Diabetes mellitus type 2: structured care and education

Antineoplastic agents may be very effective in the first round of combination chemotherapy; however, upon subsequent treatment, many tumours display resistance. In many instances , drug resistance is observed to multiple agents which differ in structure as well as in their mechanism of action. Development of such multidrug resistance (MDR) is a major obstacle in the treatment of a variety of malignancies (Kaye, 1988). Although the altered expression of a number of proteins has been associated with MDR in different model systems, the overexpression of a 150-180 kDa glycoprotein has been the most consistent. This glycoprotein, termed P-glycoprotein, acts as an energy dependent efflux pump to reduce drug accumulation within the cell (Gerlach et al., 1986a). While overexpression of P-glycoprotein is clearly responsible for MDR in some cell systems, it is unlikely that P-glycoprotein by itself can account for the plethora of biochemical and genetic changes which occur as a cell adapts to growth in the presence of antineoplastic agents (Kaye, 1988). The isolation of MDR cell lines which do not overex-press P-glycoprotein, and the detection of P-glycoprotein in only a subset of patients with drug-resistant tumours (Gold-stein et al., 1989), support a multifactorial model of MDR A number of monoclonal antibodies have been derived with specificity for P-glycoprotein and have proven to be valuable tools in the analysis of the MDR phenotype mediated by P-glycoprotein (Kartner et al.