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Development of a new effective therapy of ischemia reperfusion injury of liver and small intestine.

Research Project

Project/Area Number 23591875
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionKeio University

Principal Investigator

SINODA Masahiro  慶應義塾大学, 医学部, 講師 (50286499)

Co-Investigator(Kenkyū-buntansha) TANABE Minoru  慶應義塾大学, 医学部, 講師(非常勤) (50197513)
TAKAYANAGI Atsushi  慶應義塾大学, 医学部, 講師 (80245464)
NISHIYAMA Ryo  慶應義塾大学, 医学部, 助教 (70528322)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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)
KeywordsHMGB1 / sRAGE / 肝虚血再灌流 / 肝移植 / 肝細胞移植 / 肝虚血再灌流障害モデル / 移植・再生医療 / ウィルス / 遺伝子 / バイオリアクター
Research Abstract

It is clear that the development of an effective therapy, which would serve as a bridge to liver transplantation or regeneration, is needed to reduce the morbidity and mortality associated with ALF.We paid attention to High-mobility group box1(HMGB1) and sRAGE. HMGB1 has recently been identified as an important mediator of various kinds of acute and chronic inflammation and sRAGE is the soluble receptor of HMGB1.
Although it was difficult to make adenovirus vector which encoded amino acids of sRAGE, we suceeded in making adenovirus vector which encoded amino acids of HMGB1 Box-A protein known to act as a competitive inhibitor of HMGB1.Then,the vector was injcected via the portal vein in rats with acute liver failure.Transfected rats showed decreased hepatic enzymes, plasma HMGB1, and histological findings and survival were significantly improved.

Report

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

    (44 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (30 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Hemoadsorption of high-mobility group box chromosomal protein 1 using a column for large animals2014

    • Author(s)
      Nishiyama R, Shinoda M, Tanabe M, Oshima G, Takano K, Miyasho T, Fuchimoto Y, Yamada S, Inoue T, Shimada K, Suda K, Tanaka M, Hayashida T, Yagi H, Kitago M, Obara H, Itano O, Takeuchi H, Kawachi S, Maruyama I, Kitagawa Y
    • Journal Title

      Eur Surg Res

      Volume: 51(3-4) Pages: 181-190

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] HMGB1制御による急性肝不全に対する新治療の開発─診療に役立つ治療法の研究─2013

    • Author(s)
      篠田昌宏,田邉稔,大島剛,高野公徳,西山亮,田中真之,林田哲,八木洋,阿部雄太,北郷実,田中克典,尾原秀明,板野理,須田康一,竹内裕也,河地茂行,北川雄光
    • Journal Title

      日本腹部救急医学会雑誌

      Volume: 33(3) Pages: 535-542

    • NAID

      10031170932

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophil elastase inhibitor improves survival rate after ischemia reperfusion injury caused by supravisceral aortic clamping in rats2013

    • Author(s)
      Fujimura N, Obara H, Suda K, Takeuchi H, Miyasho T, Kawasako K, Du W, Yamada S, Ono S, Matsumoto K, Matsuda S, Yagi H, Kitago M, Shinoda M, Itano O, Tanabe M, Sakamoto M, Maruyama I, Kitagawa Y
    • Journal Title

      J Surg Res

      Volume: 180(1) Issue: 1 Pages: 31-36

    • DOI

      10.1016/j.jss.2012.04.037

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hemoadsorption of high-mobility group box chromosomal protein 1 using a column for large animals2013

    • Author(s)
      Nishiyama R, Shinoda M, Tanabe M, Oshima G, Takano K, Miyasho T, Fuchimoto Y, Yamada S, Inoue T, Shimada K, Suda K, Tanaka M, Hayashida T, Yagi H, Kitago M, Obara H, Itano O, Takeuchi H, Kawachi S, Maruyama I, Kitagawa Y
    • Journal Title

      Eur Surg Res

      Volume: 51(3-4) Issue: 3-4 Pages: 181-90

    • DOI

      10.1159/000357563

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased plasma levels of high mobility group box 1 in patients with acute liver failure2012

    • Author(s)
      Oshima G, Shinoda M, Tanabe M, Ebinuma H, Nishiyama R, Takano K, Yamada S, Miyasho T, Masugi Y, Matsuda S, Suda K, Fukunaga K, Matsubara K, Hibi T, Yagi H, Hayashida T, Yamagishi Y, Obara H, Itano O, Takeuchi H, Kawachi S, Saito H, Hibi T, Maruyama I, Kitagawa Y
    • Journal Title

      Eur Surg Res

      Volume: 48(3) Pages: 154-162

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of high mobility group box chromosomal protein 1 in ischemia-reperfusion injury in the rat small intestine2012

    • Author(s)
      Kojima M, Tanabe M, Shinoda M, Yamada S, Miyasho T, Suda K, Hibi T, Obara H, Itano O, Kawachi S, Kitajima M, Maruyama I, Kitagawa Y
    • Journal Title

      J Surg Res

      Volume: 178(1) Issue: 1 Pages: 466-71

    • DOI

      10.1016/j.jss.2012.01.044

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury.2012

    • Author(s)
      Arisue A, Shimojima N, Tomiya M, Shimizu T, Harada D, Nakayama M, Tomita H, Shinoda M, Tanabe M, Maruyama I, Mizuno M, Kuroda T, Wakabayashi G, Morikawa Y.
    • Journal Title

      Pediatr Surg Int.

      Volume: 28 Issue: 9 Pages: 913-918

    • DOI

      10.1007/s00383-012-3144-0

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alarmin (HMGB1) など―代表的Alarmin, HMGB1研究の今―2012

    • Author(s)
      篠田昌宏
    • Journal Title

      日本外科感染症学会雑誌

      Volume: 9 Pages: 335-341

    • Related Report
      2012 Research-status Report
  • [Journal Article] Suppressive effects of Interleukin-18 on liver function in rat liver allografts2012

    • Author(s)
      Ono S
    • Journal Title

      J Surg Res

      Volume: 176 Issue: 1 Pages: 293-300

    • DOI

      10.1016/j.jss.2011.07.053

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased plasma levels of high mobility group box 1 in patients with acute liver failure2012

    • Author(s)
      Oshima G, Shinoda M, Tanabe M, Ebinuma H, Nishiyama R, Takano K, Yamada S, Miyasho T, Masugi Y, Matsuda S, Suda K, Fukunaga K, Matsubara K, Hibi T, Yagi H, Hayashida T, Yamagishi Y, Obara H, Itano O, Takeuchi H, Kawachi S, Saito H, Hibi T, Maruyama I, Kitagawa Y
    • Journal Title

      Eur Surg Res

      Volume: 48(3) Issue: 3 Pages: 154-62

    • DOI

      10.1159/000338363

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of mizoribine in adult living donor liver transplantation2012

    • Author(s)
      Shinoda M
    • Journal Title

      Transplant Proc

      Volume: 44 Issue: 5 Pages: 1329-1335

    • DOI

      10.1016/j.transproceed.2012.01.139

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased plasma level of High-Mobility Group Box 1 in Acute Liver Failure Patients.2012

    • Author(s)
      Oshima G, Shinoda M, Tanabe M, et al.
    • Journal Title

      Eur Surg Res

      Volume: in press

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] ラット急性肝不全モデルにおけるHMGB1 A box遺伝子導入の効果2014

    • Author(s)
      篠田昌宏
    • Organizer
      第50回日本腹部救急医学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] HMGB1に着目した急性肝不全の病態理解と治療法の開発2013

    • Author(s)
      篠田昌宏,田中真之,西山亮,大島剛,高野公徳,海老沼浩利,高柳淳,山田晋吾,宮庄拓,須田康一,林田哲,八木洋,阿部雄太,日比泰造,北郷実,尾原秀明,竹内裕也,板野理,丸山征郎,田邉稔,北川雄光
    • Organizer
      第39回日本急性肝不全研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] HMGB1制御による急性肝不全に対する新治療の開発2013

    • Author(s)
      篠田昌宏,田邉稔,田中真之,西山亮,大島剛,高野公徳,海老沼浩利,高柳淳,山田晋吾,宮庄拓,須田康一,林田哲,八木洋,阿部雄太,日比泰造,北郷実,田中克典,尾原秀明,竹内裕也,板野理,丸山征郎,北川雄光
    • Organizer
      第40回日本集中治療医学会学術集会
    • Place of Presentation
      松本
    • Related Report
      2013 Final Research Report
  • [Presentation] HMGB1に着目した急性肝不全の病態理解と体外循環吸着療法の可能性2013

    • Author(s)
      田中真之, 篠田昌宏, 西山亮, 高野公徳, 高柳淳, 丸山征郎, 田邉稔, 北川雄光
    • Organizer
      第49回日本移植学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] HMGB1 A box domainの遺伝子導入方法の確立2013

    • Author(s)
      田中真之, 篠田昌宏, 高柳淳, 西山亮, 大島剛, 高野公徳, 山田晋吾, 宮庄拓, 須田康一, 林田哲, 八木洋, 阿部雄太, 日比泰造, 北郷実, 尾原秀明, 竹内裕也, 板野理, 丸山征郎, 田邉稔, 北川雄光
    • Organizer
      第40回日本臓器保存生物医学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ラット急性肝不全モデルにおけるHMGB1 A box遺伝子導入の効果2013

    • Author(s)
      雨宮隆介, 篠田昌宏, 田中真之, 高柳淳, 西山亮, 大島剛, 山田晋吾, 宮庄拓, 須田康一, 八木洋, 林田哲, 阿部雄太, 日比泰造, 北郷実, 尾原秀明, 竹内裕也, 板野理, 丸山征郎, 田邉稔, 北川雄光
    • Organizer
      第20回外科侵襲とサイトカイン研究会
    • Place of Presentation
      渋川
    • Related Report
      2013 Annual Research Report
  • [Presentation] 急性肝不全患者におけるHMGB1動態と動物モデルにおけるHMGB1制御の効果2012

    • Author(s)
      篠田昌宏,田邉稔,高野公徳,大島剛,西山亮,海老沼浩利,高柳淳,山田晋吾,宮庄拓,松原健太郎,須田康一,林田哲,八木洋,尾原秀明,竹内裕也,板野理,河地茂行,斉藤英胤,日比紀文,丸山征郎,北川雄光
    • Organizer
      第112回日本外科学会定期学術集会
    • Place of Presentation
      幕張
    • Related Report
      2013 Final Research Report
  • [Presentation] HMGB1 A box遺伝子導入ベクタ-の樹立とラット急性肝不全モデルにおける予後改善効果2012

    • Author(s)
      篠田昌宏,田邉稔,西山亮,高柳淳,大島剛,田中真之,山田晋吾,宮庄拓,須田康一,松原健太郎,八木洋,林田哲,北郷実,尾原秀明,竹内裕也,板野理,福永興壱,河地茂行,丸山征朗,北川雄光
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] HMGB1阻害タンパクA boxの遺伝子導入ベクタ-の確立とラット急性肝不全モデルにおける予後改善効果2012

    • Author(s)
      篠田昌宏,田邉稔,西山亮,高柳淳,大島剛,田中真之,山田晋吾,宮庄拓,須田康一,福永興壱,八木洋,林田哲,松原健太郎,北郷実,尾原秀明,竹内裕也,板野理,河地茂行,丸山征朗,北川雄光
    • Organizer
      第48回日本腹部救急医学会総会
    • Place of Presentation
      金沢
    • Related Report
      2013 Final Research Report
  • [Presentation] Gene Transfer of the A box domain of HMGB1 into the Liver in rat acute liver failure model2011

    • Author(s)
      Shinoda M, Tanabe M, Nishiyama R, Takayanagi A, Oshima G, Takano K, Yagi H, Kawachi S, Maruyama I, Kitagawa Y
    • Organizer
      97th American College of Surgeons Clinical Congress
    • Place of Presentation
      San Francisco
    • Related Report
      2013 Final Research Report
  • [Presentation] HMGB1制御による急性肝不全に対する新治療の開発~診療に役立つ治療法の研究~2011

    • Author(s)
      篠田昌宏,田邉稔,高野公徳,大島剛,西山亮,海老沼浩利,山田晋吾,宮庄拓,須田康一,竹内裕也,板野理,河地茂行,齋藤英胤,丸山征郎,日比紀文,北川雄光
    • Organizer
      第47回日本腹部救急医学会総会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Hemoadsorption of High-Mobility Group Box 1 in swine acute liver failure model.2011

    • Author(s)
      Nishiyama R, Shinoda M, tanabe M et, et al.
    • Organizer
      ASAIO 57th Annual Conference
    • Place of Presentation
      Washington, DC
    • Related Report
      2011 Research-status Report
  • [Presentation] Gene Transfer of the High Mobility Group Box 1 Inhibitor in Rat Acute Liver Failure Model.2011

    • Author(s)
      Shinoda M, Tanabe M, Takayanagi A, et al.
    • Organizer
      The 2011 Joint International Congress of ILTS, ELITA, & LICAGE
    • Place of Presentation
      Valencia
    • Related Report
      2011 Research-status Report
  • [Presentation] Hemoadsorption of high-mobility group box 1 in swine acute liver failure model.2011

    • Author(s)
      Nishiyama R, Shinoda M, Tanabe M, et al.
    • Organizer
      International Surgical Week ISW 2011
    • Place of Presentation
      Pacifico Yokohama(神奈川)
    • Related Report
      2011 Research-status Report
  • [Presentation] Gene Transfer of the A box domain of HMGB1 into the Liver in rat acute liver failure model.2011

    • Author(s)
      Shinoda M, Tanabe M, Nishiyama R, et al.
    • Organizer
      97th American College of Surgeons Clinical Congress
    • Place of Presentation
      San Francisco
    • Related Report
      2011 Research-status Report
  • [Presentation] Establishment of rat hepatocyte producing high mobility group box 1 inhibitor.2011

    • Author(s)
      Shinoda M, Nishiyama R, Tanabe M, et al.
    • Organizer
      XXXVIII Congress of the European Society for Artificial Organs (ESAO 2011) and IV Biennial Congress of the International Federation on Artificial Organs (IFAO 2011)
    • Place of Presentation
      Portugal
    • Related Report
      2011 Research-status Report
  • [Presentation] 急性肝不全患者におけるHMGB1動態と動物モデルにおけるHMGB1制御の効果

    • Author(s)
      篠田昌宏
    • Organizer
      第112回日本外科学会定期学術集会
    • Place of Presentation
      幕張
    • Related Report
      2012 Research-status Report
  • [Presentation] HMGB1 A box遺伝子導入ベクターの樹立とラット急性肝不全モデルにおける予後改善効果

    • Author(s)
      篠田昌宏
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] MGB1阻害タンパクA boxの遺伝子導入ベクターの確立とラット急性肝不全モデルにおける予後改善効果

    • Author(s)
      田中真之
    • Organizer
      第27回日本Shock学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Hemoadsorption of high-mobility group box 1 in swine acute liver failure model

    • Author(s)
      Shinoda M
    • Organizer
      American Transplant Congress 2012
    • Place of Presentation
      Boston
    • Related Report
      2012 Research-status Report
  • [Presentation] ラット急性肝不全モデルにおけるHMGB1 A box domainの肝への遺伝子導入とその効果

    • Author(s)
      田中真之
    • Organizer
      第38回日本急性肝不全研究会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] "ブタ急性肝不全モデルにおけるHigh mobility group box-1 吸着カラムの有用性の 検討"

    • Author(s)
      篠田昌宏
    • Organizer
      第30回日本肝移植研究会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Hemoadsorption of high-mobility group box 1 in swine acute liver failure mdoel

    • Author(s)
      Shinoda M
    • Organizer
      10th World Congress of the International Hepato-Pancreato-Biliary Association
    • Place of Presentation
      Paris
    • Related Report
      2012 Research-status Report
  • [Presentation] Gene transfer of the A box domain of high mobility group box 1 into the liver in rat acute liver failure model

    • Author(s)
      Shinoda M
    • Organizer
      10th World Congress of the International Hepato-Pancreato-Biliary Association
    • Place of Presentation
      Paris
    • Related Report
      2012 Research-status Report
  • [Presentation] 薬剤誘導性ラット劇症肝不全モデルの作成~DHLHISZnの病態改善効果検討へ向けて~

    • Author(s)
      田中真之
    • Organizer
      第3回癌・炎症とαリポ酸研究会
    • Place of Presentation
      由布
    • Related Report
      2012 Research-status Report
  • [Presentation] Gene transfer of A Box domain of High Mobility Group Box 1 in rat acute liver failure model

    • Author(s)
      Tanaka M
    • Organizer
      The 63rd Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Related Report
      2012 Research-status Report
  • [Presentation] Hemoadsorption of high-mobility group box 1 in a swine acute liver failure model

    • Author(s)
      Shinoda M
    • Organizer
      The 63rd Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Related Report
      2012 Research-status Report
  • [Presentation] HMGB1制御による急性肝不全に対する新治療の開発

    • Author(s)
      篠田昌宏
    • Organizer
      第40回日本集中治療医学会学術集会
    • Place of Presentation
      松本
    • Related Report
      2012 Research-status Report
  • [Presentation] 急性肝不全におけるHigh mobility group box-1吸着療法の基礎的検討

    • Author(s)
      篠田昌宏
    • Organizer
      第49回日本腹部救急医学会総会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] High mobility group box-1に着目した急性肝不全治療の基礎的検討

    • Author(s)
      篠田昌宏
    • Organizer
      第99回日本消化器病学会総会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Research-status Report
  • [Book] 慶應義塾大学における急性肝不全に対する成人ABO血液型不適合生体肝移植. ABO血液型不適合移植の新戦略―2013―, In :高橋公太,田中紘一Eds, 1Ed2013

    • Author(s)
      篠田昌宏,田邉稔,板野理,尾原秀明,北郷実,田中克典,阿部雄太,八木洋,日比泰造,藤野明浩,下島直樹,星野健,黒田達夫,北川雄光
    • Publisher
      日本医学館,東京
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] ハイモビリティーグループタンパク吸着担体2011

    • Inventor(s)
      島田薫,井上武大,北川雄光,篠田昌宏,田邉稔,西山亮
    • Industrial Property Rights Holder
      島田薫,井上武大,北川雄光,篠田昌宏,田邉稔,西山亮
    • Filing Date
      2011
    • Acquisition Date
      2012
    • Related Report
      2011 Research-status Report

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

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