Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET
Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET
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DOI：
10.1007/s00280-018-3700-y
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发表时间：
2019-01-01
影响因子：
3
通讯作者：
Yatabe, Yasushi
中科院分区：
文献类型：
--
作者：
Hijioka, Susumu;Sakuma, Keiichiro;Yatabe, Yasushi
PurposeThis研究旨在确定DNA修复酶O 6-甲基鸟嘌呤DNA甲基转移酶（MGMT）的状态和对链脲佐菌素在晚期分化良好的胰腺神经内分泌肿瘤（WD panNETs.MethodsTo测试的假设，即MGMT缺陷是所需的烷化剂反应之间的相关性，我们回顾性审查了13例WD panNETs患者的烷化剂与MGMT状态。我们还研究了MGMT表达链脲佐菌素耐药panNET细胞line.ResultsThe队列包括54%的患者和46%的MGMT表达。其中，83.3%（5/6）的MGMT阴性病例显示对链脲佐菌素的部分反应。相比之下，只有14.2%（1/7）的MGMT阳性病例显示部分缓解（P=0.013）。在BON 1细胞（一种内源性MGMT检测不到的panNET细胞系）中诱导MGMT表达可产生链脲佐菌素耐药性。敲低MGMT在QGP 1细胞，表达MGMT内源性，并没有改变对streptozocin.ConclusionsWe观察到的患者和细胞培养中的MGMT状态和streptozocin反应之间的关系。尽管检查的病例有限，但MGMT阴性表达与对链脲佐菌素治疗的反应高度一致，表明MGMT表达可能是这种治疗的潜在生物标志物。
PurposeThis study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs).MethodsTo test the hypothesis that MGMT deficiency was required for an alkylating drug response, we retrospectively reviewed the response of 13 patients with WD panNETs to alkylating agents in relation to MGMT status. We also studied MGMT expression in streptozocin resistance using panNET cell lines.ResultsThe cohort included 54% of patients with and 46% without MGMT expression. Among these, 83.3% (5/6) of MGMT-negative cases showed a partial response to streptozocin. In contrast, only 14.2% (1/7) of MGMT-positive cases showed a partial response (P=0.013). Induced expression of MGMT in BON1 cells (a panNET cell line with undetectable endogenous MGMT) produced streptozocin resistance. Knockdown of MGMT in QGP1 cells, which express MGMT endogenously, did not alter the response to streptozocin.ConclusionsWe observed a relationship between MGMT status and streptozocin response in both patients and cell culture. Despite limited cases examined, high concordance of negative expression of MGMT and response to streptozocin treatment suggest that MGMT expression can be a potential biomarker for this treatment.