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Investigate the role of TNF and EGFR in the onset and progression of lung cancer complicated with COPD

Research Project

Project/Area Number 16K09590
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionShowa University

Principal Investigator

Yamaoka Toshimitsu  昭和大学, 先端がん治療研究所, 准教授 (40384359)

Co-Investigator(Kenkyū-buntansha) 大森 亨  昭和大学, 医学部, 准教授 (10276529)
荒田 悟  昭和大学, 教養部, 教授 (20159502)
佐々木 康綱  昭和大学, 医学部, 教授 (20235279)
本間 まゆみ  昭和大学, 医学部, 講師 (20527171)
楠本 壮二郎  昭和大学, 医学部, 助教 (30465091)
中嶌 賢尚  昭和大学, 医学部, 助教 (90365768)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺癌 / 上皮成長因子受容体 / 腫瘍壊死因子 / EGFR / TNF / 発癌 / COPD / 慢性閉塞性肺疾患
Outline of Final Research Achievements

Smoking in many cases can inevitably lead to chronic obstructive pulmonary disease (COPD) and the risk increases if tobacco is smoked continuously for 40 years at 20 cigarettes/day, which is a common level in regular smokers. COPD and tobacco smoke are independent risk factors for lung cancer, however, the mechanisms of carcinogenesis of the lung involving tobacco smoke or COPD are not clear. In this research we would like to provide some progress on understanding areas such as novel mutations or cytokine production in these fields. I would like to find some novel mutations or alterations of cytokines, which might induce lung cancer in this model mouse research and eventually if possible, it would be useful to confirm human tissue samples from those suffering lung cancer combined with COPD. Understanding the carcinogen pathway would then enable us to develop intervention treatment to either prevent or reduce the risks of COPD combined lung cancer in the future.

Academic Significance and Societal Importance of the Research Achievements

肺癌は、癌による死因の第1位であり、この難治性癌の新たな治療戦略の確立が急務である。慢性閉塞性肺疾患(COPD)は喫煙とは独立した肺癌の危険因子であり、喫煙とCOPDに伴う様々な分子が肺における発癌を促している事が示唆されているが、いまだ具体的なメカニズムは解明されていない。
本研究計画によってCOPD合併肺癌の基礎から臨床展開までの一貫した研究基盤を確立できると考える。この領域の研究成果は、COPDの死因として高い比率を閉める肺癌の予防策につながる可能性が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Receptor Tyrosine Kinase-Targeted Cancer Therapy2018

    • Author(s)
      Yamaoka Toshimitsu、Kusumoto Sojiro、Ando Koichi、Ohba Motoi、Ohmori Tohru
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 11 Pages: 3491-3491

    • DOI

      10.3390/ijms19113491

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] KRAS and EGFR Amplifications Mediate Resistance to Rociletinib and Osimertinib in Acquired Afatinib-Resistant NSCLC Harboring Exon 19 Deletion/T790M in EGFR2018

    • Author(s)
      Nakatani Kaori、Yamaoka Toshimitsu、Ohba Motoi、Fujita Ken-Ichi、Arata Satoru、Kusumoto Sojiro、Taki-Takemoto Iori、Kamei Daisuke、Iwai Shinichi、Tsurutani Junji、Ohmori Tohru
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 18 Issue: 1 Pages: 112-126

    • DOI

      10.1158/1535-7163.mct-18-0591

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular-Targeted Therapies for Epidermal Growth Factor Receptor and Its Resistance Mechanisms.2017

    • Author(s)
      Yamaoka T, Ohba M, Ohmori T.
    • Journal Title

      Int J Mol Sci

      Volume: 18 Issue: 11 Pages: 2420-2442

    • DOI

      10.3390/ijms18112420

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure.2017

    • Author(s)
      Yamaoka T, Ohba M, Arata S, Ohmori T.
    • Journal Title

      J Vis Exp

      Volume: 126 Issue: 126 Pages: 1-10

    • DOI

      10.3791/55967

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distinct Afatinib Resistance Mechanisms Identified in Lung Adenocarcinoma Harboring an EGFR Mutation.2017

    • Author(s)
      Yamaoka T, Ohmori T, Ohba M, Arata S, Murata Y, Kusumoto S, Ando K, Ishida H, Ohnishi T, Sasaki Y.
    • Journal Title

      Mol Cancer Res.

      Volume: 7 Pages: 915-928

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The acquired resistant mechanisms for sequential treatment of EGFR-TKI to Met-TKI/EGFR-TKI in a Met amplified EGFR-TKI resistant lung adenocarcinoma cells, harboring EGFR activating mutation.2016

    • Author(s)
      64.Yamaoka T., Ohmori T., Ohba M., Arata S., Kishino Y., Murata Y., Kusumoto S., Ishida H., Shirai T., Hirose T., Ohnishi T., and Sasaki Y.
    • Journal Title

      Mol. Cancer Ther.

      Volume: 15 Issue: 12 Pages: 3040-3054

    • DOI

      10.1158/1535-7163.mct-16-0313

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] GFR遺伝子変異陽性(exon19del/T790M)肺腺癌細胞株におけるオシメルチニブ獲得耐性機序2019

    • Author(s)
      山岡利光, 岸野康成, 楠本壮二郎, 鶴谷純司, 相良博典, 大森亨
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] KRAS amplification mediates resistance to osimertinib in acquired afatinib-resistant NSCLC harboring exon 19 deletion/T790M in EGFR2019

    • Author(s)
      Toshimitsu Yamaoka, Motoi Ohba, Yasunari Kishino, Sojiro Kusumoto, Junji Tsurutani, Tohru Ohmori
    • Organizer
      AACR 110th Annual Meeting 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EGFR-T790Mを発現した肺腺癌細胞における第3世代EGFR-TKI,ロシレチニブの獲得耐性機序の検討2018

    • Author(s)
      山岡利光,中谷香織, 大場基, 藤田健一, 岩井信市, 大森亨
    • Organizer
      第76回日本癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 次元培養法を用いたキナーゼ阻害剤の感受性評価.2018

    • Author(s)
      伊東 里紗, 鈴木 俊宏, 山岡 利光, 大森 亨, 西尾 和人, 小笠原 裕樹
    • Organizer
      第76回日本癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] T790M-EGFRにより アファチニブ耐性をきたした肺腺癌細胞株におけるロシレチニブ耐性機序の検討2018

    • Author(s)
      山岡利光,楠本壮二郎,安藤浩一,石田博雄,大西司,相良博典,大森亨
    • Organizer
      第59回日本肺癌学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] EGFR-Mutationを伴う肺腺癌細胞株におけるEGFR-TKIとMET-TKIへの獲得耐性機序2017

    • Author(s)
      山岡利光 大森亨 大場基 村田泰規 大木康成 楠本壮二郎 大西司 相良博典
    • Organizer
      第57回日本呼吸器学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] Distinct Afatinib Resistance Mechanisms Identified in Lung Adenocarcinoma Harboring an EGFR Mutation2017

    • Author(s)
      山岡利光 大場基 荒田悟 大森亨
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] EGFR遺伝子変異を有する肺腺癌細胞株PC-9におけるafatinib獲得耐性機序の検討2017

    • Author(s)
      山岡利光 大場基 荒田悟 大森亨
    • Organizer
      第58回日本肺癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] EGFR-Mutationを伴う肺腺癌細胞株におけるEGFR-TKIとMET-TKIへの獲得耐性機序2016

    • Author(s)
      山岡利光, 大森亨, 大場基, 村田 泰規, 楠本 壮二郎, 石田 博雄, 佐々木 康綱
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Mechanism underlying acquisition of dual resistance to EGFR and MET inhibitors by EGFR-mutant lung adenocarcinoma cells2016

    • Author(s)
      山岡利光, 大森亨, 大場基, 村田 泰規, 楠本 壮二郎, 石田 博雄, 佐々木 康綱
    • Organizer
      臨床腫瘍学会
    • Place of Presentation
      神戸
    • Year and Date
      2016-07-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Mechanism underlying acquisition of dual resistance to EGFR and MET inhibitors by EGFR-mutant lung adenocarcinoma cells2016

    • Author(s)
      Yamaoka T, Ohmori T, Ohba M, Kishino Y, Murata Y, Kusumoto S, Ishida H, Ohnishi T, Sasaki Y.
    • Organizer
      AACR
    • Place of Presentation
      ニューオリンズ・米国
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 昭和大学腫瘍分子生物学研究所

    • URL

      http://inst-mol-oncol.com/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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