by Hiu-Ming Li. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 176-198). / 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.

Sze, Siu Ching. / Thesis M.Phil. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 109-124). / Abstracts also in Chinese. / Title from PDF title page (viewed on 24, October, 2016).

Leung Chin-lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 133-164). / Abstracts in English and Chinese. / Abstract --- p.iv / 摘要 --- p.vi / List of abbreviation --- p.viii / Chapter Chapter 1 --- Hepatocellular Carcinoma --- p.1 / Chapter 1.1 --- A Health Burden --- p.1 / Chapter 1.2 --- Pathology --- p.3 / Chapter 1.3 --- Epidemiology --- p.7 / Chapter 1.3.1 --- Global HCC distribution --- p.7 / Chapter 1.3.2 --- Age and Gender --- p.10 / Chapter 1.4 --- Risk Factors of HCC --- p.12 / Chapter 1.4.1 --- Hepatitis B virus (HBV) --- p.13 / Chapter 1.4.1.1 --- Chronic HBV infection --- p.13 / Chapter 1.4.1.2 --- Role of HBV in hepatocarcinogenesis --- p.16 / Chapter 1.4.1.2 a) --- Direct Oncogenesis --- p.16 / Chapter 1.4.1.2 b) --- Indirect Oncogenesis --- p.17 / Chapter 1.4.2 --- Hepatitis C virus (HCV) --- p.23 / Chapter 1.4.2.1 --- Chronic HCV infection --- p.23 / Chapter 1.4.2.2 --- Role of HCV in hepatocarcinogenesis --- p.23 / Chapter 1.4.3 --- Chemicals as liver carcinogens --- p.27 / Chapter 1.4.3.1 --- Aflatoxin Bi (AFB1) --- p.28 / Chapter 1.4.3.2 --- Vinyl chloride --- p.29 / Chapter 1.4.3.3 --- Alcoholic beverages --- p.29 / Chapter 1.4.4 --- Inborn Errors in Metabolisms --- p.30 / Chapter 1.4.4.1 --- Hereditary tyrosinemia --- p.30 / Chapter 1.4.4.2 --- Hereditary haemochromatosis --- p.30 / Chapter 1.4.4.3 --- α1-antitrypsin deficiency --- p.31 / Chapter 1.4.5 --- Liver lesions --- p.32 / Chapter 1.5 --- Genetic alterations in HCC --- p.33 / Chapter Chapter 2 --- Rationale of the study --- p.39 / Chapter Chapter 3 --- LOH study on 8p in HCC --- p.48 / Chapter 3.1 --- Introduction --- p.48 / Chapter 3.1.1 --- "Knudson's ""two-hit"" model and LOH" --- p.48 / Chapter 3.1.2 --- Microsatellite DNA and LOH study --- p.49 / Chapter 3.2 --- Materials and Methods --- p.51 / Chapter 3.2.1 --- Patients and Specimens --- p.51 / Chapter 3.2.1.1 --- Genomic DNA extraction from liver tissues --- p.53 / Chapter 3.2.1.2 --- Genomic DNA extraction from buffy coat --- p.55 / Chapter 3.3 --- LOH study on 8p in HCC --- p.57 / Chapter 3.3.1 --- Microsatellite markers --- p.57 / Chapter 3.3.2 --- 5-end labeling --- p.60 / Chapter 3.3.3 --- Amplification of microsatellite DNA --- p.60 / Chapter 3.3.4 --- Denaturing polyacrylamide gel electrophoresis --- p.61 / Chapter 3.3.5 --- Detection of LOH --- p.62 / Chapter 3.4 --- Results --- p.63 / Chapter 3.4.1 --- LOH status of 52 HCC cases --- p.63 / Chapter 3.4.2 --- Clinicopathological correlation --- p.67 / Chapter 3.4.3 --- Delineation of common deletion region (CDR) --- p.67 / Chapter 3.4.4 --- Common deletion region of interest --- p.77 / Chapter Chapter 4 --- Study on LZTS1 --- p.83 / Chapter 4.1 --- Introduction 一 LZTS1 --- p.83 / Chapter 4.2 --- Mutation analysis of LZTS1 in HCC --- p.87 / Chapter 4.2.1 --- Materials and Methods --- p.87 / Chapter 4.2.1.1 --- Patients and HCC cell lines --- p.87 / Chapter 4.2.1.2 --- Genomic DNA extraction from HCC cell lines --- p.87 / Chapter 4.2.1.3 --- Amplification of exons of LZTS1 --- p.89 / Chapter 4.2.1.3a) --- Primer pairs --- p.89 / Chapter 4.2.1.3b) --- PCR conditions --- p.90 / Chapter 4.2.1.4 --- Purification of PCR products --- p.93 / Chapter 4.2.1.5 --- Cycle sequencing reaction --- p.94 / Chapter 4.2.1.6 --- Purification of cycle sequencing reaction product --- p.94 / Chapter 4.2.1.7 --- Sequence analysis by automated sequencer --- p.95 / Chapter 4.2.1.8 --- Search for sequence variants of LZTS1 --- p.96 / Chapter 4.2.2 --- Results --- p.97 / Chapter 4.3 --- Expression analysis of LZTS1 in HCC with preliminary results --- p.103 / Chapter 4.3.1 --- Materials and Methods --- p.103 / Chapter 4.3.1.1 --- Patients and Specimens --- p.103 / Chapter 4.3.1.2 --- Total RNA extraction --- p.103 / Chapter 4.3.1.3 --- Reverse transcription --- p.104 / Chapter 4.3.1.4 --- Semi-quantitative PCR --- p.105 / Chapter 4.3.1.4a) --- Primer pairs --- p.105 / Chapter 4.3.1.4b) --- PCR conditions --- p.106 / Chapter 4.3.2 --- Results --- p.109 / Chapter Chapter 5 --- Discussion --- p.111 / Chapter 5.1 --- LOH study on 8p in HCC --- p.111 / Chapter 5.2 --- Study on LZTS1 in HCC --- p.125 / Chapter 5.2.1 --- Mutation analysis of LZTS1 --- p.125 / Chapter 5.2.2 --- Expression analysis of LZTS1 --- p.129 / Chapter 5.3 --- Future Study --- p.132 / References --- p.133

Zhang, Zhiyi. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves ). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Amplification of chr.1 q21-22 is also an aberration frequently detected in HCC. Copy number gains of the GEF-H1 gene ranked the most frequent event from array-CGH. GEF-H1 up-regulation was significant correlated in patients with advanced HCC staging (P = 0.048), presence of micro-vascular invasion (P = 0.049) and shorter overall and disease free survival of patients (P < 0.03). Similar to BOP1, functional examinations of GEF-H1 suggested profound inhibitory effects on cell motility ( P < 0.035) and invasiveness (P < 0.003) in cell lines studied. Upon GEF-H1 depletion, re-expression of epithelial markers (E-cadherin, cytokeratin 18, alpha-catenin and gamma-catenin) and down-regulations of mesenchymal markers (N-cadherin, fibronectin and vimentin) were also readily observed. In addition, reduced active form of GTP-RhoA together with its downstream effectors including cleaved ROCK 1 and phosphorylated MLC2 were also found in GEF-H1 depleted cells. / Array-CGH also defined candidate proto-oncogenes within 2 causal amplified regions in HCC, chr.8q24 and chr.1q21-q22. In resolving affected genes at chr.8q24, distinctive gains of BOP1 was further established in primary HCC tumors, where frequent BOP1 up-regulations in tumors compared to adjacent non-tumoral liver (P < 0.0001) was identified. Increased BOP1 expression correlated with advanced HCC staging (P = 0.004), micro-vascular invasion (P = 0.006) and shorter overall and disease free survival of patients (P < 0.02). siRNA-mediated suppression of BOP1 in HCC cell lines showed significant inhibition on cell invasion (P < 0.003) and migration (P < 0.05), whereas overexpression of BOP1 in immortalized hepatocyte cell line, L02, showed increase cellular invasiveness and cell migratory rate (P < 0.0001). Evident regression of the Epithelial-to-Mesenchymal Transition (EMT) phenotype was readily identified in BOP1 knockdown cells, where re-expressions of epithelial markers (E-cadherin, cytokeratin 18 and gamma-catenin) and down-regulation of mesenchymal markers (fibronectin and vimentin) were found. It was found that BOP1 likely stimulates actin stress fibers assembly through RhoA activation. / Hepatocellular carcinoma (HCC) is a highly malignant tumor that is associated with a high incidence of cancer morbidity and mortality. Elucidation of genomic aberrations of HCC holds much importance in understanding the molecular basis that underlies the disease causation and progression. Extensive research on HCC has by now revealed a number of key genomic aberrations but, for most of these loci, the underlying cancer-related gene(s) remains unknown. / In this thesis, array-based comparative genomic hybridization (array-CGH) was deployed to define target genes within HCC-associated chromosomal regions. The first part of my study focused on mapping the homozygous deletions (HDs) in HCC. Though infrequent, HD screening has been widely utilized to define tumor suppressor genes (TSGs) in cancers. A panel of HCC cell lines was systematically examined for the presence of HDs. Array-CGH identified 6 HD regions, amongst which CRYL1 (located on chr.13q12.11) displayed most common down-regulations in primary HCC tumors. Significant associations could also be drawn between repressed CRYL1 and advanced tumor staging, increased tumor size and shorter disease-free patient survival (P ≤ 0.037). Moreover, HD on CRYL1 could be detected in 36% of HCC cases with CRYL1 down-regulations. Examination of other inactivating mechanisms suggested histone deacetylation and promoter hypermethylation to be likely inactivating events as well. Re-expression of CRYL1 in SK-HEP1 cell line induced profound inhibition on cellular proliferation and cell growth (P ≤ 0.002). By Annexin V staining, CRYL1 restoration readily increased pro-apoptotic cells with an induction of P ARP cleavage. Flow cytometry further revealed CRYL1 could prolong the G2-M phase, possibly through interrupting the Cdc2/cyclin B path. / The similarities in functional behaviours of BOP1 and GEF-H1 might have implications in the fundamental biology of HCC tumorigenesis. It is known that HCC is a highly aggressive tumor often associated with intra- and extra-hepatic metastasis. The finding of 2 causal changes to be closely associated with cell migration and invasiveness may have implications in the metastatic potentials of HCC cells being predisposed earlier on from genomic events. / Cheng, Kit Chong Ibis. / Adviser: Nathalie Wong. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 177-190). / 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. / Abstract also in Chinese.

Ng, Chor Fung. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 156-169). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Chan, Ho Ching. / Thesis M.Phil. Chinese University of Hong Kong 2016. / Includes bibliographical references (leaves 159-166). / Abstracts also in Chinese. / Title from PDF title page (viewed on 15, September, 2016).

Chin Wai. / Original paper published on European Jouranl of cancer (vol. 34, no. 7, p. 1015-1022) inserted. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 70-77). / Abstracts in English and Chinese. / Dedication --- p.i / Vita --- p.ii / Acknowledgment --- p.iv / Abstract --- p.vii / Introduction --- p.1 / Hepatocellular carcinoma --- p.1 / Lung cancer --- p.3 / The role of suppressor gene PML in cancer --- p.5 / Principle of immunohistaining methods --- p.8 / Patients and methods --- p.21 / Patients and smaples --- p.21 / Slide preparing --- p.22 / Immunohistochemical staining --- p.23 / Cell culture --- p.30 / Determination of the population doubling times --- p.30 / Mtt assay --- p.35 / Results --- p.37 / "Altered expression of PML in normal liver, HCC and Secondary liver tumor" --- p.37 / Increased expression of PML in chronic hepatitis tissues --- p.38 / Differential expression of PML at the periphery and at the center of single-encapsulated lesion of HCC --- p.42 / Expression of PML in normal lung tissues --- p.43 / Suppression of PML expression in small cell lung cancer --- p.44 / Enhanced expression of PML in adenocarcinoma of the lung --- p.44 / Enhanced expression of PML in squamous cell carcinoma of the lung --- p.45 / Express of PML in metastatic lung cancer --- p.46 / Inverse correlation of the expression of PML and the proliferation marker Ki-67 in SCLC and SCC --- p.46 / Correlation of the expression of PML in macrophages with the macrophage-specific marker KP-1 --- p.47 / Expression of PML in Hela cells and Hela cells transfected with the gene --- p.48 / Altered morphology of the Hela-PML cell-clones --- p.49 / Altered growth rate in Hela-PML cells --- p.49 / Altered rate of cell-death in Hela-PML cells --- p.50 / Discussion --- p.51 / Further studies --- p.63 / References --- p.70 / Table --- p.78 / Figure legend --- p.81 / Appendix: Original paper published on European Journal of cancer --- p.106

Yu Chi Hung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 124-139). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Table of Contents --- p.ii / Abbreviations --- p.iv / Abstract --- p.v / 論文摘要 --- p.vi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- General introduction / Chapter 1.2 --- HBV and its potential oncogenic properties / Chapter 1.3 --- Aim of the present study / Chapter 1.4 --- Expressed sequence tag (EST) analysis: an approach to reveal gene expression pattern in a specific tissue / Chapter 1.5 --- cDNA subtraction / Chapter Chapter 2 --- Materials and Methods --- p.17 / Chapter 2.1 --- Plating out the adult human normal liver cDNA library / Chapter 2.2 --- PCR amplification of cloned human normal liver cDNA inserts / Chapter 2.3 --- Cycle sequencing of cloned human normal liver cDNA inserts / Chapter 2.4 --- mRNA preparation from the HCC tissue and its surrounding normal counterpart / Chapter 2.5 --- PCR-Select cDNA subtraction / Chapter 2.6 --- Construction of HCC subtracted cDNA library by T/A cloning method / Chapter 2.7 --- PCR amplification of cloned subtracted cDNA / Chapter 2.8 --- Cycle sequencing of cloned subtracted cDNA / Chapter 2.9 --- Sequence analysis / Chapter 2.10 --- Differential hybridization of HCC subtracted clones / Chapter Chapter 3 --- Results --- p.46 / Chapter 3.1 --- The sequencing results of adult human normal liver cDNA clones / Chapter 3.2 --- Categorization of ESTs sequenced from the adult normal liver / Chapter 3.3 --- Adaptor ligation efficiency analysis / Chapter 3.4 --- Primary and secondary PCR Amplification / Chapter 3.5 --- PCR analysis of subtraction efficiency / Chapter 3.6 --- The sequencing results of subtracted HCC cDNA clones / Chapter 3.7 --- Categorization of ESTs sequenced from the subtracted HCC cDNA library / Chapter 3.8 --- Differential hybridization of subtracted cDNA clones / Chapter Chapter 4 --- Discussions --- p.90 / Chapter 4.1 --- Characterization of the ESTs generated from human normal liver cDNA library / Chapter 4.2 --- EST analysis on subtracted HCC cDNA clones / Chapter 4.3 --- Candidate genes differentially expressed in HCC / Appendix A The coordinates of dot blots (in numerical order according to clone numbers) / Appendix B The coordinates of dot blots (in alphabetical order according to putative identity) / References --- p.124

Lee Siu-wah. / Thesis submitted in: December 1999. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves [106]-116). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / Abstract (in Chinese) --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Figures --- p.ix / List of Tables --- p.x / Abbreviations --- p.xi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Hepatocellular Carcinoma (HCC) --- p.2 / Chapter 1.2 --- Etiology of Hepatocellular Carcinoma --- p.5 / Chapter 1.2.1 --- Viral Infection --- p.5 / Chapter 1.2.1.1 --- Hepatitis B Virus --- p.5 / Chapter 1.2.1.2 --- Hepatitis C Virus --- p.7 / Chapter 1.2.2 --- Cirrhosis and Chronic Inflammation --- p.8 / Chapter 1.2.3 --- Aflatoxin --- p.9 / Chapter 1.3 --- Genetic Studies of Hepatocellular Carcinoma --- p.9 / Chapter 1.3.1 --- Conventional Cytogenetics --- p.9 / Chapter 1.3.2 --- Molecular Cytogenetics --- p.12 / Chapter 1.3.3 --- Molecular Genetic Studies --- p.12 / Chapter 1.3.3.1 --- Proto-oncogenes --- p.12 / Chapter 1.3.3.2 --- Tumour Suppressor Genes --- p.13 / Chapter 1.3.3.3 --- Cell Cycle Genes --- p.14 / Chapter 1.4 --- Background of Study --- p.16 / Chapter 1.5 --- Objectives of Study --- p.17 / Chapter Chapter 2 --- Material and Methods --- p.18 / Chapter 2.1 --- Materials --- p.19 / Chapter 2.2 --- Analysis of Chromosomal Imbalances by Comparative Genomic Hybridization --- p.23 / Chapter 2.2.1 --- Comparative Genomic Hybridization --- p.23 / Chapter 2.2.2 --- Methods / Chapter 2.2.2.1 --- Preparation of Normal Metaphases --- p.30 / Chapter 2.2.2.2 --- Extraction of High Molecular Weight DNA --- p.30 / Chapter 2.2.2.3 --- Labeling of DNA by Nick Translation --- p.31 / Chapter 2.2.2.4 --- Labeling Efficiency --- p.31 / Chapter 2.2.2.5 --- Preparation of Probe --- p.33 / Chapter 2.2.2.6 --- Hybridization --- p.33 / Chapter 2.2.2.7 --- Washing and Detection of Signals --- p.35 / Chapter 2.2.2.8 --- Image Acquisition and Analysis --- p.35 / Chapter 2.2.2.9 --- Control Experiments --- p.36 / Chapter 2.3 --- Positional Mapping of Novel Amplicon by Interphase Cytogenetics --- p.39 / Chapter 2.3.1 --- Fluorescence in situ Hybridization --- p.39 / Chapter 2.3.2 --- Using Yeast Artificial Chromosomes (YAC) as Probe --- p.41 / Chapter 2.3.3 --- Methods --- p.48 / Chapter 2.3.3.1 --- Culture of Yeast Artificial Chromosomes --- p.48 / Chapter 2.3.3.2 --- Extraction of Total YAC DNA --- p.48 / Chapter 2.3.3.3 --- Verification of YAC Clones for Chimerism by FISH --- p.49 / Chapter 2.3.3.4 --- Inter-Alu-PCR --- p.49 / Chapter Chapter 3 --- Assessment of Genetic Changes in HCC by Comparative Genomic Hybridization (CGH) --- p.57 / Chapter 3.1 --- Introduction --- p.58 / Chapter 3.2 --- Materials and Methods --- p.58 / Chapter 3.2.1 --- Patients and Specimens --- p.58 / Chapter 3.2.2 --- Comparative Genomic Hybridization --- p.60 / Chapter 3.2.3 --- Statistical Analysis --- p.60 / Chapter 3.3 --- Results --- p.61 / Chapter 3.3.1 --- Overall Copy Number Aberrations in 67 HCC and Surrounding Cirrhotic Tissues --- p.61 / Chapter 3.3.2 --- TNM Staging --- p.61 / Chapter 3.3.3 --- Tumour Size --- p.72 / Chapter 3.3.4 --- Serum AFP Elevation --- p.72 / Chapter 3.3.5 --- Chromosomal Aberrations in HCC arising from Cirrhotic and Non- cirrhotic Livers --- p.72 / Chapter 3.4 --- Discussion --- p.73 / Chapter 3.4.1 --- Recurrent Gains --- p.73 / Chapter 3.4.2 --- Recurrent Losses --- p.75 / Chapter 3.4.3 --- Tumour Progression --- p.76 / Chapter 3.5 --- Conclusion --- p.78 / Chapter Chapter 4 --- Positional Mapping of a Novel Amplicon on Chromosome 1q21-q25 by Interphase Cytogenetics --- p.79 / Chapter 4.1 --- Introduction --- p.80 / Chapter 4.2 --- Materials --- p.82 / Chapter 4.3 --- Methods --- p.82 / Chapter 4.3.1 --- Preparation of Paraffin-embedded Tissue Sections --- p.82 / Chapter 4.3.2 --- Verification of YAC Probes for Chimerism --- p.83 / Chapter 4.3.3 --- Hybridization Efficiency of Test and Reference Probes --- p.83 / Chapter 4.3.4 --- Slide Pretreatment and FISH with YAC Probes --- p.88 / Chapter 4.3.5 --- Scoring of FISH Signals --- p.88 / Chapter 4.4 --- Results --- p.89 / Chapter 4.4.1 --- Relative Copy Number Gain --- p.89 / Chapter 4.4.2 --- Intratumour Heterogeneity --- p.90 / Chapter 4.5 --- Discussion --- p.90 / Chapter 4.6 --- Further Studies --- p.104 / Chapter 4.6.1 --- Fine Mapping of Chromosomal Region 1 q21 --- p.104 / Chapter 4.6.2 --- Isolation of Novel Genes in the Amplicon --- p.105 / Chapter 4.6.3 --- Expression Status of the EDC Genes --- p.105 / References --- p.106