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Elucidation of pathophysiology of Sinusoidal Obstruction Syndrome and development of new prevention and treatment methods

Research Project

Project/Area Number 15K10158
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKanazawa University

Principal Investigator

Tajima Hidehiro  金沢大学, 附属病院, 講師 (00436825)

Co-Investigator(Kenkyū-buntansha) 宮下 知治  金沢大学, 附属病院, 助教 (30397210)
太田 哲生  金沢大学, 医学系, 教授 (40194170)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords肝類洞閉塞症候群 / 血小板 / veno-occlusive disease / シロスタゾール / モノクロタリン / 化学療法 / 肝類洞変則症候群 / 抗癌剤 / 肝類同閉塞症候群 / 好中球
Outline of Final Research Achievements

Chronic rejection after liver transplantation, anticancer agents such as oxaliplatin, and hematopoietic stem cell transplantation are cause sinusoid obstruction syndrome (SOS) characterized by splenomegaly and thrombocytopenia, resulting in liver dysfunction. SOS have the common feature of progressing chronically around the central vein (zone 3). If it is hypothesized that extravascular platelet aggregation in the Disse’s space cause of SOS, it will be possible to unify the series of pathogenesis that accompanies SOS. In this study, we aimed to confirm the state of platelet aggregation with rat SOS model and to examine the preventive effect of antiplatelet drug on SOS. We made rat SOS model with monocrotaline and discovered the presence of platelet aggregation in the Disse’s space around central vein (zone 3) with immunohistological examination and electron microscopy, and also certified that antiplatelet drug (cilostazol) has preventive effect for SOS.

Academic Significance and Societal Importance of the Research Achievements

血小板は核を持たないため、通常のHE染色では組織内での存在を確認することができず、その重要性は認識されながらもこれまで研究が進展してこなかった。血小板からは様々な成長因子が分泌されることが知られており、血小板が原因であると仮定するとSOS以外にも敗血症時の肝障害や癌の転移など様々な病態を説明することができることから、今後の研究の発展が期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Phosphodiesterase III inhibitor attenuates rat sinusoidal obstruction syndrome through inhibition of platelet aggregation in Disse’s space.2017

    • Author(s)
      Takashi Miyata
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 印刷中 Issue: 4 Pages: 950-957

    • DOI

      10.1111/jgh.14004

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extravasated platelet aggregation in the livers of rats with drug-induced hepatic sinusoidal obstruction syndrome2017

    • Author(s)
      Hirata M, Tajima H, Miyashita T, Miyata T, Nakanuma S, Makino I, Hayashi H, Oyama K, Takamura H, Ninomiya I, Fushida S, Nakata H, Iseki S, Harada S, Wakayama T, Ohta T
    • Journal Title

      Molecular Medicine Reports

      Volume: 15(5) Issue: 5 Pages: 3147-3152

    • DOI

      10.3892/mmr.2017.6407

    • NAID

      120006306225

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 肝類洞閉塞症候群の発生における血管外血小板凝集の関与2017

    • Author(s)
      田島秀浩
    • Journal Title

      BIO Clinica

      Volume: 10 Pages: 1128-1131

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation2016

    • Author(s)
      Tomoharu Miyashita
    • Journal Title

      European Surgery

      Volume: 48 Issue: 2 Pages: 92-98

    • DOI

      10.1007/s10353-015-0363-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oxaliplatin-based chemotherapy induces extravasated platelet aggregation in the liver.2015

    • Author(s)
      Hidehiro Tajima
    • Journal Title

      Mol Clin Oncol

      Volume: 3 Issue: 3 Pages: 555-558

    • DOI

      10.3892/mco.2015.512

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extravasated Platelet Aggregation in Liver Zone 3 Is Associated With Thrombocytopenia and Deterioration of Graft Function After Living-Donor Liver Transplant.2015

    • Author(s)
      Shinichi Nakanuma
    • Journal Title

      Exp Clin Transplant

      Volume: 6 Pages: 556-562

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extravasated platelet aggregation in liver zone 3 may correlate with the progression of sinusoidal obstruction syndrome following living donor liver transplantation: A case report.2015

    • Author(s)
      Shinichi Nakanuma
    • Journal Title

      Exp Therap Med

      Volume: 9 Issue: 4 Pages: 1119-1124

    • DOI

      10.3892/etm.2015.2245

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 肝類洞閉塞症候群の発生における血管外血小板凝集の関与2018

    • Author(s)
      田島秀浩
    • Organizer
      日本消化器病学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝類洞閉塞症候群の発生における血管外血小板凝集の関与に関する実験的研究2018

    • Author(s)
      田島秀浩
    • Organizer
      日本外科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝類洞閉塞症候群の発生における血管外血小板凝集の関与に関する実験的研究2018

    • Author(s)
      田島秀浩
    • Organizer
      第118回 日本外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝類洞閉塞症候群の発生における血管外血小板凝集の関与2018

    • Author(s)
      田島秀浩
    • Organizer
      第104回 日本消化器病学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Preoperative chemotherapy for resectable pancreatic cancer improves prognosis of node positive pancreatic head cancer2018

    • Author(s)
      Hidehiro Tajima
    • Organizer
      Pancreas 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肝類洞閉塞症候群による血管外血小板凝集抑制に伴う肝障害予防と肝再生促進に関するラットモデル基礎的実験検討2017

    • Author(s)
      宮田隆司、田島秀浩
    • Organizer
      第117回 日本外科学会総会
    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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