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Experimental research about the treatment for postoperative pathological changes : control of endothelial activation using antisense adenovirus vector

Research Project

Project/Area Number 08671385
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionShowa University

Principal Investigator

YAMAGUCHI Masahiko  Showa University, School of Medicine, Assistant Professor, 医学部, 講師 (00266149)

Co-Investigator(Kenkyū-buntansha) TAKEDA Minoru  Showa University.School of Medicine, Professor, 医学部, 教授 (50110896)
KUMADA Kaoru  Showa University, School of Medicine, Professor, 医学部, 教授 (00025602)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsAntisense therapy / Adenovirus vector / ICAM-1 / Vascular endothelial cells / PDGF-A鎖
Research Abstract

Activated vascular endothelial cells (ECs) produce various factors to contribute to the development of postoperative pathological changes. In this study, we investigated whether antisense adenovirus vector sgsist ICAM-1 mRNA could suppress ICAM-1 expression on activated ECs.
DNAs complementary to ICAM-1, VCAM-1, E-selectin, and PDGF-A chain mRNAs were produced by RT/PCR of total cellular RNA from TNF-_<alpha> activated human umbilical vein ECs using respective sense and antisense primers. cDNAs were subcloned in plasmids and checked their sequences. Checked cDNAs were reversely ligated into the specific cosmids for generation of adenovirus vector. Antisense adenovirus vectors against ICAM-1, VCAM-1, and E-selection mRNAs was generated in 293 cells, resulting from the homologous recombination between cDNAs-reversely-ligated cosmids and adenovirus DNA.The adenovirus vectors were transfected into ECs and their transcripts were checked by RT/PCR.ICAM-1 pression was analyzed by cell-ELISA on lipopolysaccharide-activated ECs which was tranfected with antisense adenovirus vector against ICAM-1 mRNA.However, ICAM-1 expression inbuced by lipopolysaccharide could not be reduced by transfection of the antisense adenovirus vector. We considered that the reasons why the vector failed to reduced the ICAM-1 expression might be due the fact that the expression cassette of the vector included a short cDNA sequence as 143bp and a long mismatchcd sequence as 200bp. Moreover, we have experienced another failure of antisense adenovirus vector. Antisense adenovirus vector against insulin failed to reduce insulin secretion from the ECs transfected with insulin adenovirus vector. Since the vector contained 334 bp-reversed cDNA and 200bp-mismatched sequence, it is suggested that mismatched sequence may really inhibit the binding of antisense mRNA to sense mRNA or that antisense treatment may not be so effective as it has been reported.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Yamaguchi M, et al.: "Dextran sulfate inhibited neutrophil adhesion to endotoxin-activated vascular endothelial cells via E-selectin-mediated cell adhesion under nonstatic conditions." J. Endotoxin Res.3. 21- (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kitamura N, Yamaguchi M, et al.: "Heparin-like glycosaminoglycans inhibit leukocyte adhesion to endotoxin-activated heuman vascular endothelial cells under nonstatic conditions." Eur Surg Res. 28. 428-435 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuzume M, Yamaguchi M, et al.: "A monoclonal antibody against ICAM-1 suppressed hepatic ischemia-reperfusion injury." Eur Surg Res. 29. 93-100 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M, et al.: "Selective inhibition of vascular cell adhesion molecule-1 expression in human vascular endothelial cells." Transplantation. 63. 759-764 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M, et al.: "Insulin gene transfer can be a new optional therapy for replacement of Pancreas" Transpl. Proc. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M, et al.: "Insulin gene transfer compensated pancreatic β cell function in diabetic rats." Transpl. Proc.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M,et al.: "Dextran sulfate inhibited neutrophil adhesion to endotoxin-activated vascular endothelial cells via E-selectin-mediated cell adhesion under nonstatic conditions." J.Endotoxin Res.3. 21 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kitamura N,Yamaguchi M,et al.: "Heparin-like glycosaminoglycans inhibit leukocyte adhesion to endotoxin-activated human vascular endothelial cells under nonstatic conditions." Eur Surg Res. 28. 428-435 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M,et al.: "Selective inhibition of vascular cell adhesion molecule-1 expression in human vascular endothelial cells." Transplantation. 63. 759-764 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuzume M,Yamaguchi M,et al.: "A monoclonal antibody against ICAM-1 suppressed hepatic ischemia-reperfusion injury." Eur Surg Res.29. 93-100 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsumoto F,Yamaguchi M,et al.: "Allopurinol reduced hepatic ischemia-reperfusion injury exacerbated by inhalation of high-concentration oxygen in rats." Eur.Surg.Res.29. 429-437 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M,et al.: "Effects of flow on neutrophil-mediated Ca2+ response in human vascuar endothelial cells." Inflamm.Res.46. S227 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M,et al.: "Insulin gene transfer can be a new optional therapy for replacement of Pancreas." Transpl.Proc.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M,et al.: "Insulin gene transfer compensated pancreatic beta cell function in diabetic rats." Transpl.Proc.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi M, et al.: "Selective inhibition of vascular cell adhesion molecule-1 expression in human vascular endothelial cells." Transplantation. 63. 759-764 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamaguchi M, et al.: "Effects of flow on neutrophil-mediated Ca2+response in human vascular endothelial cells." Inflamm.Res.46. S227 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamaguchi M, et al.: "Insulin gene transfer can be a new optional therapy for replacement of Pancreas" Transpl.Proc.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamaguchi M, et al.: "Insulin gene transfer compensated pancreatic β cell function in diabetic rats." Transpl.Proc.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Kumada K,et al.: "Amelioration of hepatocellular integrity and inhibition of sinusoidal oxidative stress by N-acetylcysteine pretreatment in cold ischemia-reperfusion injury of rat liver." Eur Surg Res. 28. 245-255 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kumada K,et al: "Histopathological response to preoperative chemotherapy including 5-fluorouracil additionally assessed by immunocytochemical and pharmacologic parameters in advanced gastric cancer patients." Surg Today. 26. 482-488 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamaguchi M,et al.: "Selective Inhibition of vascular cell adhesion molecule-1 expression in human vascular endothelial cells" Transplantation. 63. 1-6 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamaguchi M,et al.: "Prediction of postoperative decompensated liver function by technetium 99m galactosyl human serum albumin liver scintigraphy in patients with hepatocellular carcinoma" Br J Surg in press.

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamaguchi M,et al.: "A monoclonal antibody against ICAM-1 suppressed hepatic ischemia-reperfusion injury." Eur Surg Res. 29. 93-100 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamaguchi M,et al.: "Heparin-like glycosaminoglycans inhibit leukocyte adhesion to endotoxin-activated human vascular endothelial cells under nonstatic conditions." Eur Surg Res. 28. 428-435 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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