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2002 Fiscal Year Final Research Report Summary

Wider application of small-for-size partial liver grafting by gene transfer using teromerase reverse transcriptase (TERT).

Research Project

Project/Area Number 13671243
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionGrant-in-Aid for Scientific Research (C)(2)

Principal Investigator

SOEJIMA Yuji  Hospital, Assistant Professor, 大学院・医学研究院, 助手 (30325526)

Co-Investigator(Kenkyū-buntansha) TANAKA Shinji  Hospital, Assistant Professor, 大学院・医学研究院, 講師 (30253420)
Project Period (FY) 2001 – 2002
KeywordsTERT / Ex vivo gene trancefer / 30% partial liver transplantation / small-for-size injury
Research Abstract

1. Development of rat liver transplantation model using small-for-size graft:
Rat liver transplantation model using small-for-size graft (30% of whole liver volume) was established, in which 100% 3-day mortality was assured.
2. Development of gene-transfer technique:
(1) Gene transfer using electroporation (EP) technique:
An EP-mediated teromerase reverse transcriptase (TERT) gene transfer into human hepatocyte primary cultrure was carried out. A 10% of transfection effectivcess was achieved. However, gene transfer of TERT did not extend the survival of the cells. A direct damege to hepatocytes by EP technique was suggested.
(2) Gene transfer into cold-preserved rat liver:
Ex vivo EP-mediated or hydrodynamic gene transfer into a cold-preserved (UW solution, 4℃) rat liver graft was evaluated using rat liver transplantation model. The luciferase gene expression in the graft after liver transplantation was found to be increased. However, significant graft damage due to a gene transfer was observed.
Therefore, development of an alternative strategy using nano-carrier was indicated.
(3) In vivo IL-12 gene transfer using EP technique under immunosuppression:
Using mice model carrying hepatoma cells (MH134), in vivo IL-12 gene transfer using EP technique was carried out under immunosuppression by FK506. Intratumoral administration of mIL-12 vector elevated intratumoral IL-12 and IFN-γ on the days 7 and 14 of transfer and significantly inhibited not only the growth of HCC, but also the angiogenesis in the tumor through expression of antiangiogenetic chemokaine IP-10.
(4) Gene transfer using hydrodynamic method:
As an alternative to EP technique, gene transfer using hydrodynamic method was established. Expression of inciferase gene peaked at 4 hour after injection. The mechanism of the method has not been elucidated so far, thus further investigation was indicated.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Soejima Y.et al.: "Preoperative management and complications of donors related to living donor liver transplantation"Surgery. 131. 190-194 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Soejima Y.et al.: "Feasibility of duct-to-duct biliary reconstruction in left-lobe adult-living-donor liver transplantation"Transplantation. 75. 557-559 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Soejima Y.et al.: "Liver transplantation for hepatocellular carcinama"Surgery. 131. 190-194 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Soejima Y.et al.: "Beneficial effect of 3-dimensional visualization on hepatic vein reconstruction in living donor liver transplantation"Transplantation. 72(12). 1993-1996 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka S.et al.: "Oncogenic signal transduction and therapeutic strategy for hepatocellular carcinama"Surgery. 131. 142-147 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka S.et al.: "Clinicopathologic risk factor for recurrence after a curative hepatic resection for hepatocellular carcinama"Surgery. 131. 148-152 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Soejima Y. et al.: "Preoperative management and complications of donors related to living donor liver transplantation."Surgery. 131. 190-194 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Soejima Y. et al.: "Feasibility of duct-to-duct biliary reconstruction in left-lobe adult-living-donor liver transplantation."Transplantation. 785. 557-559 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Soejima Y. at al.: "Liver transplantation for hepatocellular carcinama."Surgery. 131. 190-194 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Soejima Y. et al.: "Beneficial effect of 3-dimensional visualization on hepatic vein reconstructuon in living donor liver transplantation."Transplantation. 72(12). 1993-1996 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka S. et al.: "Oncogenic signal transduction and therapeutic strategy for hepatocellular carcinama."Surgery. 131. 142-147 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka S. et al.: "Clinicopathologic risk factor for recurrence after a curative hepatic resection for hepatocellular carcinama."Surgery. 131. 148-152 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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