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?

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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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.)
Award Type: Masters by Research > M.Res.
Supervisor(s):
Supervisor(s)EmailORCID
Stankovic, TatjanaUNSPECIFIEDUNSPECIFIED
McCabe, ChrisUNSPECIFIEDUNSPECIFIED
Licence:
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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