INVESTIGATION OF CHEMORESISTANCE-RELATED GENES MESSENGER-RNA EXPRESSION FOR SELECTING ANTICANCER AGENTS IN SUCCESSFUL ADJUVANT CHEMOTHERAPYFOR A CASE OF RECURRENT GLIOBLASTOMA

BACKGROUND Glioblastoma multiforme represents one of the most malignan t forms of primary intracranial tumors, often intractable to multimoda lity of treatment including chemotherapy. The unsatisfactory results o f chemotherapy are chiefly attributed to chemoresistance. Since variou s molecules that could confer drug resistance have been elucidated, sc reening of the amount of such molecules in the tumor cells could provi de possibilities for predicting their chemoresistance beforehand and h elp select more effective drugs. METHODS We present a 45-year-old woma n with recurrent glioblastoma multiforme in the cerebellum and invadin g the brain stem, treated successfully by postoperative chemotherapy, In this patient, anticancer drugs were determined by measurements of m RNA expression of chemoresistance-related genes, such as O-6-methylgua nine-DNA methyltransferase (MGMT), mdr1, glutathione S-transferase (GS T)-pi, and metallothionein (MT) in the resected tumor. RESULTS Norther n blot analysis demonstrated the moderate mRNA level of MGMT, a major molecule causing ACNU pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosour ea hydrochloride) resistance. On the other hand, expression levels of mdr1 which codes the P-glycoprotein responsible for multidrug resistan ce, and GST-pi, a detoxification enzyme, were low. Transcript of MT, a nother thiol containing molecule for dcellular detoxification possibly associated with cisdiamminedichloroplatinum(II) (CDDP) resistance, wa s only faintly detectable. Postoperatively, the patient was treated in itially with intravenous administration of ACNU and etoposide (VP16), resulting in a minor response of tumor regression. For maintenance the rapy, we changed ACNU to CDDP according to the findings of the Norther n blot analysis. Consequently, the residual tumor showed a marked resp onse and almost disappeared after two courses of systemic chemotherapy with CDDP and VP16. CONCLUSIONS The successful tumor regression in th is case suggests that Northern blot analysis on expression of these ch emoresistance-related genes in tumor tissues could provide beneficial information for determination of optimal anticancer agents to improve the efficacy of chemotherapy.