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Functional analysis of small GTP binding protein Ral in colitis-associated cancer

Research Project

Project/Area Number 24590941
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKASE Hiroshi  京都大学, 医学(系)研究科(研究院), 講師 (60362498)

Research Collaborator HONZAWA Yusuke  
MATSUMURA Kayoko  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords炎症性腸疾患 / 炎症性大腸発がん / Ral / 自然免疫 / 炎症性大腸がん / サイトカイン / 炎症性大腸発癌 / IL-17 / IL-1beta
Outline of Final Research Achievements

The aim of this study is to elucidate the role of Small GTP binding protein Ral in development of colitis-associated cancer (CAC). We used Ral-GAPα2 KO mice (Ral continuously activated) for this study. The gene expression of pro-inflammatory cytokines was significantly up-regulated in colonic mucosa of Ral-GAPα2 KO mice than in wild type mice. Interestingly, Ral activation accelerated colonic inflammation of IL-10KO mice. In addition, we made CAC model by the injection of azoxymethane (AOM) with repeated administration of dextran sulfate sodium (DSS). The number of CAC with submucosal invasion was higher in Ral-GAPα2 KO mice treated with AOM and DSS than in wild type mice. These data indicate that Ral is involved in innate immune system and providing invasive phenotype in CAC.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (29 results)

All 2014 2013 2012 Other

All Journal Article (18 results) (of which Peer Reviewed: 17 results,  Open Access: 1 results) Presentation (10 results) (of which Invited: 6 results) Book (1 results)

  • [Journal Article] Efficacy and safety of granulocyte and monocyte adsorption apheresis for ulcerative colitis : a meta-analysis2014

    • Author(s)
      Yoshino T, Nakase H, Minami N, Yamada S, Matsuura M, Yazumi S, Chiba T
    • Journal Title

      Dig Liver Dis

      Volume: 46 Issue: 3 Pages: 219-26

    • DOI

      10.1016/j.dld.2013.10.011

    • NAID

      120005385891

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Use of capsule endoscopy in patients with Crohn's disease in Japan: a multicenter survey.2014

    • Author(s)
      Esaki M, Matsumoto T, Watanabe K, Arakawa T, Naito Y, Matsuura M, Nakase H, Hibi T, Matsumoto T, Nouda S, Higuchi K, Ohmiya N, Goto H, Kurokawa S, Motoya S, Watanabe M.
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 29(1) Issue: 1 Pages: 96-101

    • DOI

      10.1111/jgh.12411

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of interleukin-17A-induced expression of heat shock protein 47 in intestinal fibrosis in Crohn's disease2014

    • Author(s)
      Honzawa Y, Nakase H, Shiokawa M, Yoshino T, Imaeda H, Matsuura M, Kodama Y, Ikeuchi H, Andoh A, Sakai Y, Nagata K, Chiba T
    • Journal Title

      Gut

      Volume: 63 Issue: 12 Pages: 1902-12

    • DOI

      10.1136/gutjnl-2013-305632

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term efficacy of infliximab for refractory ulcerative colitis: results from a single center experience.2014

    • Author(s)
      Yamada S, Yoshino T, Minami N, Toyonaga T, Honzawa Y, Matsuura M, Nakase H.
    • Journal Title

      BMC Gastroenterol

      Volume: 14 Issue: 1 Pages: 80-80

    • DOI

      10.1186/1471-230x-14-80

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A randomized clinical trial of mesalazine suppository: The usefulness and problems of central review of evaluations of colonic mucosal findings.2014

    • Author(s)
      Kobayashi K, Hirai F, Naganuma M, Watanabe K, Ando T, Nakase H, Matsuoka K, Watanabe M.
    • Journal Title

      J Crohns Colitis

      Volume: 8 Issue: 11 Pages: 1444-1453

    • DOI

      10.1016/j.crohns.2014.05.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic effect of intensve granulocyte and monocyte adsorption apheresis combined with thiopurines for steroids and biologics naive Japanese patients with early-diagnosed Crohn's Disease2014

    • Author(s)
      Fukuchi T, Nakase H, Ubukata S, Matsuura M, Yoshino T, Toyonaga T, Koga H, Eguchi T, Yamashita H, Ito D, Ashida K.
    • Journal Title

      BMC Gastroenterol

      Volume: 13 Issue: 1 Pages: 124-124

    • DOI

      10.1186/1471-230x-14-124

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unique endoscopic findings of colitis-associated colorectal cancer in a patient with ulcerative colitis and Lynch syndrome2014

    • Author(s)
      Minami N, Yoshio T, Nakase H
    • Journal Title

      J Crohns Colitis

      Volume: 8 Issue: 4 Pages: 336-337

    • DOI

      10.1016/j.crohns.2013.11.009

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pulmonary Mycobacterium avium infection in a patient with2014

    • Author(s)
      Hirano T, Matsuura M, Nakase H
    • Journal Title

      Case Rep Gastroenterol

      Volume: 8 Issue: 2 Pages: 182-185

    • DOI

      10.1159/000363376

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mesenteric lymphoma with chylous ascites2014

    • Author(s)
      Arasawa S, Nakase H, Minami N
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 29 Issue: 8 Pages: 1570-1570

    • DOI

      10.1111/jgh.12635

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Unique endoscopic findings of colitis-associated cololectal cancer in a patient with ulcerative colitis and Lynch syndrome2014

    • Author(s)
      Minami N, Yoshino T, Nakase H
    • Journal Title

      J Crohns Colitis

      Volume: 8 Pages: 336-337

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of granulocye and monocyte adsorption apheresis for ulcerative colitis: a meta-analysis2014

    • Author(s)
      Yoshino T, Nakase H, MInami N, Yamada S, Matsuura M, Yazaumi S, Chiba T
    • Journal Title

      Dig Liver Dis

      Volume: 46 Pages: 219-26

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Refractoriness of intestinal Behçet's disease with myelodysplastic syndrome involving trisomy 8 to medical therapies - our case experience and review of the literature2013

    • Author(s)
      Toyonaga T, Nakase H, Matsuura M, Minami N, Yamada S, Honzawa Y, Hukata N, Yoshino T, Chiba T, Okazaki K
    • Journal Title

      Digestion

      Volume: 88 Issue: 4 Pages: 217-21

    • DOI

      10.1159/000355341

    • NAID

      120005385869

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heparan sulfate on intestinal epithelial cells plays a critical role in intestinal crypt homeostasis via Wnt/β-catenin signaling2013

    • Author(s)
      Yamamoto S, Nakase H, Matsuura M, Honzawa Y, Matsumura K, Uza N, Yamaguchi Y, Mizoguchi E, Chiba T
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 305 Issue: 3 Pages: G241-G249

    • DOI

      10.1152/ajpgi.00480.2012

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prior use of immunomodulatory drugs improves the clinical outcome of endoscopic balloon dilation for intestinal stricture in patients with Crohn's disease.2013

    • Author(s)
      Honzawa Y
    • Journal Title

      Digestive Endoscopy

      Volume: (印刷中) Issue: 5 Pages: 535-43

    • DOI

      10.1111/den.12029

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of Intensive Granulocyte and Monocyte Adsorptive Apheresis on Patients with Ulcerative Colitis Positive for Cytomegalovirus2013

    • Author(s)
      Fukuchi T
    • Journal Title

      Journal of Crohn’s and colitis

      Volume: -

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of a novel mouse model of ulcerative colitis with concomitant cytomegalovirus infection- in vivo identification of cytomegalovirus persistent infected cells in mouse ulcerative colitis-2013

    • Author(s)
      Matsumura K
    • Journal Title

      Inflamm Bowel Dis

      Volume: -

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mucosal PCR for diagnosis of cytomegalovirus infection in refractory ulcerative colitis2012

    • Author(s)
      Yoshino T
    • Journal Title

      Aliment Pharmacol Ther

      Volume: 36 Issue: 8 Pages: 811-812

    • DOI

      10.1111/apt.12009

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mediterranean mimicker2012

    • Author(s)
      Arasawa S
    • Journal Title

      Lancet

      Volume: 380 Issue: 9858 Pages: 2052-2052

    • DOI

      10.1016/s0140-6736(12)61377-4

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Asian Forum 1. The Current Status of IBD Care in Asia. Treatment of IBD in Asia2014

    • Author(s)
      Nakase H
    • Organizer
      The 2nd Annual meeting of AOCC
    • Place of Presentation
      Korea
    • Year and Date
      2014-06-19 – 2014-06-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] nvolvement of IL-34 in intestinal inflammation of Crohn’s disease2014

    • Author(s)
      Yoshino T, Matsuura M, Nakase H
    • Organizer
      The 2nd Annual meeting of AOCC
    • Place of Presentation
      Korea
    • Year and Date
      2014-06-19 – 2014-06-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Efficacy of Probiotic treatment with bifidobacterium longum 536 for induction of remission in active ulcerative colitis : a randomized multicenter trial.2014

    • Author(s)
      Tamaki H, Nakase H, Shibatoge M.
    • Organizer
      The 2nd Annual meeting of AOCC.
    • Place of Presentation
      Korea
    • Year and Date
      2014-06-19 – 2014-06-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] ここまでわかってきた炎症性腸疾患―現在そしてこれからの課題―急激に増えている腸の病気 潰瘍性大腸炎クローン病2014

    • Author(s)
      仲瀬裕志
    • Organizer
      埼玉市民公開講座
    • Place of Presentation
      埼玉
    • Year and Date
      2014-06-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Short and long-term outcome of severe ulcerative colitis patients treated with tacrolimus and infliximab2014

    • Author(s)
      Minami N, Yoshino T, Matsuura M, Nakase H
    • Organizer
      Digestive Disease Week 2014
    • Place of Presentation
      USA
    • Year and Date
      2014-05-02 – 2014-05-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] IFX治療後の難治性潰瘍性大腸炎の長期経過

    • Author(s)
      仲瀬 裕志
    • Organizer
      第85回日本消化器内視鏡学会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] 炎症性腸疾患における栄養管理の重要性

    • Author(s)
      仲瀬 裕志
    • Organizer
      第17回日本病態栄養学会年次学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 炎症性腸疾患治療と今後の課題

    • Author(s)
      仲瀬 裕志
    • Organizer
      日本内科学会東海支部 第53回生涯教育講演会
    • Place of Presentation
      浜松(アクトシティ浜松コングレスセンター)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 粘膜治癒を目指した潰瘍性大腸炎に対する治療法―ステロイドフリーの時代へー

    • Author(s)
      仲瀬 裕志
    • Organizer
      第114回日本消化器病学会北陸支部例会 第27回教育講演会
    • Place of Presentation
      福井(福井県民ホール)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 難治性炎症性腸疾患に対する今後の治療

    • Author(s)
      仲瀬 裕志
    • Organizer
      第98回日本消化器病学会近畿支部例会 第41回教育講演会
    • Place of Presentation
      神戸(神戸ポートピアホテル)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] 特集 炎症性腸疾患攻略の手引き2014

    • Author(s)
      仲瀬 裕志(監修・編集)
    • Total Pages
      199
    • Publisher
      東京:医学書院
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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