EMT inhibitor for the treatment of idiopathic pulmonary fibrosis

2017 Fiscal Year Annual Research Report

• Project/Area Number: 26461200
• Research Institution: Juntendo University
• Principal Investigator: 高橋 史行 順天堂大学, 医学部, 准教授 (70327823)
• Co-Investigator(Kenkyū-buntansha): 高橋 和久 順天堂大学, 医学部, 教授 (80245711)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 特発性肺線維症 / 上皮間葉転換

Outline of Annual Research Achievements

特発性肺線維症（Idiopathic pulmonary fibrosis; IPF）は、肺において高度に線維化が進行する原因不明の難治性疾患である。近年、IPFにおける肺線維化の機序に上皮間葉転換 (Epithelial mesenchymal transition; EMT)の重要性が示唆されているが、いまだにEMTを標的とした有効なIPF治療法の開発・臨床応用には至っていない。本研究において我々はEMT阻害作用を有する薬剤Xを同定した。この薬剤はヒト肺胞上皮細胞A549におけるTFGb誘導性EMTを著明に抑制すること、またIn vivoでもブレオマイシン肺線維症モデルマウスにおける肺線維化を著明に抑制することを見出した。また薬剤Xの非活性側鎖にFGビーズを固定し、それらを用いて薬剤標的蛋白分子を同定した。

Research Products

• [Journal Article] Non-small cell lung carcinoma with diffuse co-expression of thyroid transcription factor-1 and ΔNp63/p40 (2018)
  • Author(s): Hayashi Takuo、Takamochi Kazuya、Yanai Yuka、Mitani Keiko、Tomita Hisashi、Mogushi Kaoru、Suehara Yoshiyuki、Takahashi Fumiyuki、Suzuki Kenji、Saito Tsuyoshi、Yao Takashi
  • Journal Title: Human Pathology Volume: S0046-8177 Pages: 30037-6
  • DOI: 10.1016/j.humpath.2018.01.023
  • Peer Reviewed
• [Journal Article] Surfactant protein-D predicts prognosis of interstitial lung disease induced by anticancer agents in advanced lung cancer: a case control study (2017)
  • Author(s): Nakamura Kota、Kato Motoyasu、Shukuya Takehito、Mori Keita、Sekimoto Yasuhito、Ihara Hiroaki、Kanemaru Ryota、Ko Ryo、Shibayama Rina、Tajima Ken、Koyama Ryo、Shimada Naoko、Nagashima Osamu、Takahashi Fumiyuki、Sasaki Shinichi、Takahashi Kazuhisa
  • Journal Title: BMC Cancer Volume: 17 Pages: 302
  • DOI: 10.1186/s12885-017-3285-6
  • Peer Reviewed
• [Journal Article] A method of high-throughput functional evaluation of EGFR gene variants of unknown significance in cancer (2017)
  • Author(s): Kohsaka Shinji、Nagano Masaaki、Ueno Toshihide、Suehara Yoshiyuki、Hayashi Takuo、Shimada Naoko、Takahashi Kazuhisa、Suzuki Kenji、Takamochi Kazuya、Takahashi Fumiyuki、Mano Hiroyuki
  • Journal Title: Science Translational Medicine Volume: 9 Pages: 416
  • DOI: 10.1126/scitranslmed.aan6566
  • Peer Reviewed
• [Journal Article] DNA mismatch repair deficiency in surgically resected lung adenocarcinoma: Microsatellite instability analysis using the Promega panel (2017)
  • Author(s): Takamochi Kazuya、Takahashi Fumiyuki、Suehara Yoshiyuki、Sato Eiichi、Kohsaka Shinji、Hayashi Takuo、Kitano Shigehisa、Uneno Toshihide、Kojima Shinya、Takeuchi Kengo、Mano Hiroyuki、Suzuki Kenji
  • Journal Title: Lung cancer Volume: 110 Pages: 26～31
  • DOI: 10.1016/j.lungcan.2017.05.016
  • Peer Reviewed
• [Presentation] Dasatinib Suppresses TGFβ-induced Epithelial Mesenchymal Transition and Inhibits Pulmonary Fibrosis. (2017)
  • Author(s): Kanemaru R, Kato M, Takahashi F, et al.
  • Organizer: Congress of American Thoracic Society (ATS)
  • Int'l Joint Research
• [Presentation] Bleomycin Induced Epithelial Mesenchymal Transition in Mice. (2017)
  • Author(s): Kato M, Takahashi F, et al.
  • Organizer: Congress of American Thoracic Society (ATS)
  • Int'l Joint Research