Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer.
Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer.
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DOI：
10.1038/bjc.2012.502
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发表时间：
2012-12-04
影响因子：
8.8
通讯作者：
Beppu, T.
中科院分区：
文献类型：
--
作者：
Baba, H.;Watanabe, M.;Okabe, H.;Miyamoto, Y.;Sakamoto, Y.;Baba, Y.;Iwatsuki, M.;Chikamoto, A.;Beppu, T.
更新后的随机 2/3 期 FIRIS 研究证明，对于转移性结直肠癌，IRIS（伊立替康和 S-1）不劣于 FOLFIRI（伊立替康、亚叶酸和 5-FU）。同时，在包括既往接受过含奥沙利铂化疗的患者的子集分析中，IRIS组显示出比FOLFIRI组更长的生存期。然而，这一结果背后的分子机制仍不清楚。利用美国国家癌症研究所 60 (NCI60) 细胞系组数据来建立该假设。验证研究纳入了总共 45 名未接受过伊立替康且接受过肝切除术的转移性结直肠癌患者。通过定量 RT-PCR 评估切除修复交叉互补组 1 (ERCC1)、二氢嘧啶脱氢酶 (DPD) 和拓扑异构酶 1 (TOP1) 的 mRNA 表达。还通过免疫组织化学评估了 ERCC1 和 DPD 的表达。 60 个细胞系对奥沙利铂的敏感性与 5-FU 显着相关。奥沙利铂耐药细胞的 ERCC1 和 DPD 表达显着高于敏感细胞。在验证研究中，FOLFOX（奥沙利铂、亚叶酸和 5-FU）治疗的患者 (N=24) 的癌细胞中 ERCC1 和 DPD 但不包括 TOP1 的表达显着高于未治疗的患者 (N=21)。接受 FOLFOX 治疗的患者中 ERCC1 和 DPD 蛋白表达也显着升高。一线化疗患者中ERCC1和DPD的mRNA和蛋白表达水平显着高于未接受奥沙利铂的患者。与 FOLFIRI 相比，采用 DPD 抑制性氟嘧啶的 IRIS 方案可能对 DPD 高肿瘤（例如，用奥沙利铂治疗的肿瘤）表现出优异的活性。
The updated randomised phase 2/3 FIRIS study demonstrated the noninferiority of IRIS (irinotecan and S-1) to FOLFIRI (irinotecan, folinic acid, and 5-FU) for metastatic colorectal cancer. Meanwhile, in the subset analysis including patients who previously have undergone oxaliplatin-containing chemotherapy, the IRIS group showed longer survival than the FOLFIRI group. However, the molecular mechanism underlying this result is still unknown. The National Cancer Institute 60 (NCI60) cell line panel data were utilised to build the hypothesis. A total of 45 irinotecan-naive metastatic colorectal cancer patients who had undergone hepatic resection were included for the validation study. The mRNA expressions of excision repair cross-complementing group 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), and topoisomerase-1 (TOP1) were evaluated by quantitative RT–PCR. The expressions of ERCC1 and DPD were also evaluated by immunohistochemistry. Sensitivity to oxaliplatin in 60 cell lines was significantly correlated with that of 5-FU. Resistant cells to oxaliplatin showed significantly higher ERCC1 and DPD expression than sensitive cells. In validation study, ERCC1 and DPD but not TOP1 expressions in cancer cells were significantly higher in FOLFOX (oxaliplatin, folinic acid, and 5-FU)-treated patients (N=24) than nontreated patients (N=21). The ERCC1 and DPD protein expressions were also significantly higher in FOLFOX-treated patients. The ERCC1 and DPD expression levels at both mRNA and protein levels were significantly higher in patients with oxaliplatin as a first-line chemotherapy than those without oxaliplatin. The IRIS regimens with the DPD inhibitory fluoropyrimidine may show superior activity against DPD-high tumours (e.g., tumours treated with oxaliplatin) compared with FOLFIRI.
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影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
影响因子：
4.7
作者：
Losi, L;Baisse, B;Benhattar, J
通讯作者：
Benhattar, J
影响因子：
11.5
作者：
Baldus, Stephan E.;Schaefer, Karl-L.;Gabbert, Helmut E.
通讯作者：
Gabbert, Helmut E.
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.