Cellular and molecular target therapy for hepatic ischemia-reperfusion injury

• Project/Area Number: 21591748
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hiroshima University
• Principal Investigator: TASHIRO Hirotaka 広島大学, 大学院・医歯薬学総合研究科, 准教授 (90359894)
• Co-Investigator(Kenkyū-buntansha): KIMURA Yasuhiro 広島大学, 大学院・医歯薬学総合研究科, 准教授 (80314756)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝虚血再灌流障害 / 肝星細胞 / Rhoキナーゼ阻害剤 / リポソーム / ビタミンA / 肝虚血再潅流障害 / 分子・細胞標的治療

Research Abstract

We have developed the vitamine A-coupled liposomes containing Rho kinase inhibitor to attenuate the hepatic ischemia-reperfusion injury in rat. First, GFP was specifically detected in the sinusoidal linings when the vitamine A-coupled liposome containing GFP was administered systemically. We have also confirmed that the liposomes have ameliorated the ischemia-reperfusion injuries at the dose of one-hundreds compared with alone Rho kinase inhibitor, with attenuating the side effects such as a hypotension

Research Products

• [Journal Article] Rho inhibitor prevents ischemia-reperfusion injury in the rat steatotic liver (2012)
  • Author(s): Kuroda S, Tashiro H, Igarashi Y, Tanimoto Y, Nambu J, Oshita A, Kobayashi T, Amano H, Tanaka Y, Ohdan H.
  • Journal Title: J Hepatology Volume: 56 Pages: 146-152
  • Peer Reviewed
• [Journal Article] Impact of pegylated-interferon therapy on outcomes of patients with hepatitis C virus-related hepatocellularcar cinoma after curative hepatic resection (2012)
  • Author(s): Tanimoto Y, Tashiro H, Aikata H, AmanoH, Oshita A, Kobayashi T, Kuroda K, Tazawa H, Takahashi S, Itamoto T, Chayama K, Ohdan H.
  • Journal Title: Ann Surg Oncol Volume: 19 Pages: 418-425
  • Peer Reviewed
• [Journal Article] Identification of patients likely to benefit from metastasectomy in stage IV colorectal cancer (2012)
  • Author(s): Shimomura M, Okajima M, Hinoi T, Egi H, Takakura Y, Kawaguchi Y, Tokunaga M, Adachi T, Tashiro H, Ohdan H.
  • Journal Title: Int J Colorectal Dis Volume: (in press.)
  • Peer Reviewed
• [Journal Article] Safety and Feasibility of Diet-Treated Donors With Steatotic Livers at the Initial Consultation for Living-Donor Liver Transplantation (2012)
  • Author(s): Oshita A, Tashiro H, Amano H, Kobayashi T, Onoe T, Ide K, Takaki S, Takahashi S, Arihiro K, Chayama K, Ohdan H.
  • Journal Title: Transplantation Volume: (in press.)
  • Peer Reviewed
• [Journal Article] Prognostic Significance of Antithrombin III Levels for Outcomes in Patients with Hepatocellular Carcinoma After Curative Hepatectomy (2012)
  • Author(s): Iwako H, Tashiro H, Amano H, TanimotoY, Oshita A, Kobayashi T, Kuroda S, Tazawa H, Nambu J, Mikuriya Y, Abe T, Ohdan H.
  • Journal Title: Ann Surg Oncol Volume: (in press.)
  • Peer Reviewed
• [Journal Article] Impact of pegylated interferon therapy on outcomes of patients with hepatitis C virus-related hepatocellular carcinoma after curative hepatic resection (2012)
  • Author(s): Tanimoto Y, Tashiro H, Aikata H, Amano H, Oshita A, Kobayashi T, Kuroda S, Tazawa H, Takahashi S, Itamoto T, Chayama K, Ohdan H
  • Journal Title: Ann Surg Oncol Volume: 19 Issue: 2 Pages: 418-425
  • DOI: 10.1245/s10434-011-1866-1
  • Peer Reviewed
• [Journal Article] No Impact of Perioperative Blood Transfusion on Recurrence of Hepatocellular Garcinoma after Hepatectomy (2012)
  • Author(s): Kuroda S, Tashiro H, Kobayashi T, Oshita A, Amano H, Ohdan H
  • Journal Title: World J Surg Volume: 36 Issue: 3 Pages: 651-658
  • DOI: 10.1007/s00268-012-1425-3
  • Peer Reviewed
• [Journal Article] Evidence for the immunosuppressive potential of calcineurin inhibitor sparing in liver transplant recipients with impaired renal function (2012)
  • Author(s): Ide K, Tanaka Y, Onoe T, Banshodani M, Tazawa H, Igarashi Y, Basnet NB, Doskali M, Tashiro H, Ohdan H
  • Journal Title: J Transplant Volume: (In press) Pages: 1-6
  • DOI: 10.1155/2011/483728
  • Peer Reviewed
• [Journal Article] Identification of patients likely to benefit from metastasectomy in stage IV colorectal cancer (2012)
  • Author(s): Shimomura M, Okajima M, Hinoi T, Egi H, Takakura Y, Kawaguchi Y, Tokunaga M, Adachi T, Tashiro H, Ohdan H
  • Journal Title: Int J Colorectal Dis Volume: (In press) Issue: 10 Pages: 1339-1346
  • DOI: 10.1007/s00384-012-1454-2
  • Peer Reviewed
• [Journal Article] Optimization of immunosuppressive therapy based on a multiparametric mixed lymphocyte reaction assay reduces infectious complications and mortality in living donor liver transplant recipients (2012)
  • Author(s): Tanaka Y, Tashiro H, Onoe T, Ide K, Ishiyama K, Ohdan H
  • Journal Title: Transplant Proc Volume: 44 Issue: 2 Pages: 555-559
  • DOI: 10.1016/j.transproceed.2012.01.038
  • Peer Reviewed
• [Journal Article] Complex Vascular Reconstruction Using Donor's Vessel Grafts in Orthotopi (2012)
  • Author(s): Shimizu S, Onoe T, Ide K, Oshita A, Amano H, Kobayashi T, Tanaka Y, Igarashi Y, Tashiro H, Ohdan H
  • Journal Title: Transplant Proc Volume: 44 Pages: 574-578
  • Peer Reviewed
• [Journal Article] IL28B SNP of donors and recipients can predict virological response to PE GIFN/RBV therapy in patients with recurrent hepatitis C after living donor liver transplantation (2012)
  • Author(s): Kawaoka T, Takahashi S, Takaki S, Hiramatsu A, Waki K, Hiraga N, Miki D, Tsuge M, Imamura M, Kawakami Y, Aikata H, Ochi H, Onoe T, Tashiro H, Ohdan H, Chayama K
  • Journal Title: J Gastroenterol Hepatol Volume: (In press) Issue: 9 Pages: 1467-1472
  • DOI: 10.1111/j.1440-1746.2012.07129.x
  • Peer Reviewed
• [Journal Article] External Validation of two nomograms for predicting patients survival after hepatic resection for metastatic colorectal cancer (2011)
  • Author(s): Takakura Y, Okajima M, Kanemitsu Y, Kuroda S, Egi H, Hinoi T, Tashiro H, Ohdan H.
  • Journal Title: World JSurg Volume: 35 Pages: 2275-2282
  • Peer Reviewed
• [Journal Article] Significance of platelet count in the outcomes of hepatectomized patients with hepatocellular carcinoma exceeding the Mi lan criteria (2011)
  • Author(s): Amano H, Tashiro H, Oshita A, Kobayashi T, Tanimoto Y, Kuroda S, Tazawa H, Itamoto T, Asahara T, Ohdan H.
  • Journal Title: J Gastrointest Surg Volume: 15 Pages: 1173-1181
  • Peer Reviewed
• [Journal Article] Treatment strategy for early hepatocellular carcinomas : Comparison of radiofrequency ablation with or without transcatheter arterial chemoembolization and surgical resection (2011)
  • Author(s): Tashiro H, Aikata H, Waki K, Amano H, Oshita H, Kobayashi T, Tanimoto Y, Kuroda S, Tazawa H, Chayama K, AsaharaT, Ohdan H.
  • Journal Title: J Surg Oncol Volume: 104 Pages: 3-9
  • Peer Reviewed
• [Journal Article] Factors relating to tumor do not influence the prognosis of solitary hepatocellular carcinoma afterpartial hepatectomy (2011)
  • Author(s): Kobayashi T, Itamoto T, Tashiro H, Kuroda S, Tazawa H, Tanimoto Y, Ushitora Y, Oshita A, Amano H, Ohdan H.
  • Journal Title: J HBP science Volume: 18 Pages: 689-699
  • Peer Reviewed
• [Journal Article] SelectionCriteria for Hepatectomy in Patients with Hepatocellular Carcinoma Classified as Child-Pugh Class B (2011)
  • Author(s): Kuroda S, Tashiro H, Kobayashi T, Oshita A, Amano H, Ohdan H.
  • Journal Title: World J Surg Volume: 35 Pages: 834-841
  • Peer Reviewed
• [Journal Article] Splenectomy in chronic hepatic disorders : portal veinthrombosis and improvement of liver function (2011)
  • Author(s): Ushitora Y, Tashiro H, Takahashi S, Amano H, Oshita A, Kobayshi T, ChayamaK, Ohdan H.
  • Journal Title: Digestive Surgery Volume: 28 Pages: 9-14
  • Peer Reviewed
• [Journal Article] Splenectomy in chronic hepatic disorders : portal vein thrombosis and improvement of liver function (2011)
  • Author(s): Ushitora Y, Tashiro H, Takahashi S, Amano H, Oshita A, Kobayshi T, Chayama K, Ohdan H
  • Journal Title: Digestive Surgery Volume: 28 Issue: 1 Pages: 9-14
  • DOI: 10.1159/000321886
  • Peer Reviewed
• [Journal Article] Selection Criteria for Hepatectomy in Patients with Hepatocellular Carcinoma Classified as Child-Pugh Class B (2011)
  • Author(s): Kuroda S, Tashiro H, Kobayashi T, Oshita A, Amano H, Ohdan H
  • Journal Title: World J Surg Volume: 35 Issue: 4 Pages: 834-841
  • DOI: 10.1007/s00268-010-0929-y
  • Peer Reviewed
• [Journal Article] Possibility of adoptive immunotherapy with peripheral blood-derived CD3-CD56+ and CD+CD56+ cells for inducing antihepatocellular carcinoma and antihepatitis C virus activity (2011)
  • Author(s): Doskali M, Tanaka Y, Ohira M, Ishiyama K, Tashiro H, Chayama K, Ohdan H
  • Journal Title: J Immunother Volume: 34 Issue: 2 Pages: 129-138
  • DOI: 10.1097/cji.0b013e3182048c4e
  • Peer Reviewed
• [Journal Article] Therapeutic potential of propagated hepatocyte transplantation in liver failure (2011)
  • Author(s): Amano H, Hino H, Tateno C, Emoto K, Imaoka Y, Yamasaki C, Itamoto T, Tashiro H, Asahara T, Ohdan H, Yoshizato K
  • Journal Title: J Surg Res Volume: 167 Issue: 1 Pages: e29-e37
  • DOI: 10.1016/j.jss.2010.12.008
  • Peer Reviewed
• [Journal Article] Factors relating to tumor do not influence the prognosis of solitary hepatocellular carcinoma after partial hepatectomy (2011)
  • Author(s): Kobayashi T, Itamoto T, Tashiro H, Kuroda S, Tazawa H, Tanimoto Y, Ushitora Y, Oshita A, Amano H, Ohdan H
  • Journal Title: J HBP science Volume: 18 Issue: 5 Pages: 689-699
  • DOI: 10.1007/s00534-011-0379-4
  • Peer Reviewed
• [Journal Article] Significance of platelet count in the outcomes of hepatectomized patients with hepatocellular carcinoma exceeding the Milan criteria (2011)
  • Author(s): Amano H, Tashiro H, Oshita A, Kobayashi T, Tanimoto Y, Kuroda S, Tazawa H, Itamoto T, Asahara T, Ohdan H
  • Journal Title: J Gastrointest Surg Volume: 15 Issue: 7 Pages: 1173-1181
  • DOI: 10.1007/s11605-011-1538-2
  • Peer Reviewed
• [Journal Article] Long-term outcome of hepatic artery reconstruction after living-donor liver transplantation (2011)
  • Author(s): Banshodani M, Tashiro H, Onoe T, Ide K, Ohdan H
  • Journal Title: Transplant Proc Volume: 43 Issue: 5 Pages: 1720-1742
  • DOI: 10.1016/j.transproceed.2011.03.051
  • Peer Reviewed
• [Journal Article] Impact of adjuvant immunotherapy using liver allograft-derived lymphocytes on bacteremia in living donor liver trahsplantation (2011)
  • Author(s): Tashiro H, Ishiyama K, Ohira M, Igarashi Y, Tahara H, Ide K, Onoe T, Tanaka Y, Ohdan H
  • Journal Title: Transplantation Volume: 92 Issue: 5 Pages: 575-580
  • DOI: 10.1097/tp.0b013e318225db92
  • Peer Reviewed
• [Journal Article] External Validation of two nomograms for predicting patients survival after hepatic resection for metastatic colorectal cancer (2011)
  • Author(s): Takakura Y, Okajima M, Kanemitsu Y, Kuroda S, Egi H, Hinoi T, Tashiro H, Ohdan H
  • Journal Title: World J Surg Volume: 35 Issue: 10 Pages: 2275-2282
  • DOI: 10.1007/s00268-011-1194-4
  • Peer Reviewed
• [Journal Article] Kinetics of cellular and humoral immunity in a successful case positive kidney transplantation : a case report (2011)
  • Author(s): Tanimine N, Ide K, Yamashita M, Tanaka Y, Igarashi Y, Banshodani M, Tazawa H, Basnet NB, Doskali M, Onoe T, Tashiro H, Ohdan H
  • Journal Title: Transplant Proc Volume: 43 Issue: 6 Pages: 2411-2414
  • DOI: 10.1016/j.transproceed.2011.05.039
  • Peer Reviewed
• [Journal Article] IL28B polymorphism may guide pegylated interferon plus ribavirin therapy even after curative treatment for hepatitis C virus-related hepatooellular carcinoma (2011)
  • Author(s): Kawaoka T, Aikata H, Takaki S, Hiramatsu A, Waki K, Hiraga N, Miki D, Tsuge M, Imamura M, Kawakami Y, Takahashi S, Ochi H, Tashiro H, Ohdan H, Chayama K
  • Journal Title: J Viral Hepat Volume: 18 Issue: 10 Pages: e550-e560
  • DOI: 10.1111/j.1365-2893.2011.01468.x
  • Peer Reviewed
• [Journal Article] Eradication of hepatitis C virus genotype 1 after liver transplantation by interferon therapy before surgery : Report of three patients with analysis of interleukin-28 polymorphism, hepatitis C virus core region and interferon-sensitivity determining region (2011)
  • Author(s): Kawaoka T, Aikata H, Miyaki D, Murakami E, Azakami T, Takaki S, Nagaoki Y, Hashimoto Y, Katamura Y, Hiramatsu A, Waki K, Hiraga N, Miki D, TsugeM, Imamura M, Kawakami Y, Takahashi S, Ochi H, Tashiro H, Ohdan H, Chayama K
  • Journal Title: Hepatol Res Volume: 41 Issue: 11 Pages: 1126-1131
  • DOI: 10.1111/j.1872-034x.2011.00853.x
  • NAID: 10031144190
  • Peer Reviewed
• [Journal Article] Achievement of Sustained Viral Response after Switching Treatment from Pegylated Interferon alpha-2b to alpha-2a and Ribavirin in Patients with Recurrence of Hepatitis C Virus Genotype 1 Infection after Liver Transplantation : A Case Report (2011)
  • Author(s): Kawaoka T, Hiraga N, Takahashi S, Takaki S, Tsuge M, Nagaoki Y, Hashimoto Y, Katamura Y, Muki D, Hiramatsu A, Waki K, Imamura M, Kawakami Y, Aikata H, Ochi H, Tashiro H, Ohdan H, Chayama K
  • Journal Title: Intervirology (Elpub 25 Aug.) Volume: (Epub) Issue: 4 Pages: 306-310
  • DOI: 10.1159/000328661
  • Peer Reviewed
• [Journal Article] A huge metastatic liver tumor from leiomyosarcoma of the inferior vena cava : report of a case (2011)
  • Author(s): Hashimoto M, Kobayashi T, Tashiro H, Amano H, Oshita A, Tanimoto Y, Kuroda S, Tazawa H, Aikata H, Chayama K, Fujii M, Arihiro K, Ohdan H
  • Journal Title: Surg Today (Epub 30 Nov.) Volume: (Epub) Issue: 5 Pages: 505-508
  • DOI: 10.1007/s00595-011-0070-z
  • NAID: 10030621850
  • Peer Reviewed
• [Journal Article] Selection criteria for hepatectomy in patients with hepatocellular carcinoma classified as child-pugh class B. (2011)
  • Author(s): Kuroda S, Tashiro H, Kobayashi T, Oshita A, Amano H, Ohdan H.
  • Journal Title: World Journal of Surgery Volume: 35 Pages: 834-841
  • Peer Reviewed
• [Journal Article] Splenectomy in chronic hepatic disorders : portal vein thrombosis and improvement of liver function. (2011)
  • Author(s): Ushitora Y, Tashiro H, Takahashi S, Amano H, Oshita A, Kobayashi T, Chayama K, Ohdan H.
  • Journal Title: Digestive Surgery Volume: 28 Pages: 9-14
  • Peer Reviewed
• [Journal Article] Tumor-related factors do not influence the prognosis of solitary hepatocellular carcinoma after partial hepatectomy. (2011)
  • Author(s): Kobayashi T, Itamoto T, Tashiro H, Amano H, Oshita A, Tanimoto Y, Kuroda S, Tazawa H, Ohdan H.
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: (in press)
  • NAID: 10029688478
  • Peer Reviewed
• [Journal Article] Treatment strategy for early hepatocellular carcinomas : Comparison of radiofrequency ablation with or without transcatheter arterial chemoembolization and surgical resection (2011)
  • Author(s): Tashiro H, Aikata H, Waki K, Amano H, Oshita H, Kobayashi T, Tanimoto Y, Kuroda S, Tazawa H, Chayama K, Asahara T, Ohdan H.
  • Journal Title: J Surg Oncol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Therapeutic potential of propagated hepatocyte transplantation in liver failure. (2010)
  • Author(s): Amano H, Hino H, Tateno C, Emoto K, Imaoka Y, Yamasaki C, Itamoto T, Tashiro H, Asahara T, Ohdan H, Yoshizato K.
  • Journal Title: J Surg Res Volume: 167 Pages: 29-37
  • Peer Reviewed
• [Journal Article] Suppression of hepatocellular carcinoma recurrence after rat liver trans plantation by FTY720, a sphingosine-1-phosphate analog (2009)
  • Author(s): Ushitora Y, Tashiro H, Ogawa T, Tanimoto Y, Kuroda S, Kobayashi T, Miyata Y, Itamoto T, Asahara T, Ohdan H
  • Journal Title: Transplantation 88 Pages: 980-986
  • Peer Reviewed
• [Presentation] Child-PughB原発性肝細胞癌に対する肝切除・肝移植症例の検討 (2011)
  • Author(s): 黒田慎太郎, 田代裕尊, 藤國宣明, 楠部潤子, 田澤宏文, 谷本新学, 小林剛, 大下彰彦, 天野尋暢, 番匠谷将孝, 井手健太郎, 尾上隆司, 大段秀樹
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-07-13
• [Presentation] Child-Pugh B原発性肝細胞癌に対する肝切除・肝移植症例の検討 (2011)
  • Author(s): 黒田慎太郎, 田代裕尊, 藤國宣明, 楠部潤子, 田澤宏文, 谷本新学, 小林剛, 大下彰彦, 天野尋暢, 番匠谷将孝, 井手健太郎, 尾上隆司, 大段秀樹
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-07-13
• [Presentation] 脂肪肝における虚血再潅流障害の機序とその治療法 (2011)
  • Author(s): 黒田慎太郎, 田代裕尊, 五十嵐友香, 谷本新学, 大下彰彦, 小林剛, 天野尋暢, 楠部潤子, 大段秀樹
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-02
• [Presentation] C型慢性肝炎関連肝細胞癌切除後のPEG-IFN療法による予後改善効果 (2011)
  • Author(s): 田代裕尊, 相方浩, 谷本新学, 天野尋暢, 大下彰彦, 小林剛, 茶山一彰, 大段秀樹
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-02
• [Presentation] 再肝切除における術後胆汁漏の予防 (2011)
  • Author(s): 田代裕尊, 天野尋暢, 大下彰彦, 小林剛, 尾上隆司, 井手健太郎, 大段秀樹
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 名古屋
• [Presentation] ドナー由来活性化リンパ球細胞療法による生体肝移植後の敗血症予防 (2011)
  • Author(s): 田代裕尊, 茶山一彰, 大段秀樹
  • Organizer: 第15回日本肝臓学会大会
  • Place of Presentation: 福岡
• [Presentation] 生体肝移植における胆管・胆管吻合法と術後胆管狭窄に対する治療 (2011)
  • Author(s): 田代裕尊, 天野尋暢, 大下彰彦, 小林剛, 尾上隆司, 石山宏平, 井手健太郎, 佐々木民人, 茶山一彰, 大段秀樹
  • Organizer: 第29回日本肝移植研究会
  • Place of Presentation: 仙台
• [Presentation] 脂肪肝における虚血再潅流障害の機序とその治療戦略 (2010)
  • Author(s): 黒田慎太郎、田代裕尊、五十嵐友香、谷本新学、大下彰彦、小林剛、天野尋暢、楠部潤子、大段秀樹
  • Organizer: 第37回日本臓器保存生物医学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2010-11-20
• [Presentation] 術後再発に対する治療戦略-再発危険因子の解析と再肝切除、肝移植の役割シンポジウム(「肝細胞癌術後再発への治療戦略-長期予後を目指して-」) (2010)
  • Author(s): 天野尋暢、田代裕尊、大下彰彦、小林剛、谷本新学、黒田慎太郎、田澤宏文、板本敏行、浅原利正、大段秀樹
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 下関
  • Year and Date: 2010-07-14
• [Presentation] 肝移植後における抗アロおよび抗HCV応答のクロストーク機構の解明と新規抗HCV療法への展開 ワークショップ(「C型肝炎に対する肝移植」) (2010)
  • Author(s): 大段秀樹、田代裕尊、浅原利正、茶山一彰
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Presentation] 肝細胞癌に対する外科治療とその成績 シンポジウム(「肝細胞癌の治療方針の変遷と展望」) (2010)
  • Author(s): 田代裕尊、天野尋暢、大下彰彦、小林剛、尾上隆司、井手健太郎、伊禮俊充、谷本新学、黒田慎太郎、田澤宏文、板本敏行、浅原利正、大段秀樹
  • 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: 2010-04-08
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/home2ge/index.html