Chan Ching-Man Loren. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 126-144). / Abstracts in English and Chinese. / Acknowledgement --- p.ii / Abstract --- p.iii / Table of Content --- p.vii / List of Figure --- p.ix / List of Abbreviations --- p.xii / Chapter Chapter One --- General Introduction / Chapter 1.1 --- Doxorubicin --- p.1 / Chapter 1.2 --- Antioxidants --- p.11 / Chapter 1.3 --- Flavonoids --- p.17 / Chapter 1.4 --- Protection against doxorubicin-induced cardiotoxicity by antioxidant --- p.25 / Chapter 1.5 --- Aim of research --- p.25 / Chapter Chapter Two --- Study of Cardioprotection Effect of Flavonoids Against Doxorubicin-induced Toxicity in Sprague-Dawley Rats / Chapter 2.1 --- Introduction --- p.27 / Chapter 2.2 --- Materials and Methods --- p.29 / Chapter 2.3 --- Results --- p.37 / Chapter 2.4 --- Discussion --- p.51 / Chapter ChapterThree --- Study of Effect of Flavonoids in Chemotherapy of Doxorubicinin Tumor-bearing Mice / Chapter 3.1 --- Introduction --- p.54 / Chapter 3.2 --- Materials and Methods --- p.56 / Chapter 3.3 --- Results --- p.63 / Chapter 3.4 --- Discussion --- p.80 / Chapter ChapterFour --- Study of the Effect of Flavonoids on Doxorubicin-induced Cytotoxicity on Human Tumor Cell Line and Doxorubicin-resistant Human Tumor Cell Line / Chapter 4.1 --- Introduction --- p.83 / Chapter 4.2 --- Materials and Methods --- p.86 / Chapter 4.3 --- Results --- p.94 / Chapter 4.4 --- Discussion --- p.120 / Chapter Chapter five --- Conclusion --- p.122 / References --- p.126

by Chan Hung Chuen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 143-151). / Abstract also in Chinese. / Acknowledgments --- p.i / Abstract --- p.ii / Abstract (Chinese version) --- p.v / Abbreviations --- p.viii / Content --- p.ix / Chapter CHAPTER ONE --- INTRODUCTION / Chapter 1. --- Free radical and free radical-mediated antitumor drugs --- p.1 / Chapter 2. --- Mitomycin C (MC) / Chapter 2.1 --- Drug actions of MC --- p.2 / Chapter 2.2 --- Adverse side effects of MC --- p.5 / Chapter 3. --- Doxorubicin (DOX) / Chapter 3.1 --- Drug actions of DOX --- p.7 / Chapter 3.2 --- Adverse side effects of DOX --- p.8 / Chapter 4. --- Antioxidants --- p.14 / Chapter 5. --- Effects of exogenous ATP on the antitumor activity of Doxorubicin and Mitomycin C / Chapter 5.1 --- Glutathione (GSH) and related enzymes --- p.17 / Chapter 5.2 --- Glutathione (GSH) and Anticancer Quinones --- p.19 / Chapter 5.3 --- Glutathione and the cardiac toxicity of the anticancer drugs --- p.20 / Chapter 5.4 --- Glutathione depletion in tumor cells by exogenous ATP --- p.21 / Chapter 6. --- Aim of research --- p.24 / Chapter CHAPTER TWO --- THE EFFECT OF ANTIOXIDANTS ON DOXORUBICIN- OR MITOMYCIN C-INDUCED CYTOTOXICITY ON HUMAN TUMOR AND NORMAL CELL LINES / Chapter 2.1 --- Introduction --- p.26 / Chapter 2.2 --- Materials and Methods --- p.28 / Chapter 2.3 --- Results --- p.36 / Chapter 2.4 --- Discussion --- p.60 / Chapter CHAPTER THREE --- STUDY OF CARDIOPROTECTIVE EFFECTS OF ANTIOXIDANTS AGAINST DOXORUBICIN- OR MITOMYCIN C-INDUCED TOXICITY BY LANGENDORFF PERFUEED ISOLATED RAT HEART MODEL / Chapter 3.1 --- Introduction --- p.64 / Chapter 3.2 --- Materials and Methods --- p.67 / Chapter 3.3 --- Results --- p.75 / Chapter 3.4 --- Discussion --- p.76 / Chapter CHAPTER FOUR --- THE EFFECT OF ANTIOXIDANTS DURING CHEMOTHERAPY OF DOXORUBICIN OR MITOMYCIN C IN TUMOR-BEARING MICE / Chapter 4.1 --- Introduction --- p.78 / Chapter 4.2 --- Materials and Methods --- p.80 / Chapter 4.3 --- Results --- p.83 / Chapter 4.4 --- Discussion --- p.93 / Chapter CHAPTER FIVE --- HISTOLOGICAL STUDY AND LIPID PEROXIDATION STUDY OF PROTECTIVE EFFECT OF ANTIOXIDANTS IN TUMOR-BEARING MICE TREATED WITH DOXORUBICIN OR MITOMYCIN C / Chapter 5.1 --- Introduction --- p.95 / Chapter 5.2 --- Materials and Methods --- p.98 / Chapter 5.3 --- Results --- p.103 / Chapter 5.4 --- Discussion --- p.117 / Chapter CHAPTER SIX --- EFFECT OF EXOGENOUS ATP ON THE ANTITUMOR ACTIVITY OF DOXORUBICIN AND MITOMYCIN C ON CULTURED HUMAN HEPATOMA CELLS / Chapter 6.1 --- Introduction --- p.122 / Chapter 6.2 --- Materials and Methods --- p.124 / Chapter 6.3 --- Results --- p.126 / Chapter 6.4 --- Discussion --- p.136 / Chapter CHAPTER SEVEN --- CONCLUSION / Chapter 7.1 --- Conclusion --- p.139 / Chapter 7.2 --- Future perspective --- p.141 / Bibliography --- p.142

To Man Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 85-105). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / (in Chinese) --- p.iv / Acknowledgements --- p.vi / Publications --- p.viii / Table of Contents --- p.ix / List of Tables --- p.xii / List of Figures --- p.xiii / List of Abbreviations --- p.xiv / Chapter CHAPTER 1: --- General Introduction --- p.1 / Chapter Section 1.1 --- Background and Clinical Application of Anthracylines --- p.1 / Chapter Section 1.2 --- DOX-induced Cardiotoxicity --- p.3 / Chapter 1.2.1 --- Types of Cardiotoxicity --- p.4 / Chapter 1.2.1.1 --- Acute Cardiotoxicity --- p.4 / Chapter 1.2.1.2 --- Chronic Cardiotoxicity --- p.5 / Chapter 1.2.2 --- Subcellular Effects of DOX --- p.6 / Chapter 1.2.2.1 --- Ultrastructural Lesions --- p.6 / Chapter 1.2.2.2 --- Effects on Mitochondrial Functions --- p.7 / Chapter 1.2.2.3 --- Effects on Sarcoplasmic reticulum (SR) Functions --- p.8 / Chapter Section 1.3 --- Mechanisms of DOX-induced Cardiotoxicity --- p.8 / Chapter 1.3.1 --- Formation of Free Radicals --- p.9 / Chapter 1.3.1.1 --- Generation of Free Radicals by DOX --- p.10 / Chapter 1.3.1.2 --- Cardiac damage by Free radicals --- p.12 / Chapter 1.3.2 --- Induction of Apoptosis --- p.14 / Chapter 1.3.2.1 --- Characteristics and Pathway of Apoptosis --- p.14 / Chapter 1.3.2.2 --- Mitochondria and Apoptosis --- p.15 / Chapter 1.3.2.3 --- Caspases and Apoptosis --- p.17 / Chapter 1.3.2.4 --- Apoptosis and DOX-induced Cardiotoxicity --- p.18 / Chapter Section 1.4 --- Strategies to Reduce DOX-induced Cardiotoxicity --- p.19 / Chapter 1.4.1 --- Dosage optimization and Schedule modification --- p.19 / Chapter 1.4.2 --- Anthracycline Analogues --- p.21 / Chapter 1.4.3 --- Cardioprotective Agents --- p.21 / Chapter Section 1.5 --- Thrombopoietin --- p.23 / Chapter CHAPTER 2: --- Hypotheses and Objectives --- p.30 / Chapter CHAPTER 3: --- Methodology --- p.33 / Chapter Section 3.1 --- Methods --- p.33 / Chapter 3.1.1 --- Culture of Rat H9C2 Myoblast Cell Line and Primary Neonatal Rat Cardiomyocytes --- p.33 / Chapter 3.1.1.1 --- Maintenance of Cell Line --- p.33 / Chapter 3.1.1.2 --- Culture of Primary Neonatal Rat Cardiomyocytes --- p.34 / Chapter 3.1.2 --- Effects of Thrombopoietin on Cell Viability of Rat H9C2 Myoblast Cell Line and Beating Rates of Primary Rat Cardiomyocytes --- p.35 / Chapter 3.1.2.1 --- Cell Viability assay --- p.35 / Chapter 3.1.2.2 --- Beating Rate of Primary Beating Cardiomyocytes --- p.36 / Chapter 3.1.3 --- Effects of Thrombopoietin on the Protection against DOX-induced Heart Injury In Vivo --- p.36 / Chapter 3.1.3.1 --- Animals --- p.36 / Chapter 3.1.3.2 --- Experimental Protocol --- p.37 / Chapter 3.1.3.3 --- Echocardiography --- p.38 / Chapter 3.1.3.4 --- Blood Cell Counts --- p.39 / Chapter 3.1.3.5 --- Histopathology --- p.39 / Chapter 3.1.4 --- Effects of Thrombopoietin on Apoptosis and Mitochondrial Integrity of Rat H9C2 Myoblast Cell Line and Apoptosis In Vivo --- p.40 / Chapter 3.1.4.1 --- Determination of Externalized Phosphatidylserine --- p.40 / Chapter 3.1.4.2 --- Determination of Active Caspase-3 Expression --- p.41 / Chapter 3.1.4.3 --- Assessment of Mitochondrial Integrity --- p.42 / Chapter 3.1.4.4 --- TUNEL assay --- p.43 / Chapter 3.1.5 --- Statistical Analysis --- p.44 / Chapter CHAPTER 4: --- Effects of Thrombopoietin on Cell Viability of Rat H9C2 Myoblast Cell Line and Beating Rates of Primary Neonatal Rat Cardiomyocytes --- p.46 / Chapter Section 4.1 --- Results --- p.46 / Chapter 4.1.1 --- Effects of TPO on DOX-induced Cell Death --- p.46 / Chapter 4.1.2 --- Effects of TPO on the Beating Rates of Primary Cardiomyocytes --- p.47 / Chapter Section 4.2 --- Discussion --- p.47 / Chapter CHAPTER 5： --- Effects of Thrombopoietin on the Protection Against DOX-induced Heart Injury In Vivo --- p.54 / Chapter Section 5.1 --- Results --- p.54 / Chapter 5.1.1 --- General Observations and Survival --- p.54 / Chapter 5.1.2 --- Blood Cell Counts --- p.55 / Chapter 5.1.3 --- Cardiac Functions by Echocardiography --- p.56 / Chapter 5.1.4 --- Gross Anatomic Changes and Pathology of the Myocardium --- p.57 / Chapter Section 5.2 --- Discussion --- p.58 / Chapter CHAPTER 6: --- Effects of Thrombopoietin on Apoptosis and Mitochondrial Integrity of H9C2 Cell Line and Apoptosis In Vico --- p.69 / Chapter Section 6.1 --- Results --- p.69 / Chapter 6.1.1 --- Determination of Externalized Phosphatidylserine --- p.69 / Chapter 6.1.2 --- Determination of Active Caspase-3 Activity --- p.70 / Chapter 6.1.3 --- Assessment of Mitochondrial Membrane Potential --- p.70 / Chapter 6.1.4 --- Determination of Apoptosis by TUNEL assay --- p.72 / Chapter Section 6.2 --- Discussion --- p.72 / Chapter CHAPTER 7： --- General Discussion and Conclusion --- p.83 / References --- p.85