Identification of real target of VEGF receptor inhibitor which shows dramatic cytotoxic effect against pleural mesothelioma

• Project/Area Number: 19590900
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: YANO Seiji Kanazawa University, がん研究所, 教授 (30294672)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 胸膜中皮腫 / 血管新生 / 同所移植モデル / RET / チロシンキナーゼ阻害薬 / VEGF / 胸水 / 分子標的治療 / 抗体治療 / 抗癌剤

Research Abstract

胸膜中皮腫細胞株EHMES-10においてチロシンキナーゼ活性を有した蛋白(RET)が活性型変異の結果恒常的にリン酸化されており、VEGF 受容体阻害薬であるVandetanib がRETリン酸化を阻害し殺細胞活性を示すこと、SCID マウスにEHMES-10 を移植する同所移植モデルにおいても胸腔内腫瘤および胸水形成を著明に抑制し生存期間を有意に延長することを明らかにし、胸膜中皮腫に対する有用な分子標的薬になりうる可能性を示した。

Research Products

• [Journal Article] Intensification therapy of anti-parathyroid hormone-related protein antibody combined with zoledronic acid for bone metastasis of small cell lung cancer cells in severe combined immunodeficient mice (2009)
  • Author(s): Yamada T, Muguruma H, Yano S, Ikuta K, Ogino H, Kakiuchi S, Hanibuchi M, Uehara H, Nishioka Y, Sone S
  • Journal Title: Mol Cancer Ther 8 Pages: 119-126
  • Peer Reviewed
• [Journal Article] Combined chemotherapy with carboplatin plus irinotecan showed favo-rable efficacy in a case with relapsed small cell carcinoma of the prostate complicated with meningeal carcinomatosis. (2009)
  • Author(s): Yamada T, Yano S, et al.
  • Journal Title: Int J Clin Oncol (In press)
  • Peer Reviewed
• [Journal Article] Novel osteoblastic bone metastasis model with osteolytic changes for lung cancer in natural killer-cell depleted SCID mice. (2009)
  • Author(s): Ohtsuka S, Yano S, et al.
  • Journal Title: Oncol Res (In press)
  • Peer Reviewed
• [Journal Article] Novel dual targeting strategy with vandetanib induces tumor cell apoptosis and inhibits angiogenesis in malignant pleural mesothelioma cells expressing RET oncogenic rearrangement (2008)
  • Author(s): Ogino H, Yano S, Kakiuchi S, Yamada T, Ikuta K, Nakataki E, Goto H, Nishioka Y, Ryan A, Sone S
  • Journal Title: Cancer Letter 265 Pages: 55-66
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma cells with EGF receptor mutations (2008)
  • Author(s): Yano S, Wang W, Li Q, Matsumoto K, Sakurama H, Nakamura T, Ogino H, Kakiuchi S, Hanibuchi M, Nishioka Y, Uehara H, Mitsudomi T, Yatabe Y, Nakamura T, Sone S
  • Journal Title: Cancer Res 68 Pages: 9479-9487
  • Peer Reviewed
• [Journal Article] Follistatin suppresses the production of experimental multiple-organ metastasis by small cell lung cancer cells in NK cell-depleted SCID mice (2008)
  • Author(s): Ogino H, Yano S, Kakiuchi S, Muguruma H, Ikuta K, Uehara H, Tsuchida K, Sugino H, Sone S
  • Journal Title: Clin Cancer Res 14 Pages: 660-667
  • Peer Reviewed
• [Journal Article] Lysophosphoatidic acid stimulated proliferation and motility of malignant pleural mesothelioma cells through LPA receptors, LPA_1 and LPA_<2-> (2008)
  • Author(s): Yamada T, Yano S, Ogino H, Ikuta K, Kakiuchi S, Hanibuchi M, Taniguchi, Sekido Y, Sone S
  • Journal Title: Cancer Sci 99 Pages: 1603-1610
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma cells with EGF receptor mutations. (2008)
  • Author(s): Yano S, et al.
  • Journal Title: Cancer Res 68 Pages: 9479-9487
  • Peer Reviewed
• [Journal Article] Follistatin suppresses the production of experimental multiple-organ metast-asis by small cell lung cancer cells in NK cell-depleted SCID mice. (2008)
  • Author(s): Ogino H, Yano S, et al.
  • Journal Title: Clin Cancer Res 14 Pages: 660-667
  • Peer Reviewed
• [Journal Article] Novel dual targeting strategy with vandetanib induces tumor cell apoptosis and inhibits angiogenesis in malignant pleural mesothelioma cells expressing RET oncogenic rearrangement. (2008)
  • Author(s): Ogino H, Yano S, et al.
  • Journal Title: Cancer Letter 265 Pages: 55-66
  • Peer Reviewed
• [Journal Article] Lysophosphoatidic acid stimulated proliferation and motility of malignant pleural mesothelioma cells through LPA receptors, LPA_1 and LPA_2 (2008)
  • Author(s): Yamada T, Yano S, et al.
  • Journal Title: Cancer Sci 99 Pages: 1603-1610
  • Peer Reviewed
• [Journal Article] Intensification therapy of anti-parathyroid hormone-related protein anti-body combined with zoledronic acid for bone metastasis of small cell lung cancer cells in severe combined immunodeficient mice. (2008)
  • Author(s): Yamada T, Yano S, et al.
  • Journal Title: Mol Cancer Ther 8 Pages: 119-126
  • Peer Reviewed
• [Journal Article] Follistatin Suppresses the Production of Experimental Multiple-Organ Metastasis by Small Cell Lung Cancer Cells in Natural Killer Cell-Depleted SCID Mice (2008)
  • Author(s): Ogino H., et. al.
  • Journal Title: Clin Cancer Res 14 Pages: 660-667
  • Peer Reviewed
• [Journal Article] Novel dual targeting strategy with vandetanib induces tumor cell apoptosis and inhibits angiogenesis in malignant pleural mesothelioma cells expressing RET oncogenic rearrangement (2008)
  • Author(s): Ogino H., et. al.
  • Journal Title: Cancer Letters (in press)(掲載定)
  • Peer Reviewed
• [Journal Article] Levels of soluble vascular endothelial growth factor receptorl are elevated in the exudative pleural effusions (2007)
  • Author(s): Tomimoto, H., et. al.
  • Journal Title: J Med Invest 54 Pages: 146-153
  • Peer Reviewed
• [Journal Article] Autofluorescence bronchoscopy,a novel modality for the early detection of bronchial premalignant and malignant lesions (2007)
  • Author(s): Hanibuchi, M., et. al.
  • Journal Title: J Med Invest 54 Pages: 261-266
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis and its therapeutic modalities of lung cancer metastasis to bone (2007)
  • Author(s): Sone, S., et. al.
  • Journal Title: Cancer and Metastasis Reviews 26 Pages: 685-689
  • Peer Reviewed
• [Journal Article] The therapeutic efficacy of anti vascular endothelial growth factor antibody,bevacizumab,and pemetrexed against orthotopically implanted human pleural mesothelioma cells in severe combined immunodeficient mice (2007)
  • Author(s): Li Q., et. al.
  • Journal Title: Clin Cancer Res 13 Pages: 5918-5925
  • Peer Reviewed
• [Journal Article] Combined chemotherapy with carboplatin plus irinotecan showed favorable efficacy in a case with relapsed small cell carcinoma of the prostate complicated with meningeal carcinomatosis
  • Author(s): Yamada T, Ohtsubo K, Mouri H, Yamashita K, Yasumoto K, Izumi K, Zen Y, Watanabe H, Yano S
  • Journal Title: Int J Clin Oncol (in press)
  • Peer Reviewed
• [Journal Article] Novel osteoblastic bone metastasis model with osteolytic changes for lung cancer in natural killer-cell depleted SCID mice
  • Author(s): Otsuka S, Yano S, Hanibuchi M, Ikuta K, Ogino H, Yamada T, Kakiuchi S, Sone S
  • Journal Title: Oncol Res (in press)
  • Peer Reviewed
• [Presentation] 肝細胞増殖因子(HGF)はEGFR活性型遺伝子変異を有する肺腺癌のゲフィチニブ耐性を誘導する (2008)
  • Author(s): 矢野聖二、山田忠明、埴淵昌毅、柿内聡司、西岡安彦、光冨徹哉、谷田部恭、曽根三郎
  • Organizer: 第49回日本肺癌学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-11-13
• [Presentation] 肝細胞増殖因子(HGF)はEGFR活性型遺伝子変異を有する肺腺癌のゲフィチニブ耐性を誘導する. (2008)
  • Author(s): 矢野聖二
  • Organizer: 第49回日本肺癌学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-11-13
• [Presentation] EGFR-TKI耐性 (2008)
  • Author(s): 矢野聖二
  • Organizer: 第23回日本肺癌学会ワークショップ
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-07-19
• [Presentation] Respiratory year in review : 肺がんの分子標的治療 (2008)
  • Author(s): 矢野聖二
  • Organizer: 第48回日本呼吸器学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2008-06-15
• [Presentation] Respiratory year in review : 肺がんの分子標的治療. (2008)
  • Author(s): 矢野聖二
  • Organizer: 第48回日本呼吸器学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2008-06-15
• [Presentation] マウスモデルによる肺癌多臓器転移の分子機構解析 (2008)
  • Author(s): 矢野聖二
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢市
  • Year and Date: 2008-05-16
• [Presentation] Therapeutic strategy targeting angiogenic factors against pleural mesothelioma (2008)
  • Author(s): 矢野 聖二
  • Organizer: The U.S.-Japan Cooperateive Cancer Research Program Workshop 2008
  • Place of Presentation: 京都市平安会館
  • Year and Date: 2008-03-20
• [Presentation] Molecular pathogenesis of pleural mesothelioma and its molecular targeted therapy (2007)
  • Author(s): 矢野 聖二
  • Organizer: 第66回日本癌学会
  • Place of Presentation: パシフイコ横浜
  • Year and Date: 2007-10-04
• [Presentation] 中皮腫の分子病態と治療の展望 (2007)
  • Author(s): 矢野 聖二
  • Organizer: 第16回日本がん転移学会
  • Place of Presentation: 富山国際会議場
  • Year and Date: 2007-07-10
• [Presentation] Combination therapy by anti-VEGF antibody and pemetrexed against human pleural mesothelioma cells (2007)
  • Author(s): Li Qi, et. al.
  • Organizer: 第16回日本がん転移学会総会
  • Place of Presentation: 富山国際会議場
  • Year and Date: 2007-07-09
• [Presentation] 呼吸器悪性腫瘍とVEGF (2007)
  • Author(s): 矢野 聖二, ら
  • Organizer: 第47回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2007-05-12
• [Remarks]
  • URL: http://syuyounaika.w3.kanazawa-u.ac.jp/index.html
• [Remarks]
  • URL: http://syuyounaika.w3.kanazawa-u.ac.jp/index.html