Yip, Wai Ki. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 203-228). / Abstracts in English and Chinese. / ACKNOWLEDGMENTS --- p.i / ABBREVIATIONS --- p.iii / ABSTRACT --- p.x / 撮要 --- p.xiv / TABLE OF CONTENTS --- p.xvii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION / Chapter 1.1 --- Hematopoiesis and Leukemia / Chapter 1.1.1 --- An Overview on Hematopoiesis Development --- p.1 / Chapter 1.1.1.1 --- Hematopoietic Growth Factors --- p.4 / Chapter 1.1.1.2 --- Site Switching of Hematopoiesis --- p.5 / Chapter 1.1.2 --- An Overview on Leukemia --- p.7 / Chapter 1.1.2.1 --- Classification of Leukemia --- p.7 / Chapter 1.1.2.2 --- Conventional Therapy of Leukemia --- p.10 / Chapter 1.1.2.3 --- Novel Approaches to Leukemia Therapy: Apoptosis and Differentiation Induction --- p.13 / Chapter 1.2 --- Polysaturated Fatty Acids / Chapter 1.2.1 --- An Overview on Polyunsaturated Fatty Acids --- p.16 / Chapter 1.2.2 --- An Overview on Essential Fatty Acids --- p.17 / Chapter 1.2.2.1 --- Alpha Linolenic Acids (ALA) --- p.17 / Chapter 1.2.2.2 --- Gamma Linolenic Acid (GLA) --- p.18 / Chapter 1.2.3 --- "An Overview on Conjugated Fatty Acids: Conjugated Linoleic Acid (CLA), Conjugated EPA and Conjugated DHA" --- p.20 / Chapter 1.2.4 --- Conjugated Linolenic Acid (CLN) --- p.24 / Chapter 1.2.4.1 --- Identification and Production of CLN --- p.28 / Chapter 1.2.4.2. --- Metabolism of CLN --- p.29 / Chapter 1.2.4.3 --- Anti-Obese and Hypolipidemic Effect of CLN --- p.30 / Chapter 1.2.4.4 --- Anti-Proliferative Effect of CLN --- p.30 / Chapter 1.2.4.5 --- Other Novel Effects of CLN --- p.32 / Chapter 1.3 --- Aims and Scopes of This Investigation --- p.34 / Chapter CHAPTER 2: --- MATERIALS AND METHODS / Chapter 2.1 --- Materials --- p.36 / Chapter 2.1.1 --- Animals --- p.36 / Chapter 2.1.2 --- Human Cell Lines --- p.36 / Chapter 2.1.3 --- "Cell Culture Medium, Buffers and Other Reagents" --- p.38 / Chapter 2.1.4 --- Reagents and Buffer for Flow Cytometry --- p.44 / Chapter 2.1.5 --- Reagents for DNA Extraction --- p.47 / Chapter 2.1.6 --- Cell Death Detection ELISApLus --- p.48 / Chapter 2.1.7 --- Reagents for Measuring Caspase Activity --- p.50 / Chapter 2.1.8 --- Reagents for FACE´ёØ ELISA Kit --- p.53 / Chapter 2.1.9 --- Reagents for Western Blotting --- p.55 / Chapter 2.2 --- Methods --- p.65 / Chapter 2.2.1 --- Culturing the Tumor Cell Lines --- p.65 / Chapter 2.2.2 --- "Isolation, Preparation and Culturing of Murine Peritoneal Macrophages and Bone Marrow Cells" --- p.66 / Chapter 2.2.3 --- Anti-proliferation Assays --- p.67 / Chapter 2.2.4 --- Cell Viability Determination --- p.68 / Chapter 2.2.5 --- Determination of Anti-leukemia Activity In Vivo (In Vivo Tumorigenicity Assay) --- p.69 / Chapter 2.2.6 --- Cell Cycle Analysis by Flow Cytometry --- p.69 / Chapter 2.2.7 --- Detection of Apoptosis --- p.70 / Chapter 2.2.8 --- Assessment of Differentiation-associated Characteristics --- p.74 / Chapter 2.2.9 --- Measurement of Caspase Activities --- p.76 / Chapter 2.2.10 --- Protein Expression Study --- p.78 / Chapter 2.2.11 --- Detection of Phosphorylation of JNK by FACE´ёØ JNK ELISA Kit --- p.83 / Chapter 2.2.12 --- Detection of Phosphorylation of NF-kB by FACE´ёØ NF-kB p65 Profiler --- p.85 / Chapter 2.2.13 --- Statistical Analysis --- p.85 / Chapter CHAPTER 3: --- STUDIES ON THE ANTI PROLIFERATIVE EFFECTS OF CONJUGATED LINOLENIC ACIDS ON THE HUMAN MYELOID LEUKEMIA CELLS / Chapter 3.1 --- Introduction --- p.86 / Chapter 3.2 --- Results / Chapter 3.2.1 --- Anti-proliferative Activity of CLN Isomers on Various Myeloid Leukemia and Lymphoma Cell Lines In Vitro --- p.88 / Chapter 3.2.2 --- Direct Cytotoxic Effect of Jacaric Acid on HL-60 Cells In Vitro --- p.95 / Chapter 3.2.3 --- Cytotoxic Effect of Jacaric Acid on Primary Murine Cells and Human Normal Cell Lines In Vitro --- p.98 / Chapter 3.2.4 --- Kinetics and Reversibility Studies of the Anti-proliferative Effect of Four CLN Isomers on the Human Promyelocytic Leukemia HL-60 Cells --- p.101 / Chapter 3.2.5 --- Synergistic Anti-proliferative Effect of Jacaric Acid with Vitamin D3 and All Trans-Retinoic Acid (ATRA) on the Human Promyelocytic Leukemia HL-60 Cells In Vitro --- p.114 / Chapter 3.2.6 --- Effect of Jacaric Acid on the Cell Cycle Profile of the HL-60 Cells In Vitro --- p.116 / Chapter 3.2.7 --- Effect of Jacaric Acid on the In Vivo Tumorigenicity of the HL-60 Cells --- p.119 / Chapter 3.3 --- Discussion --- p.121 / Chapter CHAPTER 4: --- STUDIES ON THE APOPTOSIS-INDUCING AND DIFFERENTIATION-INDUCING EFFECTS OF CONJUGATED LINOLENIC ACIDS ON THE HUMAN MYELOID LEUKEMIA CELLS / Chapter 4.1.1 --- Introduction --- p.128 / Chapter 4.2 --- Results / Chapter 4.2.1 --- Induction of Apoptosis in the Human Promyelocytic Leukemia HL-60 Cells by Jacaric Acid --- p.134 / Chapter 4.2.2 --- Apoptosis-Inducing Effect of Jacaric Acid on the Human Promyelocytic Leukemia HL-60 Cells as Detected by Annexin V-GFP PI Double Staining Method --- p.138 / Chapter 4.2.3 --- Effect of Jacaric Acid on the Mitochondrial Membrane Potential in the Human Promyelocytic Leukemia HL-60 Cells --- p.140 / Chapter 4.2.4 --- Effects of Jacaric Acid on the Caspase Activities in the Human Promyelocytic Leukemia HL-60 Cells --- p.142 / Chapter 4.2.5 --- Effects of Jacaric Acid and Antioxidants on the ROS Induction in the Human Promyelocyic Leukemia hl-6 Cells --- p.147 / Chapter 4.2.6 --- Effect of N-acetyl-L-Cysteine on the Apoptosis-Inducing Activity of Jacaric Acid in the Human Promyelocytic Leukemia HL-60 Cells --- p.149 / Chapter 4.2.7 --- Morphological Studies on the Jacaric Acid-treated Human Promyelocytic Leukemia HL-60 Cells --- p.151 / Chapter 4.2.8 --- Cell Size and Granularity of the Human Promyelocytic Leukemia HL-60 Cells after Treatment with Different CLN Isomers --- p.153 / Chapter 4.2.9 --- Expression of Differentiation-Related Cell Surface Markers in the Human Promyelocytic Leukemia HL-60 Cells after Treatment with Jacaric Acid --- p.155 / Chapter 4.3 --- Discussion --- p.158 / Chapter CHAPTER 5: --- STUDIES ON THE APOPTOSIS-ASSOCIATED PROTEINS AND SIGNALING PATHWAYS IN CONJUGATED LINOLENIC ACID-INDUCED APOPTOSIS OF THE HUMAN MYELOID LEUKEMIA CELLS / Chapter 5.1 --- Introduction --- p.165 / Chapter 5.2 --- Results / Chapter 5.2.1 --- Expression of Fas and Fas Ligand Proteins in the Jacaric Acid- treated Human Promyelocytic Leukemia HL-60 Cells --- p.171 / Chapter 5.2.2 --- Expression of Bcl-2 Family Member Proteins in the Jacaric Acid- treated Human Promyelocytic Leukemia HL-60 Cells --- p.173 / Chapter 5.2.3 --- Cytochrome c Release in the Jacaric Acid-treated Human Promyelocytic Leukemia HL-60 Cells --- p.175 / Chapter 5.2.4 --- Cleavage of Poly(ADP-ribose) Polymerase (PARP) in the Jacaric Acid-treated Human Promyelocytic Leukemia HL-60 Cells --- p.177 / Chapter 5.2.5 --- Phosphorylation of ERK in the Jacaric Acid-treated Human Promyelocytic Leukemia HL-60 Cells --- p.179 / Chapter 5.2.6 --- Phosphorylation of JNK in the Jacaric Acid-treated Human Promyelocytic Leukemia HL-60 Cells --- p.181 / Chapter 5.2.7 --- Phosphorylation of NF-kB Protein in the Jacaric Acid-treated Human Promyelocytic Leukemia HL-60 Cells --- p.183 / Chapter 5.3 --- Discussion --- p.185 / Chapter CHAPTER 6: --- CONCLUSIONS AND FUTURE PERSPECTIVES --- p.195 / REFERENCES --- p.203

Yau Wai Lok. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 195-205). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABBREVIATIONS --- p.ii / ABSTRACT --- p.vii / 撮要 --- p.x / PUBLICATIONS --- p.xii / TABLE OF CONTENTS --- p.xiii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION / Chapter 1.1 --- Hematopoiesis & Leukemia --- p.1 / Chapter 1.1.1 --- An Overview on Hematopoiesis --- p.1 / Chapter 1.1.2 --- An Overview of Leukemia --- p.4 / Chapter 1.1.2.2 --- Classification and Epidemiology of Leukemia --- p.5 / Chapter 1.1.2.3 --- Conventional Approaches to Leukemia Therapy --- p.8 / Chapter 1.1.2.4 --- Novel Approaches to Leukemia Therapy --- p.9 / Chapter 1.1.2.4.1 --- Differentiation Therapy --- p.10 / Chapter 1.1.2.4.2 --- Induction of Apoptosis --- p.10 / Chapter 1.1.2.4.3 --- Natural Products as a Source of Anti-leukemia Drug --- p.11 / Chapter 1.2 --- Cytokinins --- p.12 / Chapter 1.2.1 --- Historical Development and Occurrence of Cytokinins --- p.12 / Chapter 1.2.2 --- Functions of Cytokinins and the Signal Transduction of Cytokinins in Plants --- p.13 / Chapter 1.2.3 --- Phytochemistry and Metabolism of Cytokinins --- p.15 / Chapter 1.2.3.1 --- Chemical Structures of Cytokinins --- p.15 / Chapter 1.2.3.2 --- Biosynthesis of Cytokinins in Plants --- p.19 / Chapter 1.2.3.3 --- Metabolisms of Cytokinins in Plants and Animals --- p.22 / Chapter 1.2.4 --- Biological and Pharmacological Activities of Cytokinins in Animals --- p.23 / Chapter 1.2.4.1 --- Anti-aging Effect --- p.24 / Chapter 1.2.4.2 --- Anti-thrombosis Effect and Inhibition of Blood Platelet Aggregation --- p.24 / Chapter 1.2.4.3 --- Anti-tumor Effect --- p.25 / Chapter 1.3 --- Aims and Scopes of This Investigation --- p.27 / Chapter CHAPTER 2: --- MATERIALS AND METHODS / Chapter 2.1 --- Materials --- p.29 / Chapter 2.1.1 --- Animals --- p.29 / Chapter 2.1.2 --- Cell Lines --- p.29 / Chapter 2.1.3 --- "Cell Culture Medium, Buffers and Other Reagents" --- p.32 / Chapter 2.1.4 --- Reagents and Buffers for Flow Cytometry --- p.37 / Chapter 2.1.5 --- Reagents for DNA Extraction --- p.41 / Chapter 2.1.6 --- Cellular DNA Fragmentation ELISA Kit --- p.42 / Chapter 2.1.7 --- Reagents for Total RNA Isolation --- p.44 / Chapter 2.1.8 --- Reagents and Buffers for Reverse Transcription-Polymerase Chain Reaction (RT-PCR) --- p.46 / Chapter 2.1.9 --- Reagents and Buffers for Gel Electrophoresis for Nucleic Acids --- p.50 / Chapter 2.1.10 --- Reagents for Measuring Caspase Activity --- p.51 / Chapter 2.2 --- Methods --- p.54 / Chapter 2.2.1 --- Culture of the Tumor Cell Lines --- p.54 / Chapter 2.2.2 --- "Isolation, Preparation and Culture of Murine Peritoneal Macrophages" --- p.55 / Chapter 2.2.3 --- Determination of Cell Proliferation by [ 3H]-TdR Incorporation Assay --- p.55 / Chapter 2.2.4 --- Cytotoxicity Measurement by LDH Release Assay --- p.56 / Chapter 2.2.5 --- Determination of Cell Viability --- p.57 / Chapter 2.2.6 --- Determination of Anti-leukemic Activity In Vivo --- p.58 / Chapter 2.2.7 --- Analysis of Cell Cycle Profile/DNA Content by Flow Cytometry --- p.59 / Chapter 2.2.8 --- Measurement of Apoptosis --- p.59 / Chapter 2.2.9 --- Assessment of differentiation-associated characteristics --- p.63 / Chapter 2.2.10 --- Gene Expression Study --- p.67 / Chapter 2.2.11 --- Measurement of Caspase Activity --- p.68 / Chapter 2.2.12 --- Statistical Analysis --- p.70 / Chapter CHAPTER 3: --- STUDIES ON THE ANTI-PROLIFERATIVE EFFECT OF CYTOKININS ON LEUKEMIA CELLS / Chapter 3.1 --- Introduction --- p.71 / Chapter 3.2 --- Results --- p.72 / Chapter 3.2.1 --- Effect of Various Cytokinins and Their Riboside Derivatives on the Proliferation of Murine Myelomonocytic Leukemia WEHI-3B JCS Cells In Vitro --- p.72 / Chapter 3.2.2 --- Cytotoxicity of Kinetin and Kinetin Riboside on the WEHI-3B JCS Cells In Vitro --- p.86 / Chapter 3.2.3 --- Effects of Kinetin and Kinetin Riboside on the Proliferation of Various Leukemia Cell Lines In Vitro --- p.90 / Chapter 3.2.4 --- Cytotoxicity of Kinetin and Kinetin Riboside on Non-tumor Cell Lines and Primary Myeloid Cells In Vitro --- p.103 / Chapter 3.2.5 --- Kinetic and Reversibility Studies of the Anti-proliferative Effect of Kinetin and Kinetin Riboside on the WEHI-3B JCS Cells In Vitro --- p.107 / Chapter 3.2.6 --- Effects of Kinetin and Kinetin Riboside on the Cell Cycle Profile of WEHI-3B JCS Cells In Vitro --- p.115 / Chapter 3.2.7 --- Expression of Cell Cycle Related Genes in Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells In Vitro --- p.118 / Chapter 3.2.8 --- Effects of Kinetin and Kinetin Riboside on the In Vivo Tumorigenicity of WEHI-3B JCS Cells --- p.123 / Chapter 3.2.9 --- In Vivo Anti-tumor Effect of Kinetin and Kinetin Riboside on WEHI-3B JCS Cells --- p.126 / Chapter 3.3 --- Discussion --- p.129 / Chapter CHAPTER 4: --- STUDIES ON THE APOPTOSIS-INDUCING EFFECT OF CYTOKININS / Chapter 4.1 --- Introduction --- p.134 / Chapter 4.2 --- Results --- p.136 / Chapter 4.2.1 --- Induction of DNA Fragmentation of Cytokinins in the Murine Myeloid Leukemia WEHI-3B JCS Cells In Vitro --- p.136 / Chapter 4.2.2 --- Mitochondrial Membrane Potential of Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells In Vitro --- p.144 / Chapter 4.2.3 --- Caspase Activities of Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells In Vitro --- p.147 / Chapter 4.2.4 --- Induction of Reactive Oxygen Species in Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells In Vitro --- p.154 / Chapter 4.2.5 --- Expression of Apoptosis Regulatory Genes in Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells In Vitro --- p.157 / Chapter 4.3 --- Discussion --- p.163 / Chapter CHAPTER 5: --- STUDIES ON THE DIFFERENTIATION-INDUCING EFFECT OF CYTOKININS / Chapter 5.1 --- Introduction --- p.168 / Chapter 5.2 --- Results --- p.170 / Chapter 5.2.1 --- Morphology of Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells --- p.170 / Chapter 5.2.2 --- Cell Size and Granularity of Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells --- p.175 / Chapter 5.2.3 --- Changes in Surface Antigen Expression of Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells --- p.178 / Chapter 5.2.4 --- Monocytic Serine Esterase Activity in Kinetin- and Kinetin Riboside-treated WEHI-3B JCS Cells --- p.185 / Chapter 5.3 --- Discussion --- p.188 / Chapter CHAPTER 6: --- CONCLUSIONS AND FUTURE PERSPECTIVES --- p.190 / REFERENCES --- p.195

Lui Oi Lan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves [216]-240). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABBREVIATIONS --- p.ii / ABSTRACT --- p.vii / 撮要 --- p.x / PUBLICATIONS --- p.xiii / TABLE OF CONTENTS --- p.xiv / Chapter CHAPTER 1: --- GENERAL INTRODUCTION / Chapter 1.1 --- Hematopoiesis and Leukemia --- p.1 / Chapter 1.1.1 --- An Overview on Hematopoietic Development --- p.1 / Chapter 1.1.2 --- Leukemia --- p.8 / Chapter 1.1.2.1 --- General Diagnostic Tests for Leukemia --- p.9 / Chapter 1.1.2.2 --- Classification and Epidemiology of Leukemia --- p.10 / Chapter 1.1.2.3 --- Conventional Approaches to Leukemia Therapy --- p.17 / Chapter 1.1.2.4 --- Novel Approaches to Leukemia Therapy --- p.20 / Chapter 1.2 --- Conjugated Linoleic Acid --- p.23 / Chapter 1.2.1 --- Introduction: Historical Development and Occurrence of Conjugated Linoleic Acid --- p.23 / Chapter 1.2.2 --- Phytochemistry and Metabolism of Conjugated Linoleic Acid --- p.24 / Chapter 1.2.2.1 --- Chemical Structures of Conjugated Linoleic Acid Isomers --- p.24 / Chapter 1.2.2.2 --- Biosynthesis of Conjugated Linoleic Acid --- p.26 / Chapter 1.2.2.3 --- Metabolism of Conjugated Linoleic Acid --- p.30 / Chapter 1.2.2.4 --- Mode of Entry and Tissue Incorporation of Conjugated Linoleic Acid --- p.33 / Chapter 1.2.2.5 --- Toxicology of Conjugated Linoleic Acid --- p.33 / Chapter 1.2.3 --- Physiological Activities of Conjugated Linoleic Acid: Reported Health Benefits --- p.35 / Chapter 1.2.3.1 --- Anti-adipogenesis / Chapter 1.2.3.2 --- Anti-diabetogenesis --- p.36 / Chapter 1.2.3.3 --- Anti-atherosclerosis --- p.38 / Chapter 1.2.3.4 --- Anti-carcinogenesis --- p.39 / Chapter 1.2.3.5 --- Anti-tumor Activity --- p.40 / Chapter 1.2.3.6 --- Effects of Conjugated Linoleic Acid on Lipid Metabolism --- p.44 / Chapter 1.2.3.6.1 --- Actions on Phospholipids by Conjugated Linoleic Acid --- p.45 / Chapter 1.2.3.6.2 --- Conjugated Linoleic Acid as a Ligand for the PPAR System --- p.47 / Chapter 1.2.3.7 --- Immunomodulation --- p.47 / Chapter 1.3 --- Aims and Scopes of This Investigation --- p.50 / Chapter CHAPTER 2: --- MATERIALS AND METHODS / Chapter 2.1 --- Materials / Chapter 2.1.1 --- Animals --- p.52 / Chapter 2.1.2 --- Cell Lines --- p.52 / Chapter 2.1.3 --- "Cell Culture Medium, Buffers and Other Reagents" --- p.52 / Chapter 2.1.4 --- Reagents for 3H-Thymidine Incorporation Assay --- p.54 / Chapter 2.1.5 --- Reagents and Buffers for Flow Cytometry --- p.58 / Chapter 2.1.6 --- Reagents for DNA Extraction --- p.59 / Chapter 2.1.7 --- Cell Death Detection ELISAPLUS Kit --- p.63 / Chapter 2.1.8 --- Reagents for Measuring Caspase Activity --- p.65 / Chapter 2.1.9 --- Reagents for Total RNA Isolation --- p.66 / Chapter 2.1.10 --- Reagents and Buffers for RT-PCR --- p.69 / Chapter 2.1.11 --- Reagents and Buffers for Gel Electrophoresis of Nucleic Acids --- p.74 / Chapter 2.1.12 --- "Reagents, Buffers and Materials for Western Blot Analysis" --- p.75 / Chapter 2.2 --- Methods / Chapter 2.2.1 --- Culture of the Tumor Cell Lines --- p.80 / Chapter 2.2.2 --- "Isolation, Preparation and Culture of Mouse Peritoneal Macrophages" --- p.81 / Chapter 2.2.3 --- Determination of Cell Viability --- p.82 / Chapter 2.2.4 --- Determination of Cell Proliferation by [3H]-TdR Incorporation Assay --- p.83 / Chapter 2.2.5 --- In Vivo Tumorigenicity Study --- p.83 / Chapter 2.2.6 --- Analysis of Cell Cycle Profile / DNA Content by Flow Cytometry --- p.83 / Chapter 2.2.7 --- Measurement of Apoptosis --- p.84 / Chapter 2.2.8 --- Determination of the Mitochondrial Membrane Potential --- p.86 / Chapter 2.2.9 --- Measurement of Caspase Activity --- p.87 / Chapter 2.2.10 --- Study of Intracellular Accumulation of Reactive Oxygen Species (ROS) --- p.88 / Chapter 2.2.11 --- Study of the Scavenging Activity of Antioxidants --- p.88 / Chapter 2.2.12 --- Gene Expression Study --- p.89 / Chapter 2.2.13 --- Protein Expression Study --- p.92 / Chapter 2.2.14 --- Measurement of Cell Differentiation --- p.95 / Chapter 2.2.15 --- Statistical Analysis --- p.98 / Chapter CHAPTER 3: --- STUDIES ON THE ANTI-TUMOR ACTICITY OF CONJUGATED LINOLEIC ACID ON MYELOID LEUKEMIA CELLS / Chapter 3.1 --- Introduction / Chapter 3.2 --- Results --- p.99 / Chapter 3.2.1 --- Anti-proliferative Activity of CLA-mix and CLA Isomers on Various Myeloid Leukemia Cell Lines In Vitro --- p.101 / Chapter 3.2.2 --- Cytotoxic Effect of CLA-mix on the WEHI-3B JCS Cells In Vitro --- p.109 / Chapter 3.2.3 --- Cytotoxic Effect of CLA-mix on Primary Murine Myeloid Cells In Vitro --- p.111 / Chapter 3.2.4 --- Kinetic and Reversibility Studies of the Anti-proliferative Activity of CLA-mix on the WEHI-3B JCS Cells --- p.113 / Chapter 3.2.5 --- Effect of CLA-mix and its isomers on the Cell Cycle Profiles of the WEHI-3B JCS Cells In Vitro --- p.116 / Chapter 3.2.6 --- Effect of CLA-mix and its isomer on the Expression of Cell Cycle-regulatory Genes in the WEHI-3B JCS Cells --- p.123 / Chapter 3.2.7 --- Effect of CLA-mix and its isomer on the In V Tumorigenicity of the WEHI-3B JCS Cells ivo --- p.128 / Chapter 3.3 --- Discussion --- p.131 / Chapter CHAPTER 4: --- STUDIES ON THE APOPTOSIS-INDUCING ACTIVITY OF CONJUGATED LINOLEIC ACID ON MYELOID LEUKEMIA CELLS / Chapter 4.1 --- Introduction --- p.141 / Chapter 4.2 --- Results --- p.141 / Chapter 4.2.1 --- Induction of Apoptosis in Both Murine and Human Myeloid Leukemia Cells by CLA --- p.144 / Chapter 4.2.2 --- Effect of CLA and its Isomer on the Mitochondrial Membrane Potential of the WEHI-3B JCS Cells --- p.151 / Chapter 4.2.3 --- Effect of CLA-mix and its Isomer on the Expression of Apoptosis-regulatory Genes of the Bcl-2 Family in the WEHI-3B JCS Cells --- p.154 / Chapter 4.2.4 --- Effect of CLA-mix and its Isomer on the Expression of Apoptosis-regulatory Proteins in the WEHI-3B JCS Cells --- p.158 / Chapter 4.2.5 --- Effect of CLA-mix and its Isomer on the Induction of Caspase Activity in the WEHI-3B JCS Cells --- p.161 / Chapter 4.2.6 --- Effect of CLA-mix and its Isomer on the Induction of ROS in the WEHI-3B JCS Cells --- p.170 / Chapter 4.2.7 --- Effect of Antioxidants on the Induction of ROS by CLA-mix and its Isomer in the WEHI-3B JCS Cells --- p.173 / Chapter 4.2.8 --- Effect of Antioxidants on the Induction of Apoptosis by CLA-mix and its Isomer in the WEHI-3B JCS Cells --- p.176 / Chapter 4.2 --- Discussion / Chapter CHAPTER 5: --- STUDIES ON THE DIFFERENTIATION-INDUCING ACTIVITY OF CONJUGATED LINOLEIC ACID ON MYELOID LEUKEMIA CELLS / Chapter 5.1 --- Introduction --- p.187 / Chapter 5.2 --- Results --- p.190 / Chapter 5.2.1 --- Morphological Alterations in CLA-mix- and CLA isomer-treated WEHI-3B JCS Cells --- p.190 / Chapter 5.2.2 --- Effects of CLA-mix on the Cell Size and Granularity of WEHI-3B JCS Cells --- p.196 / Chapter 5.2.3 --- Studies of the Surface Phenotypic Changes in the CLA-mix-treated WEHI-3B JCS cells --- p.198 / Chapter 5.2.4 --- Studies on the Induction of Monocytic Serine Esterase (MSE) Activity in the CLA-mix-treated WEHI-3B JCS Cells --- p.200 / Chapter 5.2.5 --- Studies on the Induction of Endocytic Activity in the CLA-mix-treated WEHI-3B JCS Cells --- p.201 / Chapter 5.2.6 --- Studies on the Expression of the Differentiation-regulatory Cytokine Genes in the CLA-mix-treated WEHI-3B JCS Cells --- p.202 / Chapter 5.3 --- Discussion --- p.204 / Chapter CHAPTER 6: --- CONCLUSIONS AND FUTURE PERSPECTIVES REFERENCES --- p.208 / REFERENCES --- p.217

Chin, Chi Hou. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves [165]-178). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract in Chinese (摘要） --- p.iv / Acknowledgements --- p.vi / Abbreviations --- p.vii / List of Figures and Tables --- p.xi / Publications --- p.xv / Chapter Chapter 1 --- General Introduction / Chapter 1.1. --- Hematopoiesis and Leukemia --- p.2 / Chapter 1.1.1. --- Hematopoiesis --- p.2 / Chapter 1.1.2. --- Leukemia --- p.8 / Chapter 1.1.2.1. --- Overview of leukemia --- p.8 / Chapter 1.1.2.2. --- Symptoms and diagnosis of leukemia --- p.9 / Chapter 1.1.2.3. --- Classification of leukemia --- p.9 / Chapter 1.1.2.4. --- Epidemiology of leukemia --- p.13 / Chapter 1.1.2.5. --- Conventional treatments for leukemia --- p.15 / Chapter 1.1.2.6. --- Novel approaches to leukemia treatment --- p.18 / Chapter 1.2. --- Statins --- p.22 / Chapter 1.2.1. --- Overview of statins --- p.22 / Chapter 1.2.2. --- Chemical structures of statins --- p.24 / Chapter 1.2.3. --- Pharmacokinetics of statins --- p.26 / Chapter 1.2.4. --- Pleiotropic effects of statins --- p.29 / Chapter 1.2.4.1. --- Anti-inflammatory and immunomodulatory effects of statins --- p.29 / Chapter 1.2.4.2. --- Anti-angiogenic effects of statins --- p.30 / Chapter 1.2.4.3. --- Anti-tumor effects of statins --- p.31 / Chapter 1.3. --- Objectives and scope of the present study --- p.33 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1. --- Materials --- p.36 / Chapter 2.1.1. --- Animals --- p.36 / Chapter 2.1.2. --- Cell lines --- p.36 / Chapter 2.1.3. --- "Cell culture media, buffers and other reagents" --- p.37 / Chapter 2.1.3.1. --- Cell culture media and reagents --- p.37 / Chapter 2.1.3.2. --- Drugs and chemicals --- p.40 / Chapter 2.1.3.3. --- Reagents and buffers for primary culture --- p.42 / Chapter 2.1.3.4. --- Dye solutions --- p.43 / Chapter 2.1.3.5. --- Reagents for cell proliferation assays --- p.44 / Chapter 2.1.3.6. --- Reagents and buffers for flow cytometry --- p.44 / Chapter 2.1.3.7. --- Reagents for Hoechst staining --- p.45 / Chapter 2.1.3.8. --- Reagents and buffers for DNA isolation --- p.46 / Chapter 2.1.3.9. --- Reagents and buffers for DNA agarose gel electrophoresis --- p.48 / Chapter 2.1.3.10. --- Reagents and buffers for Cell Death ELISA --- p.50 / Chapter 2.1.3.11. --- Reagents and buffers for measuring caspase activity --- p.51 / Chapter 2.1.3.12. --- Reagents and buffers for Western blotting --- p.55 / Chapter 2.1.3.13. --- Reagents for determining nitric oxide production --- p.63 / Chapter 2.2. --- Methods --- p.64 / Chapter 2.2.1. --- Culture of tumor cell lines --- p.64 / Chapter 2.2.2. --- "Isolation, preparation and culture of murine peritoneal macrophages" --- p.64 / Chapter 2.2.3. --- Cell proliferation and cytotoxicity studies --- p.66 / Chapter 2.2.4. --- In vivo tumorigenicity study --- p.68 / Chapter 2.2.5. --- Cell cycle profile and flow cytometric analysis --- p.69 / Chapter 2.2.6. --- Hoechst staining --- p.69 / Chapter 2.2.7. --- DNA fragmentation analysis --- p.70 / Chapter 2.2.8. --- Cell Death ELISA --- p.71 / Chapter 2.2.9. --- Mitochondrial membrane potential analysis --- p.73 / Chapter 2.2.10. --- Measurement of caspase activity --- p.73 / Chapter 2.2.11. --- Protein expression study --- p.75 / Chapter 2.2.12. --- Cell morphological staining --- p.80 / Chapter 2.2.13. --- Cell size and granularity analysis by flow cytometry --- p.81 / Chapter 2.2.14. --- Determination of nitric oxide production by macrophages --- p.81 / Chapter 2.2.15. --- Statistical analysis --- p.82 / Chapter Chapter 3 --- Anti-Proliferative Effect of Statins on Myeloid Leukemia Cells / Chapter 3.1. --- Introduction --- p.84 / Chapter 3.2. --- Results --- p.86 / Chapter 3.2.1. --- Anti-proliferative effect of statins on various murine and human myeloid leukemia cells --- p.86 / Chapter 3.2.2. --- Cytotoxicity of fluvastatin on murine myelomonocytic leukemia WEHI-3B JCS cells --- p.93 / Chapter 3.2.3. --- Cytotoxicity of fluvastatin on primary murine myeloid cells --- p.96 / Chapter 3.2.4. --- Kinetic and reversibility studies on the anti-proliferative effect of fluvastatin on WEHI-3B JCS cells --- p.98 / Chapter 3.2.5. --- Relationship between the anti-proliferative effect of fluvastatin and the cholesterol biosynthesis pathway in WEHI-3B JCS cells --- p.102 / Chapter 3.2.6. --- Effect of fluvastatin on the in vivo tumorigenicity of WEHI-3B JCS cells --- p.106 / Chapter 3.2.7. --- Effect of fluvastatin on the cell cycle profile of WEHI-3B JCS cells --- p.108 / Chapter 3.2.8. --- Effect of fluvastatin on the expression of cell cycle regulatory proteins inWEHI-3B JCS cells --- p.113 / Chapter 3.3. --- Discussion --- p.116 / Chapter Chapter 4 --- Apoptosis- and Differentiation-inducing Effects of Fluvastatin on Murine Myelomonocytic Leukemia WEHI-3B JCS Cells / Chapter 4.1. --- Introduction --- p.124 / Chapter 4.2. --- Results --- p.128 / Chapter 4.2.1. --- Induction of chromatin condensation in WEHI-3B JCS cells by fluvastatin --- p.128 / Chapter 4.2.2. --- Induction of DNA fragmentation in WEHI-3B JCS cells by fluvastatin --- p.130 / Chapter 4.2.3. --- Effect of fluvastatin on the mitochondrial membrane potential in WEHI-3B JCS cells --- p.134 / Chapter 4.2.4. --- Effect of fluvastatin on the caspase activities in WEHI-3B JCS cells --- p.138 / Chapter 4.2.5. --- Effect of fluvastatin on the expression of pro-apoptotic protein AIF in WEHI-3B JCS cells --- p.144 / Chapter 4.2.6. --- Effect of fluvastatin on the morphology of WEHI-3B JCS cells --- p.147 / Chapter 4.2.7. --- Effect of fluvastatin on the cell size and granularity of WEHI-3B JCS cells --- p.149 / Chapter 4.2.8. --- Immunomodulation of murine peritoneal macrophages by fluvastatin --- p.151 / Chapter 4.3. --- Discussion --- p.153 / Chapter Chapter 5 --- Conclusions and Future Perspectives --- p.160 / References --- p.165