By using the acridine orange (AO) staining method to examine the release of contents from lysosomes, it was found that PD released AO into the cytosol in both cell lines. However, the releasing pattern of HepG2 and RHepG2 was quite different. Upon PD treatment, the release of AO in HepG2 cells was graduate and slow while that in RHepG2 was sudden and sharp. / Cancer is one of the leading causes of death in the world. During cancer treatment, development of multidrug resistance (MDR) is always the major cause of failures of chemotherapy in human cancers. In our project, hepatocarcinoma HepG2 and its drug-resistant derivatives RHepG2 with MDR towards doxorubicin (Dox), fenretinide and Taxol were used to examine the differences in their response towards various anti-cancer agents. / From the AO staining, most of the lysosomes were found in the cytosol near the nucleus. However, some lysosomes were found inside the nucleus occasionally. When we double stained the HepG2 cells with DiOC6(3), it was found that the lysosomes were actually located inside the nuclear tubules. However, no such lysosome migration was observed after treating the HepG2 cells with PD. Thus, lysosomes inside the nuclear tubules might not be involved in the PD-induced lysosomal pathway. The mechanism that leads to the migration of lysosomes into the nuclear tubules is still unclear. / From the Western blot analysis, cathepsin D (Cat D) and cathepsin L (Cat L) were both released from the lysosomes after treating the two cell lines with PD. Also, it seemed likely that Cat L was released earlier than that of cyt c. This implies that lysosomal permeabilization is an early event in apoptosis. With the use of siRNA technology, it was found that RHepG2 with the knockdown of Cat D and Cat L were more tolerant and vulnerable towards PD, respectively. These suggest that Cat D and Cat L might act oppositely in the apoptotic pathway. Furthermore, the addition of Cat D inhibitor, pepstatin A, blocked the PD-mediated cell death in RHepG2 cells further confirms that Cat D is a pro-apoptotic protein that is involved in the apoptotic pathway. / In conclusion, PD was a potent anti-cancer agent that could reverse the MDR properties of RHepG2 and kill more RHepG2 cells through lysosomal and mitochondrial apoptotic pathway. / Next, we investigated the underlying killing mechanism and found out that PD switched on both the mitochondrial and lysosomal apoptotic pathway in both cell lines. Our results indicate that PD was able to depolarize mitochondrial membrane potential and release apoptosis inducing factor (AIF) and cytochrome c (cyt c) from the mitochondria to cytosol. Also, PD was able to act on isolated mitochondria directly, causing a stronger mitochondrial membrane permeabilization and more AIF release from the RHepG2 than that of the parental cells. / Polyphyllin D (PD) is a saponin found in a tradition Chinese herb, Paris polyphylla, which has been used to treat liver cancers in China for many years. Interestingly, from the MTT assays, we found out that RHepG2 (IC50: 2.0 muM) was more sensitive towards PD when compared to that of its parental cells (IC50: 3.9 muM). To keep the MDR properties, RHepG2 cells were routinely cultured with 1.2 muM of Dox. When we cultured RHepG2 in the absence of Dox but with 1.2 muM of PD for 28 days, the Pgp expression could not be maintained. However, such high expression level of Pgp was maintained when RHepG2 cells were treated with vincristine (1.2 muM) in the absence of Dox. This indicates that vincristine was a substrate of Pgp to keep the Pgp expression in RHepG2 cells while PD was not. / When incubated with different concentrations of Dox, RHepG2 accumulated less Dox than that of its parental HepG2 cells. When probed by the antibody against P-glycoprotein (Pgp), RHepG2 showed a strong Pgp expression. With the addition of Pgp modulator, verapamil, RHepG2 accumulated more Dox. All these findings indicate that Pgp is a mediator giving rise the MDR in RHepG2 cells. However, RHepG2 had a higher resistance to Dox than its parental line even co-cultured with verapamil. RHepG2 remained viable at the intracellular Dox concentration that was toxic to HepG2 cells. These observations suggest that the MDR properties of RHepG2 involved multiple mechanisms in addition to the effect of Pgp. / Lee, Kit Ying Rebecca. / "August 2007." / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4735. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 241-253). / 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.

Eleven known compounds were separated from Oldenlandia diffusa using the bioassay-guided methods. Among which, heptatriacontane and stearic acid (SA) were isolated from this herb for the first time. The anti-proliferative activities of ursolic acid (UA) and SA, as well as the anti-proliferative and immunomodulatory activities of quercetin, kaempferol, quercetin-3-O-D-glucoside, kaempferol-3-O-D-glucoside and kaempferol-3-O-D-galactoside, are responsible for the anti-hepatomatic effect of OD, to which UA might be the major contributor due to relatively high content in OD and potent cytotoxicity. / In conclusion, our findings provided a better elucidation on phytochemical basis responsible for the anti-cancer activities of OD and AU, and also suggested the potential of UA, SB and SD as new chemotherapeutic agents for the treatment of liver cancer in further studies. / Mechanistic study indicated that anti-proliferative effects of SB and SD due to induction of apoptosis on both HepG2 and R-HepG2 cells were established by sub-G1 accumulation in cell cycle profile and cell population with PS externalization, which were confirmed by activation of apoptosis mediators PARP and caspase-3. The induction of apoptosis was suggested to be mediated by both extrinsic and intrinsic pathways, as evidenced by activation of caspase-8 and -9, up-regulation of Bcl-XS, dysfunction of mitochondria and release of cytochrome c during SB and SD treatment. Besides, Bcl-2 and Bax expression levels were notably different on SB/SD-treated HepG2 and R-HepG2 cells, which implied that Bcl-2 and Bax might play a role in SB and SD modulation of drug resistance on R-HepG2 cells. / Motivated by the serious health hazard worldwide caused by hepatoma and side effects of chemotherapeutic agents in clinical treatment, we have initiated a research project to isolate and characterize bioactive compounds from Oldenlandia diffusa (OD) and Androsace umbellata (AU) as well as to study the molecular mechanisms of their anti-proliferative effects on human hepatoma cells. / On the other hand, phytochemical study of Androsace umbellata led to isolation of two novel triterpenoid sapogenins and five known compounds (3-O-D-glucosyl-(1→2)-L-arabinosyl cyclamiretin A, primulanin, saxifragifolin B, saxifragifolin C and saxifragifolin D). Their anti-tumor effects were firstly reported here, where saxifragifolin B (SB) and saxifragifolin (SD) showed the most potent cytotoxicities on human hepatoma cells. Structure-activity relationship study revealed that introduction of glucosyl moiety might be useful for the enhancement of cytotoxicity of this chemotype. / The action mechanism of UA has been intensively investigated. Our results showed that UA was not a substrate of p-glycoprotein, and it could bypass multidrug resistance of R-HepG2 cells. Furthermore, UA treatment also resulted in apoptotic cell death which was indicated by cell morphology observation, cell cycle analysis, DNA fragmentation and Annexin V-FITC/PI double staining assay. UA-induced apoptosis was associated with the extrinsic (death receptor-mediated) pathway, which was suggested by increase of FasL expression, activation of caspase-8 and caspase-3 as well as cleavage of PARP. Besides, changes implying the intrinsic (mitochondria-mediated) apoptotic pathway, including up-regulation of p53 and Bax, down-regulation of Bcl-2, cleavage of Bid, collapse of Deltapsi m, leakage of cytochrome c and AIF as well as activation of caspase-9, were also observed on R-HepG2 cells after UA treatment. Moreover, elevation of cytosolic calcium concentration, generation of reactive oxygen species and activation of MAPKs pathway were involved in UA-induced apoptosis. Proteomic analysis exhibited significant changes in the expression level of twelve proteins which were involved in tumor cell proliferation, invasion and apoptosis. / Zhang, Dongmei. / "September 2007." / Adviser: Kwok-Pui Fung. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4744. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 239-263). / 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.

Hung Sau Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 131-137). / Table of Contents --- p.1 / Acknowledgements --- p.V / Abbreviations --- p.VI / Aim of investigation --- p.IX / Abstract --- p.XI / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Cancer Chemotherapy --- p.2 / Chapter 1.2 --- Plants as sources of useful drugs --- p.4 / Chapter 1.3 --- Potent antitumor compounds found in Goniothalamus giganteus --- p.7 / Chapter 1.4 --- Brief introduction of GONIOTRIOL --- p.8 / Chapter 1.5 --- The study on the antitumor activities of the antitumor compounds --- p.9 / Chapter 1.6 --- Biochemistry study of the anticancer agents --- p.10 / Chapter Chapter 2 --- Materials and Methods --- p.18 / Chapter 2.1 --- Materials --- p.19 / Chapter 2.1.1 --- Animals --- p.19 / Chapter 2.1.2 --- "Buffers, Culture Media and Chemicals" --- p.19 / Chapter 2.1.3 --- Cell lines --- p.20 / Chapter 2.1.4 --- Dye solutions --- p.21 / Chapter 2.1.5 --- Reagents and buffers for Agarose gel --- p.21 / Chapter 2.1.6 --- Synthetic goniotriol and its derivatives --- p.21 / Chapter 2.2 --- Methods --- p.23 / Chapter 2.2.1 --- Radioactive Precursor Incorporation Assays --- p.23 / Chapter 2.2.2 --- MTT assay --- p.24 / Chapter 2.2.3 --- Neutral Red assay --- p.24 / Chapter 2.2.4 --- Isolation and preparation of cells --- p.25 / Chapter 2.2.5 --- Assay for the solvent effect --- p.25 / Chapter 2.2.6 --- Assay for the in vitro antitumor activity THC88 on different cell lines --- p.27 / Chapter 2.2.7 --- Assay of the effect of THC86 on solid sarcoma Scl80 in vivo --- p.28 / Chapter 2.2.8 --- Assay of the effect of THC86 on peritoneal Scl80 in vivo --- p.28 / Chapter 2.2.9 --- Assay of the effect of THC89 on peritoneal EAT in vivo --- p.28 / Chapter 2.2.10 --- Assay of synthetic compound (THC89 and THC87) on the mitogenic activity of spleen lymphocytes --- p.29 / Chapter 2.2.11 --- Assay of synthetic compound (THC87) on the proliferation of murine bone marrow cells from compound- treated mice --- p.30 / Chapter 2.2.12 --- "Assay of synthetic compounds (Ml, P51 and P1) on nonmalignant cell-line" --- p.31 / Chapter 2.2.13 --- Assay of antitumor activity of synthetic compound (THC86)on PU5-1.8 --- p.31 / Chapter 2.2.14 --- Assay of the cytocidal effect of THC86 --- p.32 / Chapter 2.2.15 --- "Assay on the effect of THC86 on the synthesis of DNA, RNA and protein" --- p.32 / Chapter 2.2.16 --- Direct DNA cleavage by THC86 --- p.33 / Chapter 2.2.17 --- DNA fragmentation assay / Chapter 2.2.18 --- Assay of the effect of the synthetic compound (THC86) on different growth fraction of the cells / Chapter 2.2.19 --- Mitosis Study / Chapter 2.2.20 --- Assay for the stability of the synthetic compounds / Chapter Chapter 3 --- Structure / activity relationship of the synthetic compounds --- p.36 / Chapter 3.1 --- Results --- p.37 / Chapter 3.1.1 --- In vitro antitumor activity of the synthetic compounds --- p.37 / Chapter 3.2 --- Discussion --- p.45 / Chapter Chapter 4 --- Antitumor activities of the synthetic compounds --- p.63 / Chapter 4.1 --- Results --- p.64 / Chapter 4.1.1 --- Solvent effect in the screening process --- p.64 / Chapter 4.1.2 --- The effect of the synthetic compound (THC88) on different cell lines --- p.69 / Chapter 4.1.3 --- In vivo anti-tumor activities of the synthetic compounds --- p.71 / Chapter 4.1.3a --- Effect of THC86 on solid sarcoma Sc180 in vivo --- p.71 / Chapter 4.1.3b --- Effect of THC86 on peritoneal Scl80 in vivo --- p.71 / Chapter 4.1.3c --- Effect of THC89 on peritoneal EAT in vivo --- p.72 / Chapter 4.1.4 --- Cytotoxic effect of the tested compounds on normal cells --- p.77 / Chapter 4.1.4a --- Cytotoxic effect of THC89 on normal splenocytes in vitro --- p.77 / Chapter 4.1.4b --- Effect of THC87 on the proliferation of splenocytes --- p.77 / Chapter 4.1.4c --- Effect of THC87 on the proliferation of murine bone marrow cells --- p.78 / Chapter 4.1.4d --- Cytotoxic effect on non-malignant cell-line BALB/c 3T3/A31 --- p.78 / Chapter 4.2 --- Discussion --- p.85 / Chapter Chapter 5 --- The study on the antiproliferative mechanisms of the synthetic compounds --- p.88 / Chapter 5.1 --- Results --- p.89 / Chapter 5.1.1 --- "Effect of the synthetic compounds on Cell Growth, DNA, RNA and Protein" --- p.89 / Chapter 5.1.1a --- Effect of THC86 on PU5-1.8 (macrophage-like tumor) --- p.89 / Chapter 5.1.1b --- Cytocidal effect of THC86 on EAT --- p.89 / Chapter 5.1.1c --- "Effect of the synthetic compounds on synthesis of DNA, RNA and protein" --- p.90 / Chapter 5.1.2 --- Study of the synthetic compounds on the interactions of DNA --- p.101 / Chapter 5.1.2a --- DNA cleavage assay --- p.101 / Chapter 5.1.2b --- DNA fragmentation assay --- p.101 / Chapter 5.1.3 --- Effect of the synthetic compounds on different growth fraction of the cells --- p.104 / Chapter 5.1.4 --- Mitosis study of the synthetic compounds --- p.106 / Chapter 5.1.5 --- Investigation of the stability of the synthetic compounds in culture medium --- p.112 / Chapter 5.2 --- Discussion --- p.117 / Chapter Chapter 6 --- General Discussion --- p.122 / References --- p.131

Wong Chun-kwan. / Thesis submitted in: December 1999. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 127-137). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgments --- p.viii / Tables of Contents --- p.ix / List of Figures --- p.xv / List of Tables --- p.xxvi / Chapter Chapter 1: --- INTRODUCTION --- p.1 / Chapter Chapter 2: --- LITERATURE REVIEW --- p.8 / Chapter 2.1 --- Toxicology --- p.8 / Chapter 2.1.1 --- Acute toxicity test --- p.8 / Chapter 2.1.2 --- Biochemical Analysis --- p.9 / Chapter 2.1.3 --- Organ weights --- p.10 / Chapter 2.2 --- Histology --- p.11 / Chapter 2.2.1 --- Light Microscope --- p.11 / Chapter 2.2.2 --- Electron Microscopy --- p.11 / Chapter 2.3 --- Tissue injury --- p.12 / Chapter 2.3.1 --- Free-radical mechanisms --- p.12 / Chapter 2.3.2 --- Lipid peroxidation --- p.13 / Chapter 2.4 --- Carbon tetrachloride (CC14) --- p.14 / Chapter 2.4.1 --- Mechanisms of carbon tetrachloride toxicity --- p.15 / Chapter 2.5 --- Trichloroethylene (TCE) --- p.18 / Chapter 2.5.1 --- Mechanisms of trichloroethylene toxicity --- p.21 / Chapter 2.6 --- Dimethyl sulfoxide (DMSO) --- p.25 / Chapter 2.7 --- N-acetylcysteine (NAC) --- p.27 / Chapter Chapter 3: --- MATERIALS AND METHODS --- p.28 / Chapter 3.1 --- Materials --- p.28 / Chapter 3.2 --- Methods --- p.31 / Chapter 3.2.1 --- Acute hepatotoxicity test on aqueous seaweed extracts --- p.31 / Chapter 3.2.1.1 --- Preparation of aqueous extracts of seaweed --- p.31 / Chapter 3.2.1.2 --- Experimental protocol --- p.31 / Chapter 3.2.1.3 --- Biochemical assays --- p.32 / Chapter 3.2.1.4 --- Organ weights --- p.36 / Chapter 3.2.1.5 --- Histopathological examination --- p.36 / Chapter 3.2.1.6 --- Statistical analysis --- p.36 / Chapter 3.2.2 --- Curative and preventive tests of seaweed aqueous extracts against the CCl4-induced hepatotoxicity --- p.37 / Chapter 3.2.2.1 --- Preparation of aqueous extracts of seaweed --- p.37 / Chapter 3.2.2.2 --- Experimental protocol --- p.37 / Chapter 3.2.2.3 --- Biochemical assays --- p.39 / Chapter 3.2.2.4 --- Organ weights --- p.39 / Chapter 3.2.2.5 --- Histopathological examination --- p.40 / Chapter 3.2.2.6 --- Statistical analysis --- p.41 / Chapter 3.2.3 --- Acute hepatotoxicity test of TCE in rats by oral and intraperitoneal routes --- p.42 / Chapter 3.2.3.1 --- Experimental protocol --- p.42 / Chapter 3.2.3.2 --- Biochemical assays --- p.43 / Chapter 3.2.3.3 --- Organ weights --- p.43 / Chapter 3.2.3.4 --- Histopathological examination --- p.44 / Chapter 3.2.3.5 --- Statistical analysis --- p.44 / Chapter 3.2.4 --- Curative and preventive tests of seaweed aqueous extracts against the TCE effective dose-induced toxicity --- p.44 / Chapter 3.2.4.1 --- Preparation of aqueous extracts of seaweed --- p.44 / Chapter 3.2.4.2 --- Experimental protocol --- p.45 / Chapter 3.2.4.3 --- Biochemical assays --- p.46 / Chapter 3.2.4.4 --- Organ weights --- p.46 / Chapter 3.2.4.5 --- Histopathological examination --- p.46 / Chapter 3.2.5 --- Antidotal effects of dimethyl sulfoxide (DMSO) and N-acetylcysteine (NAC) against CC14- and TCE- induced poisoning in rats --- p.47 / Chapter 3.2.5.1 --- Experimental protocol --- p.47 / Chapter 3.2.5.2 --- Biochemical assays --- p.48 / Chapter 3.2.5.3 --- Organ weights --- p.48 / Chapter 3.2.5.4 --- Histopathological examination --- p.49 / Chapter 3.2.6 --- Hepatoprotective effect of seaweeds' methanol extract against CC14- and TCE-induced poisoning in rats --- p.49 / Chapter 3.2.6.1 --- Preparation of methanol extracts of seaweed --- p.49 / Chapter 3.2.6.2 --- Experimental protocol --- p.50 / Chapter 3.2.6.3 --- Biochemical assays --- p.52 / Chapter 3.2.6.4 --- Organ weights --- p.52 / Chapter 3.2.6.5 --- Histopathological examination --- p.53 / Chapter Chapter 4 --- RESULTS --- p.54 / Chapter 4.1 --- Acute hepatotoxicity test on aqueous seaweed extracts --- p.54 / Chapter 4.1.1 --- The biochemical assays of the serum transaminase activity --- p.54 / Chapter 4.1.2 --- The organ weight (Aqueous seaweed crude extracts) --- p.56 / Chapter 4.2 --- Curative and preventive tests of seaweed aqueous extracts against the CCl4-induced hepatotoxicity --- p.58 / Chapter 4.2.1 --- The biochemical assays of the serum transaminase activity (Curative) --- p.58 / Chapter 4.2.2 --- The organ weight (Curative) --- p.60 / Chapter 4.2.3 --- The biochemical assays of the serum transaminase activity (Preventive) --- p.62 / Chapter 4.2.4 --- The organ weight (Preventive) --- p.64 / Chapter 4.3 --- Acute hepatotoxicity test of TCE in rats by oral and intraperitoneal routes --- p.66 / Chapter 4.3.1 --- Oral route --- p.66 / Chapter 4.3.1.1 --- One-time oral route --- p.66 / Chapter 4.3.1.2 --- Two-time oral route --- p.66 / Chapter 4.3.2 --- Intraperitoneal route --- p.66 / Chapter 4.3.3 --- Time course of the effective dose of 20% TCE in i.p. route --- p.67 / Chapter 4.4 --- Curative and preventive tests of seaweed aqueous extracts against the TCE effective dose-induced toxicity --- p.12 / Chapter 4.4.1 --- The biochemical assays of the serum transaminase activity (Curative) --- p.72 / Chapter 4.4.2 --- The organ weight (Curative) --- p.74 / Chapter 4.4.3 --- The biochemical assays of the serum transaminase activity (Preventive) --- p.76 / Chapter 4.4.4 --- The organ weight (Preventive) --- p.78 / Chapter 4.5 --- Antidotal effects of dimethyl sulfoxide (DMSO) and N-acetylcysteine (NAC) against CC14- and TCE-induced poisoning in rats --- p.80 / Chapter 4.5.1 --- The biochemical assays of the serum transaminase activity (Curative) --- p.80 / Chapter 4.5.2 --- The organ weight (Curative) --- p.82 / Chapter 4.5.3 --- The biochemical assays of the serum transaminase activity (Preventive) --- p.84 / Chapter 4.5.4 --- The organ weight (Preventive) --- p.86 / Chapter 4.6 --- Hepatoprotective effect of methanol extract of seaweed against CC14- and TCE-induced poisoning in rats --- p.88 / Chapter 4.6.1 --- The biochemical assays of the serum transaminase activity (Curative) --- p.88 / Chapter 4.6.2 --- The organ weight (Curative) --- p.89 / Chapter 4.7 --- Histopathological examinations --- p.90 / Chapter 4.7.1 --- Acute hepatotoxicity test on aqueous seaweed extracts --- p.91 / Chapter 4.7.2 --- Curative and preventive tests of seaweed aqueous extracts against the CC14-induced hepatotoxicity --- p.92 / Chapter 4.7.3 --- Acute hepatotoxicity test of TCE in rats by oral and intraperitoneal routes --- p.99 / Chapter 4.7.4 --- Curative and preventive tests of seaweed aqueous extracts against the TCE effective dose-induced toxicity --- p.100 / Chapter 4.7.5 --- Antidotal effects of dimethyl sulfoxide (DMSO) and N-acetylcysteine (NAC) against CC14- and TCE-induced poisoning in rats --- p.100 / Chapter 4.7.6 --- Hepatoprotective effect of methanol extract of seaweed against CC14- and TCE-induced poisoning in rats --- p.102 / Chapter Chapter 5 --- DISCUSSION --- p.106 / Chapter Chapter 6 --- CONCLUSION --- p.124 / REFERENCES --- p.127 / APPENDIX --- p.138

Li Ka Wai Kay. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references. / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT (ENGLISH/CHINESE) --- p.ii / TABLE OF CONTENTS --- p.viii / LIST OF FIGURES --- p.xii / LIST OF APPENDICES --- p.xiii / Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Gastric carcinomas --- p.1 / Chapter 1.1a --- Epidemiology --- p.1 / Chapter 1.1b --- Classification --- p.2 / Chapter 1.1c --- TNM staging --- p.3 / Chapter 1.1d --- Prognosis --- p.4 / Chapter 1.1e --- Etiology --- p.6 / Chapter 1.1f --- Genetic alteration in gastric cancer --- p.10 / Chapter 1.2 --- Treatment --- p.16 / Chapter 1.2a --- "Surgery, chemotherapy, and others" --- p.16 / Chapter 1.2b --- Response rate of treatments in previous studies --- p.18 / Chapter 1.2c --- Chemotherapeutic Drugs --- p.21 / Chapter 1.2c (1) --- 5-fluorouracil (5-FU) --- p.22 / Chapter 1.2c (2) --- cis-diamminedichloroplatinum (Cisplatin) --- p.23 / Chapter 1.2c (3) --- Doxorubicin (Adriamycin) --- p.23 / Chapter 1.2c (4) --- Daunorubicin --- p.25 / Chapter 1.2c (5) --- Epirubicin --- p.25 / Chapter 1.2d --- Toxicity of chemotherapeutic drugs --- p.26 / Chapter 1.2d (1) --- Side effects of 5-FU --- p.26 / Chapter 1.2d (2) --- "Side effects of anthracyc lines (adriamycin, daunobicin, epuirbicin)" --- p.27 / Chapter 1.2d (3) --- Side effects of cisplatin --- p.28 / Chapter 1.3 --- Mechanisms of drug resistance --- p.28 / Chapter 1.3a --- Drug resistance --- p.28 / Chapter 1.3b --- P-glycoprotein (MDR1 gene) --- p.29 / Chapter 1.3c --- p53 tumor suppressor gene --- p.35 / Chapter 1.4 --- Chemosensitivity testing --- p.40 / Chapter 1.4a --- Original of chemosensitivity testing --- p.40 / Chapter 1.4b --- Non-clonogentic assay --- p.40 / Chapter 1.4c --- Clonogenic assay --- p.42 / Chapter 2 --- AIM OF MY STUDY --- p.44 / Chapter 3 --- MATERIALS AND METHODS --- p.45 / Chapter 3.1 --- Patients --- p.45 / Chapter 3.2 --- Tumor collection and handling procedure --- p.46 / Chapter 3.2a --- Large tumor tissue from gastrectomy --- p.46 / Chapter 3.2b --- Pseudo-biopsies --- p.47 / Chapter 3.3 --- Chemosensitivity testing --- p.48 / Chapter 3.3a --- Cell Plating --- p.48 / Chapter 3.3b --- Drug testing --- p.49 / Chapter 3.4 --- Chemosensitivity analysis --- p.50 / Chapter 3.5 --- Conformational sensitive gel electrophoresis analysis (CSGE) and single strand conformational polymorphism (SSCP) --- p.51 / Chapter 3.5a --- Preparation of genomic DNA --- p.51 / Chapter 3.5b --- PCR condition for CSGE analysis --- p.51 / Chapter 3.5c --- Scanning PCR products by CSGE --- p.52 / Chapter 3.5d --- PCR condition for SSCP analysis --- p.53 / Chapter 3.5e --- Scanning PCR products by SSCP --- p.53 / Chapter 3.6 --- Reverse transcription-polymerase chain reaction (RT-PCR) for multi-drug drug resistance (MDR1) gene --- p.54 / Chapter 3.6a --- Isolation of RNA --- p.54 / Chapter 3.6b --- cDNA synthesis --- p.55 / Chapter 3.6c --- PCR primers --- p.55 / Chapter 3.6d --- Optimalization of PCR condition for MDR1 gene expression --- p.56 / Chapter 3.6e --- PCR of β2-m gene --- p.57 / Chapter 3.6f --- PCR of MDR1 gene and analysis of its expression --- p.57 / Chapter 3.7 --- Immunohistochemistry --- p.58 / Chapter 3.7a --- Immunostaining by DO-7 --- p.58 / Chapter 3.7b --- lmmunohistochemistochemical analysis of p53 protein expression --- p.59 / Chapter 3.8 --- Statistics --- p.59 / Chapter 4. --- RESULTS --- p.60 / Chapter 4.1 --- Chemosensitivity testing --- p.60 / Chapter 4.1a --- Tests completed --- p.60 / Chapter 4.1b --- Number of cases tested for each drug --- p.60 / Chapter 4.1c --- 〇D reading of the background samples --- p.60 / Chapter 4.1d --- Dose-dependent response curve --- p.61 / Chapter 4.1e --- Unique IC50 for each tumor in each drug test --- p.61 / Chapter 4.1f --- Wide distribution of ic50 for anti-tumor drugs --- p.61 / Chapter 4.1g --- Chemosensitivity and tumor histologic type --- p.63 / Chapter 4.1h --- Correlation of ic50 with tumor stage --- p.63 / Chapter 4.2 --- Immunohistochemical staining of p53 protein (DO-7) --- p.64 / Chapter 4.2a --- p53 protein accumulation in samples --- p.64 / Chapter 4.2b --- Correlation of p53 IHC expression and chemosensitivity --- p.64 / Chapter 4.3 --- SSCP and CSGE --- p.65 / Chapter 4.3a --- Detection of abnormal band movement --- p.65 / Chapter 4.3b --- Correlation of p53 mutations with chemosensitivity --- p.66 / Chapter 4.3c --- Concordance between IHC and SSCP/CSGE --- p.66 / Chapter 4.4 --- MDR1 gene expression --- p.67 / Chapter 4.4a --- MDR1 gene expression in normal and tumors --- p.67 / Chapter 4.4b --- Correlation of MDR1 expression and chemosensitivity --- p.68 / Chapter 4.5 --- Pseudobiopsies --- p.68 / Chapter 5 --- DISCUSSION --- p.70 / Chapter 5.1 --- p53 analysis of the tumors --- p.70 / Chapter 5.1a --- Immunohistochemistry versus mutational analysis --- p.70 / Chapter 5.1b --- Methods of mutational analysis --- p.73 / Chapter 5.1c --- Comparing IHC results with previous findings --- p.77 / Chapter 5.1d --- Comparing SSCP/ CSGE results with previous findings --- p.78 / Chapter 5.1e --- Correlation of IHC and SSCP/CSGE results --- p.81 / Chapter 5.2 --- MDR1 expression --- p.85 / Chapter 5.2a --- Methods for detecting MDR1 expression --- p.85 / Chapter 5.2b --- Comparing MDR1 expression results with published data --- p.88 / Chapter 5.2c --- Correlation between chemosensitivity and MDR1 gene expression --- p.92 / Chapter 5.3 --- Chemosensitivity testing --- p.94 / Chapter 5.3a --- Chemosensitivity testing method --- p.94 / Chapter 5.3b --- The chemosensitivity results --- p.102 / Chapter 5.3c --- Chemosensitivity and MDR1 expression --- p.108 / Chapter 5.3d --- Chemosensitivity and p53 immunohistochemical expression… --- p.110 / Chapter 5.3e --- Chemosensitivity and p53 mutations --- p.112 / Chapter 5.3f --- Limitation of this study --- p.115 / Chapter 5.3g --- Pseudobiopsies and large tumor samples --- p.118 / Chapter 6. --- conclusions --- p.121 / figures / appendices / references

Po Lai See. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 142-152). / Abstracts in English and Chinese. / TITLE PAGE --- p.p.1 / ACKNOWLEGDEMENTS --- p.p.2 / ABSTRACT --- p.p.3 / 摘要 --- p.p.6 / TABLE OF CONTENTS --- p.p.9 / LIST OF FIGURES AND TABLES --- p.p.16 / Chapter CHAPTER 1 --- GENERAL INTRODUCTION / Chapter 1.1 --- Estrogen and Estrogen Receptors and its Action --- p.p.18 / Chapter 1.1.1 --- Estrogen --- p.p.19 / Chapter 1.1.2 --- Estrogen Receptors --- p.p.19 / Chapter 1.1.3 --- Structural Differences between ERa and ERp --- p.p.21 / Chapter 1.1.4 --- Functional Differences --- p.p.22 / Chapter 1.1.5 --- Effects of Selective Estrogen Receptor Modulators --- p.p.22 / Chapter 1.1.6 --- Estrogen works --- p.p.23 / Chapter 1.1.7 --- Estrogen Receptors and Breast Cancer --- p.p.24 / Chapter 1.2 --- Flavonoids： Properties and Biological Activities --- p.p.25 / Chapter 1.2.1 --- Chemical Structure and Classification of flavonoids --- p.p.25 / Chapter 1.2.2 --- Biological Properties and Action Mechanism of Flavonoids… --- p.p.27 / Chapter 1.2.3 --- Flavonoids and breast cancer prevention --- p.p.27 / Chapter 1.3 --- Aims and Scopes of Investigation --- p.p.29 / Chapter CHAPTER 2 --- MATERIALS AND METHODS / Chapter 2.1 --- Chemicals --- p.p.30 / Chapter 2.1.1 --- Flavonoids --- p.p.30 / Chapter 2.1.2 --- Plasmids --- p.p.30 / Chapter 2.2 --- Mammalian cell culture --- p.p.31 / Chapter 2.2.1 --- Maintenance of cells --- p.p.31 / Chapter 2.2.2 --- Preparation of cell stock --- p.p.32 / Chapter 2.2.3 --- Cell recovery from liquid nitrogen stock --- p.p.32 / Chapter 2.3 --- Identification of estrogenic activity in flavonoids --- p.p.33 / Chapter 2.3.1 --- Steady Glo Luciferase Assay --- p.p.33 / Chapter 2.3.2 --- The Biorad Protein Assay kit (a modified Bradford method). --- p.p.33 / Chapter 2.4 --- Viability Assay --- p.p.34 / Chapter 2.5 --- ERE Luciferase reporter gene assay --- p.p.35 / Chapter 2.5.1 --- Transient transfect ion of cell using lipofectamine PLUS reagent --- p.p.36 / Chapter 2.5.2 --- Dual Luciferase Assay --- p.p.37 / Chapter 2.6 --- ERα competitive binding ASSAY --- p.p.37 / Chapter 2.7 --- Apoptotic death assay --- p.p.38 / Chapter 2.8 --- Semi-quantitative RT-PCR Assay --- p.p.40 / Chapter 2.8.1 --- "Isolation of RNA using TRIzol® Reagent (Life Technology,USA) " --- p.p.40 / Chapter 2.8.2 --- Quantitation of RNA --- p.p.41 / Chapter 2.8.3 --- First strand cDNA synthesis --- p.p.41 / Chapter 2.8.4 --- PCR reactions --- p.p.43 / Chapter 2.9 --- Flow Cytometry Analysis --- p.p.43 / Chapter 2.10 --- Total triglyceride and cholesterol measurement --- p.p.44 / Chapter 2.10.1 --- Determination of the total cholesterol --- p.p.45 / Chapter 2.10.2 --- Determination of the total triglyceride --- p.p.46 / Chapter 2.11 --- Manipulation of DNA and RNA --- p.p.46 / Chapter 2.11.1 --- Transformation of DH5α --- p.p.46 / Chapter 2.11.2 --- Mini preparation of plasmid DNA --- p.p.47 / Chapter 2.11.3 --- Preparation of plasmid DNA using QIAGEN-tip 100 midi-prep kit --- p.p.48 / Chapter 2.11.4 --- Preparation of plasmid DNA using QIAGEN-tip 10000 Giga-prep kit --- p.p.49 / Chapter 2.11.5 --- Ethanol preparation of DNA and RNA --- p.p.50 / Chapter 2.11.6 --- Agarose gel electrophoresis of DNA --- p.p.51 / Chapter 2.12 --- Statistical methods --- p.p.52 / Chapter CHAPTER 3 --- Estrogenic and antiproliferative activities on MCF-7 breast cancer cells by flavonoids / Chapter 3.1 --- Introduction --- p.p.53 / Chapter 3.2 --- Results --- p.p.56 / Screening of phytoestrogens for estrogenic activities on MELN cells --- p.p.56 / Cell proliferation activity of phytoestrogens on MCF-7 and MDA-MA231 cells --- p.p.59 / Estrogenic and antiestrogenic activity of phytoestrogens on ERα or erβ transfected hepg2 cells --- p.p.64 / Chapter 3.3 --- Discussion --- p.p.73 / Chapter Chapter 4 --- interaction of baicalein with estrogen receptors / Chapter 4.1 --- Introduction --- p.p.76 / Chapter 4.2 --- Results --- p.p.78 / Estrogen receptor competition assay --- p.p.78 / ERE-Luciferase gene reporter assay --- p.p.82 / Chapter 4.3 --- Discussion --- p.p.88 / Chapter Chapter 5 --- baicalein and genistein display differential actions on er transactivation / Chapter 5.1 --- Introduction --- p.p.90 / Chapter 5.2 --- Results --- p.p.92 / Estrogenic and antiestrogenic activities of genistein and baicalein on ER transactivation --- p.p.92 / Chapter 5.3 --- Discussion --- p.p.105 / Chapter CHAPTER 6 --- APOPTOTIC EFFECTS OF BAICALEIN ON MCF-7 AND MDA-MB-231 CELL LINES / Chapter 6.1 --- Introduction --- p.p.107 / Chapter 6.2 --- Results --- p.p.111 / ER POSITIVE MCF-7 AND ER NEGATIVE MDA-MB-231 cell death assay --- p.p.111 / "Bcl-2, Bax and PS2 mRNA expression " --- p.p.116 / Arrest at sub G1 phase of MCF-7 by baicalein --- p.p.124 / Chapter 6.3 --- Discussion --- p.p.127 / Chapter CHAPTER 7 --- BAICALEIN CAN REDUCE INTRACELLULAR cholesterol and triglceride / Chapter 5.1 --- Introduction --- p.p.129 / Chapter 5.2 --- Results --- p.p.130 / Baicalein has beneficial effect on lipid metabolism --- p.p.130 / Chapter 5.3 --- Discussion --- p.p.139 / Chapter chapter 8 --- Summary --- p.p.140 / BIBLIOGRAPHY --- p.p.142 / APPENDIX 1 ABBREVIATIONS --- p.p.153 / APPENDIX 2 PRIMER LISTS --- p.p.156 / APPENDIX 3 REAGENTS AND BUFFERS --- p.p.157

by Mak Wing Fun, Ingrid. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 58-64). / Questionnaire also in Chinese. / Abstract --- p.ii / Acknowledgments --- p.iii / Table of Contents --- p.iv / List of Tables --- p.vii / List of Appendix --- p.viii / CHAPTER / Chapter 1 --- Introduction And Literature Review --- p.1 / Adherence(Compliance) --- p.1 / Pattern of Non-adherence --- p.1 / Health Belief Model and Adherence-Related Attitudes --- p.2 / Non-adherence and Psychiatric Disorder --- p.2 / Drug Adherence and Affective Disorder --- p.3 / Bipolar Disorder and Lithium --- p.3 / Methods for Assessing Adherence --- p.4 / Clinical Factors Associated with Lithium Non-adherence --- p.6 / Drug Adherence of Hong Kong Chinese Patients with Affective Disorder --- p.9 / Individual Factors --- p.10 / Attitude and Belief --- p.10 / Health Locus of Control --- p.15 / Socio-Cultural Factors --- p.15 / Explanatory Model --- p.15 / Illness Attribution --- p.16 / Attitude Towards Western Medication --- p.17 / Somatisation and Social Stigma --- p.18 / Family Support --- p.20 / Purposes of the Study --- p.22 / Chapter 2 --- Method --- p.23 / Subjects --- p.23 / Outcome Measures --- p.24 / side Effect Measure --- p.25 / Attitude Measures --- p.26 / Support Measure --- p.27 / Mood State Measure --- p.27 / Memory Function Measure --- p.28 / Procedure --- p.28 / Chapter 3 --- Results --- p.29 / Non-Adherence Rate --- p.29 / Intercorrelations of Adherence Measures --- p.30 / Mean Lithium Level and Adherence Status --- p.31 / The Reliability of the Instruments --- p.33 / Comparison of Fully Adherent and Non-adherent Patients --- p.34 / Discriminant Analysis --- p.39 / Comparison of the Patients' Attitudes and Social Support by the Number of Non- adherence Criteria Met --- p.40 / Comparison of Patients' Attitudes and Perceived Support by Patient's Self-report of Adherence --- p.43 / Comparison of Patients' Attitudes and Perceived Support by Family Member's Report of Adherence --- p.45 / Comparison of Patients' Attitudes and Perceived Support by Case Psychiatrist's Report of Adherence --- p.47 / Chapter 4 --- Discussion --- p.49 / Single vs. Multiple Criteria. --- p.49 / Predicting Non-adherence --- p.51 / Other Variables Associated --- p.53 / Limitations of the Study and Recommendations --- p.56 / Chapter 5 --- References --- p.58 / Chapter 6 --- Appendix --- p.65

Xiao, Zhangang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 118-131). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

by Tsang Kit Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 179-188). / Abstracts in English and Chinese. / ABSTRACT --- p.i / ABSTRACT IN CHINESE (摘要） --- p.iii / ACKNOWLEDGEMENTS --- p.v / CONTENTS --- p.vi / LIST OF FIGURES --- p.xi / LIST OF TABLES --- p.xiv / ABBREVIATIONS --- p.xvi / Chapter CHAPTER ONE: --- INTRODUCTION --- p.1 / Chapter 1.1 --- Hepatocellular Carcinoma --- p.2 / Chapter 1.1.1 --- Incidence of Hepatocellular Carcinoma --- p.2 / Chapter 1.1.2 --- Therapies for Hepatocellular Carcinoma --- p.4 / Chapter 1.2 --- Multidrug Resistance of Tumor Cells --- p.8 / Chapter 1.3 --- Therapeutic Potential of Traditional Chinese Medicine on Human Hepatoma --- p.10 / Chapter 1.4 --- Sophora flavescens Ait --- p.13 / Chapter 1.5 --- Biological Activities of Sophorae Radix --- p.15 / Chapter 1.5.1 --- Antitumor Activities --- p.16 / Chapter 1.5.2 --- "Antibacterial, Antimalarial and Antiviral Activities" --- p.17 / Chapter 1.6 --- Objectives and Significance of Study --- p.19 / Chapter 1.6.1 --- Bioassay-guided Isolation of Active Compounds from Sophora flavescens --- p.19 / Chapter 1.6.2 --- Action Mechanisms of the Bioactive Compounds Isolated from Sophora flavescens --- p.20 / Chapter CHAPTER TWO: --- MATERIALS AND METHODS --- p.21 / Chapter 2.1 --- Cell Culture --- p.22 / Chapter 2.1.1 --- Cell Lines --- p.22 / Chapter 2.1.2 --- Cell Culture Media --- p.24 / Chapter 2.2 --- Isolation of Bioactive Compounds from Sophora flavescens --- p.25 / Chapter 2.3 --- MTT assay --- p.27 / Chapter 2.4 --- Cell Cycle Analysis --- p.28 / Chapter 2.5 --- Detection of Phosphatidylserine Externalization with Annexin V-FITC and PI --- p.29 / Chapter 2.6 --- DNA Fragmentation Assay --- p.30 / Chapter 2.7 --- Western Blot Analysis --- p.32 / Chapter 2.7.1 --- Extraction of Total Cellular Protein --- p.32 / Chapter 2.7.2 --- Extraction of Cytosolic Protein --- p.32 / Chapter 2.7.3 --- Determination of Protein Concentration --- p.33 / Chapter 2.7.4 --- Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.35 / Chapter 2.7.5 --- Electroblotting of Protein --- p.36 / Chapter 2.7.6 --- Probing of Proteins with Antibodies --- p.37 / Chapter 2.7.7 --- Enhanced Chemiluminescence (ECL) Assay --- p.39 / Chapter 2.8 --- Detection of Mitochondrial Membrane Potential by JC-1 Fluorescent dye --- p.39 / Chapter 2.9 --- cDNA Microarray Analysis --- p.40 / Chapter 2.9.1 --- Isolation of Total RNA --- p.40 / Chapter 2.9.2 --- Microarray Hybridization and Analysis --- p.41 / Chapter 2.9.3 --- Validation of Candidate Genes --- p.44 / Chapter 2.9.3.1 --- Determination of RNA Concentration --- p.44 / Chapter 2.9.3.2 --- First-Strand cDNA Synthesis --- p.44 / Chapter 2.9.3.3 --- Reverse-Transcription Polymerase Chain Reaction (RT-PCR) of Candidate Genes --- p.45 / Chapter 2.10 --- Two-Dimensional Polyacrylamide Gel Electrophoretic Analysis (2D-PAGE) --- p.47 / Chapter 2.10.1 --- Extraction of Total Cellular Protein for 2-D Gel Electrophoresis --- p.47 / Chapter 2.10.2 --- Determination of Protein Concentration --- p.47 / Chapter 2.10.3 --- First-Dimension Isoelectric Focusing (IEF) --- p.49 / Chapter 2.10.4 --- Second-Dimension SDS-PAGE --- p.49 / Chapter 2.10.5 --- Visualization of 2-D Gel by Silver Staining --- p.50 / Chapter 2.10.6 --- Identification of Differentially Expressed Proteins with Matrix Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF-MS) --- p.51 / Chapter 2.11 --- Statistical Analysis --- p.53 / Chapter CHAPTER THREE: --- BIOASSAY-GUIDED ISOLATION AND CHARACTERISATION OF BIOACTIVE COMPOUNDS FROM SOPHORA FLAVESCENS --- p.54 / Chapter 3.1 --- Bioassay-guided Isolation of Bioactive Compounds from Sophora flavescens --- p.55 / Chapter 3.2 --- Structure Identification of the Bioactive Compounds Isolated from Sophora flavescens --- p.64 / Chapter 3.3 --- In Vitro Anti-tumor Effect of the Bioactive Compounds Isolated from Sophora flavescens --- p.71 / Chapter CHAPTER FOUR: --- MECHANISTIC STUDY OF SOPHORAFLAVANONE G IN THE INDUCTION OF APOPTOSIS IN HEPATOCELLULAR CARCINOMA CELLS --- p.76 / Chapter 4.1 --- In Vitro Anti-tumor Effect of Sophoraflavanone G --- p.77 / Chapter 4.2 --- Cell Cycle Analysis of Human Hepatocellular Carcinoma Cells and Multidrug Human Hepatocellular Carcinoma Cells --- p.81 / Chapter 4.3 --- Induction of Apoptosis in Hepatocellular Carcinoma Cells by Sophoraflavanone G --- p.88 / Chapter 4.3.1 --- Induction of Phosphatidylserine Externalization in Hepatocellular Carcinoma Cells by Sophoraflavanone G --- p.89 / Chapter 4.3.2 --- Induction of DNA Fragmentation in Hepatocellular Carcinoma Cells by Sophoraflavanone G --- p.94 / Chapter 4.3.3 --- Induction of Caspase-3 activation in Hepatocellular Carcinoma Cells by Sophoraflavanone G --- p.97 / Chapter 4.4 --- Underlying Mechanisms of Sophoraflavanone G-induced Apoptosis in Human Hepatocellular Carcinoma Cells --- p.102 / Chapter 4.4.1 --- Involvement of Death Receptor Pathway in Sophoraflavanone G- induced Apoptosis in Human Hepatocellular Carcinoma Cells --- p.103 / Chapter 4.4.2 --- Involvement of Bid protein in Sophoraflavanone G-induced Apoptosis in Human Hepatocellular Carcinoma Cells --- p.105 / Chapter 4.4.3 --- Involvement of Mitochondrial Pathway in Sophoraflavanone G- induced Apoptosis in Human Hepatocellular Carcinoma Cells --- p.108 / Chapter 4.4.4 --- Induction of Mitochondrial Membrane Depolarization in Human Hepatocellular Carcinoma Cells by Sophoraflavanone G --- p.112 / Chapter 4.4.5 --- Involvement of Caspase-independent Pathway in Sophoraflavanone G-induced Apoptosis in Human Hepatocellular Carcinoma Cells --- p.116 / Chapter CHAPTER FIVE: --- MECHANISTIC STUDY OF SOPHORAFLAVANONE G ON HUMAN HEPATOCELLULAR CARCINOMA CELLS BY USING cDNA MICROARRAY ANALYSIS --- p.119 / Chapter 5.1 --- Identification of Differentially Expressed Genes in Sophoraflavanone G- treated Human Hepatocellular Carcinoma Cells by cDNA Microarray Analyasis --- p.120 / Chapter CHAPTER SIX: --- MECHANISTIC STUDY OF SOPHORAFLAVANONE G ON HEPATOCELLULAR CARCINOMA CELLS BY USING TWO-DIMENSIONAL POLYACRYLAMIDE GEL ELECTROPHORESIS --- p.136 / Chapter 6.1 --- Identification of Differentially Expressed Proteins in Sophoraflavanone G- treated Human Hepatocellular Carcinoma Cells by Two-Dimensional Polyacrylamide Gel Electrophoresis --- p.137 / Chapter CHAPTER SEVEN: --- DISCUSSION --- p.150 / Chapter 7.1 --- Bioassay-guided Isolation of Bioactive Compounds from Sophora flavescens --- p.151 / Chapter 7.2 --- Induction of Apoptosis in Human Hepatocellular Carcinoma cells and Multidrug Human Hepatocellular Carcinoma Cells --- p.154 / Chapter 7.3 --- Differential Gene Expression Induced by Sophoraflavanone G in Human Hepatocellular Carcinoma Cells --- p.161 / Chapter 7.4 --- Differential Protein Expression Induced by Sophoraflavanone G in Human Hepatocellular Carcinoma Cells and Multidrug Human Hepatocellular Carcinoma Cells --- p.164 / Chapter 7.5 --- Toxicity of Sophoraflavanone G against Normal Liver Cells --- p.170 / Chapter CHAPTER EIGHT: --- CONCLUSION AND FUTURE PERSPECTIVES --- p.173 / Chapter 8.1 --- Conclusion --- p.174 / Chapter 8.2 --- Future Prospects --- p.176 / REFERENCES --- p.179

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