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?

[摘要] Background: B-cell precursor acute lymphoblastic leukaemia (ALL) is themost 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.

[发布机构] University:University of Birmingham;Department:School of Clinical and Experiment Medicine, Department of Medicine and Medical Education

[关键词] R Medicine;R Medicine (General)