JaLCDOI 10.18926/AMO/54499
フルテキストURL 70_4_243.pdf
著者 Osawa, Masahiro| Ohashi, Kadoaki| Kubo, Toshio| Ichihara, Eiki| Takata, Saburo| Takigawa, Nagio| Takata , Minoru| Tanimoto, Mitsune| Kiura, Katsuyuki|
抄録 Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p<0.01); resistance to vandetanib occurred at 20 weeks of age and the animals died from their lung tumors at about 28 weeks of age. These data suggest that vandetanib could suppress the progression of tumors harboring an activating EGFR mutation.
キーワード vandetanib VEGFR EGFR nonsmall cell lung cancer transgenic mouse
Amo Type Original Article
発行日 2016-08
出版物タイトル Acta Medica Okayama
70巻
4号
出版者 Okayama University Medical School
開始ページ 243
終了ページ 253
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
著作権者 CopyrightⒸ 2016 by Okayama University Medical School
論文のバージョン publisher
査読 有り
PubMed ID 27549668
Web of Sience KeyUT 000384748600003
タイトル(別表記) A prospective cohort study to define the clinical and pathological features of lung cancers harboring HER2 gene aberrations (the HER2-CS Study) and a phase II study of trastuzumab emtansine (recombinant) in patients with HER2-positive non-small cell lung cancer who recurred, progressed after standard chemotherapy, or were primarily refractory to standard chemotherapy
フルテキストURL 127_127.pdf
著者 木浦 勝行| 堀田 勝幸| 佐藤 晃子| 大橋 圭明| 二宮 崇| 南 大輔| 田端 雅弘| 久保 寿夫| 加藤 有加| 平田 泰三|
キーワード 臨床研究中核病院 国立研究開発法人日本医療研究開発機構 文部科学省橋渡し研究加速ネットワークプログラム HER2-CS study trastuzumab emtansine
備考 特集(Feature Articles)
出版物タイトル 岡山医学会雑誌
発行日 2015-08-03
127巻
2号
出版者 岡山医学会
出版者(別表記) Okayama Medical Association
開始ページ 127
終了ページ 132
ISSN 0030-1558
NCID AN00032489
資料タイプ 学術雑誌論文
関連URL isVersionOf https://doi.org/10.4044/joma.127.127
言語 Japanese
著作権者 Copyright (c) 2015 岡山医学会
論文のバージョン publisher
査読 有り
DOI 10.4044/joma.127.127
NAID 130005096256
Sort Key 9
Eprints Journal Name joma
参考文献 1) Ohnoshi T, Hiraki S, Kawahara S, Yamashita H, Yonei T, Ishii J, Egawa T, Kozuka A, Hiraki Y, Kimura I : Randomized trial comparing chemotherapy alone and chemotherapy plus chest irradiation in limited stage small cell lung cancer : a preliminary report. Jpn J Clin Oncol (1986) 16, 271-277. 2) Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, Brodin O, Joss RA, Kies MS, Lebeau B, Onoshi T, Østerlind K, et al. : A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med (1992) 327, 1618-1624. 3) Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M : Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol (2004) 22, 3852-3859. 4) Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, Watanabe Y, Sugimoto K, Shibayama T, Yonei T, Ueoka H, Takemoto M, et al. : Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer : OLCSG 0007. J Clin Oncol (2010) 28, 3299-3306. 5) EBMの手法による肺癌診療ガイドライン2014年版, 日本肺癌学会編, 金原出版, 東京 (2014) . 6) Kuyama S, Hotta K, Tabata M, Segawa Y, Fujiwara Y, Takigawa N, Kiura K, Ueoka H, Eguchi K, Tanimoto M : Impact of HER2 gene and protein status on the treatment outcome of cisplatin-based chemoradiotherapy for locally advanced non-small cell lung cancer. J Thorac Oncol (2008) 3, 477-482. 7) Mazières J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T, Moro-Sibilot D, Dansin E, et al. : Lung cancer that harbors an HER2 mutation : epidemiologic characteristics and therapeutic perspectives. J Clin Oncol (2013) 31, 1997-2003. 8) Suzuki M, Shiraishi K, Yoshida A, Shimada Y, Suzuki K, Asamura H, Furuta K, Kohno T, Tsuta K : HER2 gene mutations in non-small cell lung carcinomas : Concurrence with her2 gene amplification and her2 protein expression and phosphorylation. Lung Cancer (2015) 87, 14-22. 9) Remillard S, Rebhun LI, Howie GA, Kupchan SM : Antimitotic activity of the potent tumor inhibitor maytansine. Science (1975) 189, 1002-1005. 10) Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, Blättler WA, Lambert JM, Chari RV, Lutz RJ, Wong WL, Jacobson FS, et al. : Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res (2008) 68, 9280-9290. 11) Weiler D, Diebold J, Strobel K, Aebi S, Gautschi O : Rapid response to trastuzumab emtansine in a patient with HER2-driven lung cancer. J Thorac Oncol (2015) 10, e16-17.
著者 Yasugi, Masayuki| Takigawa, Nagio| Ochi, Nobuaki| Ohashi, Kadoaki| Harada, Daijiro| Ninomiya, Takashi| Murakami, Toshi| Honda, Yoshihiro| Ichihara, Eiki| Tanimoto, Mitsune| Kiura, Katsuyuki|
発行日 2014-08-15
出版物タイトル Experimental Cell Research
326巻
2号
資料タイプ 学術雑誌論文