MULTIPLE DRUG RESISTANCE IN HUMAN SOLID TUMORS

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Multiple Drug Resistance (MDR) is a major reason for failure of cancer chemotherapy. Earlier studies on murine cell lines have identified certain biochemical mechanisms (e.g. rapid drug efflux) responsible for MDR. Cellular markers such as cell surface glycoproteins are often associated with MDR. Our knowledge about MDR in solid tumors is limited and it is important to study drug resistance in human soild tumors, as more often than not, MDR results in treatment failure. In the present study, we propose to study MDR in human solid tumor cells isolated from ascites and pleural fluid of patients and from xenografts earlier established. We will use our laser excitation method to sort and study tumor cells on the basis of their anthracycline fluorescence content. Drug transport characteristics will be studied with or without exposure to drug efflux blockers. Biochemical mechanisms responsible for MDR as well as well-known markers of MDR will be studied. It is hoped that the studies proposed will provide insights into mechanisms involved in MDR of human solid tumors.