Sensitivity to temozolomide in brain tumor initiating cells

Sensitivity to temozolomide in brain tumor initiating cells
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DOI:
10.1093/neuonc/noq032
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发表时间:
2010-07-01
期刊:
影响因子:
15.9
通讯作者:
Cairncross, J. Gregory
Cairncross, J. Gregory
中科院分区:
医学1区
文献类型:
--
作者:
Blough, Michael D.;Westgate, Morgan R.;Cairncross, J. Gregory

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胶质母细胞瘤的分子改变有可能指导治疗。在这里,我们探讨脑肿瘤起始细胞(BTIC)中替莫唑胺(TMZ)反应和O-6-甲基鸟嘌呤DNA甲基转移酶(MGMT)状态之间的关系。在20个品系中评估甲基化、表达和敏感性;通过Fisher精确检验评估相关性。一些BTIC是敏感的。对TMZ的敏感性仅与蛋白表达相关(P = .001)。存在非典型BTIC,包括TMZ抗性品系,其中甲基化特异性PCR反应显示甲基化和非甲基化条带。BTIC对TMZ的耐药性并不一致;有些是敏感的。MGMT状态不能以高精度预测TMZ应答。
Molecular alterations in glioblastoma have the potential to guide treatment. Here, we explore the relationship between temozolomide (TMZ) response and O-6-methylguanine DNA methyltransferase (MGMT) status in brain tumor initiating cells (BTICs). Methylation, expression, and sensitivity were assessed in 20 lines; associations were evaluated by Fisher's exact test. Some BTICs were sensitive. Sensitivity to TMZ was only associated with protein expression (P = .001). There were atypical BTICs including TMZ-resistant lines in which the methylation-specific PCR reaction revealed both methylated and unmethylated bands. BTICs are not uniformly resistant to TMZ; some are sensitive. MGMT status does not predict TMZ response with high precision.