抗癌剤メソトレキセート耐性と新しい癌化学療法の設計 : 絨毛癌を中心に

概要

論文の詳細を見る
Methotrexate (MTX) is one of the most powerful chemotherapeutic agents against choriocarcinoma. The resistance to MTX arises frequently in the clinical use, and it makes a difficulty in cancer chemotherapy. The mechanism of resistance to MTX has been extensively investigated, and several mechanisms have been suggested so far. Those are the decreased cell permeability, the increased synthesis of MTX target enzyme (dihydrofolate reductase), the decreased polyglutamation of MTX, and the decreased association constant of MTX with dihydrofolate reductase. Those mechanisms were studied in human choriocarcinoma cell lines (8 lines). The cell permeability and the enzyme activity in MTX resistant HM choriocarcinoma cell were compared with those in MTX sensitive HCCM-5 choriocarcinoma cell, whereas there was an induction of dihydrofolate reductase to overcome MTX in MTX resistant HM cell. By using HM cell, the experimental chemotherapy was studied in vitro and vivo. On the experimental chemotherapy and pharmacokinetics of MTX in choriocarcinomas, a new chemotherapeutic protocol was originated, and it was clinically applied on the chemotherapy against MTX resistant choriocarcinoma. The new protocol was effective on overcoming the resistance choriocarcinoma to MTX+Act-D+CPM combination therapy.
日本医療薬学会の論文
1989-06-20