A series of novel Bis 2,2':6',2″-terpyridinyl ligands, linked through a flexible alkyl chain situated at the 4' position, were synthesised and characterised by microanalysis, FTIR, NMR, UV-Visible spectroscopy, and MS-ToF. Single crystals of all the ligands were obtained, of which one has been published, one has been submitted for publication and one is in preparation for publication. These ligands were then coordinated to platinum(II) and characterised, including ¹⁹⁵Pt NMR spectroscopy. A detailed kinetic study involving the substituting the chloride co-ligand with the following nucleophiles thiourea, 1,3-dimethyl-thiourea and 1,1,3,3-tetramethyl-thiourea was conducted using stopped-flow techniques. An associative reaction mechanism was suggested for the pendant ligand substitution and the following trend in reactivity was observed: L2-Ptα > L3-Ptβ > L1-Ptχ. UV-Visible absorption spectra were recorded on sequentially diluted solutions of the ligands (in chloroform), and the platinum complexes (in water). These spectra obeyed the Beer-Lambert law. The values of the molar absorption coefficients at the wavelengths of maximum absorption for the ligands followed the trend L1 < L2 < L3, whilst for the complexes the trend was L1-Pt < L3-Pt < L2-Pt. It has been concluded that at low concentrations L2-Pt and L3-Pt undergo intramolecular folding. Variable temperature and variable concentration NMR spectroscopic studies were performed on all three complexes. At higher complex concentrations intermolecular self-association takes place for L2-Pt and L3-Pt but not for L1-Pt. The reactivity of the complexes is predominately determined by their structural conformations in solution. At low concentrations the L1-Pt complex remains in its linear conformational state, whilst the L2-Pt and L3-Pt complexes undergo intramolecular folding with the formation of an axial Pt—Pt bonded and π—π stacked dinuclear platinum terpyridine centre. The latter is believed to be more active in the substitution reaction than the original mononuclear centre. The reasons for the folding and self-association in the L2-Pt and L3-Pt systems are related to the steric crowding and stress in the spacer region of the folded or self-associated complexes. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

多年來，儘可能多的從植物中提取單體化合物一直是開發新型化學防癌劑和化學治療劑藥物的重要來源。 / 在本课题中，我们活性測試了从刺果紫玉盘（番荔枝科植物）中分离得到的14个番荔枝内酯化合物和7个多氧环己烯化合物，从三叉刺（豆科植物）和黄瑞香（瑞香科植物）中分离得到的4个黄酮化合物，从黄瑞香（瑞香科植物）和了哥王（瑞香科植物）中分离得到的2个香豆素化合物，以及从总状蕨藻（蕨藻科植物）中分离得到的1 个生物碱化合物，對11種人類常見癌症細胞株，如惡性黑色素瘤、肺癌、子宮頸上皮腺癌、肝癌、前列腺癌、結直腸癌的體外抗癌活性，用以建立一個全面的抗癌活性數據庫，為人們更好得了解番荔枝科植物奠定基礎。 / 在這些被篩選的單體化合物中，番荔枝內酯（ACGs）顯示出卓越的抗癌活性。它們對某些癌細胞株的細胞毒性甚至達到了nmol/l級別。例如番荔枝內酯desacetyluvaricin（Dau），對11條人類癌細胞株具有廣泛的抗增生活性，其半抑制濃度（IC₅₀）範圍從2.3 nM到37.4 μM。其中，Dau對結直腸癌細胞SW480的毒性最甚。Dau不僅具有高的抗癌效力，并對人正常纖維細胞Hs68幾乎沒有細胞毒性，半抑制濃度超過了247.5 μM。進一步的機理研究表明，Dau可導致SW480細胞產生大量過氧化物，進而導致細胞核內DNA斷裂。DNA損傷會讓MEK/ERK信號通路失活，並且影響了細胞週期調控蛋白的正常表達。例如影響細胞S週期的調控蛋白Cyclin A和Cyclin E的表達，以及影響G₁/S檢查點調控蛋白E2F的表達。由此，Dau促進SW480癌細胞穿過G₁/S檢查點，由G₁進入S期並在S期累計。最終被抑制在S週期的SW480細胞發生了壞死。以上機理的研究可為更好的理解ACG的作用機制提供一定的理論基礎。 / 番荔枝內酯是一系列長鏈脂肪酸的衍生物。它的結構的多樣性引發了我們極大的興趣去研究它的構效關係。我們比較了14個番荔枝內酯在細胞毒性和細胞週期控制方面對兩種不同的前列腺癌細胞LNCaP（p53基因野生型）和PC-3（p53基因缺失型）的影響。實驗結果表明，LNCaP細胞比PC-3更加敏感。番荔枝內酯的這種選擇性大概跟癌細胞中p53抑癌蛋白的表達水平有關。此外，關於構效關係的研究我們還發現：（1）在番荔枝內酯結構的核心系統中，四氫呋喃環的個數越多，化合物的抗癌活性越高；（2）在含有相鄰雙四氫呋喃環結構的化合物中，擁有threo/trans/threo/trans/erythro立體構型的化合物的細胞毒性比擁有threo/trans/threo/trans/threo立體構型的化合物高；（3）含單或雙四氫呋喃環結構的番荔枝內酯都將通過將LNCaP細胞抑制在G₁/G₀週期從而達到抗癌效果，並不會引起細胞凋亡；（4）含單四氫呋喃環結構的番荔枝內酯都將通過引發細胞凋亡從而達到抑制PC-3癌細胞的增長。然而含雙四氫呋喃環結構的番荔枝內酯會引發更多的PC-3細胞凋亡，並且有不同程度的細胞週期抑制；（5）在四氫呋喃環核心體系上，乙酰氧基會比羥基增加番荔枝內酯的細胞毒性；（6）雙鍵的取代基也會增加毒性效果。我們的研究結果印證了一些文獻已報導的關於番荔枝內酯構效關係的結論，同時我們也提出了一些新的假設。 / 本研究不僅增加了我們對番荔枝內酯強大的抗癌活性更全面的了解，並且通過機理研究還為它的選擇性毒性及構效關係特點提供了有重要的信息。番荔枝內酯是一類具有充滿前景抗癌化合物。在接下來的研究中，我們將致力於體內抗癌活性的研究，并擴大研究範圍，通過對多個ACG化合物的機理研究來證明我們對它的選擇性毒性的機理假設。 / For years and years, the discovery of phytochemicals as many as possible has always been an important strategy for the development of novel chemopreventive and chemotherapeutic drugs. / In this studies, we have screened 14 Annonaceous acetogenins and 7 polyoxygenated cyclohexenes isolated from the root of Uvaria calamistrata (Annonaceae), 4 flavonoids isolated from the stems of Trifidacanthus unifoliolatus (Fabaceae) and Daphne giraldii (Thymelaeaceae), 2 cumarins isolated from the stem bark of Daphne giraldii (Thymelaeaceae) and the root of Wikstroemia indica (Thymelaeaceae), and 1 alkaloid isolated from Caulerpa racemosa (Caulerpaceae). The in vitro anticancer effects of these 28 natural compounds on 11 human cancer cell lines, including malignant melanoma, lung carcinoma, cervix epithelial adenocarcinoma, liver carcinoma, prostate adenocarcinoma and colorectal adenocarcinoma, were tested to set up an overall anticancer activity database for better understanding of the biological actions of Annonaceous plants. / Among the screened natural compounds, Annonaceous acetogenins (ACGs) exhibited outstanding anticancer efficacy. The cytotoxicities of ACGs to some cancer cell lines were even at nmol/l level. For instance, desacetyluvaricin (Dau), an ACG, was identified as a novel antiproliferative agent with a broad spectrum of inhibitions against the tested 11 human cancer cell lines with the IC₅₀ values ranging from 2.3 nM to 37.4 μM, and was especially cytotoxic to SW480 human colorectal carcinoma cells. Despite this potency, Dau was virtually nontoxic toward Hs68 human fibroblasts with an IC₅₀ value exceeding 247.5 μM. Further cell death mechanism studies showed that Dau could induce large amounts of superoxide production, which subsequently induced nuclear DNA fragmentation. DNA damage may inactivate the MEK/ERK signaling pathway and disturbed the expressions of cell cycle regulators such as Cyclin A and Cyclin E, which are S phase regulators, and E2F which is the G1/S checkpoint regulator. Thereafter, Dau arrested SW480 cells in S phase by promoting SW480 cells passing through the G₁/S boundary, and then accumulating in S phase. Finally, the SW480 cells underwent necrotic cell death. This mechanism study may provide a better understanding on the action mode of ACGs. / ACGs are derivatives of long chain fatty acids. Its structural diversity kindled our great interests in its structure-activity relationship (SAR). Therefore, we compared the cytotoxicities and cell cycle regulations of the 14 ACG compounds on two different human prostate cancer cell lines, LNCaP (p53 wild-type) and PC-3 (p53 null-type). Results showed that LNCaP cells were more sensitive to ACGs than PC-3 cells. This selectivity may be due to the presence of p53 tumor suppressor gene. Moreover, we found about SAR study that (1) the more THF rings existing in the core structure of ACGs, the more potent anticancer effects of ACGs would be; (2) for the adjacent bis-THF ACGs, stereo-structure with threo/trans/threo/trans/erythro configuration is generally more cytotoxic than the one with threo/trans/threo/trans/threo configuration; (3) both mono-THF ACGs and bis-THF ACGs inhibited LNCaP cells growth by G₁/G₀ phase arrest without any apoptosis induction; (4) mono-THF ACGs inhibited PC-3 cells growth by inducing apoptosis without cell cycle disturbance. However, the bis-THF ACGs could induce more apoptosis in PC-3 cells with partially cell cycle arrest. (5) the -OAc substituent group instead of -OH in the THF system would enhance the cytotoxicity efficacies of ACGs; (6) the double bond substituent would also enhance the anticancer effect. Our studies have proved several reported disciplines about the SAR of ACGs, and also proposed some new hypothesis. / Taken together, this study not only increased our understanding on the potent anticancer effects of ACG, but also provided valuable information on explaining its special cytotoxicities and the SAR properties through underling mechanism study. ACGs are a group of promising anticancer compounds with potent and steady activities. In the future work, we should further examine the in vivo anticancer effects and study more ACGs on their action modes to validate our hypothesis on their sensitivities to certain cancer cell lines. / 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. / Xue, Junyi. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 215-236). / Abstracts also in Chinese.

Wu-shun, Felix Wong. / Thesis (M.D.)--Chinese University of Hong Kong, 1991. / Includes bibliographies. / Title page --- p.i / Table of contents --- p.ii / Acknowledgements --- p.vi / Abstract --- p.viii / Declaration --- p.xiii / List of abbreviation --- p.xiv / Chapter Chapter one： --- Introduction --- p.1 / Chapter 1.1 --- Overview --- p.2 / Chapter 1.2 --- Aims of the study --- p.5 / Chapter Chapter two： --- Literature review --- p.8 / Chapter 2.1 --- Cell cycle and tumour growth --- p.9 / Chapter 2.1.1 --- Cell cycle --- p.9 / Chapter 2.1.2 --- Tumour growth --- p.14 / Chapter 2.2 --- Kinetic studies --- p.21 / Chapter 2.2.1 --- Radioisotopic studies --- p.21 / Chapter 2.2.2 --- Flow cytometry --- p.28 / Chapter 2.2.3 --- Monoclonal antibody --- p.32 / Chapter 2.3 --- Monoclonal antibody Ki-67 --- p.39 / Chapter 2.3.1 --- Development of Ki-67 --- p.39 / Chapter 2.3.2 --- The nature of the Ki-67 antigen --- p.42 / Chapter 2.3.3 --- Comparison with other kinetic methods --- p.45 / Chapter 2.3.4 --- Reported studies --- p.50 / Chapter 2.4 --- immunocytochemical staining --- p.63 / Chapter 2.4.1 --- Principle of immunostaining --- p.63 / Chapter 2.4.2 --- Fixation and processing methods --- p.69 / Chapter Chapter three： --- Materials and methods --- p.75 / Chapter 3.1 --- Cell culture --- p.76 / Chapter 3.1.1 --- Culture medium --- p.76 / Chapter 3.1.2 --- Origin and maintenance of cell line --- p.76 / Chapter 3.1.3 --- Coversip monolayer culture --- p.80 / Chapter 3.1.4 --- Multicellular spheroid culture --- p.80 / Chapter 3.1.5 --- Growth curve study --- p.81 / Chapter 3.1.6 --- Cytocentrifuge slide preparation --- p.81 / Chapter 3.2 --- immunoperoxidase staining --- p.83 / Chapter 3.2.1 --- Materials of immunoperoxidase staining --- p.83 / Chapter 3.2.2 --- Immunoperoxidase staining method --- p.86 / Chapter 3.3 --- Cell counting method --- p.92 / Chapter 3.3.1 --- Interactive cell counting system --- p.92 / Chapter 3.3.2 --- Cell counting methods --- p.95 / Chapter Chapter four： --- Proliferative activities of tumour cells IN VITRO --- p.104 / Chapter 4.1 --- Identification of cell proliferation of B16 melanoma cellsin VITRO --- p.105 / Chapter 4.1.1. --- Materials and methods --- p.106 / Chapter 4.1.2. --- Results --- p.107 / Chapter 4.1.3 --- Discussion --- p.110 / Chapter 4.2 --- Staining patterns of proliferating OCC1 cells in vitro --- p.117 / Chapter 4.2.1 --- Materials and methods --- p.117 / Chapter 4.2.2 --- Results --- p.118 / Chapter 4.2.3 --- Discussion --- p.121 / Chapter 4.3 --- "Comparative in vitro studies of cell proliferation using AgNOR counts, anti-BrdU, AD203 and Ki-67" --- p.130 / Chapter 4.3.1. --- Materials and methods --- p.130 / Chapter 4.3.2. --- Results --- p.131 / Chapter 4.3.3 --- Discussion --- p.134 / Chapter 4.4 --- Proliferative activities of tumor cells in vitro --- p.139 / Chapter 4.4.1. --- Materials and methods --- p.140 / Chapter 4.4.2. --- Results --- p.141 / Chapter 4.4.3 --- Discussion --- p.146 / Chapter Chapter five： --- Growth fraction in human genital tissues --- p.156 / Chapter 5.1 --- Cell proliferation in normal and neoplastic cervical tissues --- p.157 / Chapter 5.1.1. --- Materials and methods --- p.158 / Chapter 5.1.2. --- Results --- p.161 / Chapter 5.1.3 --- Discussion --- p.154 / Chapter 5.2 --- Tumour growth fraction in cervical carcinoma --- p.172 / Chapter 5.2.1. --- Materials and methods --- p.172 / Chapter 5.2.2. --- Results --- p.173 / Chapter 5.2.3 --- Discussion --- p.177 / Chapter 5.3 --- Tumour growth fraction in ovarian carcinoma --- p.185 / Chapter 5.3.1. --- Materials and methods --- p.185 / Chapter 5.3.2. --- Results --- p.186 / Chapter 5.3.3 --- Discussion --- p.190 / Chapter Chapter six： --- Conclusion --- p.198 / Chapter 6.1 --- Overview and future work --- p.199 / Chapter 6.2 --- Conclusion --- p.211 / references --- p.213 / Appendix： --- p.246 / Chapter (A) --- Additional Experiments / Chapter Experiment 1 --- Highest selection counting method --- p.246 / Chapter Experiment 2 --- Double staining of B16 melanoma cells --- p.248 / Chapter Experiment 3 --- Trypan blue exclusion test for viability --- p.250 / Chapter (B) --- Selected publications by the author / Chapter Publication 1 --- Characteristics of a cell line established from a Chinese patient with a squamous carcinoma of the uterine cervix --- p.252 / Chapter Publication 2 --- Establishment and characterization of a new human cell line derived from ovarian clear cell carcinoma --- p.258 / Chapter Publication 3 --- "Identification of ""non-proliferating"" B16 melanoma cells using monoclonal antibody (AD203) against the Ml subunit of ribonucleotide reductase" --- p.267 / Chapter Publication 4 --- The correlation of agyrophilic nucleolar organiser regions (AgNORs) count to bromodeoxyuridine incorporation and Ki-67 scores in an ovarian carcinoma cell line --- p.275 / Chapter Publication 5 --- Immunohistochemical determination of tumour growth fraction in human ovarian carcinoma --- p.278 / Chapter Publication 6 --- Tumor growth fraction in cervical carcinoma --- p.283

by Wong Chun-kwok. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 233-246). / ABSTRACT --- p.I / ACKNOWLEDGEMENTS --- p.V / ABBREVIATIONS --- p.VI / PUBLICATIONS --- p.IX / CHAPTER / Chapter 1. --- GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- EFFECTOR CELLS MEDIATING ANTI一TUMOR IMMUNITY --- p.3 / Chapter 1.1.1 --- CYTOTOXIC T LYMPHOCYTES --- p.4 / Chapter 1.1.2 --- MACROPHAGES --- p.4 / Chapter 1.1.3 --- NATURAL KILLER CELLS --- p.5 / Chapter 1.1.4 --- LYMPHOKINE ACTIVATED KILLER CELLS --- p.7 / Chapter 1.1.5 --- TUMOR-INFILTRATING LYMPHOCYTES --- p.8 / Chapter 1.2 --- BIOLOGICAL RESPONSE MODIFIERS : THE NEW IMMUNOTHERAPY --- p.9 / Chapter 1. 3 --- CYTOKINES AS BIOLOGICAL RESPONSE MODIFIERS IN CANCER THERAPY --- p.12 / Chapter 1.3.1 --- INTERFERONS --- p.12 / Chapter 1.3.2 --- TUMOR NECROSIS FACTOR-ALPHA --- p.13 / Chapter 1.3.3 --- INTERLEUKIN-1 --- p.15 / Chapter 1.3.4 --- INTERLEUKIN-2 --- p.16 / Chapter 1.3.5 --- GRANULOCYTES /MACROPHAGES COLONY-STIMULATING FACTORS --- p.16 / Chapter 1.3.6 --- EPIDERMAL GROWTH FACTOR --- p.17 / Chapter 1.3.7 --- TRANSFORMING GROWTH FACTOR-BETA --- p.17 / Chapter 1.4 --- BIOACTIVE POLYSACCHARIDES FROM CHINESE MEDICINAL HERBS ACT AS BIOLOGICAL RESPONSE MODIFIERS --- p.18 / Chapter 2. --- AIM AND SCOPE OF INVESTIGATION --- p.27 / Chapter 3. --- MATERIALS AND METHODS --- p.30 / Chapter 3.1 --- MATERIALS --- p.30 / Chapter 3.2 --- METHODS --- p.39 / Chapter (I) --- "EXTRACTION, FRACTIONATION AND CHARACTERIZATION OF PSEUDOSTELLARIA HETEROPHYLLA" / Chapter 3.2.1 --- Hot water extraction and stepwise alcohol precipitation --- p.39 / Chapter 3.2.2 --- "Determination of carbohydrate, protein, uronic acid contents" --- p.41 / Chapter 3.2.3 --- Gel filtration --- p.41 / Chapter 3.2.4 --- Anion-exchange chromatography --- p.41 / Chapter 3.2.5 --- Paper chromatography --- p.42 / Chapter 3.2.6 --- Gas liquid chromatography --- p.43 / Chapter 3.2.7 --- Determination of molecular weight by high performance liquid chromatography --- p.44 / Chapter 3.2.8 --- SDS-polyacrylamide gel electrophoresis --- p.44 / Chapter 3.2.9 --- Determination of the bio´ؤtoxicity of samples --- p.46 / Chapter 3.2.10 --- Treatment of samples with sodium periodate or acetic acid --- p.46 / Chapter (II) --- ASSAYS OF IMMUNOMODULATORY ACTIVITIES OF PSEUDOSTELLARIA HETEROPHYLLA ON LYMPHOCYTES / Chapter 3.2.11 --- Isolation and preparation of cells --- p.48 / Chapter 3.2.12 --- In vitro lymphocyte transformation assay --- p.50 / Chapter 3.2.13 --- Mixed lymphocyte culture --- p.50 / Chapter 3.2.14 --- Depleting mouse T cells by anti-Thy-1.2 antibody plus complement treatment --- p.51 / Chapter 3.2.15 --- Depleting mouse B cells by anti-mouse B cell antibody plus complement treatment --- p.51 / Chapter 3.2.16 --- Haemolytic plaque assay --- p.52 / Chapter 3.2.17 --- Delayed-type hypersensitivity --- p.53 / Chapter 3.2.18 --- Immunofluorescent assay for interleukin-2 receptor expression --- p.54 / Chapter 3.2.19 --- Assay of murine interleukin-2 --- p.55 / Chapter (III) --- ASSAYS OF IMMUNOMODULATORY ACTIVITIES OF PSEUDOSTELLARIA HETEROPHYLLA ON MACROPHAGES / Chapter 3.2.20 --- Assay of murine interleukin-1 --- p.55 / Chapter 3.2.21 --- In vivo migration of macrophages --- p.56 / Chapter 3.2.22. --- Assay of phagocytic activity of peritoneal macrophages --- p.56 / Chapter 3.2.23 --- Northern blotting of mRNA of β-actin gene extracted from peritoneal exudate cells --- p.57 / Chapter (IV) --- ASSAYS OF ANTI-TUMOR ACTIVITIES OF PSEUDOSTELLARIA HETEROPHYLLA / Chapter 3.2.24 --- Assay of anti-tumor activity in vitro --- p.62 / Chapter 3.2.25 --- Assay of anti-tumor activity in vivo --- p.63 / Chapter 3.2.26 --- Priming effect of different fractions for the induction of TNF-α in mice --- p.63 / Chapter 3 .2.27 --- In vitro stimulation of TNF-α release from resting peritoneal macrophages --- p.64 / Chapter 3.2.28 --- Effects of P. heterophylla polysaccharides on TNF-α and IFN-gamma production as well as EAT growth in vivo --- p.64 / Chapter 3.2.29 --- Macrophage-mediated cytostatic activity --- p.65 / Chapter 3 2.30 --- Assay of lymphokine-activated killer cell activity --- p.66 / Chapter 3 2.31 --- Assay of natural killer cell activity --- p.67 / Chapter 3.2.32 --- Assay of tumor-infiltrating lymphocytes --- p.68 / Chapter (V) --- ASSAYS FOR THE EFFECTS OF PSEUDOSTELLARIA HETEROPHYLLA ON THE PROLIFERATION AND DIFFERENTIATION OF MURINE BONE MARROW CELLS AND MYELOID LEUKAEMIC Ml CELLS / Chapter 3.2.33 --- Assay of proliferation of murine bone marrow cells --- p.69 / Chapter 3.2.34 --- Assay of differentiation of murine bone marrow cells --- p.70 / Chapter 3.2.35 --- Assay of differentiation of Ml cells --- p.71 / Chapter 3.2.36 --- Induction of GM-CSF from bone marrow cells and Ml cells --- p.71 / Chapter (VI) --- ASSAYS OF THE IMMUNORESTORATIVE PROPERTIES OF PSEUDOSTELLARIA HETEROPHYLLA / Chapter 3.2.37 --- Immunorestoration in tumor-bearing mice --- p.72 / Chapter 3.2.38 --- Immunorestoration in aged mice --- p.72 / Chapter 3.2.39 --- Immunorestoration in cyclophosphamide- treated mice --- p.73 / Chapter 3.2.40 --- Statistical analysis --- p.73 / Chapter 4. --- "EXTRACTION, FRACTIONATION AND CHARACTERIZATION OF MITOGENIC FRACTIONS FROM PSEUDOSTELLARIA HETEROPHYLLA" / INTRODUCTION --- p.74 / RESULTS --- p.76 / Chapter 4.1 --- Extraction and fractionation of Pseudostellaria heterophylla --- p.76 / Chapter 4.2 --- Gel filtration and anion-exchange chromatography --- p.76 / Chapter 4.3 --- Characterization of bioactive fractions from Pseudostellaria heterophylla --- p.79 / Chapter 4.4 --- Mitogenic activity of fraction PH-I on murine lymphocytes in vitro --- p.96 / Chapter 4.5 --- Mitogenic effect of PH-I on murine lymphocytes in vivo --- p.102 / Chapter 4.6 --- Effect of PH-I on polyclonal B cell activation --- p.102 / Chapter 4.7 --- Adjuvant effect of PH-I on antibody response to SRBC in vivo --- p.106 / Chapter 4.8 --- Evidences to support the mitogenic activity of PH-I is due to its polysaccharide rather than due to the contamination by LPS --- p.106 / Chapter 4.9 --- The effects of PH-I on IL-2 production and IL-2 receptor expression on murine lymphocytes in vitro --- p.110 / Chapter 4.10 --- The mitogenic activity of the purified fractions on murine lymphocytes in vitro --- p.110 / Chapter 4.11 --- Adjuvant effect of PH-I Ab on antibody response to SRBC in vivo --- p.116 / Chapter 4.12 --- Mitogenic effect of PH-I C on murine lymphocytes in vivo --- p.116 / Chapter 4.13 --- Evidences to support the mitogenic activity of PH-I Ab is due to its polysaccharide rather than due to the contamination by LPS --- p.122 / DISCUSSION --- p.122 / Chapter 5. --- IMMUNOMODULATING AND ANTI-TUMOR ACTIVITIES OF ALCOHOL- INSOLUBLE FRACTION (PH-I) FROM THE HOT WATER EXTRACT OF PSEUDOSTELLARIA HETEROPHYLLA / INTRODUCTION --- p.133 / RESULTS --- p.135 / Chapter 5.1 --- Effect of PH-I on cytokine production --- p.135 / Chapter 5.2 --- In vivo activation of macrophages by PH-I --- p.135 / Chapter 5.3 --- Effect of PH-I on the activation of β-actin gene transcription in peritoneal macrophages --- p.142 / Chapter 5.4 --- Effect of PH-I on the in vitro growth of various tumor cell lines --- p.142 / Chapter 5.5 --- Immunorestoration of PH-I on the mitogenic response in EAT-bearing mice --- p.147 / DISCUSSION --- p.147 / Chapter 6. --- IMMUNOMODULATING AND ANTI-TUMOR ACTIVITIES OF PURIFIED FRACTIONS SEPARATED FROM PSEUDOSTELLARIA HETEROPHYLLA / INTRODUCTION --- p.154 / RESULTS --- p.157 / Chapter 6.1 --- In vitro anti-tumor activities of P. heterophylla --- p.157 / Chapter 6.2 --- In vivo anti-tumor activities of P. heterophylla --- p.165 / Chapter 6.3 --- Effect of P. heterophylla fractions on induction of delayed-type hypersensitivity --- p.165 / Chapter 6.4 --- Effect of PH-I fraction on the cytotoxic alloreactive T lymphocytes in vitro --- p.165 / Chapter 6.5 --- Effect of P. heterophylla on the production of TNF-α and IFN-gamma --- p.170 / Chapter 6.6 --- Effect of P. heterophylla on the activation of macrophages --- p.176 / Chapter 6.7 --- "Effect of P. heterophylla on the activation of NK, LAK and TIL" --- p.181 / Chapter 6.8 --- The effect of combined treatment of EAT-bearing mice with P. heterophylla amd Mur-TNF-α on the growth of EAT cells in vivo --- p.181 / Chapter 6 9 --- Immunorestorative activities of P. heterophylla in aged mice and cyclophosphamide-treated mice --- p.187 / DISCUSSION --- p.187 / Chapter 7. --- EFFECTS OF PSEUDOSTELLARIA HETEROPHYLLA ON PROLIFERATION AND DIFFERENTIATION OF MURINE BONE MARROW CELLS AND MYELOID LEUKAEMIC Ml CELLS / INTRODUCTION --- p.200 / RESULTS --- p.202 / Chapter 7.1 --- Effect of P. het erophyl1a on the proliferation and differentiation of murine bone marrow cells --- p.202 / Chapter 7 .2 --- Effects of P. heterophyl la on the proliferation and differentiation of murine myeloid leukaemia Ml cells --- p.205 / Chapter 7 .3 --- Effects of P. heterophylla on GM-CSF production by bone marow cells and myeloid leukaemia Ml cells --- p.214 / DISCUSSION --- p.218 / Chapter 8. --- CONCLUSIONS AND FUTURE PERSPECTIVES --- p.223 / BIBLIOGRAPHY --- p.233

by Chu Chi Yuen, Andrew. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 140-153). / Abstract also in Chinese. / ABSTRACT --- p.i / Chapter 1 --- INTRODUCTION --- p.3 / Chapter 1.1 --- Using Low density lipoprotein (LDL) as a drug carrier --- p.4 / Chapter 1.1.1 --- The structure of Low density lipoprotein (LDL) --- p.4 / Chapter 1.1.2 --- The metabolic pathway of LDL in human bodies --- p.4 / Chapter 1.1.3 --- The rationale for using LDL as a drug carrier --- p.7 / Chapter 1.1.4 --- Reconstitution of LDL with cytotoxic drugs --- p.9 / Chapter 1.1.5 --- Up and down regulation of LDL receptors --- p.11 / Chapter 1.2 --- Doxorubicin (DOX) --- p.12 / Chapter 1.2.1 --- Characteristics of DOX --- p.12 / Chapter 1.2.2 --- Drug actions of DOX --- p.14 / Chapter 1.2.3 --- The adverse side effects of DOX --- p.15 / Chapter 1.3 --- Multidrug resistance phenomenon in tumor cells --- p.17 / Chapter 1.3.1 --- The possible mechanisms of multidrug resistance --- p.19 / Chapter 1.3.2 --- The structure of P-glycoprotein --- p.20 / Chapter 1.3.3 --- The mechanisms of the P-glycoprotein --- p.22 / Chapter 1.3.4 --- Our aim in dealing with multidrug resistance --- p.22 / Chapter 2 --- MATERIALS AND METHODS --- p.23 / Chapter 2.1 --- Materials --- p.23 / Chapter 2.1.1 --- Animals --- p.23 / Chapter 2.1.2 --- Buffers --- p.24 / Chapter 2.1.3 --- Culture media --- p.25 / Chapter 2.1.4 --- Chemicals --- p.26 / Chapter 2.1.5 --- Culture of cells --- p.27 / Chapter 2.2 --- Methods --- p.29 / Chapter 2.2.1 --- In vitro studies --- p.29 / Chapter 2.2.2 --- In vivo studies --- p.44 / Chapter 3 --- RESULTS --- p.51 / Chapter 3.1 --- In vitro studies --- p.51 / Chapter 3.1.1 --- Preparation of LDL-DOX --- p.51 / Chapter 3.1.2 --- Comparison of the cytotoxicity of DOX and LDL-DOX on HepG2 cells --- p.59 / Chapter 3.1.3 --- Modulation of LDL receptors on HepG2 cells and ECV304 cells… --- p.63 / Chapter 3.1.4 --- The effect of combined treatment of LDL-DOX and hyperthermia on HepG2 cells --- p.84 / Chapter 3.1.5 --- The effect of LDL-DOX on resistant cell line R-HepG2 cells --- p.90 / Chapter 3.2 --- In vivo studies --- p.105 / Chapter 3.2.1 --- The comparison of organ distribution of LDL-DOX and DOXin BALB-c mice after administration --- p.105 / Chapter 3.2.2 --- The comparison of organ distribution of LDL-DOX and DOX in nude mice bearing HepG2 cells after adminstration --- p.108 / Chapter 3.2.3 --- Histological studies of heart of nude mice bearing HepG2 cells treated with DOX and LDL-DOX --- p.111 / Chapter 3.2.4 --- Myocardial injury measured by Lactate dehydrogenase (LDH) activity in nude mice bearing HepG2 treated with DOX and LDL- DOX --- p.117 / Chapter 3.2.5 --- The comparison of DOX and LDL-DOX on reducing the tumor sizes and weight in nude mice bearing HepG2 cells --- p.119 / Chapter 4 --- DISCUSSION --- p.122 / Chapter 4.1 --- In vitro studies --- p.122 / Chapter 4.1.1 --- Preparation of LDL-DOX complex --- p.122 / Chapter 4.1.2 --- The cytotoxicity ofLDL-DOX --- p.125 / Chapter 4.1.3 --- The combined treatment of hyperthermia and LDL-DOX --- p.129 / Chapter 4.1.4 --- The ability of LDL-DOX to circumvent muiltidrug resistance --- p.131 / Chapter 4.2 --- In vivo studies --- p.134 / Chapter 5 --- CONCLUSION --- p.136 / Chapter 5.1 --- Conclusion --- p.136 / Chapter 5.2 --- Future pospective --- p.139 / BIBLIOGRAPHY --- p.140

by Tung Kai Chiu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 152-166). / Abstracts in English and Chinese. / STATEMENT --- p.i / ACKNOWLEDGEMENTS --- p.ii / ABBREVIATIONS --- p.iv / ABSTRACT --- p.vii / 撮要 --- p.x / TABLE OF CONTENTS --- p.xiii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION / Chapter 1.1 --- AN OVERVIEW OF THE IMMUNE SYSTEM --- p.1 / Chapter 1.1.1 --- Innate Immunity --- p.1 / Chapter 1.1.2 --- Specific Acquired Immunity --- p.4 / Chapter 1.2 --- IMMUNE RESPONSE TO TUMOURS --- p.7 / Chapter 1.2.1 --- Specific Mechanisms --- p.7 / Chapter 1.2.1.1 --- Cellular Immune Response --- p.7 / Chapter 1.2.1.2 --- Humoral Immune Response --- p.9 / Chapter 1.2.2 --- Non-specific Mechanism --- p.10 / Chapter 1.2.2.1 --- Natural Killer Cells --- p.10 / Chapter 1.2.2.2 --- Lymphokine-activated Cells --- p.11 / Chapter 1.2.2.3 --- Tumour Infiltrating Lymphocytes --- p.12 / Chapter 1.2.2.4 --- Macrophages --- p.13 / Chapter 1.2.2.5 --- Other Cell Types Mediating Non-specific Immunity --- p.14 / Chapter 1.3 --- PHYTOCHEMICALS AS POTENTIAL IMMUNOMODULATORS and anti-tumour agents --- p.15 / Chapter 1.3.1 --- Modulation of the Immune System --- p.15 / Chapter 1.3.2 --- Induction of Cancer Cell Differentiation --- p.16 / Chapter 1.3.3 --- Stimulation of Apoptosis --- p.17 / Chapter 1.3.4 --- Other Anti-tumour Mechanisms --- p.18 / Chapter 1.4 --- GREEN TEA: GENERAL PROPERTIES AND PHARMACO- logical activities --- p.19 / Chapter 1.4.1 --- General Introduction --- p.19 / Chapter 1.4.2 --- Chemistry of Tea --- p.21 / Chapter 1.4.3 --- Physiological and Pharmacological Effects of Green Tea Catechins --- p.26 / Chapter 1.4.3.1 --- Anti-oxidative Activity --- p.26 / Chapter 1.4.3.2 --- Anti-mutagenic Activity --- p.27 / Chapter 1.4.3.3 --- Anti-carcinogenic Activity --- p.27 / Chapter 1.4.3.4 --- Anti-inflammatory Activity --- p.32 / Chapter 1.4.3.5 --- Hypocholesterolemic and Hypolipidemic Activities --- p.32 / Chapter 1.4.3.6 --- Anti-microbial Activity --- p.33 / Chapter 1.5 --- aims and scopes of this investigation --- p.34 / Chapter CHAPTER 2: --- MATERIALS AND METHODS / Chapter 2.1 --- MATERIALS --- p.36 / Chapter 2.1.1 --- Animals --- p.36 / Chapter 2.1.2 --- Cell lines --- p.36 / Chapter 2.1.3 --- Green Tea Catechins and Epicatechin Isomers --- p.38 / Chapter 2.1.4 --- Recombinant Murine Interleukin-2 (rmIL-2) --- p.38 / Chapter 2.1.5 --- Antibodies --- p.39 / Chapter 2.1.6 --- "Buffers, Culture Medium and Other Reagents" --- p.40 / Chapter 2.1.7 --- Reagents for Gel Electrophoresis --- p.47 / Chapter 2.1.8 --- Radioisotopes --- p.48 / Chapter 2.2 --- METHODS --- p.49 / Chapter 2.2.1 --- "Isolation, Purification and Characterization of Green Tea Catechins and Epicatechin Isomers" --- p.49 / Chapter 2.2.1.1 --- Extraction of Green Tea Catechins --- p.49 / Chapter 2.2.1.2 --- Analysis of Epicatechin Isomers by HPLC --- p.49 / Chapter 2.2.1.3 --- Determination of the Bio-toxicity of Green Tea Catechins --- p.50 / Chapter 2.2.1.4 --- Assay of In Vitro Cytotoxicity of Green Tea Catechins on Splenocytes --- p.51 / Chapter 2.2.2 --- Assays for the Immunomodulatory Activities of Green Tea Catechins --- p.52 / Chapter 2.2.2.1 --- Isolation and Preparation of Cells --- p.52 / Chapter 2.2.2.2 --- In Vitro Lymphocyte Transformation Assay --- p.53 / Chapter 2.2.2.3 --- Mixed Lymphocyte Culture --- p.53 / Chapter 2.2.2.4 --- Colorimetric Assay of Alloreactive Cytotoxic T Lymphocytes --- p.54 / Chapter 2.2.2.5 --- Foodpad Swelling Assay of Delayed-type Hypersensitivity --- p.55 / Chapter 2.2.2.6 --- Haemagglutination Assay of In Vivo Antibody Formation --- p.56 / Chapter 2.2.2.7 --- Characterization of the Lymphocyte Subpopulations from Spleen by Flow Cytometry --- p.56 / Chapter 2.2.2.8 --- In Vivo Migration of Macrophages --- p.57 / Chapter 2.2.2.9 --- In Vitro Assay of Phagocytic Activity of PEC --- p.58 / Chapter 2.2.2.10 --- In Vitro Assay of Macrophage-mediated Cytostatic Activity --- p.58 / Chapter 2.2.3 --- Assays for the Anti-tumour Activities of Green Tea Catechins --- p.60 / Chapter 2.2.3.1 --- Assay of In Vivo Anti-tumour Activity --- p.60 / Chapter 2.2.3.2 --- Induction and Assay of Natural Killer Cell Activity --- p.60 / Chapter 2.2.3.3 --- Induction and Assay of Lymphokine-activated Killer Cell Activity --- p.61 / Chapter 2.2.3.4 --- Assay of In Vitro Tumour Cell Proliferation --- p.62 / Chapter 2.2.3.5 --- In Vitro Tumour Clonogenicity Assay --- p.63 / Chapter 2.2.3.6 --- Induction of Myeloid Leukemic Cell Differentiation --- p.63 / Chapter 2.2.3.7 --- DNA Fragmentation Analysis --- p.64 / Chapter 2.2.3.8 --- Cell Cycle and DNA Content Evaluation --- p.66 / Chapter 2.2.4 --- Statistical Analysis --- p.66 / Chapter CHAPTER 3: --- "Extraction, Purification and Characterization of GTCs" / Chapter 3.1 --- INTRODUCTION --- p.67 / Chapter 3.2 --- RESULTS --- p.69 / Chapter 3.2.1 --- "Extraction of Catechins from the Chinese Green Tea, Ji Pin Long Jing" --- p.69 / Chapter 3.2.2 --- Analysis of Epicatechin Isomers by HPLC --- p.69 / Chapter 3.2.3 --- Bio-toxicity Determination by Brine Shrimp Bioassay --- p.71 / Chapter 3.2.4 --- Effect of GTCs on the Viability of Murine Splenocytes --- p.72 / Chapter 3.3 --- DISCUSSION --- p.74 / Chapter CHAPTER 4: --- The Immunomodulatory Activities of GTCs / Chapter 4.1 --- INTRODUCTION --- p.75 / Chapter 4.2 --- RESULTS --- p.77 / Chapter 4.2.1 --- Effects of GTCs on the In Vitro Proliferation of Murine Splenocytes --- p.77 / Chapter 4.2.2 --- In Vitro Co-mitogenic Effect of GTCs on Murine Splenocytes --- p.77 / Chapter 4.2.3 --- Stimulation of Lymphocyte Proliferation In Vitro by Intraperitoneal Administration of GTCs --- p.81 / Chapter 4.2.4 --- Effect of In Vivo Treatment of GTCs on In Vitro Mixed Lymphocyte Reaction --- p.81 / Chapter 4.2.5 --- Effect of In Vivo Administration of GTCs on Splenic Lymphocytes Subpopulations --- p.87 / Chapter 4.2.6 --- Effect of In Vivo Administration of GTCs on the Induction of Alloreactive Cytotoxic T Lymphocytes --- p.87 / Chapter 4.2.7 --- In Vivo Induction of Delayed-type Hypersensitivity (DTH) Response to Sheep Red Blood Cells (SRBC) by GTCs --- p.91 / Chapter 4.2.8 --- Primary Humoral Immune Response to SRBC in GTCs- treated Mice --- p.91 / Chapter 4.2.9 --- Effect of GTCs on In Vivo Migration of Macrophages --- p.95 / Chapter 4.2.10 --- Effect of GTCs on the Phagocytic Activity of Thioglycollate- elicited Macrophages In Vitro --- p.95 / Chapter 4.2.11 --- Effect of In Vivo Administration of GTCs on Phagocytic Activity of Thioglycollate-elicited Macrophages In Vitro --- p.98 / Chapter 4.2.12 --- Effect of GTCs on In Vitro Cytostatic Activity of Picolinic Acid-activated Macrophages --- p.98 / Chapter 4.2.13 --- Effect of In Vivo Administration of GTCs on the Cytostatic Activity of Picolinic Acid-activated Macrophages --- p.101 / Chapter 4.3 --- DISCUSSION --- p.103 / Chapter CHAPTER 5: --- THE ANTI-TUMOUR ACTIVITIES OF GTCs / Chapter 5.1 --- introduction --- p.107 / Chapter 5.2 --- RESULTS --- p.109 / Chapter 5.2.1 --- Effects of GTCs on the Growth of Transplantable Tumour Cells In Vivo --- p.109 / Chapter 5.2.2 --- Effect of GTCs on In Vivo Induction of Natural Killer Cells --- p.109 / Chapter 5.2.3 --- Effect of GTCs on In Vitro Induction of Lymphokine- activated Killer Cell Activity --- p.113 / Chapter 5.2.4 --- In Vitro Cytotoxicity of Green Tea Epicatechin Isomers on Murine and Human Tumour Cell Lines --- p.115 / Chapter 5.2.5 --- In Vitro Cytostatic Effect of EGCG on Various Tumour Cell Lines --- p.118 / Chapter 5.2.6 --- Effect of EGCG on the In Vitro Clonogenicity of Myeloid Leukemia Cells --- p.127 / Chapter 5.2.7 --- Induction of Apoptosis of Myeloid Leukemia HL-60 Cells In Vitro --- p.130 / Chapter 5.2.8 --- Effect of EGCG on the Cell Cycle Kinetics of Myeloid Leukemia HL-60 Cells In Vitro --- p.131 / Chapter 5.2.9 --- Effect of EGCG on the Morphological Changes of Myeloid Leukemia Cells --- p.136 / Chapter 5.2.10 --- Effect of EGCG on the Endocytic Activity of Myeloid Leukemia Cells --- p.136 / Chapter 5.3 --- discussion --- p.141 / Chapter CHAPTER 6: --- CONCLUSIONS AND FUTURE PERSPEC- TIVES --- p.145 / REFERENCES --- p.152

Chan Wai Sing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 199-210). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABBREVIATIONS --- p.ii / ABSTRACT --- p.vi / CHINESE ABSTRACT --- p.x / TABLE OF CONTENTS --- p.xiii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION / Chapter 1.1 --- What is hematopoiesis? --- p.1 / Chapter 1.1.1 --- The development of hematopoietic progenitor cells --- p.1 / Chapter 1.1.2 --- The regulation of hematopoiesis by environmental factors --- p.4 / Chapter 1.1.3 --- The regulation of hematopoiesis by transcription factors --- p.7 / Chapter 1.2 --- Leukemia --- p.9 / Chapter 1.2.1 --- Classification of leukemia --- p.11 / Chapter 1.2.2 --- Pathology and etiology of leukemia --- p.15 / Chapter 1.2.2.1 --- Inheritance --- p.15 / Chapter 1.2.2.2 --- Environmental factors --- p.16 / Chapter 1.2.2.3 --- Virus infection --- p.17 / Chapter 1.2.3 --- Genetics of leukemia --- p.17 / Chapter 1.2.3.1 --- Point mutations --- p.17 / Chapter 1.2.3.2 --- Translocations --- p.18 / Chapter 1.2.3.3 --- Gene and chromosomal deletions --- p.18 / Chapter 1.2.3.4 --- Chromosomal duplication or gene amplification --- p.18 / Chapter 1.2.4 --- Current therapeutic strategies for leukemia --- p.20 / Chapter 1.2.4.1 --- Chemotherapy --- p.20 / Chapter 1.2.4.2 --- Stem cell transplantation --- p.21 / Chapter 1.2.4.3 --- Immunotherapy --- p.22 / Chapter 1.2.4.4 --- Gene therapy --- p.23 / Chapter 1.2.5 --- Novel approaches for the treatment of leukemia --- p.23 / Chapter 1.2.5.1 --- Differentiation therapy of leukemia --- p.24 / Chapter 1.2.5.2 --- Induction of apoptosis in the treatment of leukemia --- p.25 / Chapter 1.3 --- Topoisomerase-targeting agents --- p.27 / Chapter 1.3.1 --- What is topoisomerase? --- p.27 / Chapter 1.3.2 --- Structures and action mechanisms of Top I- and Top II-targeting agents --- p.28 / Chapter 1.3.3 --- Anti-tumor activities of topoisomerase-targeting agents --- p.37 / Chapter 1.4 --- Aims and scopes of this investigation --- p.39 / Chapter CHAPTER 2: --- MATERIALS AND METHODS / Chapter 2.1 --- Materials --- p.42 / Chapter 2.1.1 --- Mice --- p.42 / Chapter 2.1.2 --- Cell lines --- p.42 / Chapter 2.1.3 --- "Cell culture medium, buffers and other reagents" --- p.43 / Chapter 2.1.4 --- Radioisotope and scintillation fluid --- p.47 / Chapter 2.1.5 --- Reagents and buffers for flow cytometry --- p.48 / Chapter 2.1.6 --- Antibodies for flow cytometry --- p.50 / Chapter 2.1.7 --- Recombinant cytokines --- p.51 / Chapter 2.1.8 --- Reagents for DNA extraction --- p.52 / Chapter 2.1.9 --- Reagents for total RNA isolation --- p.53 / Chapter 2.1.10 --- Reagents and buffers for RT-PCR --- p.54 / Chapter 2.1.11 --- Reagents and buffers for gel electrophoresis --- p.58 / Chapter 2.1.12 --- Reagents and buffers for Western blot analysis --- p.59 / Chapter 2.1.13 --- Reagents for measuring caspase activity --- p.64 / Chapter 2.2 --- Methods --- p.67 / Chapter 2.2.1 --- Culture of the leukemia cell lines --- p.67 / Chapter 2.2.2 --- Isolation and preparation of normal hematopoietic cells --- p.67 / Chapter 2.2.3 --- [3 H]-TdR proliferation assay --- p.68 / Chapter 2.2.4 --- Determination of cell viability --- p.69 / Chapter 2.2.5 --- Assay for anti-leukemic activity in vivo --- p.70 / Chapter 2.2.6 --- Assessment of differentiation-associated characteristics --- p.71 / Chapter 2.2.7 --- Assays for apoptosis --- p.73 / Chapter 2.2.8 --- Cell cycle analysis (DNA content evaluation) --- p.75 / Chapter 2.2.9 --- Gene expression study --- p.75 / Chapter 2.2.10 --- Protein expression study --- p.79 / Chapter 2.2.11 --- Measurement of caspase activity --- p.82 / Chapter 2.2.12 --- Statistical analysis 一 --- p.83 / Chapter CHAPTER 3: --- STUDIES ON THE ANTI-PROLIFERATIVE EFFECT OF TOPOISOMERASE-TARGETING AGENTS ON LEUKEMIA CELLS / Chapter 3.1 --- Introduction --- p.84 / Chapter 3.2 --- Results --- p.86 / Chapter 3.2.1 --- The anti-proliferative effect of topoisomerase-targeting agents on human and murine leukemia cells in vitro --- p.86 / Chapter 3.2.2 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on the clonogenicity of the murine myeloid leukemia WEHI-3B JCS cells in vitro --- p.105 / Chapter 3.2.3 --- Effects of 10-hydroxy-camptothecin and etoposide phosphate on the tumorigenicity and proliferation of the murine myeloid leukemia WEHI-3B JCS cells invivo --- p.106 / Chapter 3.2.4 --- Cytotoxic effect of 10-hydroxy-camptothecin and etoposide phosphate on normal hematopoietic cells and WEHI-3B JCS cells in vitro --- p.109 / Chapter 3.2.5 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on the cell cycle kinetics of WEHI-3B JCS cells --- p.114 / Chapter 3.2.6 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on the expression of cell cycle-regulatory genes in the murine myeloid leukemia WEHI-3B JCS cells --- p.116 / Chapter 3.2.7 --- Combination effect of 10-hydroxy-camptothecin or etoposide phosphate with cytokines on the proliferation of the murine myeloid leukemia WEHI-3B JCS cells --- p.123 / Chapter 3.3 --- Discussion --- p.127 / Chapter CHAPTER 4: --- STUDIES ON THE DIFFERENTIATION-INDUCING EFFECT OF 10-HYDROXY-CAMPTOTHECIN AND ETOPOSIDE PHOSPHATE ON THE MURINE MYELOID LEUKEMIA WEHI-3B JCS CELLS / Chapter 4.1 --- Introduction --- p.132 / Chapter 4.2 --- Results --- p.134 / Chapter 4.2.1 --- Morphological changes in the murine myeloid leukemia WEHI-3B JCS cells treated with 10-hydroxy-camptothecin and etoposide phosphate --- p.134 / Chapter 4.2.2 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on the size and granularity of the murine myeloid leukemia WEHI-3B JCS cells --- p.138 / Chapter 4.2.3 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on the plastic adhering property of the murine myeloid leukemia WEHI-3B JCS cells --- p.140 / Chapter 4.2.4 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on the NBT-reducing activity of the murine myeloid leukemia WEHI-3B JCS cells --- p.142 / Chapter 4.2.5 --- Surface antigen immunophenotyping of the murine myeloid leukemia WEHI-3B JCS cells treated with 10-hydroxy- camptothecin and etoposide phosphate --- p.145 / Chapter 4.2.6 --- Induction of non-specific esterase activity in the murine myeloid leukemia WEHI-3B JCS cells by 10-hydroxy- camptothecin and etoposide phosphate --- p.152 / Chapter 4.3 --- Discussion --- p.154 / Chapter CHAPTER 5: --- STUDIES ON THE APOPTOSIS-INDUCING EFFECT OF 10-HYDROXY-CAMPTOTHECIN AND ETOPOSIDE PHOSPHATE ON THE MURINE MYELOID LEUKEMIA WEHI-3B JCS CELLS / Chapter 5.1 --- Introduction --- p.157 / Chapter 5.2 --- Results --- p.160 / Chapter 5.2.1 --- Induction of nuclear disintegration in the murine myeloid leukemia WEHI-3B JCS cells by 10-hydroxy-camptothecin and etoposide phosphate --- p.160 / Chapter 5.2.2 --- Induction of DNA fragmentation in the murine myeloid leukemia WEHI-3B JCS cells by 10-hydroxy-camptothecin and etoposide phosphate --- p.162 / Chapter 5.2.3 --- Induction of phosphatidylserine translocation in murine myeloid leukemia WEHI-3B JCS cells by 10-hydroxy- camptothecin and etoposide phosphate --- p.167 / Chapter 5.2.4 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on the expression of apoptosis-regulatory genes in the murine myeloid leukemia WEHI-3B JCS cells --- p.171 / Chapter 5.2.5 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on the expression of apoptosis-regulatory proteins in the murine myeloid leukemia WEHI-3B JCS cells --- p.177 / Chapter 5.2.6 --- Induction of mitochondrial membrane depolarization in the murine myeloid leukemia WEHI-3B JCS cells by 10-hydroxy- camptothecin and etoposide phosphate --- p.179 / Chapter 5.2.7 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate on caspase activity in the murine myeloid leukemia WEHI-3B JCS cells --- p.181 / Chapter 5.2.8 --- Effect of 10-hydroxy-camptothecin and etoposide phosphate intracellular Ca2+ level in the murine myeloid leukemia WEHI-3B JCS cells --- p.186 / Chapter 5.3 --- Discussion --- p.189 / Chapter CHAPTER 6: --- CONCLUSIONS AND FUTURE PERSPECTIVES --- p.192 / REFERENCES --- p.199

No description available.

"August 2004" / Errata inside front cover. / Bibliography: leaves 126-159. / xi, 159, [12] leaves : ill., plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine and The Hanson Centre, Institute of Medical and Veterinary Science, 2004

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.