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Inhibitory role of Gas6-mediated innate immunity in intestinal tumorigenesis

Research Project

Project/Area Number 23590937
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionKyoto University

Principal Investigator

SENO Hiroshi  京都大学, 医学(系)研究科(研究院), 講師 (90335266)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords大腸 / 腸炎 / 腫瘍 / マウス / マクロファージ / 癌 / 炎症 / 大腸癌 / 自然免疫
Research Abstract

Commensal microbiota affects on the maintenance of systemic homeostasis by the interaction with innate immune cells. Growth arrest specific gene 6 (Gas6) regulates innate immune responses through Stat1/3 signaling. Genetic deletion of Gas6 ameliorated inflammation and tumor formation in the mouse intestines caused by AOM/DSS treatment or insertion of Apc gene mutation. Gas6 knockout mice with intestinal tumors showed significantly shorter survival compared to wild type littermates. As well, colorectal cancer patients with lower Gas6 expression showed shorter survival. These data suggested the importance of innate immunity in the treatment of colorectal cancer.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (18 results)

All 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (10 results) Book (1 results)

  • [Journal Article] Inhibitory Role of Gas6 in Intestinal Tumorigenesis.2013

    • Author(s)
      Yuki Nakanishi, et. al.
    • Journal Title

      Carcinogenesis

      Volume: (印刷中) Issue: 7 Pages: 1567-1574

    • DOI

      10.1093/carcin/bgt069

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dclk1 distinguishes between tumor and normal stem cells in the intestine.2013

    • Author(s)
      Yuki Nakanishi, et. al.
    • Journal Title

      Nature Genetics

      Volume: 45 Issue: 1 Pages: 98-103

    • DOI

      10.1038/ng.2481

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of Hes genes in intestinaldevelopment, homeostasis and tumorformation2012

    • Author(s)
      Ueo T, Imayoshi T, Kobayashi T, OhtsukaT, Seno H, Nakae H, Chiba T, Kageyama R
    • Journal Title

      Development

      Volume: 139 Issue: 6 Pages: 1071-1082

    • DOI

      10.1242/dev.069070

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signaling via enhanced ectodomain shedding of TNF-a2012

    • Author(s)
      Kanda K, Komekado H, Kawada M, et al
    • Journal Title

      EMBO Molecular Medicine

      Volume: (印刷中) Issue: 5 Pages: 396-411

    • DOI

      10.1002/emmm.201200216

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer2012

    • Author(s)
      Kawada M, et al
    • Journal Title

      Oncogene

      Volume: (印刷中) Issue: 26 Pages: 3111-3123

    • DOI

      10.1038/onc.2011.498

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] COX-2 inhibition alters the phenotype of tumor associated macrophages from M2 to M1 in ApcMin/+ mouse polyps2011

    • Author(s)
      Nakanishi Y, Seno H, Kawada M, et al
    • Journal Title

      Carcinogenesis

      Volume: 32(9) Issue: 9 Pages: 1333-1339

    • DOI

      10.1093/carcin/bgr128

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Indigenous Clostridium Species regulate systemic immune responses by induction of colonic regulatory T cells.2011

    • Author(s)
      Chiba T, Seno H.
    • Journal Title

      Gastroenterology

      Volume: 141 Issue: 3 Pages: 1114-1116

    • DOI

      10.1053/j.gastro.2011.07.013

    • Related Report
      2011 Research-status Report
  • [Presentation] Dclk1 discriminates between tumor and normal stem cells in the intestine.シンポジウムがん幹細胞研究に基づく新たながん治療戦略2013

    • Author(s)
      妹尾浩, 中西祐貴, 千葉勉
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸神戸国際会議場
    • Year and Date
      2013-12-04
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸腫瘍幹細胞特異的マーカーDclk1の同定. International Sessionsがん幹細胞2013

    • Author(s)
      中西祐貴, 上尾太郎, 妹尾浩
    • Organizer
      第72回日本癌学会総会
    • Place of Presentation
      横浜パシフィコ横浜
    • Year and Date
      2013-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Intestinal tumors are continuously renewed by Dclk1-positive tumor stem cells2013

    • Author(s)
      Nakanishi Y, Seno H, Chiba T
    • Organizer
      American Association of Cancer Research, Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA, Walter E. Washington Convention Center
    • Year and Date
      2013-04-10
    • Related Report
      2013 Final Research Report
  • [Presentation] 正常腸管および腸腫瘍におけるDclk1/Lgr5陽性細胞の役割2013

    • Author(s)
      中西祐貴, 妹尾浩, 上尾太郎
    • Organizer
      第99回日本消化器病学会総会
    • Place of Presentation
      鹿児島かごしま県民交流センター
    • Year and Date
      2013-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] The role of Dclk1-positive cells in the intestinal homeostasis2012

    • Author(s)
      Nakanishi Y, Seno H, Ueo T, Chiba T
    • Organizer
      2012 James W. Freston Single Topic Conference : Gastrointestinal Stem Cell Biology and Pathobiology
    • Place of Presentation
      Chicago, USA, Intercontinental Hotel Chicago
    • Year and Date
      2012-08-27
    • Related Report
      2013 Final Research Report
  • [Presentation] Dclk1 discriminates between tumor and normal stem cells in the intestine2012

    • Author(s)
      Seno H
    • Organizer
      GI Research Academy 2012
    • Place of Presentation
      Tokyo, Japan, Keidanren Hall
    • Year and Date
      2012-06-15
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸腫瘍幹細胞特異的マーカーDcamkl1の同定2012

    • Author(s)
      中西祐貴, 上尾太郎, 妹尾浩
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京京王プラザホテル
    • Year and Date
      2012-04-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Hes1は大腸上皮細胞の位置を規定し, ニッチ由来のWntやBMPシグナルによる分化制御に関与する2012

    • Author(s)
      上尾太郎, 妹尾浩, 仲瀬裕志:
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京京王プラザホテル
    • Year and Date
      2012-04-19
    • Related Report
      2013 Final Research Report
  • [Presentation] ナルディライジンはTNF-αのシェディングを促進し内因性サイトカインシグナル経路を活性化して胃癌細胞の増殖を制御する2011

    • Author(s)
      神田啓太郎、米門秀行、妹尾浩、千葉勉、西英一郎
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2011 Research-status Report
  • [Presentation] 腸腫瘍幹細胞特異的マーカーDcamkl1の同定

    • Author(s)
      中西祐貴
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Research-status Report
  • [Book] Proton pump inhibitors and gastrointestinal side effects. Proton Pump Inhibitors : A Balanced View. Front Gastrointest Res. Vol.322013

    • Author(s)
      Nakamura S, Seno H, Chiba T (Chiba T, Malfertheiner P, Satoh H (eds))
    • Publisher
      Basel, Karger
    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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