Browsing by Author "Parker, M I"

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    Chemotherapeutic drugs, 5-fluorouracil and cisplatin, differentially affect exprssion of drug metabolising enzyme genes in an oesophageal cancer cell line
    (2014) Hassen, Naseeha; Dandara, Collet; Mowla, Shaheen; Parker, M I
    Cancer is a leading cause of death worldwide. Oesophageal cancer in particular is the sixth most common cause of cancer deaths globally and its incidence and mortality rates in Southern Africa are among the highest in the world. One of the major challenges with cancer treatment is the vast variability in patient response to chemotherapy, which is predominantly due to genetic variability. The most relevant genes in this context encode the CYP and GST drug metabolising enzymes (DMEs) as these enzymes metabolise up to 90% of clinically-prescribed medication. Patients are also exposed to a variety of other compounds that along with chemotherapeutic drugs may alter DME gene expression. Changes in DME gene expression influence the therapeutic outcomes for patients; thus, understanding the effects of drugs and compounds on the expression of DMEs is crucial for the advancement of personalised medicine. The aim of this study was to determine the effects of two commonly-used chemotherapeutic drugs, as well as a CYP-inducing compound, on the differential expression of four pharmacogenetically relevant DME-encoding genes, CYP1A1, 1A2, 1B1 and GSTP1, in a human oesophageal cancer cell line.
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    Open Access
    Identification of signalling pathways regulating TBX2 gene expression and its target genes
    (2008) Teng, Huajian; Prince, Sharon; Parker, M I
    Members of the T-box family of transcription factors provide an important link between development and cancer. T-box factors play critical roles in embryonic development and results from recent studies suggest that they function in controlling cell cycle progression and also in the genesis of cancer. Importantly, the T-box factors Tbx2 and Tbx3 are overexpressed in several cancers including melanoma, small cell lung carcinoma, breast, pancreatic, liver and bladder cancers and can suppress senescence, a cellular process which serves as a barrier to cancer development. However, the precise role of most T-box factors is poorly defined, in part, because their target genes are still poorly characterised and very little is known of the signalling pathways that regulate their expression and activity. The broad aim of this study was therefore to contribute towards the identification of Tbx2 target genes as well as to identify signalling pathways that regulate TBX2 expression. The specific aims were thus to (1) investigate the regulation of type1 collagen gene expression by Tbx2; (2) clone the human TBX2 regulatory region and to identify cis-acting elements involved in the basal transcription of the TBX2 gene and (3) investigate the regulation of TBX2 gene expression by signalling pathways.