No description available.

The development and progression of carcinogenesis is a major area of interest to many scientists. Numerous factors, including both environmental and genetic have been implicated in the causation of cancer. It is clear that both these factors and others contribute to neoplastic development and progression. Microsatellites are short tandem repeat sequences which are located in the intron segments of the genome. These noncoding sequences range from 2 to 6 base pairs. An increase or decrease in the number of repeat sequences is referred to as microsatellite instability, also referred to as genetic instability. It is thought that microsatellite instability arises as a result of defects in DNA repair process. During DNA synthesis, the DNA repair genes ensure that the correct nucleotide is incorporated into the newly synthesised DNA strand, so when a mismatch base is incorporated, this is promptly removed and replaced with the correct base. However, if the repair system is defective this would give rise to numerous genetic aberrations along that region of the genome. Recently, microsatellite instability and allelic imbalance/loss of heterozygosity have been shown to play an important role in the development of many cancers, especially colorectal cancer (CRC) associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. This study was undertaken to investigate microsatellite instability and allelic imbalance in colorectal and oesophageal carcinomas in the KwaZulu Natal region of South Africa. The molecular analysis was correlated with clinicopathological data to establish a baseline level on which further studies could be performed. In addition, this study represents the first fluorescent based microsatellite analysis of these two common cancers in South Africa. Normal and tumour DNA was isolated from formalin fIxed paraffin embedded tissue. Fluorescent-based DNA technology using an automated DNA sequencer (Alf Express Automated DNA Sequencer) was employed. CY5 labelled primers for microsatellite markers (DCC, D18S34, D18S58, D3S659, D2S123 and D3S1255) were used. The data was captured and analysed using the Fragment Manager Software. The informativity of the microsatellite markers used in this study ranged from 50% to 71.8%. LOH/AI in the region of the DCC gene in the under 35 years of age CRC was 39.1%, while MSI in this region occurred in 31.25% of cases. The DNA repair gene status in these young patients was as follows: LOH/AI: 31.3% and MSI: 40.4%. In the over 50 years of age CRC, LOH/AI in the 18q region was 28% and MSI was 38%. The DNA repair genes (hMSH2 and hMLH1) in this cohort showed LOH/AI in 24% and MSI also in 24%. As regards oesophageal cancer, LOH/AI in the 18q region was 20.5% and MSI 7.7%. The repair genes showed LOH/AI in 17.9% and MSI in 10.25% of cases. When the molecular events were correlated with clinicopathological features, no statistically significant pattern emerged. However, it must be remembered that relatively small numbers of cases (39) were analysed.In conclusion: • No statistical correlation was found between clinicopathological characteristics and the molecular analysis in either CRC and oesophageal cancer. • LOH/AI and MSI was higher in the under 35 age group. • LOH/AI and MSI in 18q, 2p and 3p in sporadic CRC were similar to other fluorescent-based studies in patients over 50 years of age. • LOH/AI and MSI in 18q, 2p and 3p in oesophageal cancer was similar to studies from other geographical areas. • Finally, fluorescent-based microsatellite PCR and analysis was found to be an objective and efficient technique. / Thesis (Ph.D.)-University of Natal, 1998.

Errata pages inserted behind leaf 293. / Includes bibliography (leaves 255-293). / xv, 293, [60] leaves, [33] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to determine the molecular mechanism by which expression of Fas is lost in colorectal tumours and investigates the effects of re-introducing Fas into colon cancer cells. An animal study was undertaken in addition to the studies of colorectal cancer, to investigate the role of Fas signalling in hormone-dependent involution of the prostate gland. / Thesis (Ph.D.)--University of Adelaide, Dept. of Surgery, 1998?

Errata pages inserted behind leaf 293. / Includes bibliography (leaves 255-293). / xv, 293, [60] leaves, [33] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to determine the molecular mechanism by which expression of Fas is lost in colorectal tumours and investigates the effects of re-introducing Fas into colon cancer cells. An animal study was undertaken in addition to the studies of colorectal cancer, to investigate the role of Fas signalling in hormone-dependent involution of the prostate gland. / Thesis (Ph.D.)--University of Adelaide, Dept. of Surgery, 1998?

Thesis (Ph. D.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 154-168).

No description available.

published_or_final_version / abstract / toc / Medicine / Master / Doctor of Medicine

In the past, patients with peritoneal surface malignancy were considered incurable and were only offered palliative treatments. However, in a substantial number of patients, disease progression that is isolated to peritoneum may occur. It has been realised that elimination of peritoneal surface tumours may have an impact on the survival of these cancer patients, in whom a prominent cause of death is peritoneal carcinomatosis. The focus of this PhD. thesis is on the combined treatment of cytoreductive surgery and perioperative intrapersonal chemotherapy for diffuse malignant peritoneal mesothelioma, pseudomyxoma peritonei, colorectal peritoneal carcinomatosis and resectable gastric cancer. Section one describes the major principles of management for peritoneal surface malignancy, covering the historical perspectives, the treatment rationales and the learning curve associated with the combined procedure. Section two is devoted to peritoneal mesothelioma, in trying to examine this disease from its clinical, radiologic and histopathologic aspects. A radiologic classification and a histopathologic staging system for this disease are proposed. In section three, the results of the combined treatment for pseudomyxoma peritonei are presented, including a systematic review of the literature, a case series of 50 patients from our Australian centre and a treatment failure analysis of 402 patients from the Washington Cancer Institute. These studies suggest that a disease-free state is important for long-term survival for patients with pseudomyxoma peritonei. In section four, the current evidence on the combined treatment for colorectaI peritoneal carcinomatosis is demonstrated by conducting a systematic review of the literature and survival and perioperative outcome analyses of two separate patient cohorts. These results suggest that the combined treatment is associated with an improved survival, as compared with historical controls. In the last section, a metaanalysis of the randomised controlled trials on adjuvant intraperitoneal chemotherapy for resectable gastric cancer shows that a significant improvement in survival is associated with hyperthermic intraoperative intraperitoneal chemotherapy alone or in combination with early postoperative intraperitoneal chemotherapy.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / Pathology / Doctoral / Doctor of Philosophy