Thesis (Ph.D.) -- University of Adelaide, Dept. of Medicine, 2000. / Errata pasted onto t.p. verso. Bibliography: leaves 129-148.

Thesis (M. Phil.)--University of Hong Kong, 1994. / Includes bibliographical references (leaves 208-230).

published_or_final_version / Community Medicine / Master / Master of Public Health

No description available.

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Aberrant cell proliferation is a fundamental feature of cancer. It is thus not unexpected that many studies have been devoted to the exploration of tumour cell proliferation as a potential indicator of outcome. Indeed, in most malignancies, high expression of proliferation markers and more accurately, increased expression of proliferation-related genes have been strongly associated with poor outcome. In colorectal cancer (CRC), however, discordant results have been reported and the prognostic significance of cell proliferation has not been demonstrated in this type of cancer. As these results were mostly based on the subjective assessment of a single proliferation marker, this work set out to evaluate the association between the proliferative activity of CRCs and their malignant potential using an objective microarray-based multi-gene proliferation signature. In the first step, a gene proliferation signature (GPS) was derived from analysis of a CRC cell line model. Ten CRC cell lines were harvested under semi- and fully-confluent conditions to obtain RNA from two stages that differed in their proliferative activity. Gene expression profiles of the two growth stages were analyzed on oligonucleotide arrays and a GPS was identified by gene ontology analysis of differentially expressed genes. In the second step, the performance of the signature to classify patients into prognostic groups was examined using two independent cohorts of primary CRC tumours (cohort A: 73 tumours in stages I-IV, cohort B: 55 tumours in stages I-II). Further, the signature was applied to a population of liver metastases to establish its association with the malignant potential of CRC. Finally, the capacity of the signature to detect clinically distinct CRC populations was compared with that of the proliferation marker Ki-67 in a classic immunohistochemical approach. The GPS consisted of 38 mitotic cell cycle genes, which were over-expressed in actively cycling cells relative to growth-inhibited cells in vitro. Intriguingly, a reduced GPS expression was associated with (i) the presence of lymph node or distant metastasis in cohort A, (ii) an increased risk of recurrence, and (iii) shorter overall and recurrence-free survival in both cohorts of primary CRCs (p<0.05). While the association between the GPS and clinical outcome was not independent of the disease stage in cohort A, reduced GPS expression was an independent predictor of outcome in cohort B. Importantly, adjuvant therapy had no impact on this association. Furthermore, GPS expression was reduced in CRC liver metastases, confirming that decreased proliferation is an indicator of the malignant potential in CRC. While reduced proliferation in liver metastases was also observed by Ki-67 immunostaining, the classic proliferation marker was not able to stratify primary CRCs into different prognostic groups. To the best of our knowledge, this study is the first to report an association between the reduced expression of a multi-gene proliferation signature and poor outcome in cancer. This finding contradicts the long-held belief that increased proliferation is an indicator of tumour malignancy. In contrast to many other cancers, reduced proliferation appears to be a significant component of a biological signature associated with malignant potential of CRC tumours. Investigating the reasons why CRC differs from other cancer types may provide insights into important underlying biological mechanisms. If this association can be verified in larger cohorts, the GPS may have important clinical implication for identification of high-risk early stage CRC patients.

published_or_final_version / Medicine / Master / Master of Medical Sciences

Background Colorectal cancer (CRC) is one of the most common cancers with high morbidity and mortality among both genders and yet it carries a better prognosis when detected early. Colorectal cancer screening using faecal occult blood test (FOBT) is proven to be cost-effective, however worldwide FOBT uptake rate is suboptimal which directly affects the cost-effectiveness of the screening program. Identifying those factors that influence the uptake of colorectal cancer screening using FOBT will allow implementation of relevant measures when planning a population based screening program. Methods A structured electronic search using PubMed and Medline was conducted in order to identify studies that included factors influencing the uptake of CRC screening by using FOBT. Qualities of included studies were assessed by quality assessment checklist STROBE. Results Factors that contributed to the low uptake rate of CRC screening by FOBT were identified and summarized. They were broadly divided into 3 groups. Demographic factors: age, gender, social economic status, insurance status and education, for ethnicity, employment status and obesity further studies in the future may be needed. Subject factors: subject’s attitudes and knowledge towards CRC screening, type of FOBT screening, health concerned behavior, frequency of clinical visit and physiciancomment. Provider factors: health care system factor and physicians’ factors. Conclusion Different factors, in particular those factors that were associated with low FOBT uptake rate in CRC screening, were reviewed and summarized in this paper. With the continuous effort from worldwide as well as local investigators, timely measures can be implemented to tackle this deathly disease and to ensure cost effectiveness of a screening program. / published_or_final_version / Public Health / Master / Master of Public Health

BACKGROUND: Colorectal cancer is usually asymptomatic until later stage and the 5-year survival for stage III or IV are 68% and 10 % because of delayed diagnosis. Worldwide, it is the 4th leading cause of death among cancers which accounted for 694,000 deaths in 2012. While healthy diet and lifestyle helps prevent colorectal cancer, increased surveillance through screening has been suggested to attribute to the decreasing trend of colorectal cancer incidence in the United States in the past decade. Identifying what type of colorectal cancer screening methods is more effective is of public health relevance to Hong Kong where colorectal cancer ranks the top leading cancer. OBJECTIVES: To conduct a systematically review on current literatures to examine whether endoscopy screening by flexible sigmoidoscopy or colonoscopy is more effective for reducing the mortality and incidence of colorectal cancer than no screening as many colorectal cancers arise from adenomatous polyps, which polypectomy is hypothesized to be protective. Meanwhile, different countries adopt different kinds of colorectal cancer screening modalities, but yet, there is no agreement for the types of screening. METHODS: Four databases, Medline (OVIDSP), Pubmed, CINAHL plus (EBSCOhost), Embase (OVIDSP) were used to search for published journals. Reference list of the identified articles were screened for more relevant studies. RESULTS: A total of 8 studies were included in this systematic review. There were only 2 randomized controlled trials (RCTs) on screening for colorectal cancer using flexible sigmoidoscopy in asymptomatic and average-risk people and no RCT was found for colonoscopy. Based on the studies reviewed, findings were inconsistent on whether endoscopy screening is more effective in reducing overall colorectal cancer incidence and mortality than no screening. Endoscopy screening, either sigmoidoscopy or colonoscopy was associated with lower incidence of distal colorectal cancer. CONCLUSION: Screening by flexible sigmoidoscopy or colonoscopy is not clearly associated with lower overall colorectal cancer risks based on current systematic review. Randomized controlled trials or retrospective cohorts are required to clarify the effectiveness of endoscopy screening before considering the implementation of population-wide colorectal cancer screening. / published_or_final_version / Public Health / Master / Master of Public Health

Colorectal cancer is a serious health problem that has concerned people for decades. In Hong Kong, it is the most common cancer and the second leading cause of death. Among colorectal cancer patients, around 40-50% of them will develop metastatic disease. Chemotherapy is playing an important role all the time in the treatment of advanced colorectal cancer. In the past decade, the application of targeted therapies in treatment has largely improved efficacy and prolonged survival. Bevacizumab and cetuximab are two commonly used targeted agents in daily clinical practice of Hong Kong. Since multiple clinical trials have studied bevacizumab and cetuximab in combination with other chemotherapies, limited data is available in Asian patients. Therefore, we conduct three 5-year retrospective analyses based on patients received treatment in Hong Kong Queen Mary Hospital, to investigate the clinical efficacy and toxicity of those two drugs. The first study examined the use of bevacizumab in treating KRAS mutated type patients. We found the efficacy and results were consistent with historical data. In the next analysis of cetuximab, comparable data were shown which suggested the consistency with previous studies. The last study is aim to compare bevacizumab and cetuximab in previously untreated wild-type KRAS patients. Identical response rates, progression-free survival and overall survival were finally reported. / published_or_final_version / Medicine / Master / Master of Philosophy