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Title: The investigation of novel agents for the therapy of acute myeloid leukaemia
Author: Jenkins, Christopher
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2009
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There have been marked improvements in survival with patients suffering from AML over the last thirty years, however a significant number of patients will either not respond to conventional therapy, or will relapse following treatment. Advances in the molecular mechanisms that underlie haematological malignancies have fuelled a drive for new targeted therapies to improve the prognosis. The aims of this study were to investigate the effects of two novel drugs, namely LC1 - an NF-kB inhibitor and CHR 2797 - an aminopeptidase inhibitor. Initially, NF-kB was investigated into its potential as a molecular target for therapy. Constitutive up-regulation in human myeloid blasts was shown, together with a clear correlation between NF-kB expression and in vitro cytoprotection. High NF-kB expression was also found in many of the poor prognostic AML subtypes. LC1, a dimethylamino-parthenolide analogue, was found to be preferentially cytotoxic to AML cells in vitro in a dose dependent manner, mediated through the induction of apoptosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available