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2000 Fiscal Year Final Research Report Summary

Selective gene therapy of glioma by inducing differentiation with neural RNA binding protein, Hu.

Research Project

Project/Area Number 11470289
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionHyogo College of Medicine

Principal Investigator

NORIO Arita  Hyogo College of Medicine, Neurosurgery, Professor, 医学部, 教授 (80159508)

Co-Investigator(Kenkyū-buntansha) OKANO Hideyuki  Osaka University Graduate School of medicine, Neuroanatomy, Professor, 大学院・医学系研究科, 教授 (60160694)
IKEMOTO Hideyasu  Hyogo College of Medicine, Neurosurgery, Assistant, 医学部, 助手 (30278824)
MATSUMOTO Tsuyoshi  Hyogo College of Medicine, Neurosurgery, Associate Professor, 医学部, 講師 (00181777)
Project Period (FY) 1999 – 2000
Keywordsneural stem cell / MSI1 / glioma / glioblastoma / astrocytoma / oligodendroglioma / GFAP / Hu
Research Abstract

Tumor cells often express phenotypic markers that are specific to the cells from which they originated. A neural RNA-binding protein, Musashil, is an evolutionarily well-conserved marker for neural stem cells/progenitor cells. To examine the origin of gliomas, we examined the expression of the human Musashil homolog, MSI1, in human glioma tissues and in normal human adult and fetal brains. As we had seen previously in rodents, in the normal human brain, MSI1 was expressed in cells located in the ventricular and subventricular zones, in GFAP-negative glial cells, and in GFAP-positive astrocytes. In glioblastomas, MSI1 was expressed in GFAP-negative tumor cells forming foci that were clearly demarcated and surrounded by GFAP-positive cells. Tumor cells arranged in pseudopalisades were also strongly immunoreactive with MSI1 antibodies. The percentage of MSI1-labeled tumor cells increased in higher-grade astrocytomas and correlated with proliferative activity, as estimated by an MIB-1 staining index. Our results indicate MSI1 is an excellent marker for neural progenitor cells including neural stem cells in normal human brains. Furthermore, the expression of MSI1 correlates well with the immature nature as well as the malignancy of tumor cells in human gliomas. Thus, we expect the analysis of MSI1 expression to contribute to the understanding of the cellular origin and biology of human gliomas.

  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Kanemura Y,Arita N, et al: "Isolation and expression analysis of a novel human homologue of the Drosopila glial cells mission (gcm) gene."FEBS Letters. 442. 151-156 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiraga S,Arita N, et al: "Rapid infusion of high-dose methotrexate resulting in cnhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas."J Neurosurg. 91. 221-230 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikemoto H,Arita N, et al: "Calphostin C-mediacted translocation and integration of Bax into mitochondria induces cytochrome c release before mitochondrial dysfunction."Cell Death Differ. 7. 511-520 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kuratsu J,Arita N, et al: "Phase II trial of pre-irradiation KRN8602(MX2) in malignant glioma patients."J Neuro-Oncol. 48. 145-149 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawaguchi A,Okano H, et al: "Nestin-EGFP transgenic mice : Visualization of the self-renewal and multipotency of CNS stem cells."Mol Cell Neurosci. 17. 259-273 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaneko Y,Okano H, et al: "Musashi L : an evolutionally conserved marker for CNS progenitor cells including neural stem cells."Dev Neurosci. 22. 139-153 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 有田憲生 他: "Neurosurgery Headline 6"三輪書店. 6 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] 有田憲生: "脳神経外科の最先端No.2、21世紀の新領域とニューテクノロジー"先端医療技術研究所. 8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanemura Y, Arita N, et al: "Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene."FEBS Letters. 442. 151-156 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuratsu J, Arita N, et al: "A phase II study of KRN8602 (MX2), a novel morpholino anthracycline derivative, in patients with recurrent malignant glioma"J Neuro-Oncol. 42. 177-181 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiraga S, Arita N, et al: "Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas."J Neurosurg. 91. 221-230 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hagihara Y, Arita N, et al: "Long-term functional assessment of encapsulated cells transfected with Tet-on system."Cell Transplant. 8. 431-434 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Huang TY, Arita N, et al: "ACNU, MTX and 5-FU penetration of rat brain tissue and tumors."J Neurooncol. 45. 9-17 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kanuka H, Okano H, et al: "Protein, nucleotide control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator."Mol Cell. 4. 757-69 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Hirota Y, Okano H et al: "Musashi and seven in absentia downregulate tramtrack through distinct mechanisms in Drosophila eye development."Mech Dev. 87. 93-101 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Akamatsu W, Okano H, et al: "Mammalian ELAV-like neuronal RNA-binding proteins HuB and HuC promote neuronal development in both the central and the peripheral nervous systems."Proc Natl Acad Sci USA. 96. 9885-90 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Sawamoto K, Okano H, et al: "The Drosophila Ral GTPase regulates developmental cell shape changes through the Jun NH (2)-terminal kinase pathway."J Cell Biol. 146. 361-72 (1999)

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  • [Publications] Araki T, Okano H, et al: "Caspase activity is required for nephrogenesis in the developing mouse metanephros."Exp Cell Res. 248. 423-9 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Sawamoto K, Okano H, et al: "Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development."Oncogene. 18. 1967-74 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Takagi M, Arita N, et al: "Estrogen deficiency is a potential cause for osteopenia in adult male patients with Noonan's syndrome."Calcif Tssue Int. 66. 200-203 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Ikemoto H, Arita N, et al: "Calphostin C-mediated translocation and integration of Bax into mitochondria induces cytochrome c release before mitochondrial dysfunction."Cell Death Differ. 7. 511-520 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kasayama S, Arita N, et al: "Impaired β-cell function in the presence of reduced insulin sensitivity determines glucose tolerance statusin acromegalic patients."Clin Endocrinol. 52. 549-555 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kohmura E, Arita N, et al: "Usefulness of synaptophysin immunohistochemistry in an adult case of choroid plexus carcinoma."Neurol Res. 22. 478-480 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Ohnishi T, Arita N, et al: "Intracavernous sinus ectopic adrenocorticotropin-secreting tumours causing therapeutic failure in transsphenoidal surgery for Cushing's disease."Acta Neurochir. 142. 855-864 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuratsu J, Arita N, et al: "Phase II trial of preirradiation KRN8602 (MX2) in malignant glioma patients."J Neuro-Oncol. 48. 145-149 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kishi N, Okano H, et al: "Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis."Int J Dev Neurosci. 19. 21-35 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawaguchi A, Okano H et al: "Nestin-EGFP Transgenic Mice : Visualization of the self- renewal and multipotency of CNS stem cells."Mol Cell Neurosci. 17. 259-273 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hisahara S, Okano H, et al: "Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination."J Exp Med. 193. 111-22 (2001)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Hisahara S, Okano H, et al: "Role of caspase-1 subfamily in cytotoxic cytokine-induced oligodendrocyte cell death"J Neural Transm Suppl.2000 ; (58) : 135-42. Review..

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      「研究成果報告書概要(欧文)」より
  • [Publications] Yoda A, Okano H, et al: "MSI-1, a neural RNA-binding protein, is involved in male mating behavior in Caenorhabditis elegans."Genes Cells. 5. 885-895 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Sawa H, Okano H, et al: "Components of the SWI/SNF complex are required for asymmetric cell division in C.elegans."Mol Cell.. 6. 617-24 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Shibata M, Okano H, et al: "Caspases determine the vulnerability of oligodendrocytes in the ischemic brain."J Clin Invest. 106. 643-53 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Araki T, Okano H, et al: "Conditional expression of anti-apoptotic protein p35 by Cre-mediated DNA recombination in cardiomyocytes from loxP-p35-transgenic mice."Cell Death Differ. 7. 485-92 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Takano R, Okano H, et al: "Nerve growth factor protects oligodendrocytes from tumor necrosis factor-alpha-induced injury through Akt-mediated signaling mechanisms."J Biol Chem. 275. 16360-5 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Jin MH, Okano H, et al: "The interaction between the Drosophila secreted protein argos and the epidermal growth factor receptor inhibits dimerization of the receptor and binding of secreted spitz to the receptor."Mol Cell Biol. 20. 2098-107 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Tabuchi K, Okano H, et al: "GAL4/UAS-WGA system as a powerful tool for tracing Drosophila transsynaptic neural pathways."J Neurosci Res. 59. 94-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaneko Y, Okano H, et al: "Musashil : an evolutionally conserved marker for CNS progenitor cells including neural stem cells."Dev Neurosci. 22. 139-53 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Igaki T, Okano H, et al: "Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death."Proc Natl Acad Sci USA. 97. 662-7 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura Y, Okano H, et al: "The bHLH gene hes1 as a repressor of the neuronal commitment of CNS stem cells."J Neurosci. 20. 283-93 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Hisahara S, Okano H, et al: "Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against autoimmune-mediated demyelination."EMBO J. 19. 341-348 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Roy NS, Okano H, et al: "In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus."Nature Med. 6. 271-277 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Roy NS, Okano H, et al: "Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone."J Neurosci Res. 59. 321-331 (2000)

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      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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