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Investigation in the microenvironment of lung cancer and malignant pleural mesothelioma for the development of biomarker for the resistance to bevacizumab

Research Project

Project/Area Number 26461191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

GOTO Hisatsugu  徳島大学, 大学院医歯薬学研究部(医学系), 講師 (00437641)

Co-Investigator(Kenkyū-buntansha) 埴淵 昌毅  徳島大学, 大学院医歯薬学研究部(医学系), 准教授 (80335794)
柿内 聡司  徳島大学, 大学院医歯薬学研究部(医学系), 非常勤講師 (50380100)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺癌 / 悪性胸膜中皮腫 / 血管新生阻害薬 / 薬剤耐性 / 血管新生阻害剤
Outline of Final Research Achievements

This study aimed to clarify the mechanism of resistance to anti-angiogenic therapy in cancer. Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. In this study, using mouse model of malignant pleural mesothelioma, we found that fibroblast growth factor (FGF) 2 played important role in the resistance to bevacizumab. We identified fibrocytes as the producer of FGF2 in the tumor tissue. In clinical specimens of lung cancer, the number of fibrocyte was significantly increased in bevacizumab-treated tumors, and is correlated with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocytes as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (16 results)

All 2017 2016 2015 2014 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (4 results) Remarks (1 results)

  • [Journal Article] Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab2015

    • Author(s)
      Mitsuhashi A, Goto H, Saijo A, Trung VT, Aono Y, Ogino H, Kuramoto T, Tabata S, Uehara H, Izumi K, Yoshida M, Kobayashi H, Takahashi H, Gotoh M, Kakiuchi S, Hanibuchi M, Yano S, Yokomisa H, Sakiyama S, Nishioka Y
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 8792-8792

    • DOI

      10.1038/ncomms9792

    • NAID

      120006999406

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Fibrocytes mediate acquired resistance to anti-angiogenic therapy with bevacizumab in thoracic tumors.2016

    • Author(s)
      Goto H, Mitsuhashi A, Saijo A, Kuramoto T, Tabata T, Aono Y, Uehara H, Hanibuchi M, Nishioka Y.
    • Organizer
      ATS 2016 International Conference
    • Place of Presentation
      サンフランシスコ(アメリカ合衆国)
    • Year and Date
      2016-05-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms of acquired resistance to anti-angiogenic therapy and new insights toward the overcoming2015

    • Author(s)
      Yasuhiko Nishioka, Hisatsugu Goto
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] The role of fibrocytes in the resistance to anti-angiogenic therapy in malignant pleural mesothelioma and lung cancer2015

    • Author(s)
      Hisatsugu Goto, Atsushi Mitsuhashi, Atsuro Saijo, Yoshinori Aono, Hirokazu Ogino, Hirohisa Ogawa, Soji Kakiuchi, Masaki Hanibuchi, Yasuhiko Nishioka
    • Organizer
      International Conference of Cancer Immunotherapy and Macrophages 2015
    • Place of Presentation
      東京大学伊藤国際学術センター(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 線維細胞(fibrocytes)が関わる血管新生阻害剤に対する獲得耐性メカニズム2015

    • Author(s)
      三橋 惇志、後東 久嗣、西條 敦郎、埴淵 昌毅、西岡 安彦
    • Organizer
      第19回日本がん分子標的治療学会学術集会
    • Place of Presentation
      松山全日空ホテル(愛媛県松山市)
    • Year and Date
      2015-06-11
    • Related Report
      2015 Research-status Report
  • [Presentation] The Role of Fibrocytes in the Acquired Resistance to Anti-Angiogenic Therapy with Bevacizumab in Malignant Pleural Mesothelioma2015

    • Author(s)
      Hisatsugu Goto, Atsushi Mitsuhashi, Atsuro Saijo, Takuya Kuramoto, Sho Tabata, Yoshinori Aono, Hisanori Uehara, Soji Kakiuchi, Masaki Hanibuchi, Yasuhiko Nishioka
    • Organizer
      American Thoracic Society 2015 International Conference
    • Place of Presentation
      Denver(アメリカ合衆国)
    • Year and Date
      2015-05-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fibrocytes mediate acquired resistance to anti-angiogenic therapy with bevacizumab2015

    • Author(s)
      Hisatsugu Goto, Atsushi Mitsuhashi, Atsuro Saijo, Takuya Kuramoto, Sho Tabata, Yoshinori Aono, Soji Kakiuchi, Masaki Hanibuchi, Yasuhiko Nishioka
    • Organizer
      第55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(東京都千代田区)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Research-status Report
  • [Presentation] ベバシズマブに対する獲得耐性メカニズムとしての線維細胞(fibrocytes)の役割2014

    • Author(s)
      後東久嗣
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ベバシズマブに対する獲得耐性メカニズムとしての線維細胞(fibrocytes)の役割2014

    • Author(s)
      後東久嗣
    • Organizer
      第18回日本がん分子標的治療学会学術集会
    • Place of Presentation
      仙台市情報・産業プラザ(宮城県仙台市)
    • Year and Date
      2014-06-27
    • Related Report
      2014 Research-status Report
  • [Presentation] The role of fibrocytes in the resistance to anti-angiogenic therapy in malignant pleural mesothelioma and lung cancer.2014

    • Author(s)
      Hisatsugu Goto
    • Organizer
      ATS 2014 International Conference
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2014-05-21
    • Related Report
      2014 Research-status Report
  • [Presentation] 呼吸器疾患における慢性炎症と fibrocyte2014

    • Author(s)
      後東久嗣
    • Organizer
      第54回日本呼吸器学会学術講演会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2014-04-27
    • Related Report
      2014 Research-status Report
  • [Book] 分子呼吸器病2017

    • Author(s)
      後東久嗣,三橋惇志,西岡安彦
    • Total Pages
      119
    • Publisher
      先端医学社
    • Related Report
      2016 Annual Research Report
  • [Book] 分子呼吸器病2016

    • Author(s)
      後東久嗣,三橋敦志,西岡安彦
    • Total Pages
      137
    • Publisher
      先端医学社
    • Related Report
      2016 Annual Research Report
  • [Book] 呼吸と循環2016

    • Author(s)
      後東久嗣,青野純典,三橋惇志,西岡安彦
    • Total Pages
      208
    • Publisher
      医学書院
    • Related Report
      2016 Annual Research Report
  • [Book] 医学のあゆみ2015

    • Author(s)
      後東 久嗣、西岡 安彦
    • Total Pages
      70
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2015 Research-status Report
  • [Remarks] 徳島大学大学院医歯薬学研究部呼吸器・膠原病内科学分野ホームページ

    • URL

      http://www.sannai.umin.jp/

    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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