Abstract not available. / Pak Wai Martin. / Adviser: Charles Andrew van Hasselt. / Source: Dissertation Abstracts International, Volume: 72-10, Section: B, page: . / Thesis (M.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 245-269). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

Xie Tong. / "May 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 113-126). / 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.

Lam Wai-man Wynnie. / "April 2002." / Thesis (M.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 109-134). / 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.

Deletion on the short arm of chromosome 3 is one of the most important genetic abnormalities in the tumorigenesis of nasopharyngeal carcinoma (NPC). Both physical mapping and functional studies have targeted an NPC-related tumor suppressor gene(s) to chromosome 3p21.3. Our group has previously reported that the Ras Association Domain Family 1A (RASSF1A) gene, located within a 120-kb minimal deleted region on 3p21.3, was frequently inactivated by promoter hypermethylation in NPC. These findings suggest that RASSF1A may be a critical tumor suppressor gene in NPC. In this study, the functions of RASSF1A in NPC was characterized with the following specific aims: (1) the role of RASSF1A as a tumor suppressor in NPC cells; (2) the identification of novel RASSF1A-modulated genes and pathways in NPC; (3) the effect of RASSF1A knockdown in immortalized nasopharyngeal epithelial cells; (4) the aberrant transcription and epigenetic changes of other RASSF family of genes ( RASSFS/NORE1 and RASSF4/AD037) in NPC. / In summary, RASSF1A is a major tumor suppressor gene from 3p21.3 in NPC. RASSF1A may exert its tumor suppressor function through various biochemical pathways. The novel findings from this study revealed the role of RASSF1A in the tumorigenesis of NPC. It also led to the better understanding of the molecular pathogenesis of this endemic cancer. (Abstract shortened by UMI.) / RASSF1A is a member of the RASSF family of proteins characterized by a consensus Ras-association domain at the C-terminus. The expression and methylation status of two other members of RASSF gene family, RASSF4/AD037 and RASSF5/NORE1, were investigated in NPC. The study showed that RASSF1A, but not other members of the RASSF family, is the target tumor suppressor in this particular cancer type. / Restoration of wild-type RASSF1A, by means of transfection, in a RASSF1A-deficient NPC cell line (C666-1) led to marked growth inhibition in the NPC cells. Isolated stable clones expressing RASSF1A demonstrated retarded cell proliferation in vitro . Soft-agar assay showed decreased number and sizes of colonies formed by these clones. The expression of RASSF1A in NPC cells also led to a dramatic reduction in tumorigenic potential in nude mice. The findings provide functional evidence that RASSF1A is a target tumor suppressor gene on 3p21.3 in NPC. / Chow Shuk Nga Lillian. / "May 2005." / Adviser: Kwok Wai Lo. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3588. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 112-124). / 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. / Abstract in English and Chinese. / School code: 1307.

by Cheung Siu Tim. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (p. 155-160). / 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.

Common amplicons were delineated throughout the NPC genome in a large panel of NPC cell lines, xenografts, and primary tumors by two high-density genomic arrays with ∼1 Mb and 35 kb resolution. Apart from the genetic changes reported in previous studies, a number of novel chromosomal aberrations were discovered, including gains at 7p11, 16p13.3, 19p13, 19q13-q43 and 20q13. Most distinctively, common amplicons at 11q13 and 12p13 were found in this cancer. Two smallest amplification regions with 5.4 Mb and 2.16 Mb were delineated at 11q13.1-q13.3 and 12p13.31 respectively. The high prevalence of these 2 amplified regions have led to the hypothesis that activation of the target oncogenes in these regions are critical events for NPC development. / Expression of candidate genes located within 11q13.3 was examined and consistent overexpression of CCND1 in cell lines and xenografts were identified in the 11q13.3. Frequent concordant gains and overexpression of CCND1 were further confirmed in primary tumors. Knockdown of CCND1 mRNA by siRNA technique was found to inhibit cell growth and lead to cell cycle arrest at G1. Alterations of protein expressions of other cell cycle components were also observed. Moreover, inactivation of p16 and overexpression of cyclin D1 were commonly occurred in NPC. These findings provided evidence that cyclin D1 may have cell cycle-independent functions, which is critical in NPC tumongenesis. / Frequent gains of 12p13.31 region were confirmed by fluorescence in situ hybridization (FISH) analysis. According to expression array and real-time RT-PCR results, LTbetaR, TNFRSF1A and FLJ10665 were the three genes showing concordant amplification and overexpression in NPC xenograft. The LTbetaR protein, which is a lymphotoxin beta receptor, was confirmed to be recurrently overexpressed in NPC primary tumors and its overexpression may be involved in the activation of NF-kappaB in NPC. The findings suggested that it is one of the candidate oncogenes of this cancer. / In summary, three candidate NPC-associated oncogenes locating at 3q26.32, 11q13.3 and 12p13.31 were identified by genome-wide mapping analysis. Molecular and functional characterizations of these genes have provided evidences that they play critical roles in NPC tumorigenesis. / In this study, detailed investigation was carried out on a candidate NPC-associated oncogene, PIK3CA at 38q26.32, an amplicon reported previously. Copy number gains and amplifications of this gene, but not mutation, were demonstrated to be common events in NPC. The findings hence implied the importance of PIK3CA in NPC tumorigenesis. / Nasopharyngeal carcinoma is a common cancer in Southern China. Despite multiple genetic changes have been reported previously, limited information of NPC-associated oncogene is available. Since amplification is one of the major mechanisms in oncogene activation, a comprehensive characterization of common amplicons in human cancers is expected to facilitate the identification of the oncogenes involved in tumorigenesis. The aims of the present study is to define and characterize the common amplicons in NPC genome and then to identify NPC-associated oncogenes. / Or Yan Yan. / "July 2006." / Adviser: Kwok Wai Lo. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5715. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 179-201). / 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.

by Angela Bik-Yu Hui. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 119-133). / Acknowledgements / Table of Contents / List of Tables / List of Figures / Abstract / Chapter CHAPTER 1 --- LITERATURE REVIEW --- p.1 / Chapter I. --- Nasopharyngeal carcinoma --- p.1 / Chapter II. --- Etiology of NPC --- p.3 / Chapter II a. --- Geographical & Environmental factors --- p.3 / Chapter II b. --- Epstein-Barr virus Infection --- p.5 / Chapter II c. --- Genetic Factors --- p.8 / Chapter III. --- Cytogenetic Studies of NPC --- p.10 / Chapter III a. --- Traditional Cytogenetics --- p.10 / Chapter III b. --- Previous cytogenetic findings of NPC --- p.12 / Chapter III.c. --- Fluorescence in-situ hybridization --- p.15 / Chapter III.d. --- The new NPC cell line: Cell-666 --- p.18 / Chapter IV. --- Molecular Genetic Studies in NPC --- p.19 / Chapter IV a. --- Oncogenes --- p.20 / Chapter IV b. --- Tumor suppresser genes (TSGs) --- p.22 / Chapter IV c. --- Loss of Heterozygosity Studies --- p.29 / Chapter IV d. --- LOH on Chromosome 11 --- p.32 / Chapter IV e. --- ATM Gene --- p.35 / Chapter CHAPTER 2 --- OBJECTIVE OF STUDY --- p.38 / Chapter CHAPTER 3 --- MATERIALS AND METHODS --- p.41 / Chapter I： --- Study of loss of heterozygosity on chromosome 11 --- p.41 / Chapter I a. --- Patients and Specimens --- p.41 / Chapter I.b. --- DNA extraction --- p.45 / Chapter I c. --- Microsatellite Polymorphism Analysis --- p.47 / Chapter I d. --- Multiplex PCR analysis --- p.52 / Chapter II. --- Cytogenetic Studies --- p.54 / Chapter II a. --- Culture of cell-666 --- p.54 / Chapter II b. --- Cytogenetic Analysis --- p.56 / Chapter II c. --- Fluorescence in-situ hybridization (FISH) --- p.58 / Chapter II d. --- FISH analysis of other NPC cell lines) --- p.62 / Chapter CHAPTER 4 --- RESULTS --- p.63 / Chapter I: --- Study of loss of heterozygosity on chromosome 11 --- p.63 / Chapter I a. --- LOH analysis --- p.63 / Chapter I b. --- Regions with L OH --- p.73 / Chapter I c. --- Multiplex PCR analysis --- p.79 / Chapter II: --- Cytogenetic Study --- p.83 / Chapter II a. --- Cytogenetic analysis of cell-666 --- p.83 / Chapter II.b. --- Fluorescence in-situ Hybridization (FISH) --- p.91 / Chapter CHAPTER 5 --- DTSCUSSION --- p.102 / Chapter I. --- LOH of Chromosome 11 Studies --- p.102 / Chapter II. --- Comparison with LOH studies of other chromosomes --- p.110 / Chapter III. --- Cytogenetic Studies --- p.113 / REFERENCES --- p.119

Man, Cheuk Him. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 219-263). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vi / Table of Contents --- p.vii / List of Figures --- p.xii / List of Tables --- p.xvi / List of Publications --- p.xvii / Chapter Ch.l --- Introduction --- p.1 / Chapter 1.1 --- Aim of study --- p.1 / Chapter 1.2 --- Literature review --- p.3 / Chapter 1.2.1 --- Nasopharyngeal carcinoma (NPC) --- p.3 / Chapter 1.2.1.1 --- Structure and function of nasopharynx --- p.3 / Chapter 1.2.1.2 --- Histopathology of NPC --- p.3 / Chapter 1.2.1.3 --- Epidemiology of NPC --- p.4 / Chapter 1.2.2 --- Etiology of NPC --- p.6 / Chapter 1.2.2.1 --- Genetic factors --- p.6 / Chapter 1.2.2.2 --- Environment factors --- p.13 / Chapter 1.2.2.3 --- Epstein-Barr virus (EBV) infection --- p.14 / Chapter 1.2.3 --- Therapeutic treatment of NPC --- p.24 / Chapter 1.2.3.1 --- Radiotherapy (RT) --- p.24 / Chapter 1.2.3.2 --- Chemotherapy --- p.25 / Chapter 1.2.4 --- Notch signaling pathway --- p.26 / Chapter 1.2.4.1 --- Notch receptors and their ligands --- p.26 / Chapter 1.2.4.2 --- Activation of Notch signaling pathway --- p.29 / Chapter 1.2.4.3 --- Regulators of Notch signaling pathway --- p.32 / Chapter 1.2.4.4 --- Effectors of Notch signaling pathway --- p.32 / Chapter 1.2.5 --- Role of Notch signaling pathway in tumorigenesis --- p.33 / Chapter 1.2.5.1 --- Cell proliferation --- p.34 / Chapter 1.2.5.2 --- Cell survival --- p.35 / Chapter 1.2.5.3 --- Angiogenesis --- p.36 / Chapter 1.2.5.4 --- Cell invasion and metastasis --- p.36 / Chapter 1.2.6 --- Notch and oncogenic virus --- p.37 / Chapter 1.2.7 --- Crosstalk between Notch and other signaling pathways --- p.38 / Chapter 1.2.7.1 --- NFkB signaling pathway --- p.38 / Chapter 1.2.7.2 --- Ras signaling pathway --- p.39 / Chapter 1.2.7.3 --- Wnt signaling pathway --- p.40 / Chapter 1.2.7.4 --- Akt signaling pathway --- p.40 / Chapter 1.2.7.5 --- ErbB2 signaling pathway --- p.41 / Chapter 1.2.8 --- Notch as therapeutic target for cancer --- p.41 / Chapter Ch.2 --- Materials and Methods --- p.45 / Chapter 2.1 --- "Cell lines, xenografts and primary tumors" --- p.45 / Chapter 2.1.1 --- Cell lines --- p.45 / Chapter 2.1.2 --- Xenografts --- p.46 / Chapter 2.1.3 --- Primary tumors --- p.48 / Chapter 2.2 --- Reverse-transcription polymerase chain reaction (RT-PCR) --- p.50 / Chapter 2.2.1 --- Sample preparation for RT-PCR --- p.50 / Chapter 2.2.1.1 --- RNA extraction --- p.50 / Chapter 2.2.1.2 --- Quantitation of total RNA --- p.50 / Chapter 2.2.2 --- Conventional RT-PCR --- p.51 / Chapter 2.2.3 --- Quantitative RT-PCR --- p.51 / Chapter 2.3 --- Western immunoblot --- p.55 / Chapter 2.3.1 --- Protein extraction --- p.55 / Chapter 2.3.2 --- SDS-PAGE and immunoblotting --- p.55 / Chapter 2.4 --- Immunohistochemistry --- p.59 / Chapter 2.5 --- Cloning and plasmid DNA preparation --- p.62 / Chapter 2.5.1 --- Polymerase chain reaction (PCR) and purification of PCR products --- p.62 / Chapter 2.5.2 --- Restriction enzyme double digestion --- p.65 / Chapter 2.5.3 --- Ligation of plasmid and insert sequence --- p.65 / Chapter 2.5.4 --- Bacterial transformation --- p.66 / Chapter 2.5.5 --- Plasmid DNA extraction --- p.66 / Chapter 2.5.6 --- DNA sequencing --- p.67 / Chapter 2.6 --- Transient transfection of NPC cell lines --- p.67 / Chapter 2.7 --- Drug treatment on NPC cell lines --- p.69 / Chapter 2.8 --- Cell proliferation assays --- p.71 / Chapter 2.8.1 --- WST-1 assay --- p.71 / Chapter 2.8.2 --- BrdU assay --- p.71 / Chapter 2.9 --- Flow cytometry analysis --- p.72 / Chapter 2.9.1 --- Sample preparation --- p.72 / Chapter 2.9.2 --- Cell cycle analysis by propidium iodide staining --- p.73 / Chapter 2.9.3 --- Apoptosis analysis by AnnexinV-PI staining --- p.73 / Chapter 2.10 --- Apoptosis analysis by Caspase-3 activity assay --- p.74 / Chapter 2.11 --- RBP-Jk reporter assay --- p.75 / Chapter 2.12 --- NFKB1 reporter assay --- p.77 / Chapter 2.13 --- Dual luciferase reporter assay --- p.77 / Chapter 2.14 --- Expression array --- p.78 / Chapter 2.15 --- Statistical analysis --- p.79 / Chapter Ch.3 --- Characterization of Notch Signaling Molecules in NPC --- p.80 / Chapter 3.1 --- Introduction --- p.80 / Chapter 3.2 --- Results --- p.81 / Chapter 3.2.1 --- "Expression of Notch ligands, receptors, effectors and regulators in NPC cell lines and xenografts" --- p.81 / Chapter 3.2.2 --- "Expression of Notch ligands, receptors, regulators and effectors in NPC primary tumors" --- p.104 / Chapter 3.3 --- Discussion --- p.111 / Chapter 3.3.1 --- Overexpression of Jagl and D114 in NPC --- p.112 / Chapter 3.3.2 --- Overexpression of Notch receptors in NPC --- p.114 / Chapter 3.3.3 --- "Downregulation of Negative regulator, Numb, in NPC" --- p.116 / Chapter 3.3.4 --- Overexpression of Notch effectors in NPC --- p.117 / Chapter 3.4 --- Summary --- p.119 / Chapter Ch.4 --- Mechanisms of Activation of Notch Signaling Pathway in NPC --- p.120 / Chapter 4.1 --- Introduction --- p.120 / Chapter 4.2 --- Results --- p.122 / Chapter 4.2.1 --- EBV mediated Notch activation --- p.122 / Chapter 4.2.1.1 --- No effect of EBERs and EBNA1 on the expression of Notch Components --- p.122 / Chapter 4.2.1.2 --- LMP1 induces expression of Notch components --- p.129 / Chapter 4.2.1.3 --- LMP2A induces expression of Notch components --- p.133 / Chapter 4.2.2 --- Effect of CXCR4 on Notch signaling pathway in C666-1 --- p.137 / Chapter 4.3 --- Discussion --- p.139 / Chapter 4.3.1 --- EBV-mediated induction of Notch components --- p.139 / Chapter 4.3.2 --- Regulation of Notch expression by CXCR4 signaling pathway --- p.142 / Chapter 4.4 --- Summary --- p.145 / Chapter Ch.5 --- Investigation of the Oncogenic Role of Notch3 --- p.146 / Chapter 5.1 --- Introduction --- p.146 / Chapter 5.2 --- Results --- p.148 / Chapter 5.2.1 --- Effect of knockdown Notch 1 by siRNA on the growth of C666-1 --- p.148 / Chapter 5.2.2 --- Effect of knockdown Notch3 by siRNA on the growth of C666-1 --- p.151 / Chapter 5.2.2.1 --- Effect of knockdown Notch3 by siRNA on the RBP-Jk promoter activity of C666-1 --- p.153 / Chapter 5.2.2.2 --- Effect of knockdown Notch3 by siRNA on the proliferation of C666-1 --- p.155 / Chapter 5.2.2.3 --- Effect of knockdown Notch3 by siRNA on cell cycle progression of C666-1 --- p.158 / Chapter 5.2.2.4 --- Effect of knockdown Notch3 by siRNA on resistant to apoptosis in C666-1 --- p.160 / Chapter 5.2.3 --- Investigation of the anti-proliferation effect of therapeutic agents targeting Notch signaling pathway in NPC cells --- p.168 / Chapter 5.2.3.1 --- "Effect of DAPT on the proliferation of HEK293T, C666-1 and HK-1" --- p.168 / Chapter 5.2.3.2 --- Effect of AMD3100 on Notch signaling pathway and proliferation of NPC cells --- p.172 / Chapter 5.2.4 --- Study of downstream targets of Notch3 in NPC cells --- p.178 / Chapter 5.3 --- Discussion --- p.200 / Chapter 5.3.1 --- Oncogenic role of Notch3 in C666-1 --- p.200 / Chapter 5.3.2 --- Potential therapeutic approach in treating NPC via Notch inhibition --- p.206 / Chapter 5.3.2.1 --- "Gamma secretase inhibitor, DAPT" --- p.206 / Chapter 5.3.2.2 --- "CXCR4 antagonist, AMD3100" --- p.207 / Chapter 5.4 --- Summary --- p.209 / Chapter Ch.6 --- General Discussion --- p.210 / Chapter Ch.7 --- Conclusion --- p.217 / Reference --- p.219 / Appendices --- p.263 / Appendix 1 Summary of immunohistochemical staining results on 23 primary NPC samples --- p.264 / Appendix 2 Summary of 581 selected genes from the expression array --- p.265

Xie, Shaohua = 室內燃香與香港華人的鼻咽癌發病風險 : / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 124-153). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; appendixes includes Chinese. / Xie, Shaohua = Shi nei ran xiang yu Xianggang Hua ren de bi yan ai fa bing feng xian :

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.