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However, the relationship between dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, and EGFR mutation status is unknown. Here, we focus on clinicopathologic factors and in vitro correlations between DPD expression and EGFR mutation status.\nPatients and Methods\nEGFR mutations and messenger RNA (mRNA) levels of DPD and thymidylate synthase (TS) were analyzed in 47 resected NSCLC tumors by laser-capture microdissection. In addition, relationships between EGFR mutation status and the immunohistochemical expression of DPD and TS in 49 patients with primary NSCLC who were treated with a 5-FU derivative of S-1 postoperatively were examined. Correlations among clinicopathologic factors were evaluated. The effect of epidermal growth factor on DPD expression was also investigated in vitro in various cell lines.\nResults\nAdenocarcinoma in situ showed significantly higher DPD mRNA levels and more EGFR mutation frequency than other histological types (P \u003c .05). 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High Expression of Dihydropyrimidine Dehydrogenase in Lung Adenocarcinoma is Associated With Mutations in Epidermal Growth Factor Receptor: Implications for the Treatment of Non?Small-Cell Lung Cancer Using 5-Fluorouracil
http://hdl.handle.net/10069/34284
http://hdl.handle.net/10069/3428440d0ab32-a0bc-43ce-86d4-344aab9fdc9e
名前 / ファイル | ライセンス | アクション |
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CLC15_136.pdf (869.2 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2014-04-21 | |||||
タイトル | ||||||
タイトル | High Expression of Dihydropyrimidine Dehydrogenase in Lung Adenocarcinoma is Associated With Mutations in Epidermal Growth Factor Receptor: Implications for the Treatment of Non?Small-Cell Lung Cancer Using 5-Fluorouracil | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Adenocarcinoma in situ | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Dihydropyrimidine dehydrogenase | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | epidermal growth factor receptor mutation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | epidermal growth factor receptor tyrosine kinase inhibitor | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Mochinaga, Koji
× Mochinaga, Koji× Tsuchiya, Tomoshi× Nagasaki, Toshiya× Arai, Junichi× Tominaga, Tetsuro× Yamasaki, Naoya× Matsumoto, Keitaro× Miyazaki, Takuro× Nanashima, Atsushi× Hayashi, Tomayoshi× Tsukamoto, Kazuhiro× Nagayasu, Takeshi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background It has been shown that 5-fluorouracil (5-FU) sensitivity in patients with non?small-cell lung cancer (NSCLC) is associated with epidermal growth factor receptor (EGFR) mutation status. However, the relationship between dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, and EGFR mutation status is unknown. Here, we focus on clinicopathologic factors and in vitro correlations between DPD expression and EGFR mutation status. Patients and Methods EGFR mutations and messenger RNA (mRNA) levels of DPD and thymidylate synthase (TS) were analyzed in 47 resected NSCLC tumors by laser-capture microdissection. In addition, relationships between EGFR mutation status and the immunohistochemical expression of DPD and TS in 49 patients with primary NSCLC who were treated with a 5-FU derivative of S-1 postoperatively were examined. Correlations among clinicopathologic factors were evaluated. The effect of epidermal growth factor on DPD expression was also investigated in vitro in various cell lines. Results Adenocarcinoma in situ showed significantly higher DPD mRNA levels and more EGFR mutation frequency than other histological types (P < .05). DPD immunopositive cases were more frequently observed in adenocarcinoma, in females, and in nonsmokers. DPD immunopositive cases were correlated with EGFR mutation status (P < .003). The prognoses of wild-type EGFR and mutated EGFR populations were similarly favorable with postoperative S-1 treatment, which overcomes the problem of 5-FU degradation in mutated EGFR. In vitro, EGFR-mutated cell lines showed high DPD mRNA and protein expression. Conclusion High DPD expression was shown to be correlated with EGFR mutation in adenocarcinoma cells and tissues. Clinicians should take this finding into consideration when using 5-FU to treat patients with NSCLC. |
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書誌情報 |
Clinical Lung Cancer 巻 15, 号 2, p. 136-144, 発行日 2014-03 |
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出版者 | ||||||
出版者 | Elsevier | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 15257304 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.cllc.2013.09.002 | |||||
権利 | ||||||
権利情報 | c 2014 Elsevier Inc. All rights reserved. | |||||
権利 | ||||||
権利情報 | NOTICE: this is the author’s version of a work that was accepted for publication in Clinical Lung Cancer. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Clinical Lung Cancer, 15, 2, (2014) | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Clinical Lung Cancer, 15(2), pp.136?144; 2014 |