published_or_final_version / abstract / toc / Nursing Studies / Master / Master of Nursing in Advanced Practice

published_or_final_version / Gerontology / Master / Master of Social Sciences

published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

published_or_final_version / Pathology / Doctoral / Doctor of Philosophy

Fu Zhenming. / Thesis submitted in: December 2003. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 138-162). / Abstracts in English and Chinese. / List of abbreviations --- p.i / Abstract (in English) --- p.ii / 摘要（中文） --- p.iii / Acknowledgement --- p.iv / Chapter Chapter 1. --- Introduction and Objectives of Study --- p.1 / Chapter 1.1 --- Hepatocellular carcinoma in general --- p.2 / Chapter 1.1.1 --- "Epidemiology, risk factors" --- p.2 / Chapter 1.1.2 --- Pathology and staging --- p.4 / Chapter 1.1.3 --- Treatment --- p.6 / Chapter 1.1.4 --- Improvement of early detection and treatment of HCC --- p.7 / Chapter 1.2 --- General aspects of mitochondria and mitochondrial DNA (mtDNA) --- p.10 / Chapter 1.2.1 --- Structure and dynamics of mitochondria --- p.10 / Chapter 1.2.1.1 --- General introduction of mitochondria --- p.10 / Chapter 1.2.1.2 --- Respiration chain of mitochondria --- p.11 / Chapter 1.2.2 --- The mitochondrial genome --- p.14 / Chapter 1.2.2.1 --- Strucure --- p.14 / Chapter 1.2.2.2 --- Genes for structure proteins --- p.16 / Chapter 1.2.2.3 --- Genes for translation --- p.17 / Chapter 1.2.2.4 --- Imported proteins and RNAs --- p.17 / Chapter 1.2.3 --- Mitochondrial DNA maintenance --- p.19 / Chapter 1.2.4 --- Mitochondrial DNA replication --- p.25 / Chapter 1.2.5 --- Mitochondrial DNA transcription --- p.30 / Chapter 1.2.6 --- Mitochondrial DNA translation --- p.32 / Chapter 1.3 --- MtDNA diseases --- p.35 / Chapter 1.4 --- MtDNA mutation and HCC --- p.35 / Chapter 1.5 --- Aims of the study --- p.39 / Chapter Chapter 2. --- Materials and Methods --- p.41 / Chapter 2.1 --- Materials --- p.42 / Chapter 2.1.1 --- Chemicals --- p.42 / Chapter 2.1.2 --- Primers --- p.42 / Chapter 2.1.3 --- Enzymes --- p.45 / Chapter 2.1.4 --- Cell line --- p.45 / Chapter 2.1.5 --- Collection of specimens --- p.46 / Chapter 2.2 --- Methodology --- p.47 / Chapter 2.2.1 --- "DNA extraction from hcc tissues, cell line Hep3B and PBMCs" --- p.47 / Chapter 2.2.1.1 --- DNA extraction from HCC tissues --- p.47 / Chapter 2.2.1.2 --- DNA extraction from cell line Hep3B --- p.49 / Chapter 2.2.1.3 --- DNA extraction from and PBMCs --- p.50 / Chapter 2.2.1.3.1 --- Preparation of PBMCs --- p.50 / Chapter 2.2.1.3.2 --- DNA extraction from and PBMCs --- p.51 / Chapter 2.2.2 --- Detection of mt whole genome mutation by direct sequencing --- p.51 / Chapter 2.2.2.1 --- Design of mtDNA primers --- p.51 / Chapter 2.2.2.2 --- PCR amplification of the whole mt genome --- p.51 / Chapter 2.2.2.3 --- Direct sequencing of the whole mt genome --- p.52 / Chapter 2.2.2.3.1 --- Primer used in sequencing --- p.52 / Chapter 2.2.2.3.2 --- Purification of the PCR products of the whole mt genome --- p.53 / Chapter 2.2.2.3.3 --- Dye terminator cycle sequencing reaction --- p.53 / Chapter 2.2.2.3.4 --- Purification of extension products --- p.54 / Chapter 2.2.3 --- Detection of mtDNA control region mutation --- p.55 / Chapter 2.2.3.1 --- PCR amplification of D310 in the mtDNA control region --- p.55 / Chapter 2.2.3.2 --- Screening of D310 mutation by PFLDA --- p.55 / Chapter 2.2.3.2.1 --- Making 8% denatured gel mixture --- p.55 / Chapter 2.2.3.2.2 --- Setting up and Pouring the denatured gel --- p.56 / Chapter 2.2.3.2.4 --- Preparing and Loading the PCR products --- p.57 / Chapter 2.2.3.2.5 --- Electrophoresis --- p.57 / Chapter 2.2.3.2.6 --- "Gel fixing, silver staining and color development " --- p.58 / Chapter 2.2.3.3 --- Direct sequencing of D310 in the mtDNA control region --- p.59 / Chapter 2.2.4 --- Detection of mt DNA coding region mutation --- p.60 / Chapter 2.2.4.1 --- PCR amplification of the 5 respiratory chain subunit genes --- p.60 / Chapter 2.2.4.2 --- Restriction enzyme digestion of 5 genes in mtDNA coding region --- p.60 / Chapter 2.2.4.3 --- Screening of mtDNA coding region mutation by SSCP --- p.61 / Chapter 2.2.4.3.1 --- Making 6% 49:1 acrylamide/Bis SSCP gel mixture --- p.61 / Chapter 2.2.4.3.2 --- "Setting up the SSCP gel, loading sample, fixing, staining and developing of the gel " --- p.62 / Chapter 2.2.4.4 --- Sequencing conformation of the mtDNA coding region mutation --- p.62 / Chapter 2.2.5 --- Statistics --- p.63 / Chapter 2.2.5.1 --- The chi-square test --- p.63 / Chapter 2.2.5.2 --- The Friedman test --- p.63 / Chapter 2.2.5.3 --- Wilcoxon signed ranks test --- p.63 / Chapter Chapter 3. --- Results --- p.64 / Chapter 3.1 --- Detection mt DNA whole genome mutation --- p.65 / Chapter 3.1.1 --- Identification of mtDNA whole genome by direct sequencing --- p.65 / Chapter 3.2 --- Detection mt DNA D-loop mutation --- p.76 / Chapter 3.2.1 --- Screening of C-tract alteration in HCC tissus by PCR fragments length detection assay (PFLDA) --- p.76 / Chapter 3.2.2 --- Screening of coding region alteration in HCC tissues by SSCP --- p.77 / Chapter 3.2.2.1 --- Identification of C-tract alterations in HCC and non-tumorous tissues by direct sequencing --- p.77 / Chapter 3.2.3 --- Identification of C-tract alterations by direct sequencing --- p.82 / Chapter 3.2.3.1 --- Identification of C-tract alterations in HCC tissues by direct sequencing --- p.82 / Chapter 3.2.3.2 --- Identification of C-tract alteration in PBMC of normal subjects by direct sequencing --- p.82 / Chapter 3.2.3.3 --- Identification of C-tract alteration in PBMC of HCC patients by direct sequencing --- p.82 / Chapter 3.2.4 --- Statistics of the analysis of C-tract alterations --- p.82 / Chapter 3.3 --- Detection mt DNA mutation in the coding region --- p.87 / Chapter Chapter 4. --- Discussion --- p.98 / Chapter 4.1 --- Detection mtDNA whole genome mutation --- p.99 / Chapter 4.2 --- Detection mtDNA D-loop mutation --- p.107 / Chapter 4.3 --- Detection mtDNA mutation in the coding region --- p.119 / Chapter 4.4 --- Possible mechanisms of mtDNA mutation in HCC carcinogenesis --- p.125 / Chapter 4.5 --- Proposals for prospective studies --- p.126 / Chapter 4.5.1 --- Function of C7 in D310 --- p.128 / Chapter 4.5.2 --- Function changes of mtDNA coding region mutation --- p.130 / Chapter 4.5.3 --- Detection of D310 C-tract mutation in patients' plasma --- p.131 / Chapter 4.5.4 --- Relationship between nMSl and mtMSI --- p.132 / Chapter 4.6 --- Summary --- p.134 / References --- p.137

Increasing number of people is diagnosed with colorectal neoplasms (CRN) in the form of polyps or cancers. Colorectal cancer (CRC) is one of the most common causes of cancer deaths among Chinese in Hong Kong. Advances in diagnosis and treatments have increased the survival rate of CRN patients, resulting in a large group of cancer survivors. Preserving and maintaining health-related quality of life (HRQOL) has become an important direction in research and clinical care of patients with CRN. This research aimed to evaluate the HRQOL and its association with socio-demographics and disease-related characteristics among patients with CRN, and illustrate how HRQOL data could be converted to preference for the estimation of quality adjustment of life years in health economic evaluations. This research comprised of three parts. First was the establishment of the validity and reliability of the traditional Chinese version of Functional Assessment of Cancer Therapy-Colorectal (FACT-C) as a HRQOL measure for Chinese patients by a cross-sectional sample of 536 adult patients with CRN. Psychometric testing and concurrent validation of the FACT-C with European Organization for Research and Treatment of Cancer Core Questionnaire plus Colorectal-specific Module Questionnaire and the Short-Form 12-item Health Survey_Version2 (SF-12V2) were carried out. Second was a longitudinal study on the HRQOL of 554 CRN patients at baseline, six (n=479) and twelve (n=414) months of recruitment. The associations of HRQOL with socio-demographics and disease-related factors, and change of HRQOL over time were explored. Comparisons of HRQOL between CRN patients and the general population and among different CRN groups were made. Cross-sectional data were used to develop mapping functions to estimate SF-6D preference scores from FACT-C subscale scores. Third was the application of the health preference scores by CRN stages collected at baseline of the longitudinal study, in combination with survival data extracted from the literature in a Markov model on the cost-effectiveness of different CRC screening strategies (colonoscopy, guaiac and immunochemical fecal occult blood tests) in comparison to no screening in terms of quality-adjusted life-years gained. This research comprised of three parts. First was the establishment of the validity and reliability of the traditional Chinese version of Functional Assessment of Cancer Therapy-Colorectal (FACT-C) as a HRQOL measure for Chinese patients by a cross-sectional sample of 536 adult patients with CRN. Psychometric testing and concurrent validation of the FACT-C with European Organization for Research and Treatment of Cancer Core Questionnaire plus Colorectal-specific Module Questionnaire and the Short-Form 12-item Health Survey_Version2 (SF-12V2) were carried out. Second was a longitudinal study on the HRQOL of 554 CRN patients at baseline, six (n=479) and twelve (n=414) months of recruitment. The associations of HRQOL with socio-demographics and disease-related factors, and change of HRQOL over time were explored. Comparisons of HRQOL between CRN patients and the general population and among different CRN groups were made. Cross-sectional data were used to develop mapping functions to estimate SF-6D preference scores from FACT-C subscale scores. Third was the application of the health preference scores by CRN stages collected at baseline of the longitudinal study, in combination with survival data extracted from the literature in a Markov model on the cost-effectiveness of different CRC screening strategies (colonoscopy, guaiac and immunochemical fecal occult blood tests) in comparison to no screening in terms of quality-adjusted life-years gained. Psychometric analysis confirmed that FACT-C had satisfactory reliability, construct validity and responsiveness in Chinese patients Patients with CRN reported worse physical HRQOL but better mental HRQOL and similar health preference score compared to the general population. Disease severity indicated by tumor stage at initial diagnosis was the most significant determinant of HRQOL of CRN patients. Rectal cancer also significantly associated with a decrease in physical HRQOL and health preference scores. Markov modelling showed that immunochemical fecal occult blood (I-FOBT) yearly was the most effective and two-yearly was the most cost-effective screening strategy compared to no screening. / published_or_final_version / Family Medicine and Primary Care / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Social Work / Master / Master of Social Work

published_or_final_version / Social Work / Master / Master of Social Work