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Investigation for the proliferation mechanism of lung cancer stem cells

Research Project

Project/Area Number 23890020
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Thoracic surgery
Research InstitutionTohoku University

Principal Investigator

SUZUKI Takaya  東北大学, 加齢医学研究所, 非常勤講師 (80611996)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords癌幹細胞 / 海洋由来天然化合物 / マクロリド化合物 / 肺癌 / 肺癌幹細胞 / 海洋由来マクロリド化合物 / Erk / Akt / PKC / MAPキナーゼカスケード / Aktシグナル
Research Abstract

Previously we identified the lung specific tissue stem cells named alveolar epithelial progenitor cells (AEPCs). The novel marine macrolide (-)-exiguolide significantly inhibit the proliferation of AEPCs. We hypothesized that (-)-exiguolide inhibit proliferation of lung cancer stem cells. Global gene expression analysis suggested the involvement of protein kinase C (PKC), extracellular regulated kinase and phosphoinositide 3 kinase (PI3K)/Akt signalling pathway in the tumour inhibition of (-)-exiguolide. Western blotting analysis confirmed the potential activity of (-)-exiguolide; p21 up-regulation through PKCα activation, MEK inhibition and PI3K/Akt/GSK3β pathway modulation resulting in apoptosis.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • Research Products

    (23 results)

All 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (5 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Increased severity of H1N1 pandemic influenza virus infection in alveolar typeII cells from patients with pulmonary fibrosis2013

    • Author(s)
      Fujino N, Kubo H, Ota C, Suzuki T, Takahashi T, Yamada M, Suzuki S, Kondo T, Nagatomi R, Tando Y, Yamaya M.
    • Journal Title

      J Infect Dis

      Volume: 207 Pages: 692-693

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Total synthesis and biological evaluation of (-)-exiguolide analogues: Importance of the macrocyclic backbone2013

    • Author(s)
      Haruhiko Fuwa, Kana Mizunuma, Makoto Sasaki, Takaya Suzuki, Hiroshi Kubo
    • Journal Title

      Organic & Bimolecular Chemistry

      Volume: 11 Issue: 21 Pages: 3442-3450

    • DOI

      10.1039/c3ob40131f

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Administration of a specific inhibitor of neutrophil elastase attenuates pulmonary fibrosis after acute lung injury in mice2012

    • Author(s)
      Fujino N, Kubo H, Suzuki T, He M, Suzuki T, Yamada M, Takahashi T, Ota C, Yamaya M.
    • Journal Title

      Exp Lung Res

      Volume: 38 Pages: 28-36

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of gene expression profiles in alveolar epithelial type II-like cells differentiated from human alveolar epithelial progenitor cells2012

    • Author(s)
      Fujino N, Ota C, Suzuki T, Suzuki S, Hegab AE, Yamada M, Takahashi T, HeM, Kondo T, Kato H, Yamaya M, Kubo H.
    • Journal Title

      Respir Invest

      Volume: 50 Pages: 110-116

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Surgical stress increases circulating endothelial microparticles inthe elderly2012

    • Author(s)
      Takahashi T, Kubo H, Fujino N, Suzuki T, Ota C, Yamada M, Yamaya M, Suzuki S, Kurosawa S.
    • Journal Title

      Anaesthesia & Intensive Care

      Volume: 40 Pages: 899-902

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel method for isolating individual cellular components from the adult human distal lung2012

    • Author(s)
      Fujino N, Kubo H, Ota C, Suzuki T, Suzuki S, Yamada M, Takahashi T, He M, Suzuki T, Kondo T, Yamaya M.
    • Journal Title

      Am J Respir Cell Mol Biol

      Volume: 46 Pages: 422-430

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiles of alveolar type II cells of chronic obstructive pulmonary disease: A case-control study2012

    • Author(s)
      Fujino N, Ota C, Takahashi T, Suzuki T, Suzuki S, Yamada M, Nagatomi R, Kondo T, Yamaya M, Kubo H
    • Journal Title

      BMJ Open

      Volume: 2 Issue: 6 Pages: e001553-e001553

    • DOI

      10.1136/bmjopen-2012-001553

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility2012

    • Author(s)
      Takahashi T, Kobayashi S, Fujino N, Suzuki T, Ota C, He M, Yamada M, Suzuki S, Yanai M, Kurosawa S, Yamaya M, Kubo H.
    • Journal Title

      Thorax

      Volume: 67 Pages: 1067-1074

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Total synthesis and biological assessment of (-)-exiguolide and analogues2011

    • Author(s)
      Fuwa H, Suzuki T, Kubo H, Yamori T, Sasaki M.
    • Journal Title

      Chemistry-A European Journal

      Volume: 17 Pages: 2678-2688

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Theincrease in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury2011

    • Author(s)
      Yamada M, Kubo H, Kobayashi S, Ishizawa K, He M, Suzuki T, Fujino N, Kunishima H, Hatta M, Nishimaki K, Aoyagi T, Tokuda K, Kitagawa M, Yano H, Tamamura H, Fujii N, Kaku M.
    • Journal Title

      Cellular& Molecular Immunology

      Volume: 5 Pages: 305-314

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of alveolar epithelial type II progenitor cells from adult humanlungs2011

    • Author(s)
      Fujino N, Kubo H, Suzuki T, Ota C, Hegab AE, He M, Suzuki S, Suzuki T, Yamada M, Kondo T, Kato H, Yamaya M.
    • Journal Title

      Lab Invest

      Volume: 91 Pages: 363-378

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] RAGE binds phosphatidylserine and assists in the clearance of apoptotic cells2011

    • Author(s)
      He M, Kubo H, Morimoto K, Fujino N, Suzuki T, Takahashi T, Yamada M, Yamaya M, Maekawa T, Yamamoto Y, Yamamoto H.
    • Journal Title

      EMBO Reports

      Volume: 12 Pages: 358-364

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evidence for Human Lung Stem Cells (correspondence)2011

    • Author(s)
      Suzuki T, Kondo T, Kubo H.
    • Journal Title

      New Engl J Med

      Volume: 365 Pages: 464-466

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evidence for human lung stem cell (Correspondence)2011

    • Author(s)
      鈴木隆哉, 久保裕司, 近藤丘
    • Journal Title

      New England Journal of Medicine

      Volume: 365 Pages: 464-466

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total synthesis and biological assessment of (-)-exiguolide and analogues2011

    • Author(s)
      不破晴彦, 鈴木隆哉, 久保裕司, 他
    • Journal Title

      Chemistry-A Europian Journal

      Volume: 17 Pages: 2678-2688

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of alveolar epithelial type II progenitor cells from adult human lungs2011

    • Author(s)
      藤野直也, 久保裕司, 鈴木隆哉, 他
    • Journal Title

      Laboratory Investigation

      Volume: 91 Pages: 363-378

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] An anti-cancer effect of newly synthesized marine macrolide,(-)-Exiguolide2012

    • Author(s)
      Suzuki T, Kubo H, Yamada M, Fuwa H, Fujino N, Takahashi T, Ota C, Yamaya M, Kondo T.
    • Organizer
      Am J Respir Crit Care Med 2012;185:A6278
    • Place of Presentation
      サンフランシスコ,米国
    • Year and Date
      2012-05-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 海洋生物由来新規マクロリド化合物Exiguolideの抗腫瘍作用2011

    • Author(s)
      鈴木隆哉, 近藤丘
    • Organizer
      日本肺癌学会
    • Place of Presentation
      大阪
    • Year and Date
      2011-11-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] An anti-cancer effect of newly synthesized marine compounds. American Thoracic Society International Conference 20112011

    • Author(s)
      Suzuki T, Kubo H, Fuwa H, Kondo T.
    • Organizer
      Am J Respir Crit CareMed 2011;183:A5069
    • Place of Presentation
      デンバー,米国
    • Year and Date
      2011-05-17
    • Related Report
      2012 Final Research Report
  • [Presentation] An anti-cancer effect of newly synthesized marine macrolide, (-)-Exiguolide

    • Author(s)
      Suzuki, T
    • Organizer
      American Thoracic Society International Conference 2012
    • Place of Presentation
      サンフランシスコ・アメリカ合衆国
    • Related Report
      2012 Annual Research Report
  • [Presentation] 海洋由来新規マクロリド化合物Exiguolideの抗腫瘍作用

    • Author(s)
      鈴木隆哉
    • Organizer
      第65回日本胸部外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗がん作用を有するマクロライド化合物2011

    • Inventor(s)
      不破春彦,佐々木誠,久保裕司,鈴木隆哉
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Filing Date
      2011-10-23
    • Related Report
      2012 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 抗がん作用を有するマクロライド化合物2011

    • Inventor(s)
      不破春彦, 佐々木誠, 久保裕司, 鈴木隆哉
    • Industrial Property Rights Holder
      東北大学
    • Filing Date
      2011-10-23
    • Related Report
      2011 Annual Research Report
    • Overseas

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Published: 2011-09-05   Modified: 2019-07-29  

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