Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy.

Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy.
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DOI:
10.1038/clpt.2011.330
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发表时间:
2012-06
影响因子:
6.7
通讯作者:
--
中科院分区:
医学2区
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--
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ABCC2(MRP2;cMOAT)表达与体外顺铂耐药有关。在小鼠中,顺铂的处置和毒性不受 Abcc2 敲除的影响。此外,在癌症患者(n=237)中,顺铂的药代动力学(P>0.12)和疗效(P>0.41)与ABCC2中的7个SNP无关。这些 SNP 也与 NCI60 组中的 ABCC2 表达(P>0.26)或顺铂诱导的细胞毒性(P=0.21)不相关。这些发现强调了通过人体体外测试验证药物转运蛋白相互作用的重要性。
ABCC2 (MRP2; cMOAT) expression has been implicated in cisplatin resistance in vitro. In mice, cisplatin disposition and toxicity were unaffected by Abcc2 knockout. Moreover, in cancer patients (n=237), cisplatin pharmacokinetics (P>0.12) and efficacy (P>0.41) were not associated with 7 SNPs in ABCC2. These SNPs were also not correlated with ABCC2 expression in the NCI60 panel (P>0.26) or cisplatin-induced cytotoxicity (P=0.21). These findings highlight the importance of verifying drug-transporter interactions from in vitro tests in humans.
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