Longman, Joanna (2013). Project 1: Novel bromodomain and extra-terminal (BET) protein inhibitor JQ1 sensitises dexamethasone-resistant ALL cells to dexamethasone-induced cell killing and Does microRNA deregulation contribute to PTTGl-Binding Factor (PBF) overexpression in thyroid carcinoma? Project 2: Does microRNA deregulation contribute to PTTG1-Binding Factor (PBF) overexpression in thyroid carcinoma? University of Birmingham. M.Res.
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Longman13MRes.pdf
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Abstract
Background: B-cell precursor acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Proto-oncogene MYC functions as a DNA binding transcriptional activator. BET family proteins facilitate MYC transcription, and have recently emerged as a potential therapeutic target in heamopoitic malignancies. JQl is a cell-permeable small molecule that binds competitively to the acetyl-lysine recognition motifs with high specificity for the bromodomains of BET family members, preventing their ability to transcribe MYC. JQI inhibitor bas previously demonstrated drastic anti-tumour activity in Vitro and in pre clinical models of c-Myc dependent malignancies. Aim: To investigate the sensitivity of ALL cells to JQI-mediated BET inhibition, and whether JQ1 is capable of sensitising cytotoxic agent Dexamethasone resistant ALL cells to Dexamethasone induced cell killing both in vitro and in vivo. Methods: Cytotoxicity assays were used to investigate JQl-mediated Dexamethasone sensitisation in ALL cells in vitro. A Xenograft model was used to investigate this in NOG mice in vivo.Results: JQl-dexamethasone co-treatment resulted insignificantly increased cell killing in vitro and complete tumour suppression in vivo. Discussion: JQl is capable of sensitising Dexamethasone resistant ALL cells to Dexamethasone induced cell killing both in vitro and in vivo.
| Type of Work: | Thesis (Masters by Research > M.Res.) | |||||||||
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| Award Type: | Masters by Research > M.Res. | |||||||||
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| College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
| School or Department: | School of Clinical and Experiment Medicine, Department of Medicine and Medical Education | |||||||||
| Funders: | None/not applicable | |||||||||
| Subjects: | R Medicine > R Medicine (General) | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/4574 |
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