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Title: Primary tissue-based proteomic analysis of apoptosis-regulating pathways in malignant pleural mesothelioma (MPM)
Author: Klabatsa, Astero
ISNI:       0000 0004 2701 2044
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2011
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Malignant pleural mesothelioma (MPM) is an aggressive and fatal malignancy associated with resistance to chemotherapy and radiotherapy. Programmed cell death or apoptosis underlies the efficacy of cytotoxic anti-cancer modalities, and failure to engage the cellular death machinery in cancer cells accounts for failure of therapy and poor prognosis. Little is understood of the basic apoptosis biology underlying the apoptosis resistant phenotypes of MPM. There is now greater understanding of the basic core apoptosis machinery of the cell, allowing the characterization of anti-apoptosis mechanisms in MPM. Cancer cell apoptosis threshold is ultimately determined by the location and function of proteins. This study explores the expression and significance of several proteins directly or indirectly involved in the apoptosis pathway. Histology samples were used to produce a tissue microarray (TMA) on which immunohistochemistry was employed. Proteins HIF-1α, CD31, Glut-1, CASP3, Survivin, BAX, BAK, Cyt-C, APAF-1 and PARP were analyzed and their protein expression profiles were correlated with patient survival. The findings show that MPM exhibits hypoxia. Increased glucose intake was also demonstrated by overexression of Glut-1. BAX and BAK were shown to be synergistically downregulated, with a direct effect into survival, demonstrating the compromised function of the mitochondria due to increased glucose uptake. Information yielded from this project might allow further exploitation of apoptotic proteins either as targets for new therapeutic agents, or as markers for prognosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine