3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item The identification of differentially expressed cell cycle -related genes in breast and colon cancer cell lines in response to chemotherapeutic drugs(2010-01-27T11:15:07Z) Rupnarain, CharleenWith the high prevalence and high mortality rate of cancer in the global community, it is increasingly essential to accelerate our understanding of the disease, to identify new genetic targets for therapy, and to pursue avenues for improving on the therapies in development and in current use. The aim of this study is to identify cell cycle-related genes whose expression is influenced by the chemotherapeutic drugs curcumin, SAHA, lycopene and thalidomide in breast and colon cancer and normal cell lines. These drugs are currently not in clinical use for cancer in South Africa, and while there have been investigative studies of these chemotherapeutic agents, this study aims to identify the specific genes that are influenced by the drugs. The result of this is that several genes that were not previously documented as targets of these drugs are highlighted. The cell cycle pathway is the area of focus as loss of regulation in the cell cycle is one of the important factors involved in promoting cancer initiation and progression. In the first instance, flow cytometry was used to identify optimal drug concentrations relative to the cell cycle stages. Following this, alterations in gene expression were assessed using a PCR-based differential display after each drug treatment. Subsequently, a more focussed approach was taken in a PCR-array analysis of panels of cell cyclerelated genes. A subset of genes is identified that is implicated in oncogenic transformation in breast cancer. This has the potential to inhibit the genetic pathways involved in breast malignancy by providing targets that perhaps may not be manipulated in current therapies. The gene expression studies here suggest that lycopene and thalidomide function in inhibiting this transformation, and play significant roles in suppressing the oncogenic state of breast cancer. Curcumin and SAHA also exhibit important functions in inhibiting tumourigenesis in colon cancer. While the results propose that the drugs have clear roles in inhibiting breast and colon cancer, they are also implicated in promoting cancer. This research has defined the genes that must be carefully monitored during drug administering as they may promote these and other cancers. The availability of these results to researchers will aid in selecting the criteria for assessing the success rate of these drugs.Item Characterization of the novel domain with no name gene in colon cancer(2006-03-23) Rupnarain, CharleenNormal colonic epithelium bombarded by a range of molecular changes, affecting cell proliferation and apoptosis, result in the initiation of an adenoma and consequently an invasive carcinoma, which is usually lethal. One of the main characteristics of tumour progression is the loss of regulation between the cell cycle and apoptosis. Under normal circumstances, these processes are strictly controlled by a number of regulators and inhibitors. Previous studies have implicated the novel Domain With No Name gene in apoptosis. This study aimed to characterize the expression patterns and levels of the gene in colon cancer and to determine its role in apoptosis. In situ hybridisation, immunocytochemistry and quantitative PCR localised the gene and its products in cancerous and normal colon tissue. Combined with apoptosis detection studies, proliferation assays and Bcl-2 assays, the results suggest that the gene is involved in promoting apoptosis in cancerous cells i.e. the targeting of undesirable cells. Helicobacter pylorus was implicated in the progression of noninvasive colon cancer to the invasive state. From this study DWNN is proposed to be a pro-apoptotic participant in programmed cell death and classification studies such as these allow for potential manipulation of the apoptotic system to serve as a therapeutic corridor.