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The development of new therapy for pulmonary fibrosis by using exogenous protein delivery system mimicked biological mechanism

Research Project

Project/Area Number 15K15322
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Respiratory organ internal medicine
Research InstitutionNagoya University

Principal Investigator

HASHIMOTO NAOZUMI  名古屋大学, 医学部附属病院, 講師 (30378020)

Co-Investigator(Kenkyū-buntansha) 長谷川 好規  名古屋大学, 医学系研究科, 教授 (20270986)
Research Collaborator Miyazaki Shinichi  名古屋大学, 大学院医学系研究科
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords分子細胞尾呼吸器学 / 線維芽細胞 / 細胞内導入デリバリーシステム / PTEN / 肺線維症 / 上皮細胞 / 微小環境 / 上皮間葉系移行
Outline of Final Research Achievements

We established the cells with the GFP-fused domain to induce secretion of PTEN (N173GFP). The additional kozak sequence to an alternative translation start site of PTEN improved the expression level of N173GFP. Although intracellular expression of N173GFP was detected, N151GFP, the secreted type of N173GFP, could not be detected in the culture media. To directly treat epithelial cells with exogenous PTEN, we established the cells which produce the GFP-fused secreted alternative domain of PTEN (N151GFP). When exogenous administration of GFPN151 to epithelial cells was performed in vitro, immunofluorescent evaluation could not show GFP expression in the cells. By not only the gene modification of alternative translation start site of PTEN to improve expression rate but also the determination of appropriate condition to improve recovery rate of secreted PTEN protein, we establish the new therapeutic strategy to regulate tissue microenvironment.

Report

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

    (11 results)

All 2016 2015

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

  • [Journal Article] Clinical impact of the lower limit of normal of FEV1/FVC on survival in lung cancer patients undergoing thoracic surgery2016

    • Author(s)
      Matsuzaki A, Hashimoto N, Okachi S, Taniguchi T, Kawaguchi K, Fukui T, Wakai K, Yokoi K, Hasegawa Y.
    • Journal Title

      Respir Investig

      Volume: 54 Pages: 184-192

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Impact of thin-section computed tomography-determined combined pulmonary fibrosis and emphysema on outcomes among patients with resected lung cancer2016

    • Author(s)
      Hashimoto N, Iwano S, Kawaguchi K, Fukui T, Fukumoto K, Nakamura S, Mori S, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y.
    • Journal Title

      Ann Thorac Surg

      Volume: 102 Pages: 440-447

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers2016

    • Author(s)
      Kohnoh T, Hashimoto N, Ando A, Sakamoto K, Miyazaki S, Aoyama D, Kusunose M, Kimura M, Omote N, Imaizumi K, Kawabe T, Hasegawa Y.
    • Journal Title

      Cancer Cell International

      Volume: 16 Pages: 33-42

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Factors Affecting the Diagnostic Yield of Transbronchial Biopsy Using Endobronchial Ultrasonography with a Guide Sheath in Peripheral Lung Cancer2016

    • Author(s)
      Okachi S, Imai N, Imaizumi K, Iwano S, Ando M, Hase T, Aso H, Morise M, Wakahara K, Ito S, Hashimoto N, Sato M, Kondo M, Hasegawa Y.
    • Journal Title

      Intern Med

      Volume: 55 Pages: 1705-1712

    • NAID

      130005161019

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Antineutrophil Cytoplasmic Antibody-associated Vasculitis Superimposed on Infection-related Glomerulonephritis Secondary to Pulmonary Mycobacterium avium Complex Infection2016

    • Author(s)
      Asano S, Mizuno S, Okachi S, Aso H, Wakahara K, Hashimoto N, Ito S, Kozaki Y, Katsuno T, Maruyama S, Hasegawa Y.
    • Journal Title

      Intern Med

      Volume: 55 Pages: 2439-2445

    • NAID

      130005262546

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Risk stratification by the lower limit of normal of FEV1/FVC for postoperative outcomes in patients with COPD undergoing thoracic surgery.2015

    • Author(s)
      Osuka S, Hashimoto N, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y.
    • Journal Title

      Respir Investig

      Volume: 53 Issue: 3 Pages: 117-123

    • DOI

      10.1016/j.resinv.2015.01.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Evaluation of emphysema using three-dimensional computed tomography: association with postoperative complications in lung cancer patients.2015

    • Author(s)
      Kawakami K, Iwano S, Hashimoto N, Hasegawa Y, Naganawa S.
    • Journal Title

      Nagoya J Med Sci

      Volume: 77 Pages: 113-122

    • NAID

      120005549557

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute respiratory distress syndrome in mice.2015

    • Author(s)
      Wakayama H, Hashimoto N, Matsushita Y, Matsubara K, Yamamoto N, Hasegawa Y, Ueda M, Yamamoto A
    • Journal Title

      Cytotherapy

      Volume: 17 Issue: 8 Pages: 1119-1129

    • DOI

      10.1016/j.jcyt.2015.04.009

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bronchus sign on thin-section computed tomography is a powerful predictive factor for successful transbronchial biopsy using endobronchial ultrasound with a guide sheath for small peripheral lung lesions: a retrospective observational study.2015

    • Author(s)
      Minezawa T, Okamura T, Yatsuya H, Yamamoto N, Morikawa S, Yamaguchi T, Morishita M, Niwa Y, Takeyama T, Mieno Y, Hoshino T, Uozu S, Goto Y, Hayashi M, Isogai S, Matsuo M, Nakanishi T, Hashimoto N, Okazawa M, Imaizumi K.
    • Journal Title

      BMC Medical Imaging

      Volume: 21 Pages: 21-21

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct regulation of transforming growth factor β-induced epithelial-mesenchymal transition by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells.2015

    • Author(s)
      Kusunose M, Hashimoto N, Kimura M, Ogata R, Aoyama D, Sakamoto K, Miyazaki S, Ando A, Omote N, Imaizumi K, Kawabe T, Hasegawa Y.
    • Journal Title

      Cancer Science

      Volume: 106 Issue: 12 Pages: 1693-704

    • DOI

      10.1111/cas.12831

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The PTEN protein, not lipid, phosphatase activity negatively regulate TGFβ-induced EMT in lung alveolar cells.2015

    • Author(s)
      Hashimoto N, Aoyama D, Hasegawa Y
    • Organizer
      The 2015 American Thoracic Society (ATS) International Conference
    • Place of Presentation
      デンバー、米国
    • Year and Date
      2015-05-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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