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2002 Fiscal Year Final Research Report Summary

Regulation of cell cycle progression by ganglioside-a novel strategy against malignant glioma

Research Project

Project/Area Number 13671434
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

IZUMOTO Shuichi  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40324769)

Co-Investigator(Kenkyū-buntansha) NAKATSUJI Yuji  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20332744)
Project Period (FY) 2001 – 2002
KeywordsGanglioside / GM3 / glycolipid / glioma / brain tumor / malignant glioma / apotosis
Research Abstract

To investigate whether gangliosides modulate the progression of glioma cells, GM3, the simplest ganglioside, was administered into the culture of glioma cells and into the glioma-bearing rats via the cistema magna. (1) Four primary glioma cells and 4 glioma cell lines were cultured with GM3. MTT assay demonstrated that the glioma pells were inhibited those proliferation by GM3 with the concentration of 20 to 200 micromole(P<0.05). The inhibition was dependent on the concentration of GM3. (2) Rat glioma model for the in vivo analysis was made by the inoculation of C6 glioma cells into the rat meningeal space. Treated rats (n=20), those were administered GM3 on 10 days after glioma-cell-inoculation, survived 22.0 days, whereas the control rats(n=15) survived 19.5 days(P<0.05). Acute toxicity was not detected on the rats after GM3 administration. (3) On the pathological examination by TUNEL method,GM3 was found to induce apoptosis on the glioma cells. The apoptotic cells were detected from 1 to 3 days after administration of GM3 in the rat brain and detected only on the surface of the mass of glioma cells. Those results demonstrated that GM3 does not infiltrate well into the brain or into the mass of glioma cells.
To investigate whether GM3 interfere with the invasion of the glioma cells, Boyden chamber assay and invasion assay with slice culture model were performed.(4) As a result, glioma cells were inhibited its motility and invasion by GM3, that was dependent on the concentration of GM3.
These results demonstrate that GM3 inhibits both the proliferation and invasion of glioma cells. The local administration of GM3 as a new strategy for the control of glioma may be a useful and safe method.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Manabu Kinoshita: "Primary malignant lymphoma of the trigeminal region treated with rapid infusion of high-dose MTX and radiation case report and review of the literature"Surgical Neurology. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ken Koguchi: "Modulation of astrocyte proliferation by cyclin-dependent kinase inhibitor p27(Kip1)"Glia. 37. 93-104 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nakatsuji: "Density dependent modulation of cell cycle protein expression in astrocytes"Journal of Neuroscience Research. 66. 487-496 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki M: "Improvement of anti-Hu-associated paraneoplastic sensory neuropathy after chemoradiotherapy in a small cell lung cancer patient"Internal Medicine. 40. 1140-1143 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nakatsuji: "Selective cell-cycle arrest and induction of apotosis in proliferating neural cells by ganglioside GM3"Experimental Neurology. 168. 290-299 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shuichi Izumoto: "PTEN mutations in malignant gliomas asnd their relation with meningeal gliomatosis"Journal of Neuro-Oncology. 53. 21-26 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nakatsuji: "Regulation of cell cycle progression in astrocytes"Hertz L, ed Elsevier Science : Non-neuronal cells of the nervous system : Function and dysfunction. Advances in molecular and cell biology. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Manabu Kinoshita: "Primary malignant lymphoma of the tritgeminal region treated with rapid infusion of high-dose MTX and radiation case report and review of the literature"Surgical Neurology. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ken Koguchi: "Modulation of astrocyte proliferation by cyclin-dependent kinase inhebitor p27 (Kip 1)"Glia. 37. 93-104 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Nakatsuji: "Density dependent modulation of cell cycle protein expression in astrocytes"Journal of Neuroscience Research. 66. 487-496 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki M: "Improvement of anti-Hu-associated paraneoplastic sensory neuropathy after chemoradiotherapy in a small cell lung cancer patient"Internal Medicine. 40. 1140-1143 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Nakatsuji: "Selective cell-cycle arrest and induction of apotosis in proliferating neural cells by ganglioside GM3"Experimental Neurology. 168. 290-299 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shuichi Izumoto: "PTEN mutations in malignant gliomas asnd their relation with meningeal gliomatosis"Journal of Neuro-Oncology. 53. 21-26 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Nakatsuji: "Regulation of cell cycle progression in astrocytes. In: Non-neuronal cells of the nervous system: Function and dysfunction"(Hertz L,ed) Elsevier Science. in press Advances in molecular and cell biology.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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