / Chapter 2.5.2 --- Solution preparation --- p.54 / Chapter 2.5.3 --- Procedures --- p.54 / Chapter Chapter 3 --- Result --- p.56 / Chapter Chapter 4 --- Discussion --- p.70 / Chapter 4.1 --- Dose- and Time- Dependent Inhibitory Effects of Tet were found on HuH-7 And JHH-4 Cell Lines --- p.70 / Chapter 4.2 --- Tet Is More Selective Towards Liver Cancer Cells --- p.71 / Chapter 4.3 --- The Cell Death in HuH-7 Cells Induced by Tet is Mediated Through Apoptosis --- p.72 / Chapter 4.4 --- Hepatocellular Carcinoma (HCC)Tet Induces G1 Phase Cell Cycle Arrest as Part of Its Mechanism in Inducing Apoptosis in HuH-7 Cells --- p.73 / Chapter 4.5 --- Tet Could Probably Induce G1 Phase Cell Cycle Arrest in JHH-4 Cells --- p.75 / Chapter 4.6 --- "Tet-induced Apoptosis Involves the Intrinsic, Caspase-Dependent Pathway in Both the HuH-7 and JHH-4 Cell Lines" --- p.75 / Chapter 4.7 --- Proteins in Bcl-2 Family are Involved in the Inhibitory Mechanism of Tet --- p.77 / Reference --- p.79

Li Lok Yee Mandy. / "June 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 155-165). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Hepatocellular carcinoma (HCC) is the third commonest cancer worldwide. However HCC is considered to be highly resistant to chemotherapy. Gene therapies aimed to regulate Bd-2 proteins may sensitize HCC cells to chemotherapy. Studies have demonstrated that Bid/tBid are crucial in hepatocyte apoptosis. Bid also plays important roles in the development and chemotherapeutic sensitivity of HCC. The objective of this study is to test effect of Ad/AFPtBid and chemotherapeutic agents in combination on an orthotopic HCC model. / In conclusion, (1) Ad/AFPtBid can specifically target and effectively suppress the AFP-producing HCC. (2) Ad/AFPtBid can significantly sensitize HCC to 5-FU, their combination can significantly increase the anti-tumor effectiveness. (3) Ad/AFPtBid shows little toxicity in vivo. (4) The complementary effect of tBid and 5-FU on different phases of the cell cycle may explain the better therapeutic result if both are used to treat HCC. (5) The elucidation of phase specific effect of tBid points to a possible therapeutic option that combines tBid with different phase specific agents to treat HCC. / It is well established that many apoptosis inducers act in a cell cycle-specific fashion. This leads us to hypothesize that tBid might have phase specific effect. So, we tested the susceptibility of Hep3B cells at 00/01, S or G2/M phases to tBid. The results revealed that tBid significantly reduced Hep3B cells in G0/G1 phase, increased cells in G2/M phase. On the contrary, 5-FU arrested Hep3B cells in G0/G1 phase, and significantly reduced cells in G2/M phase. The levels of cell cycle-related proteins were altered in line with the result of the cell cycle. This suggests Hep3B cells in G0/G1 phase may be more susceptible to tBid. The complementary effects tBid and 5-FU on different phases of the cell cycle may explain the better therapeutic result if both are used to treat HCC. / The mice bearing orthotopic HCC tumors were treated with Ad/AFPtBid alone or in combination with 5-FU/Dox. Serum AFP levels were measured to mornitor tumor progression. The mice were killed four weeks after treatment. Liver tissues were subjected to immunohistochemical staining of proliferation cell nuclear antigen (PCNA) and TUNEL staining. Another batch of mice was observed for survival rate over a six month period. In addition, possible side effects of Ad/AFPtBid were tested in BALB/c mice. Results demonstrated that Ad/AFPtBid significantly inhibited Hep3B tumor growth. The combination of Ad/AFPtBid with 5-FU was more effective in tumor regression than either agent alone. However, the combination of Ad/AFPtBid with Dox treatment failed to demonstrated better effect than Dox treatment alone because the mice that received Dox exhibited serious weight loss. Tumor tissues from Ad/AFPtBid alone or combination treatment groups showed a decrease in cells positive for PCNA, and an increase in apoptosis by TUNEL staining, indicating that Ad/AFPtBid induced tumor regression through its pro-apoptotic effect. Inflammatory cell infiltration was also increased. Furthermore, Ad/AFPtBid did not suppress the hepatic tumor formed by non-AFP producing SK-HEP-1 or DLD-1. Finally, Ad/AFPtBid and 5-FU in combination results in better survival rate. No acute toxic effect of Ad/AFPtBid was observed. / Ma, Shihong. / "December 2009." / Adviser: CHEN Gong George. / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 114-138). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.