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Hepatotoxicity investigated in chemo-naive patients by proteomics

Research Project

Project/Area Number 25462101
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Nakano Hiroshi  聖マリアンナ医科大学, 医学部, 准教授 (10241035)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsジヌソイド閉塞 / 抗癌剤起因性肝障害 / デフィブリド / ヒトジヌソイド内皮 / 共焦点顕微鏡 / フローサイトメトリー / sinusoidal obstruction / defibrotide / ジヌソイド内皮細胞 / endocytic pathways / internalization kinetics / flow cytometry / oxaliplatin / CCL20
Outline of Final Research Achievements

Defibrotide (DF) is a recognized as an endothelial protective agent. The aim of the study was to investigate the interaction of DF with endothelial cells (ECs). A human hepatic EC line was exposed to different DF concentrations. Using inhibitory assays and flow cytometry techniques along with confocal microscopy, we explored: DF-EC interaction, endocytic pathways, and internalization kinetics. Confocal microscopy showed interaction of DF with EC membranes followed by internalization, though DF did not reach the cell nucleus even after 24 hours. Flow cytometry revealed concentration, temperature, and time dependent uptake of DF in 2 EC models but not in other cell types. Moreover, inhibitory assays indicated that entrance of DF into ECs occurs primarily through macropinocytosis. The antiinflammatory and antioxidant properties of DF seem to be caused by the interaction of the drug with the cell membrane.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (3 results)

All 2015 2014 2013

All Journal Article (2 results) (of which Open Access: 1 results,  Acknowledgement Compliant: 1 results,  Peer Reviewed: 1 results) Presentation (1 results)

  • [Journal Article] 大腸癌化学療法に関連した肝障害の病態とその予防対策2015

    • Author(s)
      中野浩
    • Journal Title

      日本臨床

      Volume: 74 Pages: 627-632

    • Related Report
      2015 Annual Research Report
    • Open Access / Acknowledgement Compliant
  • [Journal Article] A Splenic Volume Increase Due to Preoperative Chemotherapy May Impair the Long-Term Outcome After Hepatectomy in Patients with Initially Non-Optimally Resectable Colorectal Cancer Liver Metastases.2013

    • Author(s)
      Katayama M, Nakano H, et al
    • Journal Title

      Hepatogastroenterology

      Volume: 126 Pages: 1420-1425

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] A Splenic Volume Increase Due to Preoperative Chemotherapy May Impair the Long-Term Outcome After Hepatectomy in Patients with Initially Non-Optimally Resectable Colorectal Cancer Liver Metastases.2014

    • Author(s)
      Nakano H, et al
    • Organizer
      12th IHPBA
    • Place of Presentation
      Seoul
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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