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消化器癌の増殖・転移に対する血管内皮前駆細胞の関与と遺伝子治療への応用

Research Project

Project/Area Number 11671204
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIZOI Takayuki  Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (90271949)

Co-Investigator(Kenkyū-buntansha) KATAYOSE Yu  Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (20302151)
ISHII Seiichi  Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (60221066)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordscarcinoma of digestive organs / colorectal cancer / endothelial cells / endothelial progenitor cells / angiogenesis
Research Abstract

1. Isolation of Endothelial Progenitor Cells (EPCs) from Human Peripheral Blood We isolated CD34-positive mononuclear cells from human peripheral blood by using magnetic beads conjugated with an anti-CD34 antibody. These isolated cells were cultured on the plastic plates coated with or without fibronectin. we used the culture medium containing some endothelial cell growth factors. Spindle-shaped adherent cells appeared on the plates 48 hr after the culture. These spindle-shaped cells proliferated and differentiated more extensively when mixed with CD34-negative mononuclear cells. These cells were positive for CD34 by immunofluorescent staining, and incorporated Dil-labeled acetylated low-density lipoprotein such as endothelial cells.
2. In Vivo Experiments
(1) 2x10^6 of human colon carcinoma cells were subcutaneously inoculated in immunodeficient mice. Human EPCs which were labeled with BCECF-AM were injected into tail vein in the mice. The subcutaneous tumors were excised 1 week after the inoculation and the frozen sections of the tumors were observed by a fluorescent microscopy. BCECF-AM-positive cells, however, were not detected in the samples.
(2) Human EPCs labeled with BCECF-AM were not observed in the subcutaneous tumors when more EPCs were subcutaneously injected into tail vein of the mice with subcutaneous tumors. In vivo microscopy did not detect the accumulation of EPCs around the subcutaneous tumors as well. Subcutaneous tumor models of other cancer cell lines were also tested but EPCs were not accumulated in the subcutaneous tumors.
Taken together, EPCs could be isolated and cultured in vitro, but EPCs were not accumulated in the mice tumor models in vivo. These results suggest the application of EPCs to gene therapy against cancer is not possible up to the present.

Report

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

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 溝井賢幸: "大腸癌細胞へのCD44変異体の遺伝子導入による機能解析"外科治療. 80・2. 256-257 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jessup J.M.: "Carcinoembryonic antigen facilitates experimental metastasis through a mechanism that does not involve adhesion to liver cells"Clinical & Experimental Metastasis. 17. 481-488 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada N.: "Introduction of antisense CD44s cDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colonic carcinoma cells"International Journal of Cancer. 91. 67-75 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizoi T.: "Functional analysis of colorectal carcinoma cells introduced with CD44 variants cDNA."Geka chiryo. 80. 256-257 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jesup J.M.: "Carcinoembryonic antigen facilitates experimental metastasis through a mechanism that does not involve adhesion to liver cells."Clinical & Experimental Metastasis.. 17. 481-488 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada N.: "Introduction of antisense CD44s cDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colonic carcinoma cells."International Journal of Cancer. 91. 67-75 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 溝井賢幸: "大腸癌細胞へのCD44変異体の遺伝子導入による機能解析"外科治療. 80・2. 256-257 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jessup J.M.: "Carcinoembryonic antigen facilitates experimental metastasis through a mechanism that dose not involve adhesion to liver cells"Clinical & Experimental Metastasis. 17. 481-488 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Harada N.: "Introduction of antisense CD44s cDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colonic carcinoma cells"International Journal of Cancer. 91. 67-75 (2001)

    • Related Report
      2000 Annual Research Report

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

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