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Clarify of the mechanism of anti-angiogenesis by PEDF and clinical application of PEDF gene therapy

Research Project

Project/Area Number 18591496
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HIRANO Satoshi  Hokkaido University, Graduate School of medicine, Associate Professor (50322813)

Co-Investigator(Kenkyū-buntansha) KONDO Satoshi  Satoshi Hokkaido University, Graduate School of medicine, Professor (30215454)
MIYAMOYO Masaki  Masaki Hokkaido University, Hokkaido University Hospital, Research Associate (40333611)
SHHINOHE Toshiaki  Toshiaki Hokkaido University, Graduate School of medicine, Lecture (70374353)
HIDA Yasuhiro  Hokkaido University, Hokkaido University Hospital, Lecturer (30399919)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsAnti-angiogenesis / PEDF / gene therapy / cancer / 膵癌 / 血管新生阻害 / 受容体 / 食道癌
Research Abstract

Pigment epithelium-derived factor (PEDF), which has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, is also expressed in the pancreas. Previously, we have screened the expression of PEDF by immunohistochemical analysis and demonstrated that PEDF expression is associated with increased risk of hepatic metastasis and short survival. In this study, we investigated both in vitro and in vivo growth characteristics of human pancreatic adenocarcinoma cell lines that were stably transfected to overexpress human PEDF. We discovered that cells secreted PEDF protein in the media, and this exhibited strong inhibitory effects on proliferation and migration of human umbilical vein endothelial cells. The size of PEDF-overexpressing pancreatic adenocarcinoma cells was significantly smaller than that of control cells in subcutaneous tumor models. Moreover, the growth of PEDF-overexpressing pancreatic adenocarcinoma cells was significantly suppressed in comparison with control cells in peritoneal metastasis models. In gene transfer models, intratumoral injection of a lentivirus. vector encoding PEDF (LV-PEDF) caused significant inhibition of tumor growth. The antitumor effect observed after treatment with LV-PEDF was associated with decreased microvessel density in tumors. The data presented here show that lentivirus-mediated gene transfer of PEDF could significantly reduce tumoral neoangiogenesis and tumor growth in animal models with human pancreatic adenocarcinoma. In conclusion, our data suggest that PEDF may exert a biological effect on tumor angiogenesis, and PEDF gene therapy may provide a new approach for treatment of pancreatic adenocarcinom

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (32 results)

All 2007 2006 Other

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (26 results)

  • [Journal Article] DRD2/DARPP-32expression correlates with lymph node metastasis and tumor progression in patients with esophageal squamous cellcarcinoma2006

    • Author(s)
      Li L, Miyamoto M, etc
    • Journal Title

      World J Surg 30

      Pages: 1672-1679

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Subcarinal Node Is the Significant Node That Affects Survival in Resec ted Small Cell Lung Cancer2006

    • Author(s)
      Miyamoto M, Morikawa T etc
    • Journal Title

      Surg Today 36

      Pages: 671-675

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cance2006

    • Author(s)
      T Oshikiri, M Miyamoto etc
    • Journal Title

      Cancer Gene Ther 13

      Pages: 856-863

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] DRD2/DARPP-32expression correlates with lymph node metastasis and tumor progression in patients with esophageal squamous cell carcinoma2006

    • Author(s)
      Li L, Miyamoto M, etc
    • Journal Title

      World J Surg 30

      Pages: 1672-1679

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Subcarinal Node Is the Significant Node That Affects Survival in Resected Small Cell Lung Cancer2006

    • Author(s)
      Miyamoto M, Morikawa T etc
    • Journal Title

      Surg Today 36

      Pages: 671-675

    • NAID

      10018169453

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer

    • Author(s)
      T Oshikiri, M Miyamoto etc
    • Journal Title

      Cancer Gene Ther 13

      Pages: 856-863

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 血管新生阻害因子PEDFによる遺伝子治療2007

    • Author(s)
      宮本正樹
    • Organizer
      日本消化器癌発生学会
    • Place of Presentation
      札幌
    • Year and Date
      2007-11-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 食道扁平上皮癌におけるCD40-CD154発現の検討2007

    • Author(s)
      松村祥幸
    • Organizer
      日本消化器癌発生学会
    • Place of Presentation
      札幌
    • Year and Date
      2007-11-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Gene therapy with angiogenesis inhibitor thrombospondin2007

    • Author(s)
      Miyamoto M
    • Organizer
      Japanese Society for Gastroenterological Carcinogenesis
    • Place of Presentation
      Sapporo
    • Year and Date
      2007-11-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of CD40-CD154 esophageal squamous cell carcinoma2007

    • Author(s)
      Matsumura Y
    • Organizer
      Japanese Society for Gastroenterological Carcinogenesis
    • Place of Presentation
      Sapporo
    • Year and Date
      2007-11-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Preoperative serum CYFRA is a prognostic factor of resected non-small cell lung cancer2007

    • Author(s)
      樋田泰浩
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Up-regulation of CD40 with juxtacrine activity in human non-small lung cancer cells correlates with poor prognosis2007

    • Author(s)
      石川慶大
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulatory T Cell Numbers Strongly Correlate with the CD8/CD4 Ratio in Esophageal Squamous Cell Carcinoma2007

    • Author(s)
      吉岡達也
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Preoperative serum CYFRA is a prognostic factor of resecte non-small cell lung cancer2007

    • Author(s)
      Hida Y
    • Organizer
      Japanese Association.
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Up-regulation of CD40 with juxtacrine activity in human Plays a Significant Role in Human Lung Carcinogenesis non-small lung cancer cells correlates with poor prognosis2007

    • Author(s)
      Ishikawa K
    • Organizer
      Japanese Association.
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulatory T Cell Numbers Strongly Correlate with the CD8/CD4 Ratio in Esophageal squamous Cell Carcinoma2007

    • Author(s)
      Yoshioka T
    • Organizer
      Japanese Association.
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Low 18F-FDG uptake by primary tumor as a negative predictor of lymph node involvement in resected non-small cell lung cancers2007

    • Author(s)
      樋田泰浩
    • Organizer
      12th World Conference on Lung Cancer
    • Place of Presentation
      Korea
    • Year and Date
      2007-09-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Low 18F-FDG uptake by primary tumor as a negative predictor of lymph node involvement in resected non-small cell lung cancers2007

    • Author(s)
      Hida Y
    • Organizer
      12^<th> World Conference on Lung Cancer
    • Place of Presentation
      Korea
    • Year and Date
      2007-09-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 術前リンパ節転移予測因子からみた肺癌に対する積極的縮小手術の適応の検討2007

    • Author(s)
      樋田泰浩
    • Organizer
      日本呼吸器外科学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-05-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 非小細胞肺癌におけるCD40-CD154発現の検討2007

    • Author(s)
      石川慶大
    • Organizer
      日本呼吸器外科学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-05-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Prediction of preoperative lympth node metastasis positive reduct Operation adapt for lung cancer2007

    • Author(s)
      Hida Y
    • Organizer
      Japanese Association for chest surgery
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-05-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of CD40-CD154 with non-small cell lung cancer2007

    • Author(s)
      Ishikawa K
    • Organizer
      Japanese Association for chest surgery
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-05-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Natural VEGF antagonist SEMA3Fによる腫瘍細胞と血管内皮細胞を標的とした転移抑制。シンポジウム「癌の転移形成のメカニズムと治療戦略」2007

    • Author(s)
      樋田泰浩
    • Organizer
      日本外科学会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 非小細胞肺癌におけるCD40発現の検討2007

    • Author(s)
      石川慶大
    • Organizer
      日本外科学会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Suppression of metastasis with tumor cells and vascular endothelium For Natural VEGF antagonist SEMA3F2007

    • Author(s)
      Hida Y
    • Organizer
      Japanese surgical Society
    • Place of Presentation
      Osaka
    • Year and Date
      2007-04-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of CD40 with non-small cell lung cancer.2007

    • Author(s)
      Ishikawa K
    • Organizer
      Japanese surgical Society.
    • Place of Presentation
      Osaka
    • Year and Date
      2007-04-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A green tea polyphenol, epigallocatechin-3gallate(EGCG)inhibits migration of tumor-associated endothelial cells and endothelial progenitor cells2007

    • Author(s)
      樋田泰浩
    • Organizer
      7th AACR-JCA joint international conference in the Forefront of Basic and Translational Cancer Research
    • Place of Presentation
      HAWAII
    • Year and Date
      2007-01-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A green tea polyphenol, epigallocatechin-3gallate (EGCG) inhibits migration of tumor-associated endothelial cells and endothelia progenitor cells2007

    • Author(s)
      Hida Y
    • Organizer
      7^<th> AACR-JCA joint international conference in the Forefront of Basic 1 and Translational Cancer Research.
    • Place of Presentation
      Hawaii
    • Year and Date
      2007-01-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pigment Epithelium-Derived Factor Gene Therapy Inhibits Human Pancreatic Cancer in Mice2006

    • Author(s)
      長谷龍之介
    • Organizer
      World Congress on Advances in Oncology and 9th International Symposium on Molecular Medicine
    • Place of Presentation
      Greece
    • Year and Date
      2006-10-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 血管新生阻害因子Pigment epithelium-derived factor (PEDF)を用いた食道扁平上皮癌の遺伝子治療2006

    • Author(s)
      角谷昌俊
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Gene therapy of esophageal squamous cell carcinoma with Angiogenesis inhibitor thrombospondin Pigment epithelium-Derived factor (PEDF).2006

    • Author(s)
      Kadoya T
    • Organizer
      Japanese Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-28
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pigment Epithelium-Derived Factor Gene Therapy Inhibits Human Pancreatic Cancer in Mice

    • Author(s)
      Hase R
    • Organizer
      World Congress on Advances in Oncology and 9^<th> International Symposium on Molecular Medicine
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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