多形性胶质母细胞瘤异种移植中错配修复缺陷介导的甲基化耐药性

Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.

作者信息

Friedman H S, Johnson S P, Dong Q, Schold S C, Rasheed B K, Bigner S H, Ali-Osman F, Dolan E, Colvin O M, Houghton P, Germain G, Drummond J T, Keir S, Marcelli S, Bigner D D, Modrich P

机构信息

Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

Cancer Res. 1997 Jul 15;57(14):2933-6.

PMID:9230204

Abstract

A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-methyl-N-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, 9-aminocamptothecin, topotecan, CPT-11, cyclophosphamide, and busulfan. D-245 MG (PR) xenografts were resistant to procarbazine, temozolomide, N-methyl-N-nitrosourea, and busulfan, but they were sensitive to the other agents. Both D-245 MG and D-245 MG (PR) xenografts displayed no O6-alkylguanine-DNA alkyltransferase activity, and their levels of glutathione and glutathione-S-transferase were similar. D-245 MG xenografts expressed the human mismatch repair proteins hMSH2 and hMLH1, whereas D-245 MG (PR) expressed hMLH1 but not hMSH2.

摘要

通过用丙卡巴肼连续处理亲本异种移植瘤D - 245 MG，在无胸腺裸鼠中建立了一种对甲基化剂耐药的多形性胶质母细胞瘤异种移植瘤D - 245 MG (PR)。D - 245 MG异种移植瘤对丙卡巴肼、替莫唑胺、N -甲基- N -亚硝基脲、1,3 -双(2 -氯乙基)- 1 -亚硝基脲、9 -氨基喜树碱、拓扑替康、伊立替康、环磷酰胺和白消安敏感。D - 245 MG (PR)异种移植瘤对丙卡巴肼、替莫唑胺、N -甲基- N -亚硝基脲和白消安耐药，但对其他药物敏感。D - 245 MG和D - 245 MG (PR)异种移植瘤均未显示O6 -烷基鸟嘌呤- DNA烷基转移酶活性，且它们的谷胱甘肽和谷胱甘肽- S -转移酶水平相似。D - 245 MG异种移植瘤表达人类错配修复蛋白hMSH2和hMLH1，而D - 245 MG (PR)表达hMLH1但不表达hMSH2。