Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy.

摘要: The B-cell neoplasms, multiple myeloma and non-Hodgkin's lymphoma, frequently become drug resistant, despite initial responses to chemotherapeutic drugs. Tumor cells from eight patients with clinically drug-refractory disease were evaluated by immuno-histochemical staining for monoclonal immunoglobulin (Ig) expression, nuclear proliferation antigen, P-glycoprotein (P-gly) other cellular antigens. P-gly was detected on tumor six of drug-resistant disease. Of the P-gly-positive tumors, five had advanced one a lymphoma. Cellular RNA analysis confirmed over-expression P-gly. In an effort overcome resistance, pilot study possible verapamil enhancement chemotherapy in these patients. All developed progressive while receiving regimen containing vincristine doxorubicin, seven previously received continuous infusion doxorubicin plus oral dexamethasone (VAD). At time disease, added VAD regimen. Three who refractory alone responded when VAD. three tumors. Verapamil increased intracellular accumulation vitro both cell line two end-stage which over-expressed dose-limiting side effect associated addition temporary impairment cardiac function, manifest as hypotension arrhythmia. We conclude that expression occurs neoplasms may contribute development clinical resistance. However, factors, such proliferative activity tumor, also play role determining response chemotherapy. administration along partially circumvent resistance whose tumors over-express