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Proteomics analysis of a mechanism of sinusoidal endothelial cell injury after receiving oxaliplatin-based chemotherapy in colorectal liver metastases.

Research Project

Project/Area Number 22591509
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
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, 医学部 (10241035)

Co-Investigator(Kenkyū-buntansha) 小林 真一  聖マリアンナ医科大学, 医学部, 教授 (20129836)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords大腸癌肝転移術前化学療法 / oxaliplatin-based chermotherapy / sinusoidal obstruction syndrome / プロテオミクス / glutathione S-transferase M1 / sphingosine 1 phosphate / 大腸癌肝転移 / 肝切除 / 術前化学療法 / 肝障害 / Blue liver / Peroxiredoxin 6 / 化学療法関連肝障害 / ジヌソイド閉塞症候群 / オキザリプラチン / Aldehyde dehydrogenase / Peroxiredoxin6 / Oxaliplatin
Research Abstract

Oxaliplatin-based chemotherapy in patients with colorecatl liver metastases has been shown to be significantly associated with sinusoidal obstruction syndrome (SOS). In the present study, our proteomics study using 2-Dimensional electrophoresis and LC/MS/MS showed that Peroxiredoxin6、Aldehyde dehydrogenase 2、 α-methylacetyl-CoA racemase、Protein disulfide-isomerase A3、60-S-acid ribosomal protein P0、and Glutathione S-transferase M1 (GST-M1) significantly differed as compared with the control sinusoidal cells. Among them, GST-M1 significantly decreased in human sinusoidal endothelial cells after the administration of oxaliplatin. In addition, an administration of sphingosine 1 phosphate (S1P), which has a protective effect on sinusoidal endothelial injury, significantly attenuate the oxaliplatin-induced sinusoidal injury and showed the maintenance of GST-M1 concentration. These results suggests thatGST-M1 and S1P have a crucial role of oxaliplatin-induced sinusoidal endothelial inj.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (15 results)

All 2013 2012 2011 2010

All Journal Article (11 results) (of which Peer Reviewed: 7 results) Presentation (4 results)

  • [Journal Article] Splenic Volume Increase due to Preoperative Chemotherapy may Impair 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

      Hepatogastroenterol

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The aspartate aminotransferase to platelet ratio before chemotherapy predicts adverse events for FOLFOX and XELOX regimens including bevacizumab as the first-line therapy for stage IV, recurrent and metastatic colorectal cancer.2013

    • Author(s)
      Sato S, Nakano H, et al.
    • Journal Title

      J Gastrointest Oncol

      Volume: 4 (2) Pages: 203-209

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The AST to Platelet ratio before chemotherapy predicts adverse events for FOLFOX and XELOX regimens including bevacizumab as the first-line therapy for stage IV, recurrent and metastatic colorectal cancer2013

    • Author(s)
      Nakano H
    • Journal Title

      Journal of Gstrointestinal Oncology

      Volume: 4

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [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 Metastases2013

    • Author(s)
      Nakano H
    • Journal Title

      Hepatogastroenterology

      Volume: 126

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Comparative study of culture conditions for maintaining CYP3A4 and ATP-binding cassette transporters activity in primary cultured human hepatocytes.2011

    • Author(s)
      Takeba Y, Matsumoto N, Nakano H, Kobayashi S, et al.
    • Journal Title

      J Pharmacol Sci

      Volume: 115 (4) Pages: 516-524

    • NAID

      10029893533

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Splenomegaly in FOLFOX-naive stage IV or recurrent colorectal cancer patients due to chemotherapy-associated hepatotoxicity can be predicted by the aspartate aminotransferase to platelet ratio before chemotherapy.2011

    • Author(s)
      Miura K, Nakano H, et al.
    • Journal Title

      Int J Clin Oncol

      Volume: 16(3) Pages: 257-263

    • NAID

      10029527086

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemotherapy-induced hepatotoxicity in patients with colorectal cancer liver metastases.2011

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

      Nihon Rinsho

      Volume: 69 (3) Pages: 536-540

    • NAID

      40018805587

    • Related Report
      2012 Final Research Report
  • [Journal Article] Splenimegaly in FOLFOX-na〓ve stage IV or recurrent colorectal cancer patients due to chemotherapy-associated hepatotoxicity can be predicted by aspartate aminotransferase to platelet ratio before chemotherapy2011

    • Author(s)
      Miura K, Nakano H, et al
    • Journal Title

      Int J Clin Oncol

      Volume: 16(3) Pages: 257-263

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大腸癌-最新の研究動向-大腸癌化学療法に関連した肝障害2011

    • Author(s)
      中野浩, 他
    • Journal Title

      日本臨床

      Volume: 69 Pages: 536-540

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Splenimegaly in FOLFOX-naive stage IV or recurrent colorectal cancer patients due to chemotherapy-associated hepatotoxicity can be predicted by aspartate aminotransferase to platelet ratio before chemotherapy.2011

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

      Int J Clin Oncol

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大腸癌肝転移に対する治療のUpdate:化学療法による肝組織障害2010

    • Author(s)
      中野浩, 他
    • Journal Title

      外科治療

      Volume: 102 Pages: 857-862

    • Related Report
      2010 Annual Research Report
  • [Presentation] 進性・再発大腸癌の化学療法関連肝障害:脾容積、AST/血小板比、プロテオミクス解析によるchemotherapy-naive patientsの抽出2012

    • Author(s)
      中野浩
    • Organizer
      日本外科学会
    • Place of Presentation
      千葉・幕張(幕張メッセ)
    • Year and Date
      2012-04-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] The aspartate aminotransferase to platelet ratio before chemotherapy predicts adverse events for FOLFOX and XELOX regimens including bevacizumab as the first-line therapy for stage IV, recurrent and metastatic colorectal cancer.The best oral Session2012

    • Author(s)
      Nakano H, et al.
    • Organizer
      The 10thConcreass of the International Hepato-Pancreato-Biliary Association.
    • Place of Presentation
      Paris, France
    • Related Report
      2012 Final Research Report
  • [Presentation] 進行・再発大腸癌の化学療法関連肝障害:脾容積、 AST/ 血小板比によるchemotherapy-naive patients の抽出2012

    • Author(s)
      中野 浩
    • Organizer
      第112回日本外科学会総会
    • Place of Presentation
      千葉
    • Related Report
      2012 Final Research Report
  • [Presentation] Splenomegaly in oxaliplatin-naive patients due to chemotherapy-associated hepatotoxicity can be predicted by the aspartate aminotransferase to platelet ratio before chemotherapy in stage IV or recurrent colorectal cancer2012

    • Author(s)
      Nakano H
    • Organizer
      10th Internation Hepato-Pancreato-Biliary Association
    • Place of Presentation
      Paris
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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