Fluorescence based assay for the identification of multiduug resistance in transitional cell bladder carcinoma

Abstract

The cytotoxic response of cancer cells to chemotherapeutic drugs may be influenced by the development of multidrug resistance (MDR) which phenomenon affords cross-resistance to a variety of structurally unrelated drugs, including the anthracyclines and possibly mitomycin C. The reduction in cytotoxic efficacy seen in MDR cancer cells is associated with the interaction of a number of cellular protein systems including transmembarne glycoproteins, intracellular organelles, topoisomerases and glutathione transferases.

Superficial bladder cancer, although primarily treated by surgical resection, can be adjuvantly treated by means of intravesical chemotherapy, most commonly employing the anthracyclin epirubicin, or mitomycin C. However, the recurrence rate of these tumours can approach 60% despite such treatment. It is suggested that this represents the development of MDR in many instances. There is currently no reliable means of identifying the presence of MDR in patient tumours, and it is therefore impossible to predict an individual's likely response to intravesical chemotherapy.

The work which follows initially describes the current philosophy of intravesical chemotherapy in the management of superficial bladder cancer, the mechanisms of MDR within bladder cancer biopsy explants in culture. In addition is given a description of the place of mitomycin C in the MDR family. Finally some mechanistic observations are described on the subcellular handling of the anthracyclines, and of the membrane characteristics of MDR.

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