Development of the tools for organ stress and its surgical application

• Project/Area Number: 22659237
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Hokkaido University
• Principal Investigator: TODO Satoru 北海道大学, 大学院・医学研究科, 特任教授 (60136463)
• Co-Investigator(Kenkyū-buntansha): OZAKI Michitaka 北海道大学, 大学院・保健科学研究院, 教授 (80256510)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,140,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 生体イメージング / 脂肪肝 / 肝ストレス / メタボリック症候群 / 肝障害 / 肝再生 / 光プローブ / 外科的ストレス / 光イメージング / 非侵襲的モニタリング / 動的解析 / ストレス測定 / 分子機能プローブ / 酸化的ストレス / 小胞体ストレス / Akt

Research Abstract

Steatotic liver, very sensitive to various surgical procedures, is associated with post-operative liver failure, impaired regeneration, post-operative infection and sepsis. In the present study, we analyzed whether the surgical stress affects the post-operativeliver function, injury and regeneration of steatotic liver by newly developed optic probes for bio-imaging. We evaluated mouse liver continuously and non-invasively and analyzed the underlying mechanism of post-operative liver injury and impaired regeneration.

Research Products

• [Journal Article] Stevens-Johnson syndrome/toxic epidermal necrolysis mouse model generated by using PBMCs and the skin of patients (2013)
  • Author(s): Saito N, Yoshioka N, Abe R, Qiao H, Fujita Y, Hoshina D, Suto A, Kase S, Kitaichi N, Ozaki M, Shimizu H.J
  • Journal Title: Allergy Clin Immunol Volume: 131(2) Pages: 434-41
  • Peer Reviewed
• [Journal Article] Immunosuppressive effects of DTCM-G, a novel inhibitor of the mTOR downstreamsignaling pathway (2013)
  • Author(s): Shibasaki S, Yamashita K, Goto R, Wakayama K, Tsunetoshi Y, Zaitsu M, Igarashi R, Haga S, Ozaki M, Umezawa K, Todo S
  • Journal Title: Transplantation Volume: 95(4) Pages: 542-50
  • Peer Reviewed
• [Journal Article] Pathophysiological Characteristics of Melanoma In-Transit Metastasis in a Lymphedema Mouse Model (2013)
  • Author(s): Kohei Oashi, Hiroshi Furukawa, Hiroshi Nishihara, Michitaka Ozaki, Akihiko Oyama,Emi Funayama, Toshihiko Hayashi, Yuji Kuge and Yuhei Yamamoto
  • Journal Title: Journal of Investigative Dermatology Volume: 133(2) Pages: 537-544
  • Peer Reviewed
• [Journal Article] Rapid Methods of Detecting the Target Molecule in immunohistology using a Bioluminescence Probe. Luminescence (2013)
  • Author(s): Chun Wu, Ke-Yong Wang, Xin Guo, Masanori Sato, Michitaka Ozaki, Shyohei Shimajiri, Yoshihiro Ohmiya, Yasuyuki Sasaguri.
  • Journal Title: The Journal of Biological and Chemical Luminescence Volume: 28(1) Pages: 38-43
  • Peer Reviewed
• [Journal Article] Rapid Methods of Detecting the Target Molecule in immunohistology using a Bioluminescence Probe. Luminescence (2013)
  • Author(s): Chun Wu, Ke-Yong Wang, Xin Guo, Masanori Sato, Michitaka Ozaki, Shyohei Shimajiri, Yoshihiro Ohmiya, Yasuyuki Sasaguri
  • Journal Title: The Journal of Biological and Chemical Luminescence Volume: 28 Pages: 38-43
  • Peer Reviewed
• [Journal Article] In vivo monitoring of liver damage by caspase-3 probe (2012)
  • Author(s): Michitaka Ozaki, Sanae Haga, Takeaki Ozawa
  • Journal Title: Theranostics Volume: 2(2) Pages: 207-214
  • NAID: 10031131094
  • Peer Reviewed
• [Journal Article] In vivo monitoring of liver damage by caspase-3 probe. (2012)
  • Author(s): Michitaka Ozaki, Sanae Haga, Takeaki Ozawa
  • Journal Title: Theranostics Volume: 2 Pages: 207-214
  • NAID: 10031131094
  • Peer Reviewed
• [Journal Article] Oxidative stress enhances granulocytic differentiation in HL 60 cells, an acute promyelocytic leukemia cell line (2010)
  • Author(s): Tetsuya Ogino, Michitaka Ozaki, Akihiro Matsukawa
  • Journal Title: Free Radical Research Volume: 44 Pages: 1328-1337
  • Peer Reviewed
• [Journal Article] p66Shc plays a pivotal role in impaired liver regeneration in aged mice by a redox-dependent mechanism (2010)
  • Author(s): Sanae Haga, Naoki Morita, Kaikobad Irani, Masato Fujiyoshi, Tetsuya Ogino, Michitaka Ozaki
  • Journal Title: Laboratory Investigation Volume: 90 Pages: 1718-1726
  • Peer Reviewed
• [Presentation] p62/STSQM1 plays a central role in liver injury in steatotic liver during regeneration (2012)
  • Author(s): 芳賀早苗、小澤岳昌、森田直樹、梅澤一夫、藤堂省、尾崎倫孝
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
  • Year and Date: 2012-12-06
• [Presentation] STAT3 plays a pivotal role in cell adhesion in mouse hepatocytes by regulating E-cadherin expression (2012)
  • Author(s): S.Haga, H.Inoue, A.Kano, X.-Y.Fu, K.Terui, M. Ozaki
  • Organizer: 25th European Congress of Pathology
  • Place of Presentation: Prague Congress Centre,Czecho
• [Presentation] Bioluminescent imaging of hepatic caspase-3 activity in mice (2012)
  • Author(s): Sanae Haga, Takeaki Ozawa, MichitakaOzaki
  • Organizer: 第14回国際組織細胞化学会議
  • Place of Presentation: 国立京都国際会館
• [Presentation] 虚血/再灌流傷害における高血糖および脂肪化病態肝の反応性の相違 (2012)
  • Author(s): 芳賀早苗、小澤岳昌、森田直樹、阿部理一郎、藤堂省、尾崎倫孝
  • Organizer: 第19回肝細胞研究会
  • Place of Presentation: 札幌医科大学臨床教育研究棟講堂
• [Presentation] Bio-imaging of surgical stress: Dynamic analysis of liver oxidative stress and damage (2012)
  • Author(s): N. Morita, S. Haga, T. Ozawa, S. J.Remington, M. Ozaki
  • Organizer: 17th International Symposium onBioluminescence and Chemiluminescence (ISBC2012)
  • Place of Presentation: Delta Guelph Hotel & Conference Centre, Guelph, Ontario, Canada
• [Presentation] 「虚血/再灌流傷害における高血糖および脂肪化病態肝の反応性の相違」 (2012)
  • Author(s): 芳賀早苗、小澤岳昌、森田直樹、阿部理一郎、藤堂省、尾崎倫孝
  • Organizer: 第19回肝細胞研究会
  • Place of Presentation: 札幌医科大学臨床教育研究棟講堂(札幌市）
• [Presentation] 肝再生機序解析の現状(正常肝、加齢肝、脂肪肝) (2011)
  • Author(s): 尾崎倫孝、芳賀早苗、森田直樹
  • Organizer: 第14回日本肝臓医生物学研究会
  • Place of Presentation: 東京医科歯科大学東京(招待講演)
  • Year and Date: 2011-02-19
• [Presentation] Molecular analysis of liver regeneration in mouse: roles of cell proliferation and growth MBSJ2011 (2011)
  • Author(s): Michitaka Ozaki, Sanae Haga, Hiroshi Inoue, Wataru Ogawa
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Analysis of different cellularresponses of cells in hyperglycemic condition or steatotic hepatocytes - a simulated study of stress response in metabolic syndrome - MBSJ2011 (2011)
  • Author(s): Sanae Haga, Takeaki Ozawa, Takako Aoyama, Naoki Morita, S.James Remington, Riichiro Abe, Michitaka Ozaki
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Age-associated p66Shc induced redox-dependent liver damage and impaired regeneration after hepatectomy in aged mice (2011)
  • Author(s): Michitaka Ozaki, Sanae Haga, Kaikobad Irani, Naoki Morita, Yoshimi Kaneshima, Takeaki Ozawa
  • Organizer: 62th Annual meeting of AASLD, San Francisco, USA
  • Place of Presentation: Moscone West ConventionCenter
• [Presentation] 脂肪肝におけるFas過剰発現および細胞内酸化的ストレスによる肝再生不全の検討 (2011)
  • Author(s): 芳賀早苗,森田直樹,青山貴子,小澤岳昌,RemingtonS.James,阿部理一郎,藤堂省、尾崎倫孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Bio-imaging of Surgical Stresses-Dynamic Analyses of Liver Oxidative Stress and Damage (2011)
  • Author(s): M. Ozaki, S. Haga, T. Ozawa, N. Morita, Y. Kaneshima, J. Remington
  • Organizer: 5TH European Conference of the International Federation for Medical andBiologicalEngineering
  • Place of Presentation: Budapest Congress & World Trade Center, Budapest, Hungary
• [Presentation] 'Collagen Vitrigel Sheet' as a Novel Drug Delivery Bio- material (2011)
  • Author(s): Sanae Haga, Toshiaki Takezawa, Takeaki Ozawa, James Remington, Naoki Morita and Michitaka Ozaki
  • Organizer: 5TH European Conference of the International Federation for Medical and Biological Engineering
  • Place of Presentation: Budapest Congress & World Trade Center, Budapest, Hungary
• [Presentation] 脂肪肝における肝再生不全機序の解析 (2011)
  • Author(s): 芳賀早苗、森田直樹、小澤岳昌、レミントンジェームズ、藤堂省、尾崎倫孝
  • Organizer: 第18回肝細胞研究会
  • Place of Presentation: 東京ガーデンパレス
• [Presentation] 「脂肪肝におけるFas過剰発現および細胞内酸化的ストレスによる肝再生不全の検討」 (2011)
  • Author(s): 芳賀早苗,森田直樹,青山貴子,小澤岳昌,Remington S.James,阿部理一郎,藤堂省、尾崎倫孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都府）
• [Presentation] 「脂肪肝における肝再生不全機序の解析」 (2011)
  • Author(s): 芳賀早苗、森田直樹、小澤岳昌、レミントン ジェームズ、藤堂省、尾崎倫孝
  • Organizer: 第18回肝細胞研究会
  • Place of Presentation: 東京ガーデンパレス（東京都）
• [Presentation] 種々の病態における肝再生の分子制御磯構の解析(細胞増殖・細胞成長・細胞死の観点から) (2011)
  • Author(s): 尾崎倫孝、芳賀早苗、森田直樹、金島由実、James Remington、小澤岳昌、井上啓、松本道宏
  • Organizer: 第18回肝細胞研究会
  • Place of Presentation: 東京ガーデンパレス
• [Presentation] 外科治療による肝細胞ストレスと障害・再生への影響(生体イメージング法をもちいた動的解析 (2011)
  • Author(s): 尾崎倫孝、芳賀早苗、森田直樹,青山貴子、金島由実、Kaikobad Irani、James Remington
  • Organizer: 第18回肝細胞研究会
  • Place of Presentation: 東京ガーデンパレス
• [Presentation] 発光プローブで病理診断に挑む (2010)
  • Author(s): 近江谷克裕、呉純、尾崎倫孝
  • Organizer: 第56回日本病理学会秋期特別総会
  • Place of Presentation: 西日本総合展示場福岡(招待講演)
  • Year and Date: 2010-11-25
• [Presentation] 臓器傷害・防御・再生におけるNFkB、Jak/STAT3、P13-K/PDK1/Aktの役割とその分子メカニズム (2010)
  • Author(s): 尾崎倫孝
  • Organizer: 第15回FSRCセミナー
  • Place of Presentation: 鹿児島大学医学部鹿児島(招待講演)
  • Year and Date: 2010-09-30
• [Presentation] Oxidative stress-mediated liver damage and impaired liver regeneration in partial hepatectomy model of fatty mouse (2010)
  • Author(s): Sanae Haga, Naoki Morita, Takeaki Ozawa, Remington S.James, Michitaka Ozaki
  • Organizer: BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
  • Place of Presentation: 神戸国際会議場神戸
• [Presentation] Analysis of impaired liver regeneration by bio-imaging of oxidative stress-mediated liver damage following partial resection of fatty liver (2010)
  • Author(s): 芳賀早苗, 森田直樹, 小澤岳昌, S.James Remington, 尾崎倫孝
  • Organizer: 第19回日本バイオイメージング学会学術集会
  • Place of Presentation: 慶應義塾大学横浜