by Wong Che-cheuk, Dobe. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 98-112). / Abstract also in Chinese. / Acknowledgements --- p.i / Abstracts --- p.ii / List of Abbreviation --- p.vi / Table of Contents --- p.vii / Chapter 1. --- Introduction / Chapter 1.1 --- Stages of Cancer Development --- p.1 / Chapter 1.2 --- Comparison of Breast Cancer in Hong Kong & the United States --- p.2 / Chapter 1.2.1 --- Statistics of Breast Cancer in the United States --- p.2 / Chapter 1.2.2 --- Statistics of Breast Cancer in Hong Kong --- p.2 / Chapter 1.3 --- Factors for Breast Cancer --- p.6 / Chapter 1.3.1 --- Genetic Factor --- p.6 / Chapter 1.3.2 --- Hormonal Factor --- p.7 / Chapter 1.3.3 --- Genetic Bias --- p.9 / Chapter 1.3.4 --- Influence of Diet --- p.10 / Chapter 1.3.5 --- Obesity --- p.14 / Chapter 1.3.6 --- Xenoestrogen --- p.14 / Chapter 1.4 --- Hormonal Therapy in Breast Cancer --- p.15 / Chapter 1.4.1 --- Antiestrogen --- p.15 / Chapter 1.4.2 --- Progestin Antagonist --- p.19 / Chapter 1.4.3 --- Aromatase Inhibitor --- p.20 / Chapter 1.4.4 --- Gonadotropin Releasing Hormone (GnRH) Analogue --- p.23 / Chapter 1.5 --- Metabolism of Estrogen --- p.25 / Chapter 1.6 --- Substance with Chemopreventive Properties towards Breast Cancer --- p.29 / Chapter 1.7 --- Aryl Hydrocarbon Receptor --- p.33 / Chapter 1.8 --- Cytochrome P450s --- p.34 / Chapter 1.9 --- Yuehchukene --- p.36 / Chapter 1.10 --- Objectives of the Present Study --- p.38 / Chapter 2. --- Materials and Methods / Chapter 2.1 --- Animals --- p.40 / Chapter 2.2 --- Animal Treatment --- p.40 / Chapter 2.3 --- Preparation of Crude Microsomal Fraction --- p.41 / Chapter 2.4 --- Protein Assay --- p.41 / Chapter 2.5 --- Ethoxyresorufm-O-deethylase Assay --- p.41 / Chapter 2.6 --- Methoxyresorufin-O-deethylase Assay --- p.42 / Chapter 2.7 --- Estradiol-2-hydroxylase Assay --- p.42 / Chapter 2.8 --- Progesterone Hydroxylase Assay --- p.43 / Chapter 2.9 --- Hepatic Aromatase Activity Assay --- p.43 / Chapter 2.10 --- Inhibition of Ethoxyresorufm-O-deethylase and Estradiol-2-hydroxylase --- p.44 / Chapter 2.11 --- Free Radicals Scavenging Assay --- p.44 / Chapter 2.12 --- Chemicals --- p.45 / Chapter 3. --- Result / Chapter 3.1 --- Optimization of Condition --- p.47 / Chapter 3.1.1 --- Dosage --- p.47 / Chapter 3.1.2 --- Time for Sacrifice --- p.47 / Chapter 3.2 --- "Effect of Isoprenyl Compounds on the Body Weight, Liver Weight and Hepatic Microsomal Protein Content" --- p.50 / Chapter 3.3 --- Hepatic Enzyme Activities --- p.54 / Chapter 3.3.1 --- Ethoxyresorufm-O-deethylase --- p.54 / Chapter 3.3.2 --- Methoxyresorufm-O-deethylase --- p.57 / Chapter 3.3.3 --- Estradiol-2-hydroxylase --- p.60 / Chapter 3.3.4 --- Progesterone Hydroxylase --- p.62 / Chapter 3.3.5 --- Aromatase --- p.65 / Chapter 3.4 --- Effect of Inhibitors in Ethoxyresorufin-O-deethylase and Estradiol-2-hydroxylase Activity --- p.65 / Chapter 3.5 --- Free Radical Scavenging Activity --- p.72 / Chapter 4. --- Discussion --- p.77 / Chapter 5. --- Conclusion --- p.95 / Chapter 6. --- References --- p.98 / Chapter 7. --- Appendix --- p.113

by Winnie Yeo. / Thesis (M.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 213-256). / 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. / Mode of access: World Wide Web.

To Kin Wah. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 293-345). / 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.

Colon cancer, a disease in which malignant tumors form in the tissues of colon, is the first commonest cancer and the second leading cause of cancer-related deaths in Hong Kong. The standard treatment options for colon cancer include surgery and chemotherapy. However, multidrug resistance (MDR) develops in nearly all patients with colon cancer. In fact, most of the cancer-related deaths are due to chemotherapy failure caused by MDR, which occurs during the course of cancer progression and chemotherapy. Thus, the reversal of MDR plays an important role in the successful chemotherapy for colon cancer. This study investigated such a pharmacological action in reversing MDR in colon cancer cells by tanshinones, targeting the two common mechanisms responsible for MDR, i.e. overexpression of ATP-binding cassette (ABC) transporters and suppression of apoptosis. / Overexpression of P-glycoprotein (P-gp), one of the most important ABC transporters, can mediate the efflux of drugs out of cancer cells, leading to MDR and chemotherapy failure. The reversal of P-gp-mediated MDR by five tanshinones including tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone and miltirone was evaluated in colon cancer cells. Bi-directional transport assay showed that only cryptotanshinone and dihydrotanshinone decreased the P-gp-mediated digoxin efflux in Caco-2 cells. The two tanshinones potentiated the cytotoxicities of doxorubicin and irinotecan in P-gp overexpressing colon cancer SW620 Ad300 cells. Moreover, these two tanshinones also increased intracellular accumulation of P-gp substrate in SW620 Ad300 cells, presumably by down-regulating P-gp mRNA and protein levels, as well as inhibiting P-gp ATPase activity. / Suppression of apoptosis can lead to MDR in cancer cells to anticancer agents with pro-apoptotic property. Hence, this study also investigated the circumvention of resistance to apoptosis in drug resistant colon cancer cells by cryptotanshinone and dihydrotanshinone, two potential MDR-reversing tanshinones. The drug resistant SW620 Ad300 cells were still sensitive to both cryptotanshinone and dihydrotanshinone in the promotion of cell death. When compared with the parental SW620 cells, the two tanshinones induced less apoptosis but more autophagy in the drug resistant cells. Further studies showed that cell viability was increased after inhibition of autophagy by siRNA interference or autophagy inhibitor. Thus, autophagy induced by the two tanshinones was pro-cell death in SW620 Ad300 cells, which could overcome resistance to apoptosis. / In addition, suppression of apoptosis can be caused by p53 defects/mutations, which were found in more than 50% of all human cancers. Our results also showed that apoptosis and autophagy induced by cryptotanshinone and dihydrotanshinone were independent of the status of p53 in colon cancer cells. The p53-independent cytotoxic actions of the two tanshinones could be useful in overcoming resistance to apoptosis in cancer cells caused by p53 defects/mutations. / Taken together, the current findings indicate a great potential of cryptotanshinone and dihydrotanshinone in the reversal of MDR caused by P-gp overexpression and suppression of apoptosis. They are promising candidates to be further developed as therapeutic agents in the adjuvant therapy for colon cancer, especially for the multidrug resistant cancer types. / 結腸癌是指形成在結腸組織的惡性腫瘤，在香港常見的癌症中排第一位，亦是香港排第二位的致死癌症。結腸癌的標準治療方案主要包括手術和化療。然而，多藥耐藥是結腸癌成功化療的一個障礙。事實上，大多數癌症引起的死亡都和在癌症的發展和化療的過程中產生的多藥耐藥有關。因此，多藥耐藥的逆轉對於結腸癌的成功化療非常重要。本研究旨在通過針對多藥耐藥兩種常見的機制ABC跨膜蛋白的過表達和抑制的細胞凋亡來探討丹參酮對結腸癌細胞多藥耐藥的逆轉。 / P-gp的過表達可介導藥物排出癌細胞，從而導致多藥耐藥和化療失敗。本研究評價了tanshinone I，tanshinone IIA，cryptotanshinone，dihydrotanshinone和miltirone對P-gp介導的結腸癌細胞多藥耐藥的逆轉。雙向轉運實驗表明，只有cryptotanshinone和dihydrotanshinone可以減少P-gp介導的digoxin外排。這兩個丹參酮可以增加doxorubicin和irinotecan在P-gp過表達的結腸癌SW620 Ad300細胞中的毒性。此外，這兩個丹參酮也增加P-gp底物在SW620 Ad300細胞內的積累，推測是通過下調P-gp的mRNA和蛋白水平，以及抑制P-gp的ATP酶活性。 / 抑制的細胞凋亡可導致腫瘤細胞對促凋亡的抗癌藥物产生多藥耐藥。因此，本研究也探討了cryptotanshinone和dihydrotanshinone能否克服結腸癌細胞的凋亡耐受。結果表明cryptotanshinone和dihydrotanshinone仍然能够杀死耐藥的SW620 Ad300細胞。當與SW620細胞相比，這兩個丹參酮在耐藥細胞中誘導的細胞凋亡較少，但自噬增多。進一步研究表明，這兩個丹參酮誘導的自噬是促進細胞死亡的，從而可以克服細胞的凋亡耐受。 / 此外，p53的缺陷/突變存在於50%以上的人類癌症中，并可以抑制細胞產生凋亡。結果表明，cryptotanshinone和dihydrotanshinone誘導的凋亡和自噬與p53在結腸癌細胞中的表達無關。這兩個丹參酮不依賴於p53的細胞毒性可以用於克服p53缺陷/突變引起的凋亡耐受。 / 綜上所述，本研究結果表明cryptotanshinone和dihydrotanshinone在逆轉P-gp的過表達和抑制的細胞凋亡引起的多藥耐藥中具有巨大潛力。它們可以進一步發展為有前途的治療劑并用於結腸癌的輔助治療，尤其是用於多藥耐藥的結腸癌。 / Hu, Tao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 163-182). / Abstracts also in Chinese. / Title from PDF title page (viewed on 06, December, 2016). / Hu, Tao. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

by Wong Wah Yau. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 219-228.

by Lo Hoi Ka Elka. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 172-181). / Abstracts in English and Chinese. / ABSTRACT --- p.i / 摘要 --- p.iv / LIST OF TABLES AND FIGURES --- p.viii / ABBREVIATIONS --- p.xiv / Chapter CHAPTER 1 : --- INTRODUCTION / Chapter 1.1. --- DIFFERENT TREATMENTS OF THE CANCER THERAPY --- p.1 / Chapter 1.2. --- THE SIDE EFFECTS OF CANCER TREATMENT / Chapter 1.2.1. --- Surgery --- p.1 / Chapter 1.2.2. --- Radiotherapy --- p.2 / Chapter 1.2.3. --- Chemotherapy --- p.2 / Chapter 1.3. --- THE CHARACTERISTICS OF DOXORUBICIN (DOX) / Chapter 1.3.1. --- The structure of Dox --- p.6 / Chapter 1.3.2. --- The actions of Dox --- p.8 / Chapter 1.3.3. --- The adverse side effect of Dox --- p.8 / Chapter 1.4. --- THE RATIONALE OF USING LOW DENSITY LIPOPROTEIN (LDL) AS A TARGET CARRIER IN CANCER THERAPY / Chapter 1.4.1. --- The correlation between cholesterol and cancer --- p.9 / Chapter 1.4.2. --- Low density lipoprotein (LDL) as a target carrier --- p.11 / Chapter 1.4.3. --- The down and up regulation of LDL receptors --- p.14 / Chapter 1.4.4. --- The characteristics of Fuctus Craegus (FC) --- p.15 / Chapter 1.5. --- DIFFERENT METHODS OF THE PREPARATION OF THE LOW DENSITY LIPOPROTEIN-DRUG (LDL- DRUG) --- p.18 / Chapter 1.6. --- THE CHARACTERISTICS OF LOW DENSITY LIPOPROTEIN (LDL) / Chapter 1.6.1. --- The structure of LDL --- p.20 / Chapter 1.6.2. --- The metabolic pathway of LDL in human bodies --- p.23 / Chapter 1.7. --- THE MULTIDRUGS RESISTANCE IN TUMOR CELLS --- p.25 / Chapter 1.7.1. --- The mechanism of multidrug resistance --- p.27 / Chapter 1.7.2. --- The structure of P-glycoprotein --- p.27 / Chapter 1.7.3. --- The mechanism of P-glycoprotein --- p.30 / Chapter 1.8. --- COMBINED TREATMENT WITH HYPERTHERMIA --- p.31 / Chapter 1.9. --- AIM OF THE STUDY --- p.33 / Chapter CHAPTER 2 : --- MATERIALS AND METHODS / Chapter 2.1. --- MATERIALS / Chapter 2.1.1. --- Animals --- p.34 / Chapter 2.1.2. --- Buffers --- p.34 / Chapter 2.1.3. --- Cell culture reagents --- p.36 / Chapter 2.1.4. --- Chemicals --- p.38 / Chapter 2.1.5. --- Culture of cells --- p.40 / Chapter 2.2. --- METHODS / Chapter 2.2.1. --- In vitro studies / Chapter 2.2.1.1. --- "LDL, doxorubicin complex formation" --- p.41 / Chapter 2.2.1.2. --- Determination of the concentration of LDL-Dox --- p.42 / Chapter 2.2.1.3. --- In vitro cytotoxicity --- p.43 / Chapter 2.2.1.4. --- The cytotoxicity of the combined treatment with anticancer drugs --- p.44 / Chapter 2.2.1.5. --- The preparation of Fructus Crataegus (FC) --- p.46 / Chapter 2.2.1.6. --- Western blot --- p.47 / Chapter 2.2.1.7. --- Flow cytometry --- p.49 / Chapter 2.2.1.8. --- Confocal laser scanning microscopy --- p.52 / Chapter 2.2.2. --- In vivo studies / Chapter 2.2.2.1. --- Subcutaneous injection of R-HepG2 cells in nude mouse --- p.55 / Chapter 2.2.2.2. --- Treatment schedules --- p.55 / Chapter 2.2.2.3. --- Assay of investigating of the myocardial injury --- p.56 / Chapter 2.2.2.4. --- Tissue preparation procedure for light microscope (LM) --- p.57 / Chapter 2.2.3. --- Statistical analysis in our research --- p.59 / Chapter CHAPTER 3 : --- RESULTS / Chapter 3.1. --- in vitro STUDIES / Chapter 3.1.1. --- The preparation of low density lipoprotein-doxorubicin (LDL-Dox) --- p.60 / Chapter 3.1.2. --- Studies on human hepatoma cells line (HepG2 cells) / Chapter 3.1.2.1. --- The comparison of Dox and LDL-Dox accumulated in HepG2 cells --- p.63 / Chapter 3.1.2.2. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of Dox and LDL-Dox in HepG2 cells --- p.65 / Chapter 3.1.2.3. --- The comparsion of the cytotoxicity of Dox and LDL-Dox on HepG2 cells --- p.67 / Chapter 3.1.2.4. --- The comparison of the cytotoxicty of Dox and LDL-Dox with and without hyperthermia on HepG2 cells --- p.73 / Chapter 3.1.2.5. --- The comparison of accumulation of Dox and LDL-Dox in HepG2 cells treated with and without combination of with hyperthermia --- p.77 / Chapter 3.1.2.6. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of Dox and LDL-Dox in HepG2 treated cells with and without hyperthermia --- p.80 / Chapter 3.1.2.7. --- Modulation of LDL receptors on HepG2 cells------Up- regulation of LDL receptors by Fructus Craegtus (FC) / Chapter 3.1.2.7.1. --- The comparsion of LDL receptor expression on HepG2 cells after Fructus Craegtus (FC) pre-treatment --- p.83 / Chapter 3.1.2.7.2. --- The comparison of accumulation of LDL-Dox accumulated in HepG2 cells pre-treated with and without Fructus Craegtus (FC) --- p.85 / Chapter 3.1.2.7.3. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of LDL-Doxin HepG2 cells after Fructus Craegtus (FC) pre- treatment --- p.88 / Chapter 3.1.2.7.4. --- Cytotoxicity of combined treatment with LDL-Dox and Fructus Craegtus (FC) --- p.91 / Chapter 3.1.3. --- Studies on multidrug human resistant hepatoma cell line (R-HepG2 cells) / Chapter 3.1.3.1. --- The overexpression level of P-glycoprotein in resistant cell line R-HepG2 --- p.93 / Chapter 3.1.3.2. --- The comparison of Dox and LDL-Dox accumulated in R- HepG2 cells --- p.95 / Chapter 3.1.3.3. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of Dox and LDL-Dox in R-HepG2 cells --- p.97 / Chapter 3.1.3.4. --- The comparsion of the cytotoxicity of Dox and LDL-Dox on R-HepG2 cells --- p.99 / Chapter 3.1.3.5. --- The comparison of the cytotoxicty of Dox and LDL-Dox with and without hyperthermia on R-HepG2 cells --- p.109 / Chapter 3.1.3.6. --- The comparison of the accumulation of Dox and LDL- Dox in R-HepG2 cells treated in combination with hyperthermia --- p.113 / Chapter 3.1.3.7. --- Confocal laser scanning microscopic (CLSM) studies on the accumulation of Dox and LDL-Dox in R-HepG2 cells with and without hyperthermia --- p.117 / Chapter 3.1.3.8. --- Modulation of LDL receptors on R-HepG2 cells ------ Up-regulation of LDL receptors by Fructus Craegtus (FC) / Chapter 3.1.3.8.1. --- The comparsion of LDL receptor expression on R-HepG2 cells after Fructus Craegtus (FC) pre-treatment --- p.120 / Chapter 3.1.3.8.2. --- The comparsion of the accumulation of LDL- Dox in R-HepG2 cells after Fructus Craegtus (FC) pre-treatment --- p.122 / Chapter 3.1.3.8.3. --- Confocal laser scanning microscopic (CLSM) studies in the accumulation of LDL-Dox by Fructus Craegtus pre-treatment in R-HepG2 cells --- p.125 / Chapter 3.1.3.8.4. --- The comparison of cytotoxicity of combined treatment with LDL-Dox and Fructus Craegtus (FC) in R-HepG2 cells --- p.128 / Chapter 3.2. --- in vivo STUDIES / Chapter 3.2.1. --- The comparison of Dox and LDL-Dox on reducing the tumor sizes and weight in nude mice bearing R-HepG2 cells / Chapter 3.2.1.1. --- The comparison of Dox and LDL-Dox on reducing the tumor size in nude mice bearing R-HepG2 cells --- p.130 / Chapter 3.2.1.2. --- The comparison of Dox and LDL-Dox on reducing the tumor weight in nude mice bearing R-HepG2 cells --- p.138 / Chapter 3.2.2. --- Myocardial injury measured by Lactate dehydrogenase (LDH) activity in nude mice bearing R-HepG2 cells treated with Dox and LDL-Dox --- p.140 / Chapter 3.2.3. --- Myocardial injury measured by Creatine kinase (CK) activity in nude mice bearing R-HepG2 cells treated with Dox and LDL-Dox --- p.143 / Chapter 3.2.4. --- Histological studies of heart of nude mice bearing R-HepG2 cells treated with Dox and LDL-Dox / Chapter 3.2.4.1. --- Heart section of nude mice --- p.146 / Chapter 3.2.4.2. --- Heart section of nude mice bearing R-HepG2 cells --- p.148 / Chapter 3.2.4.3. --- Heart section of lmg/kg Dox treated nude mice bearing R- HepG2 cells --- p.150 / Chapter 3.2.4.4. --- Heart section of 2mg/kg Dox treated nude mice bearing R- HepG2 cells --- p.152 / Chapter 3.2.4.5. --- Heart section of lmg/kg LDL-Dox treated nude mice bearing R-HepG2 cells --- p.154 / Chapter CHAPTER 4 --- : DISCUSSION / Chapter 4.1. --- in vitro STUDIES / Chapter 4.1.1. --- The cytotoxicity of Dox and LDL-Dox on HepG2 cells and R- HepG2 cells --- p.156 / Chapter 4.1.2. --- The combined treatment on HepG2 cells and R-HepG2 cells --- p.157 / Chapter 4.1.3. --- The modulation of LDL-R expression --- p.159 / Chapter 4.2. --- in vivo STUDIES --- p.162 / Chapter CHAPTER 5 --- : CONCLUSION / Chapter 5.1. --- CONCLUSION / Chapter 5.1.1. --- In vitro studies --- p.167 / Chapter 5.1.2. --- In vivo studies --- p.169 / Chapter 5.2. --- FUTURE PROSPECTIVE --- p.170 / REFERENCES --- p.172

by Lai Mei Yi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 130-136). / Abstracts in English and Chinese. / Acknowledgment --- p.i / Abstract --- p.ii / 論文撮耍 --- p.v / List of Figures --- p.viii / List of Tables --- p.xi / Abbreviations --- p.xii / Table of content --- p.xiii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Facilitative glucose transporters --- p.1 / Chapter 1.1.1 --- Predicted Secondary structure of Glutl --- p.1 / Chapter 1.1.2 --- The tissue-specific distribution of glucose transporters --- p.2 / Chapter 1.2 --- Increase of glucose uptake in cancer cells --- p.5 / Chapter 1.3 --- Antisense oligonucleotide therapeutics --- p.7 / Chapter 1.3.1 --- Chemical modifications of oligonucleotides --- p.7 / Chapter 1.3.2 --- Cellular Uptake of Oligonucleotide --- p.11 / Chapter 1.3.3 --- Mechanism of action --- p.13 / Antisense-mediated RNA Cleavage --- p.14 / """Occupancy-only"" mediated mechanism" --- p.15 / Chapter 1.3.4 --- Antisense treatment in vivo --- p.17 / Chapter 1.4.5 --- Human Studies of Antisense Treatment --- p.18 / Chapter Chapter 2 --- Materials & Methods --- p.20 / Chapter 2.1 --- Materials --- p.20 / Chapter 2.2 --- Cell Culture --- p.21 / Chapter 2.2.1 --- Human colon adenocarcinoma cell Line (Caco-2) --- p.21 / Chapter 2.3 --- General Methodology for treatment of cells with antisense oligonucleotides --- p.22 / Chapter 2.3.1 --- Treatment of cells with oligonucleotides --- p.22 / Chapter 2.4 --- Cytotoxicity Assay --- p.23 / Chapter 2.4.1 --- MTT assay --- p.23 / Chapter 2.4.2 --- 3H-thymidine incorporation --- p.23 / Chapter 2.5 --- RNA extraction --- p.24 / Chapter 2.6 --- Competitive Reverse-transcription polymerase chain reaction (RT-PCR) of glucose transporters --- p.25 / Chapter 2.7 --- Measurement of 2-deoxy-D-glucose and Fructose transport --- p.27 / Chapter 2.8 --- Western blotting --- p.28 / Chapter 2.9 --- Flow cytometry --- p.30 / Chapter 2.9.1 --- Measurement of cellular accumulation of fluorophore-labeled oligonucleotide --- p.30 / Chapter 2.10 --- Design of antisense oligonucleotide --- p.31 / Chapter 2.11 --- ATP assay --- p.34 / Chapter 2.12 --- Animals studies --- p.35 / Chapter Chapter 3 --- Optimization of phosphorothioate antisense oligonucleotide delivery by Lipofectin --- p.36 / Chapter 3.1 --- Introduction --- p.36 / Chapter 3.2 --- Measurement of oligonucleotide uptake --- p.38 / Chapter 3.2.1 --- Lipofectin as a delivery system for the oligonucleotide uptake --- p.39 / Chapter 3.2.2 --- Effect of Lipofectin ratio on the oligonucleotide uptake --- p.41 / Chapter 3.2.3 --- Effect of oligonucleotide concentration on the oligonucleotide uptake --- p.41 / Chapter 3.2.4 --- Effect of incubation time on the oligonucleotide uptake --- p.44 / Chapter 3.2.5 --- Effect of oligonucleotide length on cellular uptake --- p.44 / Chapter 3.3 --- Effect of Lipofectin on cell viability --- p.47 / Chapter Chapter 4 --- In vitro effect of Antisense Oligonucleotides against glucose transporters on Caco-2 Cell --- p.49 / Chapter 4.1 --- Introduction --- p.49 / Chapter 4.2 --- Design of Antisense Oligonucleotides against Glucose Transporters gene --- p.50 / Chapter 4.3. --- Antisense effect of different regions of antisense oligonucleotide --- p.52 / Chapter 4.4 --- Antisense and Sense effect of oligonucleotide against start codon (G5 7015) on Caco-2 cells --- p.59 / Chapter 4.4.1 --- Effect of oligonucleotide to Lipofectin ratio on cell viability --- p.59 / Chapter 4.4.2 --- Dose-Response Study: effect of concentration of antisense - oligonucleotide on cell viability --- p.61 / Chapter 4.4.3 --- Effect of length´ؤof oligonucleotide on cell viability --- p.61 / Chapter 4.4.4 --- Time-Response Study: effect of antisense oligonucleotide on cell viability --- p.66 / Chapter 4.5 --- "The effect of antisense oligonucleotide against Glut1, Glut3 and Glut5 on cell viability of Caco-2 cells" --- p.70 / Chapter 4.6 --- Analysis of ATP content in Caco-2 cells by using antisense oligonucleotide flanking start codon (G5 7015) --- p.72 / Chapter 4.7 --- Effect of G5 7015 on HepG2 cells --- p.72 / Chapter Chapter 5 --- Effect of antisense oligonucleotides against Glut5 on mRNA and Protein levels of Glut5 gene --- p.76 / Chapter 5.1 --- Introduction --- p.76 / Chapter 5.2 --- RT-PCR of Glut isoform in Caco-2 cells --- p.77 / Chapter 5.3 --- Effect of antisense oligonucleotides against Glut 5 on mRNA level in Caco-2 cells --- p.77 / Chapter 5.3.1 --- Effect of oligonucleotides targeted different region of Glut5 gene on Glut5 message level --- p.77 / Chapter 5.3.2 --- Reduction in expression of mRNA level of Glut5 by using antisense oligonucleotides targeting start codon (G5 7015) --- p.81 / Chapter 5.3.3 --- Study of the dose and time dependence on inhibition of mRNA expression in G5 7015 treated Caco-2 cells --- p.83 / Chapter 5.3.4 --- Cross-Inhibition of antisense targeting glucose transporter isoforms --- p.83 / Chapter 5.4 --- Reduction in Glut5 protein level using G5 7015 antisense oligonucleotide --- p.86 / Chapter 5.5 --- Inhibition of Glut5 activity using G57015 oligonucleotide --- p.88 / Chapter 5.6 --- Inhibition of Glut5 mRNA level in vivo --- p.93 / Chapter Chapter 6 --- The possible role for Glucose Transporters in the Modification of Multidrug Resistance in Tumor cells --- p.95 / Chapter 6.1 --- Introduction --- p.95 / Chapter 6.2 --- Materials & Methods --- p.97 / Chapter 6.2.1 --- Cell culture --- p.97 / Chapter 6.2.2 --- Chemicals --- p.98 / Chapter 6.2.3 --- Measurement of doxorubicin uptake --- p.99 / Chapter 6.3 --- The expression of P-glycoprotein and Doxorubicin resistance of R-HepG2 cells --- p.99 / Chapter 6.4 --- Comparison of H3-2-deoxyglucose uptake between HepG2 and R-HepG2 cells --- p.99 / Chapter 6.5 --- Quantification of Glut1 and Glut3 expression by RT-PCR --- p.102 / Chapter 6.6 --- Comparison of doxorubicin between HepG2 and R-HepG2 cells cultured accumulation in glucose free medium --- p.104 / Chapter 6.7 --- The time course of doxorubicin accumulation in R-HepG2 cells culturing in glucose free medium --- p.106 / Chapter 6.8 --- "Cell viability of R-HepG2 cells after treatment of glucose transporter inhibitors, phloretin (PT), cytochalasin B (CB) and mitochondrial inhibitor，2,4-Dinitrophenol (DNP)" --- p.106 / Chapter 6.9 --- "Effect of glucose transporter inhibitors (PT, CB) and mitochondrial inhibitor (DNP) on doxorubicin accumulationin R-HepG2" --- p.110 / Chapter 6.10 --- Effect of antisense oligonucleotide against Glutl on doxorubicin accumulation in R-HepG2 cell --- p.113 / Chapter 6.11 --- "Analysis of ATP content and 3H-2-deoxy-D-glucose uptakein R-HepG2 after treatments of PT, CB and DNP" --- p.115 / Chapter Chapter 7 --- Discussion --- p.117 / Chapter 7.1 --- Antisense oligonucleotide against glucose transportersin Caco-2 cell --- p.117 / Chapter 7.2 --- Cellular uptake of oligonucleotide --- p.119 / Chapter 7.3 --- In vitro study of using antisense oligonucleotide against Glut5 --- p.121 / Chapter 7.4 --- In vivo study of using antisense oligonucleotide against Glut5 --- p.126 / Chapter 7.5 --- Possible role of inhibition of glucose transport in reversing P- gp --- p.127 / Chapter Chapter 8 --- References --- p.130

by Chow Ka Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 203-221). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Abstract in Chinese --- p.iv / List of Abbreviations --- p.vi / Table of Contents --- p.xi / List of Figures --- p.xviii / List of Tables --- p.xxii / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- The Characteristics of Arsenic Trioxide (AS2O3) --- p.2 / Chapter 1.2 --- The Therapeutic Applications of Arsenic Trioxide (As203) --- p.5 / Chapter 1.3 --- Acute Promyelocytic Leukemia (APL) --- p.6 / Chapter 1.3.1 --- Pathologies of APL --- p.7 / Chapter 1.3.2 --- All Trans Retinoic Acid (ATRA) Treatment of APL Patients --- p.7 / Chapter 1.3.3 --- Clinical Trials of Arsenic Trioxide (As203) on APL Patients --- p.9 / Chapter 1.3.4 --- In Vitro and In Vivo Studies of Arsenic Trioxide (As203) in the Treatment of APL --- p.10 / Chapter 1.3.4.1 --- Induction of Apoptosis --- p.11 / Chapter 1.3.4.2 --- Induction of Cell Differentiation --- p.11 / Chapter 1.3.5 --- General Toxicity and Side Effects of Arsenic Trioxide (AS2O3) on APL Patients --- p.12 / Chapter 1.4 --- Effects of Arsenic Trioxide (As203) on Other Primary Cancer Cells and Cancer Cell Lines --- p.12 / Chapter 1.5 --- Epidemiology of Breast Cancer --- p.14 / Chapter 1.6 --- Classification of Breast Cancer --- p.17 / Chapter 1.7 --- Etiology of Breast Cancer --- p.17 / Chapter 1.8 --- Hormones and Breast Cancer --- p.18 / Chapter 1.9 --- Estrogen Receptors (ER) --- p.20 / Chapter 1.9.1 --- Structures of Estrogen Receptors (ER) --- p.21 / Chapter 1.9.2 --- Estrogen Receptors (ER) Mediated Signaling Pathway --- p.22 / Chapter 1.9.2.1 --- Ligand Dependent Pathway --- p.22 / Chapter 1.9.2.2 --- Ligand Independent Pathway --- p.22 / Chapter 1.9.2.3 --- Estrogen Response Element (ERE)-Independent Pathway --- p.23 / Chapter 1.9.2.4 --- Non-Genomic Pathway --- p.23 / Chapter 1.9.3 --- Estrogen Receptors (ER) Regulated Gene Expression --- p.25 / Chapter 1.10 --- Current Therapy of Breast Cancer --- p.26 / Chapter 1.10.1 --- Hormonal Therapy (Anti-Estrogenicity) --- p.26 / Chapter 1.10.1.1 --- Tamoxifen --- p.26 / Chapter 1.10.1.2 --- Other Pure Anti-Estrogens --- p.28 / Chapter 1.10.2 --- Regulation of Estrogen Receptors (ER) and Transcription Coregulators --- p.29 / Chapter 1.10.3 --- Apoptosis Induction --- p.29 / Chapter 1.11 --- Aims of Study --- p.30 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.32 / Chapter 2.1 --- Materials --- p.33 / Chapter 2.1.1 --- Cell Lines and Culture Media --- p.33 / Chapter 2.1.1.1 --- Cell Lines --- p.33 / Chapter 2.1.1.2 --- Culture Media --- p.34 / Chapter 2.1.2 --- Chemicals --- p.35 / Chapter 2.1.3 --- Reagents and Buffers --- p.36 / Chapter 2.1.3.1 --- Reagents for MTT Assay --- p.36 / Chapter 2.1.3.2 --- Reagents for [methyl-3H] Thymidine Incorporation into DNA --- p.37 / Chapter 2.1.3.3 --- Reagents for Trypan Blue Exclusion Assay --- p.37 / Chapter 2.1.3.4 --- Reagents and Buffers for Western Blot Analysis --- p.37 / Chapter 2.1.3.5 --- Reagents and Buffers for Flow Cytometry --- p.40 / Chapter 2.1.3.6 --- Reagents and Buffers Reverse Transcription Polymerase Chain Reaction (RT-PCR) --- p.40 / Chapter 2.1.3.7 --- Reagents for Transfection and Luciferase Reporter Assay --- p.41 / Chapter 2.1.3.8 --- Reagents and Buffers for In Vivo Studies --- p.42 / Chapter 2.2 --- Methods --- p.42 / Chapter 2.2.1 --- In Vitro Studies --- p.42 / Chapter 2.2.1.1 --- Cell Treatment --- p.42 / Chapter 2.2.1.2 --- Drug Preparation --- p.43 / Chapter 2.2.1.3 --- MTT Assay --- p.43 / Chapter 2.2.14 --- Trypan Blue Exclusion Assay --- p.44 / Chapter 2.2.1.5 --- [methyl-3H] Thymidine Incorporation into DNA --- p.45 / Chapter 2.2.1.6 --- Detection of DNA Fragmentation --- p.45 / Chapter 2.2.1.7 --- ERα Competitive Binding Assay --- p.47 / Chapter 2.2.1.8 --- Cell Cycle Analysis by Flow Cytometry with Propidium Iodide (PI) Staining --- p.48 / Chapter 2.2.1.9 --- Cell Cycle Analysis by Flow Cytometry with Annexin V-PI Staining --- p.48 / Chapter 2.2.1.10 --- Cell Cycle Analysis by Flow Cytometry with JC-1 Staining --- p.49 / Chapter 2.2.1.11 --- Cell Cycle Analysis by Flow Cytometry with Hydroethidine (HE) Staining --- p.50 / Chapter 2.2.1.12 --- Western Blot Analysis of Proteins --- p.50 / Chapter 2.2.1.13 --- Assessment of the Transcriptional Activity of ERα --- p.55 / Chapter 3.2.1.14 --- Reverse Transcription Polymerase Chain Reaction (RT-PCR) --- p.57 / Chapter 2.2.2 --- In Vivo Studies --- p.61 / Chapter 2.2.2.1 --- Animal Models --- p.61 / Chapter 2.2.2.2 --- Treatment Schedules --- p.61 / Chapter 2.2.2.3 --- Sacrifice of Nude Mice --- p.61 / Chapter 2.2.2.4 --- Enzymatic Assays --- p.62 / Chapter 2.2.2.4.1 --- Aspartate Transaminase (AST) --- p.63 / Chapter 2.2.2.4.2 --- Alanine Transaminase (ALT) --- p.64 / Chapter 2.2.2.4.3 --- Creatine Kinase (CK) --- p.65 / Chapter 2.2.2.4.4 --- Lactate Dehydrogenase (LDH) --- p.66 / Chapter CHAPTER 3 --- "Effects of Arsenic Trioxide (As203) on Human Breast Adenocarcinoma Cell Line, MCF-7 Cell Line" --- p.68 / Chapter 3.1 --- Introduction --- p.69 / Chapter 3.2 --- Effect of As203 on Cell Survival of MCF-7 cells by MTT Assay --- p.70 / Chapter 3.3 --- Cytotoxicity of As203 on MCF-7 Cells by Trypan Blue Exclusion Assay --- p.72 / Chapter 3.4 --- Effect of As203 on DNA Synthesis and Cell Proliferation of MCF-7 cells by [methyl-3H] Thymidine Incorporation into DNA --- p.76 / Chapter 3.5 --- Comparison of Cytotoxicity of AS2O3 on MCF-7 Cells with that of Tamoxifen --- p.79 / Chapter 3.6 --- Summary --- p.82 / Chapter CHAPTER 4 --- Effects of Arsenic Trioxide (As203) on 17β Estradiol Stimulated MCF-7 cells --- p.83 / Chapter 4.1 --- Introduction --- p.84 / Chapter 4.2 --- Effect of 17β estradiol on Cell Viability of MCF-7 Cells by MTT Assay --- p.86 / Chapter 4.3 --- Effect of As203 and 17β Estradiol on Cell Survival of MCF-7 Cells by MTT Assay --- p.88 / Chapter 4.4 --- Cytotoxicity of As203 on 17β Estradiol Stimulated MCF-7 cells by Cell Number Counting with Hemacytometer --- p.92 / Chapter 4.5 --- Growth Inhibitory Effect of As203 on 17β Estradiol stimulated MCF-7 cells by [methyl-3H] Thymidine Incorporation into DNA --- p.94 / Chapter 4.6 --- "Effect of As203 on Cell Survival of Hormone Independent Breast Cancer Cell Line, MDA-MB-231 Cells" --- p.96 / Chapter 4.7 --- Summary --- p.100 / Chapter CHAPTER 5 --- Effects of Arsenic Trioxide (As203) on Normal Cells --- p.102 / Chapter 5.1 --- Introduction --- p.103 / Chapter 5.2 --- "Effect of As203 on Normal Human Fibroblast Cell Line, Hs68" --- p.104 / Chapter 5.3 --- Effects of As203 on the Normal Cells of Nude Mice --- p.106 / Chapter 5.3.1 --- Effect of AS2O3 on Aspartate Transaminase (AST) Activity of Nude Mice --- p.107 / Chapter 5.3.2 --- Effect of As203 on Alanine Transaminase (ALT) Activity of Nude Mice --- p.109 / Chapter 5.3.3 --- Effect of As203 on Creatine Kinase (CK) Activity of Nude Mice TABLE OF CONTENTS --- p.111 / Chapter 5.3.4 --- Effect of As203 on Lactate Dehydrogenase (LDH) Activity of Nude Mice --- p.113 / Chapter 5.4 --- Summary --- p.115 / Chapter CHAPTER 6 --- Action Mechanisms underlying the Survival Inhibitory Effects of Arsenic Trioxide (As203) on MCF-7 cells --- p.116 / Chapter 6.1 --- Introduction --- p.117 / Chapter 6.2 --- Detection of Apoptosis --- p.119 / Chapter 6.2.1 --- Detection of DNA Fragmentation --- p.119 / Chapter 6.2.2 --- Phosphatidylserine (PS) Externalization Detected by Flow Cytometry with Annexin V-PI Staining --- p.124 / Chapter 6.2.2.1 --- The Principle --- p.124 / Chapter 6.2.2.2 --- PS Externalization upon AS2O3 Treatment --- p.126 / Chapter 6.3 --- Analysis of Cell Cycle Distribution of MCF-7 Cells --- p.130 / Chapter 6.3.1 --- The Principle --- p.130 / Chapter 6.3.2 --- Regulation of Cell Cycle Distribution of MCF-7 Cells upon As2O3 Treatment --- p.131 / Chapter 6.4 --- The Action Mechanisms Underlying As203 Induced Apoptosis or Cell Cycle Arrest --- p.137 / Chapter 6.4.1 --- Effect of As203 on Mitochondrial Membrane Potential of MCF-7 Cells --- p.137 / Chapter 6.4.2 --- Regulation of Free Oxidative Species (ROS) Production in MCF-7 Cells upon AS2O3 Treatment --- p.140 / Chapter 6.4.2.1 --- Analysis of Superoxide Production in MCF-7 Cells upon AS2O3 Treatment by Flow Cytometry with Hydroethidine (HE) Staining --- p.140 / Chapter 6.4.2.2 --- Effect of As203 on Cell Survival of MCF-7 Cells Co-treated with N-Acteyl-L-Cysteine (NAC) by MTT Assay --- p.143 / Chapter 6.4.3 --- Regulation of Bcl-2 Protein Level in MCF-7 Cells upon As2O3 Treatment --- p.145 / Chapter 6.4.4 --- Regulation of p53 Protein Level in MCF-7 Cells upon AS2O3 Treatment --- p.147 / Chapter 6.5 --- Summary --- p.149 / Chapter CHAPTER 7 --- Effects of Arsenic Trioxide (As203) on Estrogen Receptor a (ERα) Mediated Signaling Pathway in MCF-7 cells --- p.150 / Chapter 7.1 --- Introduction --- p.151 / Chapter 7.2 --- Effect of As203 on Estrogen Binding to Estrogen Receptor a (ERα) by ERα Competitive Binding Assay --- p.152 / Chapter 7.3 --- Regulation of Estrogen Receptor a (ERα) mRNA Level upon As2O3 Treatment by RT-PCR --- p.156 / Chapter 7.4 --- Regulation of Estrogen Receptor a (ERα) Protein Level upon As2O3 Treatment --- p.159 / Chapter 7.5 --- Regulation of Estrogen Receptor a (ERα) Transcriptional Activity upon AS2O3 treatment --- p.161 / Chapter 7.6 --- "Regulation of Estrogen Target Gene, c-myc, Protein Level upon As2O3 Treatment" --- p.164 / Chapter 7.7 --- Effects of As203 on Cell Cycle Distribution of MCF-7 Cells under Estrogens Stimulation --- p.167 / Chapter 7.8 --- Summary --- p.173 / Chapter CHAPTER 8 --- Discussion --- p.174 / Chapter 8.1 --- The Anti-Tumor Effects of As203 on MCF-7 Cells --- p.175 / Chapter 8.2 --- Cytotoxicity of As203 on MCF-7 Cells --- p.175 / Chapter 8.2.1 --- Induction of Apoptosis in MCF-7 Cells upon As2〇3 Treatment --- p.176 / Chapter 8.2.2 --- Action Mechanisms Underlying the Induction of Apoptosis by As2〇3 --- p.178 / Chapter 8.3 --- Growth Inhibition of As203 on MCF-7 Cells --- p.182 / Chapter 8.3.1 --- Cell Cycle Regulation of MCF-7 Cells upon As203 Treatment --- p.182 / Chapter 8.4 --- Growth Inhibitory Effects of As203 on Estrogen Stimulated MCF-7 Cells --- p.186 / Chapter 8.4.1 --- Regulation of Estrogen Receptor a (ERα) Signaling Pathway in MCF-7 cells upon as2o3 Treatment --- p.188 / Chapter 8.5 --- Cross Talk of ERα Signaling Pathway and Apoptosis in Mediating the Anti-Tumor Effects of As203 on MCF-7 Cells --- p.195 / Chapter 8.6 --- Toxicity of AS2O3 towards Normal Tissues --- p.197 / Chapter CHAPTER 9 --- Conclusion and Future Perspectives --- p.200 / Chapter 9.1 --- Conclusion --- p.200 / Chapter 9.2 --- Future Perspectives --- p.202 / References --- p.203

by Lam Kai Yi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 156-165). / Abstract also in Chinese. / Chapter Chapter One: --- Introduction --- p.1 / Chapter 1.1 --- Tumor Necrosis Factor-α in Cancer Treatment --- p.1 / Chapter 1.1.1 --- Historical Background --- p.1 / Chapter 1.1.2 --- Mechanisms of Action --- p.2 / Chapter 1.1.2.1 --- Production of Reactive oxidative Species / Chapter 1.1.2.2 --- Increase of Intracellular Free Calcium Concentration / Chapter 1.1.2.3 --- Activation of Ca2+/Mg2+-dependent Endonuclease / Chapter 1.1.2.4 --- Decrease of glucose uptake and Protein Synthesis / Chapter 1.1.2.5 --- Formation of Ion-permeable Channel / Chapter 1.1.2.6 --- Activation of Phospholipase / Chapter 1.1.2.7 --- Increase of S-phase Cells / Chapter 1.1.2.8 --- Immunomodulatory Effects / Chapter 1.1.3 --- Resistance of Cells to TNF-α --- p.7 / Chapter 1.1.4 --- Clinical Studies --- p.11 / Chapter 1.1.5 --- Side Effects --- p.12 / Chapter 1.2 --- Hyperthermia and Cancer Treatment --- p.14 / Chapter 1.2.1 --- Hyperthermic Agents --- p.15 / Chapter 1.2.2 --- Intrinsic Heat Sensitivity --- p.15 / Chapter 1.2.3 --- Mechanisms of Action --- p.17 / Chapter 1.2.3.1 --- Depolarization of Membrane Potential / Chapter 1.2.3.2 --- "Reduction of glucose transport and DNA, mRNA and Protein Synthesis" / Chapter 1.2.3.3 --- Decrease of Intracellular pH / Chapter 1.2.3.4 --- Calcium Imbalance / Chapter 1.2.3.5 --- Effect on Nucleolar Protein / Chapter 1.2.3.6 --- Apoptosis / Chapter 1.2.3.7 --- Induction of Autologous Tumor Killing / Chapter 1.2.3.8 --- "Blood Flow, Tumor Oxygenation and Vascular Damage" / Chapter 1.2.4 --- Clinical Studies --- p.20 / Chapter 1.3 --- Combined Treatment --- p.21 / Chapter 1.3.1 --- Combined Treatment with TNF-α and Fixed-temperature Hyperthermia --- p.22 / Chapter 1.3.2 --- Combined Treatment with TNF + Step-down Hyperthermia --- p.22 / Chapter 1.3.3 --- In Vivo Study --- p.23 / Chapter 1.3.4 --- Sequence of Treatment --- p.24 / Chapter 1.3.5 --- Proposed Mechanism of Synergism --- p.24 / Chapter 1.4 --- Objective of Study --- p.26 / Chapter 1.4.1 --- Sequence of Treatments --- p.26 / Chapter 1.4.2 --- Comparison of Treatments' Effectiveness --- p.27 / Chapter 1.4.3 --- Effect on Normal Cell --- p.27 / Chapter 1.4.4 --- Effect on Distribution of Cells in Cell Cycle Phases --- p.28 / Chapter 1.4.5 --- In Vivo Study --- p.28 / Chapter Chapter Two: --- Materials and Methods --- p.30 / Chapter 2.1. --- Materials --- p.30 / Chapter 2.1.1 --- For Cell Culture --- p.30 / Chapter 2.1.2 --- In vitro Treatments --- p.31 / Chapter 2.1.3 --- DNA Electrophoresis --- p.31 / Chapter 2.1.4 --- Flow Cytometry --- p.32 / Chapter 2.2. --- Reagent Preparation --- p.33 / Chapter 2.2.1 --- Culture Media --- p.33 / Chapter 2.2.2 --- Human Recombinant Tumor Necrosis Factor alpha (rhTNF-α) --- p.33 / Chapter 2.2.3 --- Phosphate Buffered Saline (PBS) --- p.33 / Chapter 2.2.4 --- Lysis Buffer --- p.34 / Chapter 2.2.5 --- TE Buffer --- p.34 / Chapter 2.2.6 --- Proteinase K and Ribonuclease A (RNase A) --- p.34 / Chapter 2.2.7 --- 100 Base-Pair DNA Marker --- p.34 / Chapter 2.2.8 --- Propidium Iodide (PI) --- p.35 / Chapter 2.3 --- Methods --- p.35 / Chapter 2.3.1 --- Cell Culture --- p.35 / Chapter 2.3.1.1 --- Ehrlich Ascitic Tumor (EAT) and Human Leukemia (HL-60) / Chapter 2.3.1.2 --- Human Coronary Artery Endothelial Cells (HCAEC) / Chapter 2.3.2 --- In vitro Experiments --- p.36 / Chapter 2.3.3 --- Tumor Necrosis Factor Treatment --- p.37 / Chapter 2.3.4 --- Hyperthermia Treatments --- p.37 / Chapter 2.3.5 --- Cell Counting --- p.38 / Chapter 2.3.5.1 --- Trypan Blue Exclusion Assay / Chapter 2.3.5.2 --- Neutral Red Assay / Chapter 2.3.6 --- Determination of Additive or Synergistic Effect --- p.39 / Chapter 2.3.7 --- DNA Electrophoresis --- p.40 / Chapter 2.3.8 --- Flow Cytometry --- p.42 / Chapter 2.3.7.1 --- Preparation of Samples / Chapter 2.3.7.2 --- Flow Cytometry Acquisition / Chapter 2.3.7.3 --- Analysis / Chapter 2.3.9 --- In vivo Experiments --- p.44 / Chapter 2.3.8.1 --- Animal Strain / Chapter 2.3.8.2 --- Cell Line / Chapter 2.3.8.3 --- Tumor Necrosis Factor Treatment / Chapter 2.3.8.4 --- Hyperthermia Treatments / Chapter 2.3.8.5 --- Test of Body Temperature / Chapter 2.3.8.6 --- Cell Harvesting / Chapter Chapter Three: --- Result --- p.50 / Chapter 3.1 --- Optimal Sequence of Treatments --- p.50 / Chapter 3.1.1 --- Optimal Sequence of Treatments on Murine Ehrlich Ascitic Tumor (EAT) cells --- p.50 / Chapter 3.1.1.1 --- TNF + Fixed-temperature Hyperthermia / Chapter 3.1.1.2 --- TNF + Step-down Hyperthermia2 / Chapter 3.1.1.3 --- TNF + Step-down Hyperthermia3 / Chapter 3.1.2 --- Optimal Sequence of Treatments on Human Leukemia cells HL-60 --- p.60 / Chapter 3.1.2.1 --- TNF + Fixed-temperature Hyperthermia / Chapter 3.1.2.2 --- TNF + Step-Down Hyperthermia2 / Chapter 3.1.2.3 --- TNF + Step-Down Hyperthermia3 / Chapter 3.2 --- Comparison of Effectiveness of Treatments --- p.72 / Chapter 3.2.1 --- Effectiveness of Various treatments on EAT cells --- p.72 / Chapter 3.2.2 --- Synergistic Effect between rhTNF-α and Hyperthermia on EAT cells --- p.74 / Chapter 3.2.3 --- Decrease of Relative Growth and Viability of EAT with Time --- p.79 / Chapter 3.2.3.1 --- TNF + Fixed-temperature Hyperthermia / Chapter 3.2.3.2 --- TNF + Step-down Hyperthermia2 / Chapter 3.2.3.3 --- TNF + Step-down Hyperthermia3 / Chapter 3.2.4 --- Comparison of Effectiveness of Various Treatments on HL-60 cells --- p.82 / Chapter 3.2.5 --- Synergistic Effect between rhTNF-α and Hyperthermia on HL-60 cells --- p.87 / Chapter 3.2.6 --- Change of Relative Growth and Viability of HL-60 with Time --- p.90 / Chapter 3.2.6.1 --- TNF + Fixed-temperature Hyperthermia / Chapter 3.2.6.2 --- TNF + Step-down Hyperthermia2 / Chapter 3.2.6.3 --- TNF + Step-down hyperthermia3 / Chapter 3.3 --- Cell Death Pathway --- p.96 / Chapter 3.3.1 --- Experiments on Ehrlich Ascitic Tumor (EAT) Cells --- p.96 / Chapter 3.3.2 --- Experiments on Human Leukemia (HL-60) Cells --- p.100 / Chapter 3.4 --- Experiment on Normal Cell --- p.104 / Chapter 3.5 --- Effect of TNF + Fixed-temperature Hyperthermia on the Cell Cycle Progression --- p.107 / Chapter 3.5.1 --- Different Times of TNF Administration and Distribution of EAT cells in Cell cycle --- p.107 / Chapter 3.5.2 --- Different Times of TNF Administration and Distribution of HL-60 cells in Cell Cycle --- p.114 / Chapter 3.5.3 --- Shift of Cells Cycle after TNF Treatment --- p.120 / Chapter 3.5.3.1 --- Response of Ehrlich Ascitic Tumor Cells / Chapter 3.5.3.2 --- Response of Human leukemia Cells / Chapter 3.6 --- Effectiveness of Treatments in vivo: --- p.129 / Chapter 3.6.1 --- Dose-dependent Response --- p.129 / Chapter 3.6.2 --- Change of Body Temperature During Hyperthermia --- p.131 / Chapter 3.6.3 --- Comparison of Effectiveness of Various Treatments in vivo --- p.133 / Chapter 3.6.4 --- Synergistic Effect Between rhTNF-α and Hyperthermia in vivo --- p.135 / Chapter Chapter Four: --- Discussion --- p.138 / Chapter 4.1 --- Optimal Sequence of Treatments --- p.139 / Chapter 4.2 --- Comparison of Various Treatments --- p.143 / Chapter 4.3 --- Distribution of Cells in Cell Cycle Phases --- p.149 / Chapter 4.4 --- In vivo Study --- p.153 / Chapter Chapter Five: --- References --- p.156

by Leung Wing Chung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 67-68). / Abstract also in Chinese. / Chapter 1 --- Background and Modelling --- p.5 / Chapter 1.1 --- Treatment of Cancer --- p.5 / Chapter 1.2 --- Tumour Growth Model ´ؤ Gompertz Model --- p.5 / Chapter 1.3 --- Drug Concentration and Drug Effects --- p.7 / Chapter 1.3.1 --- Drug Effects on Tumour Cells --- p.9 / Chapter 1.3.2 --- "Drug Effects with Different Values of λG,k, vth" --- p.9 / Chapter 1.4 --- Constraints on the Gompertz Model --- p.11 / Chapter 2 --- Minimization on the Gompertz Model --- p.12 / Chapter 2.1 --- Mathematical Modelling on the Gompertz Model --- p.12 / Chapter 2.1.1 --- Constraints Transformation --- p.13 / Chapter 2.2 --- Simplified Minimization Problem --- p.15 / Chapter 2.2.1 --- Avoiding Non-Minimal Stationary Points --- p.16 / Chapter 2.2.2 --- The Final Minimization Problem --- p.23 / Chapter 2.2.3 --- Existence of Optimal Solutions --- p.24 / Chapter 2.3 --- Gradients of the Objective Function and the Constraints --- p.25 / Chapter 2.3.1 --- First Derivatives --- p.25 / Chapter 2.3.2 --- Second Derivatives --- p.29 / Chapter 3 --- Numerical Methods for Minimization Problems --- p.31 / Chapter 3.1 --- Lagrangian Multiplier Method --- p.32 / Chapter 3.1.1 --- Kuhn-Tucker Condition --- p.33 / Chapter 3.1.2 --- Model Augmented Lagrangian Algorithm --- p.34 / Chapter 3.1.3 --- Armijo Algorithm --- p.36 / Chapter 3.1.4 --- Modified Augmented Lagrangian Algorithm --- p.40 / Chapter 3.2 --- Data on the Gompertz Model --- p.42 / Chapter 3.2.1 --- Optimality of Solutions --- p.42 / Chapter 3.3 --- Numerical Results --- p.45 / Chapter 3.4 --- Well-Conditioned Penalty Function Method for Constrained Optimization --- p.56 / Chapter 3.5 --- Discussion --- p.64 / Chapter 3.5.1 --- Model Augmented Lagrangian Algorithm and Modified Augmented Lagrangian Algorithm --- p.65 / Chapter 3.5.2 --- Modified Augmented Lagrangian Algorithm and Penalty Function Algorithm --- p.65 / Bibliography