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Analysis of human germ lines genes for clinical applications

Alharbi, Ahmed Mulfi (2017) Analysis of human germ lines genes for clinical applications. PhD thesis, Prifysgol Bangor University.

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Alharbi Appendix A PhD 2017.pdf

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Alharbi Appendix B, source of genes PhD 2017.pdf

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Abstract

Identification of cancer biomarkers it is essential for the diagnosis of cancer during the early stage of disease, which might increase the possibility of successful treatment and improve patient outcomes. The identification of new cancer-specific biomarkers for cancer diagnosis patient stratification is challenging, but they also provide therapeutic targets so they are of fundmental importance in addressing unmet clinical needs in oncology. Cancer/testis antigens (CTAs) genes possess unique features, as they encode proteins that are normally only present in the testis, placenta and ovary, and the expression of these genes has been associated with various types of malignant tumours. Therefore, cancer testis (CT) genes have exceptional clinical potential. Here, a cohort of genes that were reported to be associated with aggressive lung tumours has been re-validated. Among these promising 26 genes, expression profiles for 10 genes were detected in normal lungs tissue as well in a panel of different normal tissues, and consequently these 10 genes were excluded as good candidates for lung cancer biomarkers. In addition, the 26 genes were screened in normal ovary tissues, as these genes may be useful as ovarian biomarkers, but the same 10 genes were also found to be expressed in normal ovarian tissue. The other remaining 16 genes could serve as ovarian biomarkers. In total, 156 genes known as CT genes and derived from different sources were investigated. TaqMan Low Density Array (TLDA) card analysis was used to re-validate this large group of genes in normal tissues and clinical samples from different patients. Out of 156 genes, 55 were expressed in different types of normal tissue other than testis tissue and central nervous system (CNS), and thus these genes were excluded as CT genes. Brachyury is a transcription factor that has been reported to be a CTA and may represent a target for cancer treatment. New drugs that may target the cancer associated functions of Brachyury were examined to assess their efficacy and the potential for targeting CTAs. The effect of these drugs on a panel of cancer associated genes known to be specifically regulated by Brachyury was carried out. An evaluation of the drugs revealed that three of the drugs were effective in altering the proliferation rate of cancer cell line, with their action being Brachyury-specific, rather than due to general cytotoxicity.

Item Type: Thesis (PhD)
Subjects: Degree Thesis
Departments: College of Natural Sciences > School of Biological Sciences
Degree Thesis
Date Deposited: 30 Nov 2017 10:44
Last Modified: 05 Jan 2018 11:21
URI: http://e.bangor.ac.uk/id/eprint/10840
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