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analysis of novel transcript variant of tyrosine kinase gene in thymic carcinoma

Research Project

Project/Area Number 18K08185
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionJuntendo University

Principal Investigator

Takahashi Kazuhisa  順天堂大学, 医学部, 教授 (80245711)

Co-Investigator(Kenkyū-buntansha) 田島 健  順天堂大学, 医学部, 准教授 (50384102)
茂櫛 薫  順天堂大学, 大学院医学研究科, 非常勤講師 (60569292)
高橋 史行  順天堂大学, 医学部, 准教授 (70327823)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords胸腺癌 / 遺伝子異常 / チロシンキナーゼ / スクリーニング解析 / 遺伝子解析 / 新規治療標的
Outline of Final Research Achievements

Thymic carcinoma accounts for 15% of all thymic neoplasms and is a highly lethal disease. Novel therapeutic strategies are urgently needed. In this study, we conducted comprehensive analyses by the NanoString nCounter for 93 tyrosine kinase (TK) genes using RNAs from the tumor tissues of thymic carcinoma patients (12 tumors from surgical specimens and 7 tumors from biopsy samples). We identified several novel transcript variants of TK genes by the NanoString nCounter analysis and RNA sequencing. These transcript variants of TK genes may be target for the treatment of thymic carcinoma, although further studies are necessary.

Academic Significance and Societal Importance of the Research Achievements

進行期胸腺癌では、プラチナ製剤併用、アンスラサイクリン系抗癌剤併用の治療レジメンが多く用いられてきたが、その奏功率は低く、予後は極めて不良である。現在、マルチキナーゼ阻害剤であるレンバチニブも既治療胸腺癌に対して適応拡大を受けている。しかし、胸腺癌治療については、その解析症例数の少なさや生存期間の短さから有望な治療標的遺伝子異常の同定や阻害剤の開発は十分に進んでいない現状である。本研究で同定された遺伝子転写変異体については胸腺癌において、まだ報告がなく、現在、極めて難治性疾患である胸腺癌患者の新規治療標的になる可能性がある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 8 results) Presentation (12 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Development of an optimal protocol for molecular profiling of tumor cells in pleural effusions at single-cell level2021

    • Author(s)
      Takeda Nakamura I, Ikegami M, Hasegawa N, Hayashi T, Ueno T, Kawazu M, Yagishita S, Goto Y, Shinno Y, Kojima Y, Takamochi K, Takahashi F, Takahashi K, Mano H, Kohsaka S
    • Journal Title

      Cancer Sci

      Volume: - Issue: 5 Pages: 2006-2019

    • DOI

      10.1111/cas.14821

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive functional evaluation of variants of fibroblast growth factor receptor genes in cancer.2021

    • Author(s)
      Takeda Nakamura I, Kohsaka S, Ikegami M, Ueno T, Li K, Beyett T, Koyama T, Shimizu T, Yamamoto N, Takahashi F, Takahashi K, Eck M, Mano H.
    • Journal Title

      NPJ Precision Oncology

      Volume: 16 Issue: 1 Pages: 66-66

    • DOI

      10.1038/s41698-021-00204-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zinc‐finger E‐box‐binding homeobox 1 (ZEB1) plays a crucial role in the maintenance of lung cancer stem cells resistant to gefitinib2021

    • Author(s)
      Nurwidya Fariz et al.
    • Journal Title

      Thoracic Cancer

      Volume: in press Issue: 10 Pages: 1536-1548

    • DOI

      10.1111/1759-7714.13937

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Highly sensitive fusion detection using plasma cell-free RNA in non-small-cell lung cancers.2021

    • Author(s)
      Hasegawa N, Kohsaka S, Kurokawa K, Shinno Y, Takeda Nakamura I, Ueno T, Kojima S, Kawazu M, Suehara Y, Ishijima M, Goto Y, Kojima Y, Yonemori K, Hayashi T, Saito T, Shukuya T, Takahashi F, Takahashi K, Mano H.
    • Journal Title

      Cancer Sci

      Volume: 112 Issue: 10 Pages: 4393-4403

    • DOI

      10.1111/cas.15084

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of insulin-like growth factor-1 receptor confers acquired resistance to osimertinib in non-small cell lung cancer with EGFR T790M mutation2020

    • Author(s)
      Hayakawa D, Takahashi F, Mitsuishi Y, Tajima K, Hidayat M, Winardi W, Ihara H, Kanamori K, Matsumoto N, Asao T, Ko R, Shukuya T, Takamochi K, Hayashi T, Suehara Y, Takeda Nakamura I, Ueno T, Kohsaka S, Mano H, Takahashi K
    • Journal Title

      Thorac Cancer

      Volume: 11 Issue: 1 Pages: 140-149

    • DOI

      10.1111/1759-7714.13255

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Novel CD74-NRG2α Fusion From Comprehensive Profiling of Lung Adenocarcinoma in Japanese Never or Light Smokers2020

    • Author(s)
      Kohsaka S, Hayashi T, Nagano M, Ueno T, Kojima S, Kawazu M, Shiraishi Y, Kishikawa S, Suehara Y, Takahashi F, Takahashi K, Suzuki K, Takamochi K, Mano H
    • Journal Title

      Journal of Thoracic Oncology

      Volume: - Issue: 6 Pages: 30098-8

    • DOI

      10.1016/j.jtho.2020.01.021

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological characteristics of lung adenocarcinoma with compound EGFR mutations.2020

    • Author(s)
      Hayashi T, Kohsaka S, Takamochi K, Hara K, Kishikawa S, Sano K, Takahashi F, Suehara Y, Saito T, Takahashi K, Suzuki K, Yao T.
    • Journal Title

      Human Pathology

      Volume: 14 Pages: 42-51

    • DOI

      10.1016/j.humpath.2020.07.007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comprehensive assay for the molecular profiling of cancer by target enrichment from formalin‐fixed paraffin‐embedded specimens2019

    • Author(s)
      Kohsaka Shinji、Tatsuno Kenji、Ueno Toshihide、et al.
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 4 Pages: 1464-1479

    • DOI

      10.1111/cas.13968

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] EGFR promotes glioma progression by regulating xCT and GluN2B-containing NMDA receptor signaling.2018

    • Author(s)
      Suina K, Tsuchihashi K, Yamasaki J, Kamenori S, Shintani S, Hirata Y, Okazaki S, Sampetrean O, Baba E, Akashi K, Takahashi F, Takahashi K, Saya H, Nagano O.
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 12 Pages: 3874-3882

    • DOI

      10.1111/cas.13826

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic Factors and Efficacy of First-Line Chemotherapy in Patients with Advanced Thymic Carcinoma2018

    • Author(s)
      Ko R, Shukuya T, Okuma Y, Tateishi K, Imai H, Iwasawa S, Miyauchi E, Fujiwara A, Sugiyama T, Azuma K, Muraki K, Yamasaki M, Tanaka H, Takashima Y, Soda S, Ishimoto O, Koyama N, Morita S, Kobayashi K, Nukiwa T, Takahashi K; North East Japan Study Group.
    • Journal Title

      Oncologist

      Volume: unknown Issue: 10 Pages: 1210-1217

    • DOI

      10.1634/theoncologist.2017-0586

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 胸水中浮遊腫瘍細胞の網羅的遺伝子解析2021

    • Author(s)
      中村育子、高阪真路、宿谷威仁、光石陽一郎、高橋史行、高橋和久、間野博行
    • Organizer
      第62回日本肺癌学会学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Activation of IGF1R receptor confers acquired resistance to osimertinib in EGFR-mutant NSCLC with T790M mutation.2021

    • Author(s)
      Daisuke Hayakawa, Fumiyuki Takahashi, Ken Tajima, Yoichiro Mitsuishi, Ikuko Takeda Nakamura, Wira Winardi, Yukina Shirai, Yosuke Miyashita, Tomoko Yamada, Keita Miura, Masahiro Torasawa, Hironari Matsuda, Tetsuhiko Asao, Takehito Shukuya, Kazuhisa Takahashi.
    • Organizer
      第80回日本癌学会学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Highly sensitive fusion detection using plasma cell-free RNA in non-small-cell lung cancers.2021

    • Author(s)
      Nobuhiko Hasegawa, Shinji Kohsaka, Kana Kurokawa, Yuki Shinno, Ikuko Nakamura, Toshihide Ueno, Yoshiyuki Suehara, Muneaki Ishijima, Yasushi Goto, Takuo Hayashi, Tsuyoshi Saito, Takehito Shukuya, Fumiyuki Takahashi, Kazuhisa Takahashi, Hiroyuki Mano.
    • Organizer
      第80回日本癌学会学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] インスリン様成長因子1受容体の活性化はT790M遺伝子変異陽性NSCLCにおけるオシメルチニブ耐性に寄与する2020

    • Author(s)
      早川乃介、髙橋史行、光石陽一郎、田島健、中村育子、松本直久、金森幸一郎、高遼、朝尾哲彦、宿谷威仁、嶋村尚子、和泉研太、Wira Winardi、白井由紀奈、虎澤匡洋、三浦啓太、藤岡雅大、高橋和久
    • Organizer
      第61回日本肺癌学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 進行EGFR遺伝子変異/ALK融合遺伝子陽性NSCLCにおける、治療開始後5年以降の経過の検討2020

    • Author(s)
      嶋村尚子,宿谷威仁,藤岡雅大,朝尾哲彦,白井由紀奈,三浦啓太, 和泉研太, 早川乃介,高遼,光石陽一郎,田島健,柴山里奈,嶋田奈緒子,髙橋史行,高橋和久
    • Organizer
      第61回日本肺癌学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 重複癌の既往と進行非小細胞肺癌に対する1次治療ペムブロリズマブの治療効果との関連の検討2020

    • Author(s)
      三浦啓太、宿谷威仁、朝尾哲彦、阿部瞳、白井由紀奈、和泉研太、早川乃介、松本直久、金森幸一郎、嶋村尚子、光石陽一郎、田島健、柴山里奈、嶋田奈緒子、高橋史行、高遼、高橋和久
    • Organizer
      第61回日本肺癌学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] SLC7A11 expression confers cancer stem-like properties in small cell lung cancer cells2019

    • Author(s)
      Kamenori S, Suina K, Yamasaki J, Shintani S, Otsuki Y, Hirata Y, Okazaki S, Tsuchihashi K, Sampetrean O, Mitsuishi Y, Takahashi F, Takahashi K, Saya H, Nagano O
    • Organizer
      American Association of Cancer Research(AACR) Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phase I study of afatinib plus bevacizumab in patients with advanced non-small cell lung cancer harboring EGFR mutations2019

    • Author(s)
      Tokito T, Ko R, Imamura C, Shukuya T, Shimada N, Koyama R, Yamada K, Ishii H, Azuma K, Takahashi K.
    • Organizer
      World Conference on Lung Cancer (WCLC)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Usefulness of elastography strain ratio for the evaluation of benign and malignant lesions during endobronchial ultrasound-guided transbronchial needle aspiration.2019

    • Author(s)
      Fujioka M, Takagi H, Motomura H, Hayashi M, Kuwasaki E, Asao T, Ichikawa M, Mitsuishi Y, Shimada N, Nagaoka T, Suzuki T, Takahashi K.
    • Organizer
      Asian Pacific Society of Respirology (APSR), International Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of histone deacetylase in the maintenance of gefitinib-resistant lung cancer stem cells with epidermal growth factor receptor mutation.2018

    • Author(s)
      Nurwidya F, Takahashi F, Hidayat M, Wirawan A, Baskoro H, Kato M, Tajima K, Shimada N, Andarini S.L, Yunus F, Takahashi K.
    • Organizer
      American Thoracic Society 2018 International Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pneumothorax in patients with idiopathic interstitial pneumonias.2018

    • Author(s)
      Haraguchi M, Kato M, Nakamura T, Horikoshi K, Yoshikawa H, Ihara H, Asao T, Okamoto S, Takagi H, Takahashi F, Sekiya M, Seyama K, Takahashi K.
    • Organizer
      American Thoracic Society 2018 International Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Usual interstitial pneumonia pattern in the lower lung lobes as a prognostic factor in idiopathic pleuroparenchymal fibroelastosis.2018

    • Author(s)
      Kono K, Kato M, Nakamura T, Yamada T, Tajima M, Ihara H, Tajima K, Shiota S, Takahashi F, Sasaki S, Seyama K, Takahashi K.
    • Organizer
      American Thoracic Society 2018 International Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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