Zhang Aiqun. / "March 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 95-123). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Shan Sze Wan. / "July 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 125-139) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Wu Yan. / "August 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 141-170). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Hypoxia is a common patho-physiological phenomenon in many types of diseases, including tumors, myocardial infarction and cerebral ischemia. It is believed that hypoxia not only affects the cellular regulation pathways, but also interferes genome, transcriptome and proteome inside tumor, eventually enhances tumor development by increasing malignancy and metastatic potential, induction of resistance towards radiotherapy and chemotherapy, activation of angiogenic mechanism, etc. One of the major biological events for hypoxia is induction of apoptosis, which is believed to provide a selective pressure for tumor progression. However, the mechanism of hypoxia induced apoptosis is not well established. In the present study, the molecular mechanism of hypoxia induced apoptosis was investigated and was found to be different in human squamous carcinoma A431 cells and human hepatocellular carcinoma HepG2 cells. In HepG2 cells, the conventional intrinsic apoptotic pathway that involved the activation of caspase-9 and -3 was found to be triggered by hypoxia through a newly identified p53 - Bnip-3 shunt. On the other hand, caspase-4 and -10 were found to be activated under hypoxia and may be related to hypoxia induced DNA fragmentation in A431 cells. Reoxygenation prior to hypoxia is the event after blood reperfusion in tumor vasculature. It is demonstrated in this study that reoxygenation is a distinctive stress from hypoxia, and it is very likely to be induced by reactive oxygen species. Apart from apoptosis, the mechanism for the development of drug resistance after hypoxia is also not yet clearly identified. In this study, resistance towards several common chemotherapeutic drugs after cells were subjected to hypoxia/reoxygenation cycles were demonstrated. Among them, the possible role of the genes related to methotrexate and cisplatin resistance were also investigated. / Ho Yiu Fung. / "August 2006." / Adviser: Tim-Tak Kwok. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1393. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 159-176). / 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.

The ability to evade apoptosis is an acquired characteristic associated with many normal and pathophysiological processes. TMEM 85 represents a novel transmembrane domain containing human protein isolated in our previous screen for Bax suppressors, but whose function is currently unknown. Using viability and growth assays, we confirmed that TMEM 85 is anti-apoptotic. Four unique human cDNA sequences containing regions distinct from and of perfect identity to our cDNA were present in the database. Analysis of TMEM 85 suggests that it consists of five exons, alternatively spliced to produce at least four different mRNA's and proteins (TMEM 85v1-v4). RT-PCR analysis using RNA isolated from mice and humane tissues show that all transcripts are expressed. Yeast contain an orthologue of the human TMEM 85v1 protein, YGL213C. Surprisingly, the viability assay indicated that mutants lacking YGL231c do not show a hyper-responsive apoptotic phenotype, however its overexpression shows that it is nevertheless anti-apoptotic. Using a yeast strain expressing chromosomally TAP-tagged YGL231c, we found no up-regulation of the endogenous gene due to stress. The deletion mutant is also known to expresses a synthetically lethal phenotype in the presence of alpha-synuclein. While expression of alpha-synuclein caused significant death in both the wild type and deletion mutants, TMEM 85v2 was unable to exhibit a protective role. These findings demonstrate the complexity of the TMEM 85 gene and its anti-apoptotic function in both yeast and human.

No description available.

Ho, Tik Shun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 88-102). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgement --- p.vii / Table of Contents --- p.viii / List of Table --- p.x / List of Figures --- p.xi / List of Abbreviations --- p.xiii / Chapter CHAPTER 1 --- General Introduction --- p.1 / Chapter 1.1 --- Fatty Acid Synthase (FAS) - 7-domain multifunctional enzyme --- p.1 / Chapter 1.1.1 --- Functions --- p.1 / Chapter 1.1.2 --- Structure --- p.2 / Chapter 1.2 --- Fatty Acid biosynthesis reactions --- p.4 / Chapter 1.3 --- Malonyl Coenzyme A - An important mediator in lipogenesis --- p.7 / Chapter 1.4 --- FAS expression in different histotypes --- p.8 / Chapter 1.4.1 --- FAS in normal cells --- p.8 / Chapter 1.4.2 --- FAS in pathological cells --- p.8 / Chapter 1.4.3 --- Tumor-associated FAS (Oncogenic antigen-519) in cancer cells --- p.9 / Chapter 1.5 --- FAS signaling models in breast and prostate cancers --- p.12 / Chapter 1.5.1 --- Association between FAS and PI3K／Akt pathway --- p.12 / Chapter 1.5.2 --- Hypothetical model of FAS hyperactivity in breast and prostate cancer cells --- p.13 / Chapter 1.6 --- FAS inhibition to tackle cancer cell growth --- p.15 / Chapter 1.6.1 --- FAS inhibitors --- p.15 / Chapter 1.6.1.1 --- Cerulenin --- p.16 / Chapter 1.6.1.2 --- C75 --- p.17 / Chapter 1.6.2 --- Small interfering RNA --- p.17 / Chapter 1.7 --- FAS inhibition to enhance chemoresistant cancer cells sensitivity to drugs --- p.19 / Chapter 1.8 --- Hypothesis --- p.20 / Chapter CHAPTER 2 --- Methods and Materials --- p.21 / Chapter 2.1 --- Chemicals and antibodies --- p.21 / Chapter 2.2 --- Cell cultures --- p.21 / Chapter 2.3 --- MTT assay --- p.22 / Chapter 2.4 --- 5-Bromo-2'-deoxyuridine (BrdU)-labeling cell proliferation assay --- p.22 / Chapter 2.5 --- Cytotoxicity detection assay of LDH release --- p.23 / Chapter 2.6 --- DNA flow cytometry --- p.23 / Chapter 2.7 --- Confocal micocropy --- p.24 / Chapter 2.8 --- Immunoblot analysis --- p.24 / Chapter 2.8.1 --- Preparation of protein lysates --- p.24 / Chapter 2.8.2 --- Immunoblotting --- p.25 / Chapter 2.9 --- Caspase inhibitor studies --- p.26 / Chapter 2.10 --- Analysis of mitochondrial membrane potential --- p.26 / Chapter 2.11 --- Determination of caspase activities --- p.27 / Chapter 2.12 --- siRNA transfection --- p.27 / Chapter 2.13 --- Statistical analysis --- p.28 / Chapter CHAPTER 3 --- Results --- p.29 / Chapter 3.1 --- Cytostatic & cytotoxic studies of FAS inhibitors on human cancer cells --- p.29 / Chapter 3.1.1 --- Cerulenin and C75 suppress cell growth of different cancer histotypes --- p.29 / Chapter 3.1.2 --- Cerulenin and C75 suppress cell growth of A-375 dose- and time-dependently --- p.32 / Chapter 3.1.3 --- Cerulenin and C75 exert cytotoxic effect on A-375 but not normal skin HS68 cells --- p.36 / Chapter 3.1.4 --- Cerulenin and C75 arrest cell cycle progression and induce apoptosis with DNA Fragmentation --- p.39 / Chapter 3.2 --- Mechanistic studies of FAS inhibitors in A-375 cells --- p.46 / Chapter 3.2.1 --- Cerulenin and C75 induce caspase-dependent apoptosis --- p.46 / Chapter 3.2.2 --- Cerulenin- and C75-induced apoptosis involve extrinsic death receptor pathway --- p.52 / Chapter 3.2.3 --- Cerulenin- and C75-induced apoptosis involve intrinsic mitochondrial pathway --- p.57 / Chapter 3.2.4 --- Extrinsic death receptor pathway serves as a pioneer and links with intrinsic mitochondrial pathway in cerulenin- and C75-induced apoptosis --- p.65 / Chapter 3.3 --- Small interfering RNA on Fatty Acid Synthase (FAS siRNA) --- p.68 / Chapter 3.3.1 --- FAS siRNA induces PARP cleavage --- p.68 / Chapter 3.3.2 --- FAS siRNA triggers caspase-dependent apoptosis as FAS inhibitors --- p.70 / Chapter CHAPTER 4 --- Discussion --- p.72 / Chapter CHAPTER 5 --- Future Prospect --- p.85 / Chapter CHAPTER 6 --- References --- p.88

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Masters in Science. December 2015 / Cervical cancer remains a global health related issue among females of Sub-Saharan Africa, with over half a million new cases reported each year. Different therapeutic regimens have been suggested in various regions of Africa, however, over a quarter of a million women die of cervical cancer, annually. This makes it the most lethal cancer amongst black women in this area, and makes it important to search for new effective therapeutic drugs through screening of medicinal plant extracts used by many in Sub-Saharan Africa as potential anti-cervical cancer agents. The aim of this study was to evaluate the anti-proliferative effects of Cannabis sativa extracts and its isolate, cannabidiol on cervical cancer cell lines HeLa, SiHa, and ME-180. To achieve our aim, phytochemical screening, MTT assay, cell growth analysis, flow cytometry, morphology analysis, Western blot, caspase 3/7 assay, and ATP measurement assay were conducted were conducted. Results obtained indicate that both plant extracts induced cell death at an IC50 of 50 – 100μg/ml and the Inhibition of cell growth was cell line dependent. Flow cytometry confirmed that, with or without cell cycle arrest, the type of induced cell death was apoptosis. Cannabis sativa extracts led to the up-regulation of apoptosis proteins (p53, Bax, caspase-3, and caspase-9) and the down regulation of anti-apoptosis proteins (Bcl-2 and RBBP6), signalling the execution of apoptosis. Apoptosis induction was further confirmed by morphological changes, an increase in Caspase 3/7 and a decrease in the ATP levels. In conclusion, this data implies Cannabis sativa crude extracts has the potential to inhibit growth and induce apoptosis in cervical cancer cell lines, which may be due to the presence of cannabidiol. Key words: Apoptosis, cervical cancer cells, cannabidiol, and Cannabis sativa extracts

Further studies of Stk31 in spermatogenesis in vivo would allow the identification of the asymmetry machinery of GSCs and the signaling mechanism underlying cell fate determination. Further studies of STK31 in cancer stem cells would allow the development of new diagnostic and therapeutic approaches. / In the first part of the experiment, the expression and cellular localization of STK31 were investigated. RT-PCR results showed that STK31 was reactivated in 47 -- 86% of multiple cancers. Immunofluorescent study and GFP tagging experiment showed that STK31 was localized in the cytoplasm and formed aggregated granules that divide asymmetrically during mitosis. Further study by co-staining with E-cadherin demonstrated that the mouse homolog, Stk31, was expressed in the transition state between undifferentiated and differentiated spermatogonia. These data suggest the possible involvement of STK31 in mouse spermatogonia and cancer development. / In the second part of the experiment, the function of Stk31 in mouse spermatogonia was investigated- A GSC culture on an STO feeder layer was established. Studies on growing properties, expression of molecular markers and germ cell transplantation showed that GSC culture maintained spermatogonial stem cell activity. Retinoic acid was then used to induce differentiation of GSC. The differentiation status was confirmed by monitoring the expression of molecular markers. RT-PCR and immunofluorescent study showed that the expression of Stk31 was induced in RA-induced differentiation and Stk31 proteins were asymmetrically distributed during GSC division. Overexpression of Stk31 in GSCs using retroviral transduction induced the differentiation phenotypes. These data indicate the involvement of Stk31 in mouse spermatogonia cell fate determination. / In the third part of the experiment, the function of STK31 in human colon cancer was investigated. A stable STK31 knock-down Caco2 cells were established by stably transfecting two miR RNAi designs with different efficiency into Caco2 cells. Flow cytometry analysis showed that knock-down of STK31 resulted in G1 phase arrest. Cell counts and MTS assays suggested that knock-down of STK31 decreased cell proliferation in confluent cultures. Knock-down of STK31 also enhanced cell attachment to several ECM proteins and decreases cell migration as suggested by attachment assays and migration assays. Moreover, knock-down of STK31 enhanced enterocytic differentiation and inhibited tumorigenicity both in vitro and in vivo as indicated by colony formation assays and xenograft assays. Date obtained from whole genome microarray studies indicate that STK31 regulates these "stemness" properties through altering the expression of key players in various pathways including KIT, SMAD1 and Cyclin D2. These results suggest the involvement of STK31 in colon cancer as a regulator of "sternness". / Spermatogenesis is a complicated process involving mitosis, meiosis and post-meiotic differentiation. Due to the lack of in vitro models, genes that are involved in mammalian spermatogenesis are largely unknown. Spermatogenesis and tumorigenesis share important biological similarities. This co-relation can be signified by a special group of genes called cancer/testis (CT) antigens, which are only expressed in the testes and cancer. Although cancer biology has been extensively studied for decades, promising therapeutic methods are not available for every type of cancer. Recent discovery of cancer stem cells and functional genomics studies have shed light on the development of new diagnostic and therapeutic approaches. This thesis describes the expression, cellular localization and function of a novel CT gene, STK31, in spermatogonia and cancer development. / Fok, Kin Lam Ellis. / "December 2009." / Adviser: H.C. Chan. / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 143-169). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Chan Siu Lan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 149-181). / Abstracts in English and Chinese. / Abstract --- p.ii / Chinese Abstract (摘要) --- p.v / Acknowledgements --- p.viii / Publications --- p.x / Table of contents --- p.xii / List of Figures --- p.xvi / List of Table and Diagram --- p.xx / Abbreviations --- p.xxi / Chapter Chapter 1: --- Introduction / Chapter 1.1 --- Major objectives and long-term significance --- p.1 / Chapter 1.2 --- Biological significance of apoptosis --- p.1 / Chapter 1.3 --- Importance of apoptosis in the study of the female reproductive system --- p.3 / Chapter 1.4 --- Specific aims of the present project --- p.3 / Chapter 1.5 --- Experimental approaches --- p.8 / Chapter Chapter 2: --- Materials and Methods / Chapter 2.1 --- General experimental methods --- p.11 / Chapter 2.1.1 --- Culture of cells --- p.11 / Chapter 2.1.1.1 --- Culture of rabbit immortalized uterine epithelial cells --- p.11 / Chapter 2.1.1.2 --- Culture of primary mouse uterine epithelial cells --- p.12 / Chapter 2.1.1.3 --- Culture of human ovarian epithelial cancer cells --- p.13 / Chapter 2.1.2 --- Assessment of apoptotic DNA fragmentation --- p.13 / Chapter 2.1.2.1 --- DNA extraction --- p.14 / Chapter 2.1.2.2 --- Assessment of apoptotic DNA --- p.14 / Chapter 2.1.2.3 --- Assessment of apoptotic DNA by CE-LIF --- p.15 / Chapter 2.1.2.4 --- Assessment of apoptosis by Nuclear Hoechst 33248 Staining / Chapter 2.1.3 --- Assessement of protein content --- p.16 / Chapter 2.1.3.1 --- Protein extraction and western blot analysis --- p.16 / Chapter 2.1.4 --- Adenoviral infection of A2780s cells --- p.18 / Chapter 2.2 --- Preparation of solutions --- p.18 / Chapter 2.3 --- Animals and cell lines --- p.25 / Chapter 2.4 --- Statistical analysis --- p.25 / Chapter Chapter 3: --- Literature Review / Chapter 3.1 --- Morphological analysis of physiological cell death --- p.26 / Chapter 3.1.1 --- Characteristics of apoptosis --- p.27 / Chapter 3.2 --- Methods of detecting apoptosis --- p.31 / Chapter 3.3 --- Molecules controlling apoptosis --- p.33 / Chapter 3.3.1 --- Caspases --- p.33 / Chapter 3.3.2 --- The Bcl-2 family proteins --- p.34 / Chapter 3.4 --- Apoptosis signalling --- p.36 / Chapter 3.4.1 --- The death receptor-dependent pathway --- p.36 / Chapter 3.4.2 --- The mitochondria-dependent pathway --- p.38 / Chapter 3.4.3 --- The endoplasmic-reticulum-dependent pathway --- p.39 / Chapter 3.5 --- Importance of apoptosis in the female reproductive system --- p.40 / Chapter 3.5.1 --- Apoptosis in uterus epithelial cells --- p.40 / Chapter 3.5.2 --- Apoptosis in ovarian cancer cells --- p.42 / Chapter 3.6 --- Regulation of apoptosis by nitric oxide/cGMP/protein kinase G --- p.44 / Chapter 3.6.1 --- Regulation of apoptosis by nitric oxide --- p.44 / Chapter 3.6.2 --- Regulation of apoptosis by cGMP --- p.48 / Chapter 3.6.3 --- Regulation of apoptosis by soluble guanyly cyclase activator --- p.50 / Chapter Chapter 4: --- "Apoptotic DNA fragmentation caused by sodium nitroprusside, a nitric oxide donor, in uterine epithelial cells: ultrasensitive quantitation using the new capillary electrophoresis/laser-induced fluorescence (CE-LIF) technology" / Chapter 4.1 --- Abstract --- p.52 / Chapter 4.2 --- Introduction --- p.53 / Chapter 4.3 --- Results --- p.57 / Chapter 4.4 --- Discussion --- p.61 / Chapter 4.5 --- Figures of Chapter 4 --- p.66 / Chapter Chapter 5: --- Guanylyl-cyclase inhibitors NS2028 and ODQ and protein-kinase-G inhibitor KT5823 trigger apoptotic DNA fragmentation in an immortalized uterine epithelial cell line: anti-apoptotic effects of basal cGMP/PKG / Chapter 5.1 --- Abstract --- p.74 / Chapter 5.2 --- Introduction --- p.75 / Chapter 5.3 --- Results --- p.80 / Chapter 5.4 --- Discussion --- p.83 / Chapter 5.5 --- Figures of Chapter 5 --- p.89 / Chapter Chapter 6: --- "Direct, prolonged activation of soluble guanylyl cyclase by YC-1 or protein kinase G by cGMP analogs enhances the level of apoptosis in an immortalized uterine epithelial cell line, HRE-H9 cells" / Chapter 6.1 --- Abstract --- p.100 / Chapter 6.2 --- Introduction --- p.101 / Chapter 6.3 --- Results --- p.105 / Chapter 6.4 --- Discussion --- p.107 / Chapter 6.5 --- Figures of Chapter 6 --- p.114 / Chapter Chapter 7: --- "ODQ，an inhibitor of soluble guanylyl cyclase, down-regulates XIAP expression and induces apoptosis in human ovarian cancer cells" / Chapter 7.1 --- Abstract --- p.124 / Chapter 7.2 --- Introduction --- p.125 / Chapter 7.3 --- Results --- p.129 / Chapter 7.4 --- Discussion --- p.132 / Chapter 7.5 --- Figures of Chapter 7 --- p.138 / Chapter Chapter 8: --- Overall Conclusion --- p.145 / Chapter Chapter 9: --- References --- p.149