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Transport proteins in normal and malignant cells

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Dr Margery Barrand  (Retired)

Undergraduate Admissions for Downing College
Graduate Studies Prospectus at Downing College

E-Mail: mb10002@cam.ac.uk
Tel: +44 1223 334019
Fax: +44 1223 334100

Keywords

Neurobiology, ion transport, multidrug efflux proteins, blood-brain barrier, erythrocytes, malarial parasites

 

The ATP Binding Cassette superfamily of proteins contains several members that in mammalian cells are involved in drug transport. These include P-glycoprotein, multidrug-resistance associated proteins [1] and Breast Cancer Resistance Protein (BCRP). These transporters are able to confer resistance to tumour cells by removing cytotoxic drugs from intracellular target sites. Clinically these actions provide serious obstacles to effective anticancer chemotherapy. However, these same transporters exist in normal tissues and there provide protection to cells against cytotoxic stresses. Work in the laboratory has been concerned with the mechanisms by which these transporters bring about drug movements [8, 12], looking at some of the agents that impair [5, 10, 13, 14, 15] or can by-pass their actions [16] [Fig 1 shows fluorescent images of doxorubicin inside resistant lung tumour cells following exposure to either a) the free drug or b) its polymer-linked form]. These studies have been undertaken using resistant tumour cells [4, 5, 10, 14, 15] and human red blood cells [5, 8, 12, 13] and have been done in collaboration with colleagues in the Pharmacology Department (Drs Hladky and van Veen), in the Department of Chemical Engineering (Dr M Eccleston) and at the National Cancer Institute, NIH, Bethesda, MA, USA (Dr S Ambudkar)...

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