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Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study


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タイトル: Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study
著者: Baba, Hideo / Baba, Yoshifumi / Uemoto, Shinji / Yoshida, Kazuhiro / Saiura, Akio / Watanabe, Masayuki / Maehara, Yoshihiko / Oki, Eiji / Ikeda, Yasuharu / Matsuda, Hiroyuki / Yamamoto, Masakazu / Shimada, Mitsuo / Taketomi, Akinobu / Unno, Michiaki / Sugihara, Kenichi / Ogata, Yutaka / Eguchi, Susumu / Kitano, Seigo / Shirouzu, Kazuo / Saiki, Yasumitsu / Takamori, Hiroshi / Mori, Masaki / Hirata, Toshihiko / Wakabayashi, Go / Kokudo, Norihiro
発行日: 2015年 8月19日
出版者: Impact Journals LLC
引用: Oncotarget, 6(32), pp.34004-34013; 2015
抄録: Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression.
キーワード: Bevacizumab / Colorectal cancer / DPYD / ERCC1 / VEGFA
URI: http://hdl.handle.net/10069/36073
DOI: 10.18632/oncotarget.5227
権利: © Impact Journals, LLC. / This article is licensed under a Creative Commons Attribution 3.0 License.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:030 学術雑誌論文

引用URI : http://hdl.handle.net/10069/36073

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