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Analyses of tumor angiogenesis and development of antiangiogenic gene therxpy

Research Project

Project/Area Number 13671230
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MORI Akira  Kyoto University, Graduate school of Medicine, Assistant Professor, 医学研究科, 助手 (60324646)

Co-Investigator(Kenkyū-buntansha) MAEDA Masato  Kyoto University, Graduate School of Medicine., Assistant Professor, 医学研究科, 助手 (10314220)
ARAI Shigeki  Tokyo Medical and Dental University Graduate School, Professor, 医歯学総合研究科, 教授 (50151171)
IMAMURA Masayuki  Kyoto University, Graduate school of Mebicine, Professor, 医学研究科, 助手 (00108995)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsTumor angiogenesis / Antiangiogenic gene therapy
Research Abstract

1. Analyses of tumor angiogenesis from the viewpoint of microstructure
Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis. In a mouse tumor model using VEGF-transfected HT1080 human fibrosarcoma cell, we investigated morphological features and remodeling patterns of tumor angiogenesis by transmission electron microscope. VEGF-transfected tumors showed vigorous angiogenesis. Among three types of angiogenesis, I.e., sprouting, luminal division and intussusceptive microvascular growth, the number of abluminal processes leading to sprouting was significantly higher than control tumors. Mural cell coverage of endothelial cells was singificantly smaller in VEGF-transfectant. We evaluated microvessel density (MVD) and microvessel pericyte coverage index (MPI) using clinical specimen of colon cancer by immunohistochemical double staining with CD34 and α-SMA against endothelial cell and pericyte, respectively. The prognosis was poor in high-MVD group, especially … More , in high-MVD and low-MPI group. These results suggested that the interaction of endothelial cell and pericyte was a key role in tumor angiogenesis
2. Development of antiangiogenic gene therapy for cancer
We reported that repeated in vivo transduction of mouse macrophage metalloelastase (MME) gene directly into the tumor of CT-26 mouse colon cancer using HVJ-cationic liposomes suppressed the tumor growth by an antiangiogenic mechanism
We reported that administration of autologous fibroblasts transfected with soluble form of Flt-1, a VEGF receptor, suppressed the tumor growth and prolonged the survival in the wound recurrence model of RCN-9 rat colon cancer
We investigated MVD representing aerobic metabolism and expression of hexiokinase II mRNA (HK II) representing anaerobic metabolism using clinical specimens of hepatocellular carcinoma and metastatic liver cancer from colon. MVD was significantly higher in hepatocellular carcinoma and HK II was significantly higher in metastatic liver cancer. We are developing a hypoxia-induced suicide gene system for treatment of angiogenesis-independent tumor Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Weige Yang: "Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance"Cancer. 91・7. 1277-1283 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Manuel J.Gorrin-Rivas: "Mouse macrophage metalloelastase gene delivery by HVJ-cationic liposome in experimental antiangiogenic gene therapy for murine CT-26 colon cancer"International Journal of Cancer. 93. 731-735 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Weige Yang: "sFlt-1 gene-transfected fibroblasts : a wound-specific gene therapy inhibits local cancer recurrence"Cancer Research. 61. 7840-7845 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaki Mizumoto: "A novel suicide gene therapy system for p53-mutated cells using a wild-type p53-specific promoter and Cre/IoxP switch"Surgery Today. 32. 53-58 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 森 章: "VEGFレセプターと転移抑制"Surgery Frontier. 8・2. 42-46 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 森 章: "腫瘍血管新生とその制御"組織培養工学. 27・12. 492-495 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Weige Yang: "Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopatholoeic significance"Cancer. 91. 1277-1283 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Manuel J, Gorrin-Rivas: "Mouse macrophage metalloelastase gene delivery by HVJ-cationic liposomes in experimental antiangiogenic gene therapy for murine CT-26 colon cancer"Int J Cancer. 93. 731-735 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Weige Yang: "sFlt-1 gene-transfected fibroblasts: a wound-specific gene therapy inhibits local cancer recurrence"Cancer Res. 61. 7840-7845 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaki Mizumoto: "A novel suicide gene therapy system for p53-mutated cells using a wild-type p53-specific promoter and Cre/loxP switch"Surg Today. 32. 53-58 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akira Mori: "New strategy for metastasis using VEGF receptor"Surgery Frontier. 8. 42-46 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akira Mori: "New strategy for cancer therapy targeting angiogenesis"Soshikibaiyoukougaku. 27. 492-495 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Weige Yang: "sFlt-1 gene-transfected fibroblasts : a wound-specific gene therapy inhibits local cancer recurrence"Cancer Research. 61. 7840-7845 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Manuel J.Gorrin-Rivas: "Mouse macrophage metalloelastase gene delivery by HVJ-cationic liposomes in experimental antiangiogenic gene therapy for murine CT-26 colon cancer"International Journal of Cancer. 93. 731-735 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Weige Yang: "Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance"Cancer. 91. 1277-1283 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizumoto Masaki: "A novel suicide gene therapy system for p53-mutated cells using a wild-type p53-specific promoter and Cre/loxP switch"Surgery Today. 32. 53-58 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 森 章: "VEGFレセプターと転移抑制"Surgery Frontier. 8・2. 42-46 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 森 章: "腫瘍血管新生とその制御"組織培養工学. 27・12. 492-495 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Weige Yang: "sFlt-1 gene-transfected fibroblasts : A wound-specific gene therapy inhibits local cancer recurrence"Cancer Research. 61. 7840-7845 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Manuel J.Gorrin-Rivas: "Mouse macrophage metalloelastase gene delivery by HVJ-cationic liposomes in experimental entiagiogenic gene therapy for murine CT-26"International Journal of Cancer. 93. 731-735 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Weige Yang: "Human macrophage metallelasrase gene expression in colorectal carcinoma and its clinico pathologic significance"Cancer. 91. 1277-1283 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 森 章: "VEGFレセプターと転移抑制"Surgery Frontier. 8・2. 42-46 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 森 章: "腫瘍血管新生とその制御"組織培養工学. 27・12. 492-495 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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