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Hypoxia-to-reoxygenation condition as one of the internal carcinogenic factors of common cancers

Research Project

Project/Area Number 17590334
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionYamagata University

Principal Investigator

OKADA Futoshi  Yamagata University, Department of Biomolecular Function, Graduate School of Medical Science, Associate Professor, 大学院医学系研究科, 助教授 (00250423)

Co-Investigator(Kenkyū-buntansha) FUJII Junichi  Yamagata University, Department of Biomolecular Function, Graduate School of Medical Science, Professor, 大学院医学系研究科, 教授 (00222258)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsHypoxia reperfusion / Free radical / Carcinogenesis / DNA microarray / Proteomics / 悪性化
Research Abstract

We examined whether free radicals generated in a series of ischemia-reperfusion condition could act as an endogenous carcinogenic factor in normal or premalignant cells. We obtained various cell lines from human epithelial cells, rodent immortalized fibroblasts and benign fibrosarcoma cells to examine whether those cell lines could be converted into tumorigenic ones after cultivation in a series of hypoxia-reoxygenation condition. Free radicals were produced in the cells after they were cultured in the hypoxia-reoxygenation condition. Peroxides, a part of free radicals, were detected by using the specific probe 2', 7'-dichlorodihydrofluorescein diacetate (H2DCFDA). The production of peroxides was suppressed by an addition of several free radical scavengers into the culture medium. Among those cell lines, non-tumorigenic mouse fibroblast cell lines were converted into tumorigenic ones in nude mice. We then compared their gene/protein expressions with their normal counterparts. We have identified two genes possibly related with carcinogenesis by combinational analyses of DNA microarray and two-dimensional protein electrophoresis. The expression of the two genes decreased in the tumorigenic cells compared to parent cells. We found that one of the two genes actually regulated tumorigenic potential of the mouse fibroblast cells. We expect to further confirm this finding after examining expressions of those genes in a variety of human tumor tissues and rodent spontaneous arising tumors.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (26 results)

All 2006 2005

All Journal Article (25 results) Book (1 results)

  • [Journal Article] The role of nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species in the acquisition of metastatic ability of tumor cells.2006

    • Author(s)
      Okada F et al.
    • Journal Title

      Am J Pathol 169

      Pages: 294-302

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prevention of inflammation- mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available superoxide dismutase.2006

    • Author(s)
      Okada F et al.
    • Journal Title

      Br J Cancer 94(6)

      Pages: 854-862

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of reactive nitrogen oxides for acquisition of metastatic properties of benign tumors in a model of inflammation-based tumor progression.2006

    • Author(s)
      Okada F et al.
    • Journal Title

      Nitric Oxide 14 (2)

      Pages: 122-129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular mechanisms of inflammation-induced carcinogenesis.2006

    • Author(s)
      Okada F, Fujii J
    • Journal Title

      J Clin Biochem Nutr 39

      Pages: 103-113

    • NAID

      130004879097

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Suppression of tumor growth by intra-muscular transfer of naked DNA encoding adrenomedullin antagonist.2006

    • Author(s)
      Miseki T et al.
    • Journal Title

      Cancer Gene Ther 14(l)

      Pages: 39-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells.2006

    • Author(s)
      Tanaka H et al.
    • Journal Title

      Int J Cancer 118

      Pages: 1680-1691

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available superoxide dismutase.2006

    • Author(s)
      Okada F et al.
    • Journal Title

      Br J Cancer 94(6)

      Pages: 854-862

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Involvement of reactive nitrogen oxides for acquisition of metastatic properties of benign tumors in a model of inflammation-based tumor progression.2006

    • Author(s)
      Okada F et al.
    • Journal Title

      Nitric Oxide 14(2)

      Pages: 122-129

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Suppression of tumor growth by intra- muscular transfer of naked DNA encoding adrenomedullin antagonist.2006

    • Author(s)
      Miseki T et al.
    • Journal Title

      Cancer Gene Ther 14(1)

      Pages: 39-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The role of nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species in the acquisition of metastatic ability of tumor cells.2006

    • Author(s)
      Nkada F et al.
    • Journal Title

      Am J Pathol 169

      Pages: 294-302

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Suppression of tumor growth by intra-muscular transfer of naked DNA encoding adrenomedullin antagonist.2006

    • Author(s)
      Miseki T et al.
    • Journal Title

      Cancer Gene Ther 14(1)

      Pages: 39-44

    • Related Report
      2006 Annual Research Report
  • [Journal Article] siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelia cells.2006

    • Author(s)
      Tanaka H et al.
    • Journal Title

      Int J Cancer 118

      Pages: 1680-1691

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hypoxia suppresses the production of matrix metalloproteinases and migration of human monocyte-derived dendritic cells.2005

    • Author(s)
      Zhao W et al.
    • Journal Title

      Eur J Immunol 35(12)

      Pages: 3468-3477

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system.2005

    • Author(s)
      Fujii J et al.
    • Journal Title

      Reprod Biol Endocrinol 3

      Pages: 43-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Accelerated impairment of spermatogenic cells in SOD1-knockout mice under heat stress.2005

    • Author(s)
      Ishii T et al.
    • Journal Title

      Free Radic Res 39

      Pages: 697-705

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Specific inactivation of cysteine protease-type cathepsin by singlet oxygen generated from naphthalene endoperoxides.2005

    • Author(s)
      Nagaoka Y et al.
    • Journal Title

      Biochem Biophys Res Commun 331

      Pages: 215-223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prevention of tumor progression as the ultimate goal of cancel therapy.2005

    • Author(s)
      Okada F, Fujii J
    • Journal Title

      Cancer Therapy 3

      Pages: 219-226

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell lines.2005

    • Author(s)
      Hayashi E et al.
    • Journal Title

      Proteomics 5

      Pages: 1024-1032

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prevention of tumor progression as the ultimate goal of cancer therapy.2005

    • Author(s)
      Okada F, Fujii J
    • Journal Title

      Cancer Therapy 3

      Pages: 219-226

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoxia suppresses the production of matrix metalloproteinases and migration of human monocyte-derived dendritic cells.2005

    • Author(s)
      Zhao, W.et al.
    • Journal Title

      Eur J Immunol 35(12):

      Pages: 3468-3477

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system2005

    • Author(s)
      Fujii, J et al.
    • Journal Title

      Reprod Biol Endocrinol 3

      Pages: 43-52

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Accelerated impairment of spermatogenic cells in SOD1-knockout mice under heat stress2005

    • Author(s)
      Ishii, T.et al.
    • Journal Title

      Free Radic Res, 39

      Pages: 697-705

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prevention of tumor progression as the ultimate goal of cancer therapy.2005

    • Author(s)
      Okada F et al.
    • Journal Title

      Cancer Therapy 3

      Pages: 219-226

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Specific inactivation of cysteine protease-type cathepsin by singlet oxygen generated from naphthalene endoperoxides.2005

    • Author(s)
      Nagaoka, Y et al.
    • Journal Title

      Biochem Biophys Res Commun, 331

      Pages: 215-223

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Proteomic profiling for cancer progression: Differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell lines.2005

    • Author(s)
      Hayashi E et al.
    • Journal Title

      Proteomics 5

      Pages: 1024-1032

    • Related Report
      2005 Annual Research Report
  • [Book] 炎症発癌と活性酸化窒素種,「別冊医学のあゆみ,酸化ストレスver.2フリーラジカル医学生物学の最前線」(吉川敏一 編集)2006

    • Author(s)
      岡田 太
    • Total Pages
      4
    • Publisher
      医歯薬出版株式会社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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