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Transfection of NF-kB decoy oligodeoxynucleotides into macrophages reduces murine fatal liver failure after excessive hepatectomy

Research Project

Project/Area Number 18591521
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionYokohama City University

Principal Investigator

TOGO Shinji  Yokohama City University, Department of Gastroenterological Surgery, Graduate School of Medicine, associate professor (10244477)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Tetsuya  Yokohama City University, Department of Gastroenterological Surgery, Graduate School of Medicine, associate professor (60404985)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsEcessive hepatectomy / cytokine / NF-kB / apoptosis / liver regeneration / IL-6 / TN-α
Research Abstract

Background: Macrophages play an important role in the initiation of the hypercytokinemia that is involved in the development of liver failure after excessive hepatectomy. This study was aimed at evaluating whether the selective suppression of NF-kB in macrophages by decoy oligodeoxynucleotides (ODN) could prevent liver failure after excessive hepatectomy. Materials and Methods: Ninety-percent hepatectomy was performed in 8-week-old mice. NF-KB/decoy/ODN was transfected into the liver by the HVJ-liposome method. The survival rate, serum levels of IL-18, IL-6 and TNF-a, and the histological findings in the remnant liver were compared between the 90%-hepatectomized mice transfected with the decoy ODN (decoy group) and the 90%-hepatectomized mice injected with saline (control group) . Result: The control group mice died within 48 hours of the operation, while the survival rate in the decoy group at 48 hours after the operation was 35%, and at 2 weeks, 15%. The serum levels of all cytokines were significantly lower in the decoy group than in the control group. The number of TUNEL-positive cells in the remnant liver was smaller in the decoy group. Conclusion: Transfection of NF-kB/decoy/ODN reduces fatal liver failure in mice after excessive hepatectomy by suppressing hypercytokinemia, but offers only a low rate of survival.
(199 words)

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (16 results)

All 2007 2006 Other

All Journal Article (13 results) (of which Peer Reviewed: 6 results) Book (3 results)

  • [Journal Article] PAI-1 Plays an Important Role in Liver Failure After Excessive Hepatectomy in the Rat2007

    • Author(s)
      Watanabe K, Togo S, et. al.
    • Journal Title

      J Surg Res 143

      Pages: 13-19

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Adult rat hepatic bipotent progenitor cells remain dormant even after extensive hepatectomy2007

    • Author(s)
      Yamamoto H, Togo S, et. al.
    • Journal Title

      Wound Repair Regen 15

      Pages: 422-429

    • NAID

      10031181363

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] PAI-1 Plays an Important Role in Liver Failure After Excessive Hepatectomy in the Rat2007

    • Author(s)
      Watanabe, K, Togo, S, Takahashi, T, Matsuyama, R, Yamamoto, H, Shimizu, T, Makino, H, Matsuo, K, Morioka D, Kubota, T, Nagashima, Y, Shimada, H
    • Journal Title

      J Surg Res 143

      Pages: 13-19

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Adult rat hepatic bipotent progenitor cells remain dormant even after extensive hepatectomy2007

    • Author(s)
      Yamamoto, H, Togo, S, Zheng, YW, Kubota, T, Taniguchi, H, Shimada, H
    • Journal Title

      Wound Repair Regen 15

      Pages: 422-9

    • NAID

      10031181363

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] PAI-1 Playsan Important Role in Liver Failure After Excessive Hepatectomy in the Rat.2007

    • Author(s)
      Watanabe K, Togo S, et. al.
    • Journal Title

      J Surg Res 143

      Pages: 13-19

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adult rat hepatic bipotent progenitor cells remain dormant even after extensive hepatectomy.2007

    • Author(s)
      Yamamoto H, Togo S, et. al.
    • Journal Title

      Wound Repair Regen. 15

      Pages: 422-429

    • NAID

      10031181363

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Remnant liver regeneration after two-stage hepatectomy for multiple bilobar colorectal metastases.2007

    • Author(s)
      Tanaka K, Togo S et al.
    • Journal Title

      Eur J Surg Oncol 33(3)

      Pages: 329-335

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Safety limit of extent of hepatectomy for rats with moderately fatty liver : Experimental study concerning libing liver donor surgery.2006

    • Author(s)
      Morioka D, Togo S et al.
    • Journal Title

      J of Gastroenterology and Hepatology 21

      Pages: 367-373

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A rat model of a repeat 70% major hepatectomy2006

    • Author(s)
      Saito S, Togo S, et al.
    • Journal Title

      J Surg Res 134

      Pages: 322-326

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Disruption of the Middle Hepatic Vein is not Crucial for Liver Regeneration of the Remnant Liver After Right Hemihepatectomy for Hepatic Tumors2006

    • Author(s)
      Morika D, Togo S et al.
    • Journal Title

      Ann Surg Oncol 13

      Pages: 1560-1568

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Transfection of NF-xB decoy oligodeoxynucleotides into macrophages reduces murine fatal liver failure after excessive hepatectomy

    • Author(s)
      Takahashi T, Togo S, et. al.
    • Journal Title

      J Surg Res (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Transfection of NF-kB decoy oligodeoxynucleotides into macrophages reduces murine fatal liver failure after excessive hepatectomy

    • Author(s)
      Takahashi, T, Togo, S, Kumamoto, T, Watanabe, K, Kubota, T, Ichikawa, Y, Endo, I, Kunisaki, C, Nagashima, Y, Fujimoto, J, Shimada, H
    • Journal Title

      J Surg Res (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Transfection of NF-kB decoy oligodeoxynucleotides into macro phages reduces murine fatal liver failure after excessive hepatectomy

    • Author(s)
      Takahashi T, Togo S, et. al.
    • Journal Title

      J Surg Res (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Book] 肝再生と肝不全 拡大肝切除術の確立を目指して2007

    • Author(s)
      渡會 伸治編、嶋田 紘監修
    • Total Pages
      164
    • Publisher
      西村書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 肝再生と肝不全 拡大肝切除術の確立を目指して2007

    • Author(s)
      渡會伸治編、嶋田紘監修
    • Total Pages
      164
    • Publisher
      西村書店
    • Related Report
      2007 Annual Research Report
  • [Book] 肝再生と肝不全-拡大肝切除術の確立を目指して-2006

    • Author(s)
      渡會伸治 編
    • Total Pages
      164
    • Publisher
      西村書店
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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