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Title: Aspects of multidrug resistance in breast cancer
Author: Wishart, Gordon C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1992
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The use of chemotherapy in the treatment of breast cancer is compounded by the development of clinical drug resistance in a large number of cases. One mechanism of resistance, multidrug (MDR), is associated with expression of a 170kDa transmembrane protein called P-glycoprotein (P-gp) which acts as an energy-dependent drug efflux pump. Although P-gp can be encoded by several MDR genes it is only expression of the mdr-1 gene which is associated with MDR in humans. P-gp has been identified in several human tissues and tumours but previous studies have failed to provide clear evidence of its presence in human breast cancer. Detection of P-gp, by immunohistochemistry using specific monoclonal antibodies, allowed confirmation of P-gp expression at low levels in the majority of 29 untreated, primary breast cancers suggesting a population of resistant cells was present even before exposure to cytotoxic drugs. Furthermore this expression was detected in stromal cells, as well as malignant cells, and this stromal cell immunostaining has been confirmed as mdr-1 expression by competitive inhibition using a specific blocking peptide. Examination of paired samples of normal breast and tumour from the same patient revealed P-gp expression only in ductal epithelial cells, but not stromal cells, of normal breast. Finally those patients whose tumours had the highest P-gp expression in malignant cells appeared to have a worse prognosis in terms of disease-free survival.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available