Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649019
Title: An investigation of tumour cell contamination of bone-marrow and peripheral blood stem cell harvests in patients with AML
Author: Cunningham, Andrew James
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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Abstract:
Bcl-2 offers a cellular target for antisense-mediated inhibition in AML to improve the efficacy of chemotherapy and patient survival. I have studied the mechanisms of cellular uptake of antisense into cells of normal and leukaemic phenotype and its effectiveness at the induction of apoptosis in these cells. Antisense was found to be preferentially associated with monocytes, neutrophils and eosinophils with lower levels associated with lymphocytes and KG1-a (AML) cells. This uptake was found to be associated with expression of the adhesion molecule Mac-1 (CD11b-CD18). However antisense appeared to be sequestered into cytoplasmic vesicles and was predominantly functionally ineffective at reducing bcl-2 protein levels or in the induction of apoptosis. Antisense effects were also studied in the presence and absence of apoptotic stimuli from Cycloheximide, Actinomycin D or Cytosine arabinoside. There were no potentiating effects of bcl-2 antisense with either Cycloheximide or Actinomycin D at inducing apoptosis of AML cells. However there was a synergistic effect of antisense bcl-2 in the presence of Cytosine arabinoside, an agent used in the clinical treatment of AML. It was not clear whether effects of antisense could be attributed to true antisense-mediated or non-specific polyanionic effects mediated through integrin binding. Therefore antisense bcl-2 does not appear to be an effective therapy on its own for the generic treatment of AML but may function as a second-line adjunct therapy in resistant or relapsed cases of AML which fail to respond to conventional chemotherapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.649019  DOI: Not available
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