A phase II study of thioTEPA in children with recurrent solid tumor malignancies: a Children's Cancer Group study |
| |
| Authors: | JR Geyer FM Balis MD Krailo R Heideman E Broxson JK Sato D Poplack WA Bleyer |
| |
| Affiliation: | Department of Pharmacology, University of Vermont College of Medicine, Burlington 05405, USA. |
| |
| Abstract: | We report a murine leukemia cell variant (L1210/DDP), selected for cisplatin (DDP) resistance, to be cross-resistant to methotrexate (MTX). Cross-resistance of L1210 cells to DDP and MTX has been observed by others, and has also been recorded in P388 murine leukemia and SSC-25 human squamous carcinoma cells. We demonstrated that MTX resistance is not due to dihydrofolate reductase (DHFR) gene amplification, increased DHFR enzyme activity or decreased MTX binding to the target enzyme. Of the mechanisms commonly proposed for MTX resistance, only differences in transport were observed when comparing sensitive (L1210/0) and resistant (L1210/DDP) cells. Our results suggest that MTX resistance in L1210/DDP cells is due to altered methotrexate uptake. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
