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Trial research for practical use of the reagent for gene expression control by Decoy oligo nucleotide.

Research Project

Project/Area Number 11557020
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Experimental pathology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

NAKAGAWA Kazunori  KYUSHU UNIVERSITY, Graduate School of Medical Science, Lecturer, 大学院・医学系研究院, 講師 (50217668)

Co-Investigator(Kenkyū-buntansha) NAKASHIMA Yutaka  KYUSHU UNIVERSITY, Graduate School of Medical Science, Associate Professor, 大学院・医学系研究院, 助教授 (50135349)
ISHIBASHI Hiroaki  KYUSHU UNIVERSITY, Graduate School of Dental Science, Assistant, 大学院・歯学系研究院, 助手 (90254630)
SUEISHI Katsuo  KYUSHU UNIVERSITY, Graduate School of Medical Science, Professor, 大学院・医学系研究院, 教授 (70108710)
SAKAMOTO Taiji  KYUSHU UNIVERSITY, Graduate School of Medical Science, Lecturer, 医学部・附属病院, 講師 (10235179)
橋本 修一  九州大学, 大学院・医学系研究科, 助手 (00243931)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥9,100,000 (Direct Cost: ¥9,100,000)
KeywordsGene Transfer / Antisense / Liposome / Transcription Factor / Decoy / Angiogenesis / Endothelial Cell
Research Abstract

We inspected availability, reproducibility and stability of novel gene therapy using the combination of "suppression of disease-related gene expression by a decoy for transcription factor" and "gene transfer by hemagglutinating virus of Japan (HVJ)- liposome".
Using HVJ-liposome method, we transferred Sp1 decoy into cultured cancer cells (A549 and U251 cells). The TNF-alpha-mediated expression of both VEGF and TGF betal and tissue factor (TF) by the cancer cells could be simultaneously suppressed to less than 30% by transfection of Sp1 decoy but not by mutated-Sp1 decoy. In addition, in vitro invasiveness, synthesis of mRNA for urokinase-type plasminogen activator, andcell proliferation of both cell lines were also inhibited to 40% by the transfection of only Sp1 decoy. These results suggested that the Sp1 decoy strategy would be effective for regulating tumor growth by simultaneously reducing cancer cell (a) angiogenic growth factor expression, (b) proliferation, and (c) invasiveness. In rabbit balloon injury arteria carotis intima thickening model, NF-kB decoy suppressed the degree of vasoconstriction after injury to about 50%. By using HVJ- liposome, efficiency of NF-kB decoy transfer to vascular wall becomes higher than that of naked NF-kB decoy only. Otherwise, AP-1 was effective for hypoxia stimuli. These are suggested that gene therapy by decoy transfer by HVJ-liposome was extremely effective and has a great advantage for other current ones.
However, stable activity of HVJ- liposome is dependent on quality of the lipids used for liposome preparation (oxidation degrees) and conditions of lipid film. Guarantee period for relatively high efficiency of gene transfer is about 10 days under N2 gas at -20℃ in dark. Therefore, we concluded that the improvements of lipids and conservation form of product are necessary, in order to commercial supply of HVJ-liposome.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Ishibashi H, et al: "Hypoxia-induced angiogenesis of cultured human salivary gland carcinoma cells enhances vascular endothelial growth factor production and basic fibroblast growth factor release."Oral Oncology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishibashi H, et al: "Novel anti-angiogenic gene therapy by cis-trans element decoy system against TNF-a induced Sp-1 transactivation."Cancer Res. 60. 6531-6536 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa K, et al: "Angiogenesis and its regulation : Roles of vascular endothelial cell growth factor (VEGF)."Thromb Hemost. 26(1). 61-66 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitamoto S, et al: "Increased activity of nuclear factor-kappaB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats."Circulation. 102(7). 806-812 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Egashira K, et al: "Anti-monocyte chemoattractant protein-1 gene therapy inhibits vascular remodeling in rats : blockade of MCP-1 activity after intramuscular transfer of a mutant gene inhibits vascular remodeling induced by chronic blockade of NO synthesis."FASEB J. 14(13). 1974-1978 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Imakita M, et al: "The second nationwide study of atherosclerosis in infants, children, and young adults in Japan. Comparison with the first study carried out 13 years ago."Ann N Y Acad Sci.. 902. 364-368 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishibashi H, Shiratuchi T, Nakagawa K, Onimaru M, Sugiura T, Sueishi K, Shirasuna K.: "Hypoxia-induced angiogenesis of cultured human salivary gland carcinoma cells enhances vascular endothelial growth factor production and basic fibroblast growth factor release."Oral Oncology. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishibashi H, Nakagawa K, Onimaru M, Castellanous EJ, Chen YX, Shirasuna K, Sueishi K.: "Novel anti-angiogenic gene therapy by cis-trans element decoy system against TNF-a induced Sp-1 transactivation."Cancer Res. 60. 6531-6536 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa K, Chen YX, Ishibashi H, Yonemitsu Y, Murata T, Hata Y, Nakashima Y, Sueishi K.: "Angiogenesis and its regulation : roles of vascular endothelial cell growth factor."Semin Thromb Hemost. 26(1). 61-66 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitamoto S, Egashira K, Kataoka C, Koyanagi M, Katoh M, Shimokawa H, Morishita R, Kaneda Y, Sueishi K, Takeshita A.: "Increased activity of nuclear factor-kappaB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats."Circulation. 102(7). 806-812 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Egashira K, Koyanagi M, Kitamoto S, Ni W, Kataoka C, Morishita R, Kaneda Y, Akiyama C, Nishida KI, Sueishi K, Takeshita A.: "Anti-monocyte chemoattractant protein-1 gene therapy inhibits vascular remodeling in rats : blockade of MCP-1 activity after intramuscular transfer of a mutant gene inhibits vascular remodeling induced by chronic blockade of NO synthesis."FASEB J. 14(13). 1974-1978 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Imakita M, Yutani C, Sakurai I, Sumiyoshi A, Watanabe T, Mitsumata M, Kusumi Y, Katayama S, Mano M, Baba S, Mannami T, Sueishi K, Tanaka K.: "The Second nationwide study of atherosclerosis in infants, children, and young adults in Japan. Comparison with the first study carried out 13 years ago."Ann N Y Acad Sci. 902. 364-368 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikawa H, Ishibashi T, Hata Y, Inomata H, Sueishi K.: "The Suppressive effect of tecogalan sodium on in vitro angiogenesis via the periendothelial proteolytic activities."Ophthalmic Res. 32(6). 261-269 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishibashi H, et al: "Hypoxia-induced angiogenesis of cultured human salivary gland carcinoma cells enhances vascular endothelial growth factor production and basic fibroblast growth factor release."Oral Oncology. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishibashi H, et al: "Novel anti-angiogenic gene therapy by cis-trans element decoy system against TNF-a induced Sp-1 transactivation."Cancer Res. 60. 6531-6536 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakagawa K, et al: "Angiogenesis and its regulation : Roles of vascular endothelial cell growth factor (VEGF)."Thromb Hemost. 26(1). 61-66 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitamoto S, et al: "Increased activity of nuclear factor-kappaB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats."Circulation. 102(7). 806-812 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Egashira K, et al: "Anti-monocyte chemoattractant protein-1 gene therapy inhibits vascular remodeling in rats : blockade of MCP-1 activity after intramuscular transfer of a mutant gene inhibits vascular remodeling induced by chronic blockade of NO synthesis."FASEB J. 14(13). 1974-1978 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Imakita M, et al: "The second nationwide study of atherosclerosis in infants, children, and young adults in Japan. Comparison with the first study carried out 13 years ago."Ann N Y Acad Sci.. 902. 364-368 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakagawa K et al: "Angiogenesis and Its Regulation : Roles of Vascular Endothelial Cell Growth Factor (VEGF)"Semin Thromb Hemost. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakamoto T et al: "Target gene transfer to cornea by electric pulse inhibits iuntracameral fibrin formation and corneal cloudiness."Hum Gene Therapy. 10. 2251-2257 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Chen Y et al: "Immunohistochemical expression of VEGF in the atherosclerotic intimas of human coronary arteries"Arterioscler Thromb Vasc Biol. 19(1). 131-139 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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