No description available.

This study was carried out in 2 parts: 1. Genome analysis of human adenovirus species 7; 2. Search for a possible viral aetiology in oesophageal carcinoma. Sixteen laboratory isolates of adenovirus species 7, isolated in South Africa between 1975 and 1986, were characterized by restriction endonuclease analysis of their DNA genomes. Virus was propagated in human embryo fibroblast cells; genomic DNA, extracted and purified from cellular DNA extracts, was analyzed using 9 different restriction enzymes. Results of this study have demonstrated 2 new genome types of adenovirus 7c which have not previously been identified. The 2 novel strains, designated as genome types Ad7c1 and Ad7c2, were shown to differ from prototype Ad7 c according to restriction profiles with EcoRI; 2 new EcoRI sites were demonstrated in Ad7c1 and 1 in Ad7c2. The restriction sites were mapped on the viral genomes (at 3.68kb and 5.32kb from the left terminus) by double enzyme digestions, cloning of viral DNA, and nucleic acid hybridization using a cloned Ad7 probe. Strains resembling the prototype Ad7c and Ad7p (Gomen) genome types were also identified in the 1985 and 1986 Ad7 isolates. In order to investigate the possible role of a viral co-factor in the aetiology of oesophageal carcinoma, 18 probes, derived from potentially oncogenic viruses, were used to screen 3 human oesophageal carcinoma cell lines for the possible presence of integrated viral DNA. One of these, an Ad7 recombinant plasmid probe, was developed by cloning DNA from the transforming region of the Ad7cl strain into the plasmid vector pUC19. Cellular DNA, extracted from the 3 tumor lines HCU18, HCU33 and HCU39, was tested by means of both DNA dot hybridization and Southern blot hybridization for the presence of Epstein-Barr virus, human papillomavirus (types 1, 5, 6, 8, 11, 16, 18), human adenovirus (strains 5, 7, 12, 31) and human T-lymphotropic virus type I DNA. Both assays were demonstrated to be sensitive enough to detect 1 copy of viral DNA per cell. No hybridization between HPV, EBV, HTLV-I or adenovirus DNA probes, and the cellular DNA was detected. These findings indicate that the stable integration of these tumor viruses in host chromosomes did not play a role in the maintenance of the malignant phenotype of the 3 extensively passaged cell lines. Cells of the 3 oesophageal tumor lines were further examined by transmission electron microscopy, but the presence of virus particles in these cells was not observed.

The necessity to obtain accurate and reliable data pertaining to the range and/or levels of mycotoxin contamination in a variety of food and feed substrates, intended for human or animal consumption, has therefore, become important. An integral part of this study will be the provision of the most suitable analytical methods for the determination of selected Fusarium mycotoxins, in maize. The culmination will be the application of those selected methodologies to a series of Transkeian maize samples associated with human oesophageal cancer-risk.

No description available.

published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy

published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

Esophageal squamous cell carcinoma (ESCC) is a common cancer worldwide with a high mortality rate. High occurrence of ESCC is observed in Southeast Asia. Identification and characterization of ESCC important tumor suppressor genes will be highly beneficial to the understanding of the disease and for the early diagnosis and improvement of therapy for the cancer. In our previous microcell-mediated chromosome transfer (MMCT) studies, the transfer of an intact chromosome 13 into the recipient ESCC cell line revealed the tumor suppressive ability and putative tumor suppressive function of chromosome 13 in ESCC. One candidate gene, Plant-Homeodomain Finger Protein 11(PHF11), was identified from the study and selected for further functional studies in this current study. PHF11, located on chromosomal region 13q14, contains two plant homeodomain fingers and is a member of the PHD finger protein family. PHF11was reported to be associated with asthma and atopic diseases, yet no studies of PHF11havebeen reported in cancer to date. This study is the first to report the functional role of PHF11in tumor suppression. In this current study, two isoforms of PHF11, PHF11aand b, were reintroduced into ESCC cell lines by methods of transient tranfection and lentiviral-infection. In vitro studies showed both isoforms have cell proliferation and colony-formation inhibition abilities. In the nude mouse tumorigenicity assay, however, it was revealed that only thePHF11aisoform was tumor suppressive in vivo. No differences in angiogenesis-related factors and apoptosis-related factors were observed in PHF11a-and b-expressing cells. Further studies by Western blotting analysis and flow cytometry analysis showed that PHF11amay play a role in delaying cell cycle progression by the down-regulation of cyclin expression, while the PHF11bmay be functionally inactive, The results of this current study further confirm the tumor suppressive role of PHF11ain ESCC, whereas the PHF11b isoform was unable to suppress tumor formation in vivo. Further study of the PHF11 isoforms to identify their differential functions and interacting partners will provide a better understanding of the mechanism by which PHF11a suppressestumor growth. / published_or_final_version / Clinical Oncology / Master / Master of Philosophy

abstract / Anatomy / Master / Master of Philosophy