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New therapeutic strategies for malignant brain tumors by using genetic and molecular biology

Research Project

Project/Area Number 16390411
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKochi University

Principal Investigator

SHIMIZU Keiji  Kochi Medical School, Dept.of Neurosurgery, Professor, 医学部, 教授 (50162699)

Co-Investigator(Kenkyū-buntansha) PARK Kae chang  Kochi Meidical School Hospital, Dept.of Neurosurgery, Assistant Professor, 医学部附属病院, 講師 (60333514)
YAMADA Shoko  Kochi Meidical School Hospital, Dept.of Neurosurgery, Assistant Professor, 医学部附属病院, 講師 (60287761)
IKENAKA Kazuhiro  National Institutes of Natural Sciences, National Institute for Physiological Sciences, Professor, 生理学研究所, 教授 (00144527)
YAWATA Toshio  Kochi Meidical School, Dept.of Neurosurgery, Research Associate, 医学部, 助手 (40380323)
土屋 孝弘  高知大学, 医学部, 助手 (60346715)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
KeywordsGlioblastoma / Retrovirus Vecter / Promoter / Gene Therapy / MAGE-D4 / Integrin α3 / Embryonic Stem Cell / Microglia / MAGE-E1
Research Abstract

For more than 10 years, we have made some fundamental studies on brain-specific gene therapy controlled suicide gene (Herpes Simplex Virus thymidine kinase; HSV tK) with promoter expressed Myelin basic protein (MBP) gene. As these malignant gliomas show high or low MBP-expressed gene, we search a new high-titer glioma-specific gene therapy by using some new retroviral vectors transduced promoter expressing MAGE-D4 gene (Cancer Res 61: 4809-4814, 2001; Gene 277: 129-137, 2001), or other genes. And also selectively gene-inserted retroviral vectors are on-going. As most malignant brain tumors, glioblastomas multiforme (GBM) express Olig2 transcription factors in the very high level, they may be induced by distraction of Olig2-down-regulated differentiation cascade. Therefore, we start in investigate a new therapeutic strategy, which we can restore to the very high differentiated stage from the undifferentiated GBM by transduction of Olig2-down-regulated factors.
The monoclonal antibody ONS-M21 recognizes an antigen, which is integrin □3, found on the surface of some gliomas (Br J Cancer 68: 831-837, 1993; Br J Cancer 79: 333-339, 1999). Then, we explore the correlation between integrin □3 expression and MAGE-D4 gene appearance in glioma patients. We had already published about Cystatin C, CDC25B and RCAS1 expressions in gliomas. Besides, we begin to investigate new immuno-cytotherapy by using migration activities of microglia induced from mouse embryonic stem cells.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (29 results)

All 2007 2006 2005 2004 Other

All Journal Article (24 results) Book (5 results)

  • [Journal Article] Clinico-pathological significance of RCAS1 expression in gliomas : A potential mechanism of tumor immune escape.2007

    • Author(s)
      Nakabayashi H, et al.
    • Journal Title

      Cancer Letters 246

      Pages: 182-189

    • 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] Expression of MAGE-D4, a novel MAGE family antigen, is correlated with tumor-cell proliferation of non-small cell lung cancer.2006

    • Author(s)
      Ito S, et al.
    • Journal Title

      Lung Cancer 51 (1)

      Pages: 79-88

    • 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 the Olig2 transcription factor in cholinergic neuron development of the basal forebrain.2006

    • Author(s)
      Furusho M, et al.
    • Journal Title

      Developmental Biology 293(2)

      Pages: 348-357

    • 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] Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells.2006

    • Author(s)
      Masahira N, et al.
    • Journal Title

      Developmental Biology 293(2)

      Pages: 358-369

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prognostic significance of CDC25B expression in gliomas.2006

    • Author(s)
      Nakabayashi H, et al.
    • Journal Title

      Journal of Clinical Pathology 59

      Pages: 725-728

    • 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] Expression of MAGE-D4, a novel MAGE family antigen, is correlated with tumor-cell proliferation of non-small cell lung cancer.2006

    • Author(s)
      Ito S, et al.
    • Journal Title

      Lung Cancer 51(1)

      Pages: 79-88

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes,but also to a subset of astrocytes and ependymal cells.2006

    • Author(s)
      Masahira N, et al.
    • Journal Title

      Developmental Biology 293(2)

      Pages: 358-369

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of MAGE-D4, a novel MAGE family antigen, is correlate with tumor-cell proliferation of non-small cell lung cancer.2006

    • Author(s)
      Ito S, et al.
    • Journal Title

      Lung Cancer 51(1)

      Pages: 79-88

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Improved preservation of X-gal reaction product for electron microscopy using hydroxypropyl methacrylate.2005

    • Author(s)
      Masahira N, et al.
    • Journal Title

      Neuroscience Letters 374(1)

      Pages: 17-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Characterization of microglia induced from mouse embryonic stem cells and their migration into the brain parenchyma.2005

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

      Journal of Neuroimmunology 160

      Pages: 210-218

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Double-platinum chemotherapy combined with etoposide in metastatic brain tumor from small cell lung carcinoma.2005

    • Author(s)
      Yamada SM, et al.
    • Journal Title

      Journal of Neuro-Oncology 71(3)

      Pages: 259-265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Clinocopathological significance of cystatin C expression in gliomas.2005

    • Author(s)
      Nakabayashi H, et al.
    • Journal Title

      Human Pathology 36(9)

      Pages: 1008-1015

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Isolation and characterization of an N-linked oligosaccharide that is increased in glioblastoma tissue and cell lines.2005

    • Author(s)
      Tsuchiya N, et al.
    • Journal Title

      International Journal of Oncology 27

      Pages: 1231-1239

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Improved preservation of X-gal reaction product for electron microscopy using hydroxypropyl methacrylate.2005

    • Author(s)
      Masahira N, et al.
    • Journal Title

      Neuroscience Letters 374(l)

      Pages: 17-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gene therapy of gliomas.2005

    • Author(s)
      Masahira N, et al.
    • Journal Title

      New perspectives in Cancer Research and Therapy (Kuriyama S, Yoshiji H (eds.)) (Research Signpost)

      Pages: 325-335

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Primitive neuroectodermal Tumor (PNET) treated with Interferon-β after surgical removal and irradiation : case report.2004

    • Author(s)
      Park KC, et al.
    • Journal Title

      Anticancer Research 24

      Pages: 1105-1110

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Primitive neuroectodermal Tumor (PNET) treated with Interferon-Rafter surgical removal and irradiation : case report.2004

    • Author(s)
      Park KC, et al.
    • Journal Title

      Anticancer Research 24

      Pages: 1105-1110

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Primitive neuroectodernal Tumor (PNET) treated with Interferon-β after surgical removal and irradiation : case report.2004

    • Author(s)
      Park KC, et al.
    • Journal Title

      Anticancer Research 24

      Pages: 1105-1110

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of gene therapy for malignant gliomas using high-titer retroviral vectors.

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

      Trends in Cancer Research (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Development of gene therapy for malignant gliomas using high-titer retroviral vectors.

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

      Trends in Cancer Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] PU.1 is required for the activation of mouse embryonic stem cell-derived microglia.

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

      Neuroimmunology Research Focus (Broglio PV (ed)) (NOVA Science Publishers, Inc.) (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Development of gene therapy for malignant gliomas using high-titer retroviral vectors.

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

      Trends in Cancer Research (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Development of gene therapy for malignant gliomas using, high-titer retroviral vectors.

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

      Trends in Cancer Research (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prognostic significance of CDC25B expression in gliomas.

    • Author(s)
      Nakabayashi H, et al.
    • Journal Title

      Journal of Clinical Pathology (in press)

    • Related Report
      2005 Annual Research Report
  • [Book] Gene therapy of gliomas. (New perspectives in Cancer Research and Therapy)(Kuriyama S, Yoshiji H (eds.))2005

    • Author(s)
      Masahira N, et al.
    • Total Pages
      11
    • Publisher
      Research Signpost
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Gene therapy of gliomas. (New perspectives in Cancer Research and Therapy)(Kuriyama S, Yoshiji H (eds.))2005

    • Author(s)
      Masahira N, et al.
    • Total Pages
      11
    • Publisher
      Research Signpost Keraka (India)
    • Related Report
      2005 Annual Research Report
  • [Book] Gene therapy of gliomas.(Kuriyama S, Yoshiji H (eds.) : New perspectives in Cancer Research and Therapy)2005

    • Author(s)
      Masahira N, et al.
    • Total Pages
      11
    • Publisher
      Research Signpost
    • Related Report
      2004 Annual Research Report
  • [Book] PU.1 is required for the activation of mouse embryonic stem cell-derived microglia. (Neuroimmunology Research Focus)(Broglio PV (ed))

    • Author(s)
      Kaji T, et al.
    • Publisher
      NOVA Science Publishers, Inc.(in press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] PU.1 is required for the activation of mouse embryonic stem cell-derived microglia.

    • Author(s)
      Kaji T, et al.
    • Publisher
      NOVA Publishers(in press)
    • Related Report
      2006 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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