Inhibition of HMGB1 for the treatment of liver ischemia reperfusion injury

• Project/Area Number: 21791306
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: SHINODA Masahiro Keio University, 医学部, 助教 (50286499)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肝臓外科学 / HMGB1 / 肝虚血再灌流障害 / 人工肝臓 / 遺伝子治療 / 肝虚血再灌流 / サイトカイン / 治療 / 体外循環 / 吸着治療 / アデノウイルス / 遺伝子導入

Research Abstract

We established HMGB1 inhibitory substance producing hepatocytes, and HMGB1 inhibitory substance producing bioartificial liver, and HMGB1 adsorption column for the control of HMGB1 in liver ischemia reperfusion injury. We tested these modalities in animal models and found promising outcomes.

Research Products

• [Journal Article] Protective Effect of High-Mobility Group Box 1 Blockade on Acute Liver Failure in Rats. (2010)
  • Author(s): Takano K, Shinoda M, Tanabe M, Miyasho T, Yamada S, Ono S, Masugi Y, Suda K, Fukunaga K, Hayashida T, Hibi T, Obara H, Takeuchi H, Kawachi S, Kawasako K, Okamoto M, Yokota H, Maruyama I, Kitagawa Y
  • Journal Title: Shock 34 Pages: 573-579
  • Peer Reviewed
• [Journal Article] Protective Effect of High-Mobility Group Box 1 Blockade on Acute Liver Failure in Rats (2010)
  • Author(s): Takano K, Shinoda M, Tanabe M, et al.
  • Journal Title: Shock Volume: 34 Pages: 573-579
  • Peer Reviewed
• [Journal Article] Protective effect of high-mobility group box 1 blockade on acute liver failure in rats (2010)
  • Author(s): Kiminori Takano, Masahiro Shinoda
  • Journal Title: Shock 掲載決定
  • Peer Reviewed
• [Presentation] 急性肝不全患者における血清HMGB1とブタ肝不全モデルを用いたHMGB1吸着カラムの開発 (2011)
  • Author(s): 西山亮, 篠田昌宏, 田邉稔, 大島剛, 高野公徳, 海老沼浩利, 山田晋吾, 宮庄拓,須田康一, 松原健太郎, 尾原秀明, 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
  • Year and Date: 2011-03-18
• [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
  • Year and Date: 2011-03-17
• [Presentation] HMGB1制御による急性肝不全に対する新治療の開発 (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, 高柳淳, 山田晋吾,宮庄拓, 福永興壱, 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, 斎藤英胤, 日比紀文, 丸山征郎, 北川雄光
  • Organizer: 第1回HMGB1シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-02-26
• [Presentation] Highmobility group box-1に着目した急性肝不全治療の基礎的検討 (2010)
  • Author(s): 西山亮, 篠田昌宏, 田邉稔, 大島剛, 高野公徳, 海老沼浩利, 山田晋吾, 宮庄拓,須田康一, 松原健太郎, 尾原秀明, 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17回外科侵襲とサイトカイン研究会
  • Place of Presentation: 千葉
  • Year and Date: 2010-12-11
• [Presentation] High mobility group box-1に着目した急性肝不全治療の基礎的検討 (2010)
  • Author(s): 西山亮, 篠田昌宏, 田邉稔, 大島剛, 高野公徳, 海老沼浩利, 山田晋吾, 宮庄拓, 須田康一, 松原健太郎, 尾原秀明, 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17回外科侵襲とサイトカイン研究会
  • Place of Presentation: 千葉
  • Year and Date: 2010-12-11
• [Presentation] 急性肝不全患者における血清Highmobility group box1値とブタ肝不全モデルを用いたHMGB1吸着カラム開発の検討 (2010)
  • Author(s): 大島剛, 篠田昌宏, 田邉稔, 海老沼浩利,山田晋吾, 宮庄拓, 西山亮, 高野公徳,須田康一, 林田哲, 福永興壱, 山岸由幸,尾原秀明, 竹内裕也, 河地茂行, 齋藤英胤, 丸山征郎, 日比紀文, 北川雄光
  • Organizer: 第48回日本人工臓器学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2010-11-19
• [Presentation] 急性肝不全患者における血清High mobility group box 1値とブタ肝不全モデルを用いたHMGB1吸着カラム開発の検討 (2010)
  • Author(s): 大島剛, 篠田昌宏, 田邉稔, 海老沼浩利, 山田晋吾, 宮庄拓, 西山亮, 高野公徳, 須田康一, 林田哲, 福永興壱, 山岸由幸, 尾原秀明, 竹内裕也, 河地茂行, 齋藤英胤, 丸山征郎, 日比紀文, 北川雄光
  • Organizer: 第48回日本人工臓器学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2010-11-19
• [Presentation] High mobility group box 1 in acute liver failure patients and swines and establishment of an adsorption column. (2010)
  • Author(s): Oshima G, Shinoda M, Tanabe M, Ebinuma H, Takano K, Fuchimoto Y, Miyasho T, Yamada S, Suda K, Hibi T, Hayashida T, Fukunaga K, Obara H, Takeuchi H, Kawachi S, Mukai M, Hoshino K, Hibi T, Morikawa Y, Maruyama I, Kitagawa Y
  • Organizer: The American Association for the Study of Liver Diseases 61st Annual Meeting and Postgraduate Course
  • Place of Presentation: Boston (U.S.A)
  • Year and Date: 2010-11-02
• [Presentation] High mobility group box 1 in acute liver failure patients and swines and establishment of an adsorption column. (2010)
  • Author(s): Oshima G, Shinoda M, Tanabe M, Ebinuma H, Takano K, Fuchimoto Y, Miyasho T, Yamada S, Suda K, Hibi T, Hayashida T, Fukunaga K, Obara H, Takeuchi H, Karwachi S, Mukai M, Hoshino K, Hibi T, Morikawa Y, Maruyama I, Kitagawa Y.
  • Organizer: The American Association for the Study of Liver Diseases 61st Annual Meeting and Postgraduate Course
  • Place of Presentation: Boston
  • Year and Date: 2010-11-02
• [Presentation] 急性肝不全患者の血清HMGB1濃度とブタ肝不全モデルを用いたHMGB1吸着カラムの開発 (2010)
  • Author(s): 大島剛, 篠田昌宏, 田邉稔, 海老沼浩利,山田晋吾, 宮庄拓, 高野公徳, 須田康一,林田哲, 福永興壱, 山岸由幸, 竹内裕也, 河地茂行, 丸山征郎, 日比紀文, 北川雄光
  • Organizer: 第46回日本移植学会総会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-22
• [Presentation] 急性肝不全患者における血清HMGB1濃度とブタ肝不全モデルを用いたHMGB1吸着カラムの開発 (2010)
  • Author(s): 大島剛, 篠田昌宏, 田邉稔, 海老沼浩利,山田晋吾, 宮庄拓, 高野公徳, 須田康一,林田哲, 福永興壱, 山岸由幸, 尾原秀明,竹内裕也, 河地茂行, 齋藤英胤, 丸山征郎, 日比紀文, 北川雄光
  • Organizer: 第52回日本消化器病学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-14
• [Presentation] Serum high mobility group box 1 level in the patients with fulminant hepatic failure and its blockade in rat model. (2010)
  • Author(s): Shinoda M, Tanabe M, Oshima G, Takayanagi A, Miyasho T, Yamada S, Ebinuma H, Takano K, Hibi T, Suda K, Obara H, Takeuchi H, Kawachi S, Fukunaga K, Saito H, Hibi T, Maruyama I, Kitagawa Y
  • Organizer: The 4th International HMGB1 Symposium
  • Place of Presentation: Helsinki (Finland)
  • Year and Date: 2010-06-22
• [Presentation] Serum high mobility group box 1 level in the patients with fulminant hepatic failure and its blockade in rat model. (2010)
  • Author(s): Shinoda M, Tanabe M, Oshima G, Takayanagi A, Miyasho T, Yamada S, Ebinuma H, Takano K, Hibi T, Suda K, Obara H, Takeuchi H, Kawachi S, Fukunaga K, Saito H, Hibi T, Maruyama I, kitagawa Y.
  • Organizer: The 4th International HMGB1 Symposium
  • Place of Presentation: Helsinki
  • Year and Date: 2010-06-22
• [Presentation] Hemoabsorption of high-mobility group box 1 in swine fulminant hepatic failure model. (2010)
  • Author(s): Oshima G, Shinoda M, Tanabe M, Takano K, Fuchimoto Y, Miyasho T, Yamada S, Suda K, Fukunaga K, Obara H, Kawachi S, Mukai M, Hoshino K, Morikawa Y, Maruyama I, Kitagawa Y
  • Organizer: ILTS 16th Annual International Congress
  • Place of Presentation: Hong Kong (China)
  • Year and Date: 2010-06-18
• [Presentation] Protective effect of high-mobility group box 1 blockade on acute liver failure in rats. (2010)
  • Author(s): Takano K, Shinoda M, Tanabe M, Ono S, Miyasho T, Yamada S, Suda K, Fukunaga K, Hibi T, Obara H, Takeuchi H, Kawachi S, Yokota H, Maruyama I, Kitagawa Y
  • Organizer: ILTS 16th Annual International Congress
  • Place of Presentation: Hong Kong (China)
  • Year and Date: 2010-06-18
• [Presentation] Serum level of high mobility group box 1 in patients with fulminant hepatic failure and its blockade in rat model. (2010)
  • Author(s): Oshima G, Shinoda M, Tanabe M, Takayanagi A, Miyasho T, Yamada S, Ebinuma H, Takano K, Hibi T, Suda K, Obara H, Takeuchi H, Kawachi S, Fukunaga K, Hibi T, Maruyama I, Kitagawa Y
  • Organizer: ILTS 16th Annual International Congress
  • Place of Presentation: Hong Kong (China)
  • Year and Date: 2010-06-18
• [Presentation] Serum level of high mobility group box 1 in patients with fulminant hepatic failure and its blockade in rat model. (2010)
  • Author(s): Oshima G, Shinoda M, Tanabe M, Takayanagi A, Miyasho T, Yamada S, Ebinuma H, Takano K, Hibi T, Suda h, Obara H, Takeuchi H, Kawachi S, Fukunaga k, Hibi T, Maruyama I, Kitagawa Y.
  • Organizer: ILTS 16th Annual International Congress
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-18
• [Presentation] Protective effect of high-mobility group box 1 blockade on acute liver failure in rats. (2010)
  • Author(s): Takano K, Shinoda M, Tanabe M, Ono S, Miyasho T, Yamada S, Suda K, Fukunaga K, Hibi T, Obara H, Takeuchi H, Katiachi S, Yokota H, Maruyama I, kitagawa Y.
  • Organizer: ILTS 16th Annual International Congress
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-18
• [Presentation] Hemoabsorption of high-mobility group box 1 in swine fulminant hepatic failure model. (2010)
  • Author(s): Oshima G, Shinoda M, Tanabe M, Takano K, Fuchimoto Y, Miyasho T, Yamada S, Suda K, Fukunaga K, Obara H, Kawachi S, Mukai M, Hoshino K, Morikawa Y, Maruyama I, Kitagawa Y.
  • Organizer: ILTS 16th Annual International Congress
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-18
• [Presentation] 急性肝不全患者における血清中HMGB1動態の検討 (2010)
  • Author(s): 大島剛, 篠田昌宏, 田邉稔, 海老沼浩利,山田晋吾, 宮庄拓, 西山亮, 高野公徳,須田康一, 林田哲, 福永興壱, 山岸由幸,尾原秀明, 竹内裕也, 河地茂行, 齋藤英胤, 丸山征郎, 日比紀文, 北川雄光
  • Organizer: 第25回日本Shock学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-29
• [Presentation] 急性肝不全患者血清中High mobility group box-1動態の検討 (2010)
  • Author(s): 大島剛, 篠田昌宏, 田邉稔, 高野公徳,海老沼浩利, 須田康一, 竹内裕也, 山田晋吾, 宮庄拓, 福永興壱, 林田哲, 尾原秀明, 河地茂行, 日比紀文, 丸山征郎, 北川雄光
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-04-22
• [Presentation] Serum high-mobility group box 1 level in the patients with fulminant hepatic failure and its blockade effect in rat model. (2010)
  • Author(s): Oshima G, Shinoda M, Tanabe M, Takayanagi A, Miyasho T, Yamada S, Ebinuma H, Takano K, Hibi T, Suda K, Obara H, Takeuchi H, Kawachi S, Fukunaga K, Hibi T, Maruyama I, Kitagawa Y
  • Organizer: 45th Annual Meeting of the European Association for the Study of the Liver (EASL) -The International Liver Congress 2010-
  • Place of Presentation: Vienna (Austria)
  • Year and Date: 2010-04-17
• [Presentation] Serum high-mobility group box 1 level in the patients with fulminant hepatic failure and its blockade effect in rat model. (2010)
  • Author(s): Oshima G, Shinoda M, Tanabe M, Takayanagi A, Miyasho T, Yamada S, Ebinuma H, Takano K, Hibi T, Suda K, Obara H, Takeuchi H, Kawachi S, Eukunaga K, Hibi T, Maruyama I, Kitagawa Y.
  • Organizer: 45th Annual Meeting of the European Association for the Study of the Liver (EASL)-The International Liver Congress 2010-
  • Place of Presentation: Vienna
  • Year and Date: 2010-04-17
• [Presentation] ラット急性肝不全モデルに対するHigh Mobility Group Box 1制御の病態改善効果 (2010)
  • Author(s): 高野公徳, 篠田昌宏, 大島剛, 田邉稔,宮庄拓, 山田晋吾, 河地茂行, 日比泰造,竹内裕也, 石坂彰敏, 丸山征郎, 北川雄光
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-10
• [Presentation] 急性肝不全患者における血清High mobility group box-1動態の検討 (2010)
  • Author(s): 大島剛, 篠田昌宏, 田邉稔, 高野公徳,海老沼浩利, 須田康一, 竹内裕也, 山田晋吾, 宮庄拓, 福永興壱, 林田哲, 尾原秀明, 河地茂行, 日比紀文, 丸山征郎, 石坂彰敏, 北川雄光
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-10
• [Presentation] 急性肝不全におけるHigh mobility group box-1の役割 (2010)
  • Author(s): 篠田昌宏
  • Organizer: 第28回Cytoprotection研究会
  • Place of Presentation: 京都、ホテルグランヴィア京都
  • Year and Date: 2010-03-05
• [Presentation] 急性肝不全患者における血清中High mobility group box-1動態について (2010)
  • Author(s): 大島剛, 篠田昌宏
  • Organizer: 46回日本腹部救急医学会総会
  • Place of Presentation: 富山、富山国際会議場
  • Year and Date: 2010-03-05
• [Presentation] ラット、ブタ劇症肝炎モデルにおけるHigh Mobility Group Box1動態の検討 (2010)
  • Author(s): 高野公徳, 篠田昌宏
  • Organizer: 46回日本腹部救急医学会総会
  • Place of Presentation: 富山、富山国際会議場
  • Year and Date: 2010-03-05
• [Presentation] 急性肝不全患者の血清中High mobility group box-1動態についての検討 (2009)
  • Author(s): 大島剛, 篠田昌宏
  • Organizer: 第16回外科侵襲とサイトカイン研究会
  • Place of Presentation: 東京、東邦大学医療センター大森病院
  • Year and Date: 2009-12-19
• [Presentation] Protective effect of blocking high mobility group box 1 on acute liver failure in rat (2009)
  • Author(s): Kiminori Takano, Masahiro Shinoda
  • Organizer: The 60th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston,USA
  • Year and Date: 2009-10-31
• [Presentation] High-mobility group box 1 antibodies improve fulminant hepatic failire in rat model (2009)
  • Author(s): Kiminori Takano, Masahiro Shinoda
  • Organizer: American College of Surgeons 95th Annual
  • Place of Presentation: Chicago,USA
  • Year and Date: 2009-10-11
• [Presentation] 抗High Mobility Group Box1抗体投与はラット劇症肝炎モデルの病態を改善する (2009)
  • Author(s): 高野公徳, 篠田昌宏
  • Organizer: 第64回日本消化器外科学会総
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2009-07-17
• [Presentation] Anti-high mobility group box-1 antibody improved fulminant hepatic failure in a rat model (2009)
  • Author(s): Kiminori Takano, Masahiro Shinoda
  • Organizer: Transplantation Society 15th Annual International Gongress
  • Place of Presentation: New York,USA
  • Year and Date: 2009-07-08
• [Presentation] Anti-High Mobility Group Box Chromosomal Protein 1 Antibodies Improve Survival of Rats with Fulminant Hepatic Failure (2009)
  • Author(s): Kiminori Takano, Masahiro Shinoda
  • Organizer: American Transplant Congress 2009
  • Place of Presentation: Boston,USA
  • Year and Date: 2009-05-13
• [Presentation] ラット劇症肝不全モデルにおける抗High mobility group box-1抗体の予後改善効果の検討 (2009)
  • Author(s): 高野公徳, 篠田昌宏
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌、京王プラザホテル札幌
  • Year and Date: 2009-05-07
• [Presentation] 急性肝不全患者における血清High mobility group box-1動態の検討 (2009)
  • Author(s): 大島剛, 篠田昌宏
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌、京王プラザホテル札幌
  • Year and Date: 2009-05-07
• [Remarks] ホームページ等 なし
• [Patent(Industrial Property Rights)] ハイモビリティーグループタンパク吸着担体 (2010)
  • Inventor(s): 北川雄光、篠田昌宏、田邉稔, 他
  • Industrial Property Rights Holder: 東レ株式会社
  • Filing Date: 2010-05-27
• [Patent(Industrial Property Rights)] ハイモビリティーグループタンパク吸着担体 (2010)
  • Inventor(s): 北川雄光, 田邉稔, 他
  • Industrial Property Rights Holder: 東レ株式会社
  • Filing Date: 2010-05-27