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Personalized therapy targeting Met gene in lung cancer

Research Project

Project/Area Number 17K09606
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Kasahara Kazuo  金沢大学, 医学系, 准教授 (30272967)

Co-Investigator(Kenkyū-buntansha) 曽根 崇  金沢大学, 医薬保健学総合研究科, 特任准教授 (30420334)
木村 英晴  金沢大学, 附属病院, 講師 (40444202)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordscMet / 非小細胞肺癌 / 個別化療法 / cMet / シグナル伝達 / HGF / Met阻害剤 / cMET / 発現解析 / 肺癌 / MET
Outline of Final Research Achievements

We examined cMet expression and phosphorylation in non-small cell lung cancer cell lines, and 5 cell lines had higher expression and enhanced phosphorylation of cMet. In the other five types, expression was weak and phosphorylation was low. When HGF was added, phosphorylation was enhanced in the Met-highly expressing cell line, but it disappeared in a short time. The effect of Met inhibitor was correlated with Met expression and phosphorylation status. Analysis of the downstream signals under HGF stimulation revealed that HGF stimulation increased the expression of 29 genes and decreased 138 genes. To date, we have collected tumor samples and clinical information for non-small cell lung cancer, but this study did not reveal a relationship between cMet and prognosis.

Academic Significance and Societal Importance of the Research Achievements

我々は、非小細胞肺癌細胞株を用いてcMet発現、リン酸化を検討したところ、5細胞我々は、非小細胞肺癌細胞株を用いcMet発現、リン酸化を検討したところ、5細胞株で高発現、リン酸化亢進を認めた。他の5種類では発現は弱くリン酸化も低かった。HGFを添加したところMet高発現細胞株でリン酸化亢進が認めたが、短時間で消失した。Met阻害剤の効果はMet発現とリン酸化状態に相関した。HGF刺激の元で下流シグナルを解析すると、HGF刺激で29遺伝子が発現増加し,138遺伝子は低下した。現在までに非小細胞肺癌の腫瘍検体と臨床情報を集積したが、今回の研究ではcMetと予後との関連は明らかにはならなかった。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results)

  • [Journal Article] Histopathological Type of Lung Cancer and Underlying Driver Mutations in Patients with Chronic Obstructive Pulmonary Disease (COPD) versus Patients with Asthma and COPD Overlap: A Single-Center Retrospective Study2020

    • Author(s)
      Sakai T、 Hara J、Yamamura K、Abo M、Okazaki A、Ohkura N、Kasahara K
    • Journal Title

      Turkish Thoracic Journal

      Volume: 21 Issue: 2 Pages: 75-79

    • DOI

      10.5152/turkthoracj.2019.18100

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Real-World Efficacy of First-Line Pembrolizumab in Patients With Advanced or Recurrent Non?Small-Cell Lung Cancer and High PD-L1 Tumor Expression2020

    • Author(s)
      Tambo Yuichi、Sone Takashi、Shibata Kazuhiko、Nishi Kouichi、Shirasaki Hiroki、Yoneda Taro、Araya Tomoyuki、Kase Kazumasa、Nishikawa Shingo、Kimura Hideharu、Kasahara Kazuo
    • Journal Title

      Clinical Lung Cancer

      Volume: XX Issue: 5 Pages: 1-4

    • DOI

      10.1016/j.cllc.2020.02.017

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Real-World Evidence of Safety and Efficacy of Carboplatin plus Nanoparticle Albumin-Bound Paclitaxel in Patients with Advanced Non-Small-Cell Lung Cancer and Preexisting Interstitial Lung Disease: A Retrospective Study.2019

    • Author(s)
      Araya T, Kita T, Ueda T, Terada N, Sakai T, Yamamura K, Kurokawa K, Uchida Y, Sone T, Kimura H, Kasahara K
    • Journal Title

      Canadian Respiratory Journal

      Volume: Mar Pages: 1-7

    • DOI

      10.1155/2019/5315903

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tissue and Plasma EGFR Mutation Analysis in the FLAURA Trial: Osimertinib versus Comparator EGFR Tyrosine Kinase Inhibitor as First-Line Treatment in Patients with EGFR-Mutated Advanced Non?Small Cell Lung Cancer2019

    • Author(s)
      Gray J E.、Okamoto I、Sriuranpong V、Vansteenkiste J、Imamura F、Lee J S、Pang YK、Cobo Ml、Kasahara K、Cheng Y、Nogami Ni、Cho E K、Su W C、Zhang Gi、Huang X、Li-Sucholeiki X、Lentrichia B、Dearden S、Jenkins S、Saggese Matilde、Rukazenkov Yuri、Ramalingam Suresh S.
    • Journal Title

      Clinical Cancer Research

      Volume: 25 Issue: 22 Pages: 6644-6652

    • DOI

      10.1158/1078-0432.ccr-19-1126

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Osimertinib for Japanese patients with T790M‐positive advanced non‐small‐cell lung cancer: A pooled subgroup analysis2019

    • Author(s)
      Hirashima Tomonori、Satouchi Miyako、Hida Toyoaki、Nishio Makoto、Kato Terufumi、Sakai Hiroshi、Imamura Fumio、Kiura Katsuyuki、Okamoto Isamu、Kasahara Kazuo、Uchida Hirohiko、Vowler Sarah L.、Mitsudomi Tetsuya
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 9 Pages: 2884-2893

    • DOI

      10.1111/cas.14120

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of EGFR mutation-positive lung adenocarcinoma in which the T790M allele fraction was increased by repeated EGFR-TKI treatment.2019

    • Author(s)
      Kimura H, Amino Y, Koba H, Tambo Y, Ohkura N, Hara J, Sone T, Kasahara K.
    • Journal Title

      Cancer Commun (Lond).

      Volume: 39 Issue: 1 Pages: 67-67

    • DOI

      10.1186/s40880-019-0413-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] KEYNOTE-025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1-positive advanced non-small-cell lung cancer2019

    • Author(s)
      Nishio Makoto、Takahashi Toshiaki、Yoshioka Hiroshige、Nakagawa Kazuhiko、Fukuhara Tatsuro、Yamada Kazuhiko、Ichiki Masao、Tanaka Hiroshi、Seto Takashi、Sakai Hiroshi、Kasahara Kazuo、Satouchi Miyako、Han Shi Rong、Noguchi Kazuo、Shimamoto Takashi、Kato Terufumi
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 3 Pages: 1012-1020

    • DOI

      10.1111/cas.13932

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Curative thoraco-systemic therapy plus local treatment to the brain for extensive disease-small-cell lung cancer with metastasis only to the brain2019

    • Author(s)
      Shibata Kazuhiko、Iwasa Keiichi、Takanaka Tsuyoshi、Yachi Tsuyoshi、Okazaki Akihito、Shiba Yasutaka、Kasahara Kazuo
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 49 Issue: 7 Pages: 687-690

    • DOI

      10.1093/jjco/hyz079

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes2018

    • Author(s)
      Watanabe Satoshi、Saeki Keigo、Waseda Yuko、Murata Akari、Takato Hazuki、Ichikawa Yukari、Yasui Masahide、Kimura Hideharu、Hamaguchi Yasuhito、Matsushita Takashi、Yamada Kazunori、Kawano Mitsuhiro、Furuichi Kengo、Wada Takashi、Kasahara Kazuo
    • Journal Title

      Journal of Thoracic Disease

      Volume: 10 Issue: 2 Pages: 799-807

    • DOI

      10.21037/jtd.2017.12.134

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of prostaglandin I2 in the bronchoconstriction-triggered cough response in guinea pigs2018

    • Author(s)
      Sakai Tamami、Hara Johsuke、Yamamura Kenta、Okazaki Akihito、Ohkura Noriyuki、Sone Takashi、Kimura Hideharu、Abo Miki、Yoshimura Kenichi、Fujimura Masaki、Kasahara Kazuo、Nakao Shinji
    • Journal Title

      Experimental Lung Research

      Volume: 44 Issue: 10 Pages: 455-463

    • DOI

      10.1080/01902148.2019.1590883

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Remission of psoriasis with nintedanib for the treatment of idiopathic pulmonary fibrosis2018

    • Author(s)
      Murata Akari、Watanabe Satoshi、Ikawa Yuka、Saeki Keigo、Yamamura Kenta、Matsuoka Hiroki、Tanimura Kota、Tambo Yuichi、Kasahara Kazuo
    • Journal Title

      The Journal of Dermatology

      Volume: 46 Issue: 4

    • DOI

      10.1111/1346-8138.14641

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] High ratio of T790M to EGFR activating mutations correlate with the osimertinib response in non-small-cell lung cancer2018

    • Author(s)
      Ariyasu Ryo、Nishikawa Shingo、Uchibori Ken、Oh-hara Tomoko、Yoshizawa Takahiro、Dotsu Yosuke、Koyama Junji、Saiki Masafumi、Sonoda Tomoaki、Kitazono Satoru、Yanagitani Noriko、Horiike Atsushi、Inase Naohiko、Kasahara Kazuo、Nishio Makoto、Katayama Ryohei
    • Journal Title

      Lung Cancer

      Volume: 117 Pages: 1-6

    • DOI

      10.1016/j.lungcan.2017.12.018

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of prostaglandin E 2 in bronchoconstriction-triggered cough response in guinea pigs2018

    • Author(s)
      Okazaki Akihito、Hara Johsuke、Ohkura Noriyuki、Fujimura Masaki、Sakai Tamami、Abo Miki、Katayama Nobuyuki、Kasahara Kazuo、Nakao Shinji
    • Journal Title

      Pulm Pharmacol Ther

      Volume: 48 Pages: 62-70

    • DOI

      10.1016/j.pupt.2017.09.003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Selective gene amplification to detect the T790M mutation in plasma from patients with advanced non-small cell lung cancer (NSCLC) who have developed epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance2018

    • Author(s)
      Shingo Nishikawa, Hideharu Kimura, Hayato Koba, Taro Yoneda, Satoshi Watanabe, Tamami Sakai, Johsuke Hara, Takashi Sone, Kazuo Kasahara, Shinji Nakao
    • Journal Title

      Journal of Thoracic Disease

      Volume: 10 Issue: 3 Pages: 1431-1439

    • DOI

      10.21037/jtd.2018.01.144

    • Related Report
      2017 Research-status Report
    • Peer Reviewed

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Published: 2017-04-28   Modified: 2021-02-19  

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