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Identification of differentiation factor in vivo and the application of differentiation therapy to brain tumor.

Research Project

Project/Area Number 13671442
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIYAZONO Masayuki  Kyushu University, Department of Neurosurgery, Clinical Instructor, 医学部附属病院, 助手 (70325463)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsNT2 cells / differentiation / migration / transplantation / embryonal carcinoma / basal ganglia / mouse / dissemination / coculture / primary culture / くも膜 / GFP
Research Abstract

The NTera 2 (NT2) cell line is a teratocarcinoma derived from a human embryonal carcinoma (BC) cell line that has the capacity to form bulky tumors that are lethal within 70 days after transplantation into subarachnoid space, superficial neocortex, and ventricle in the adult nude mouse brain. However, when confined to the caudoputamen (CP) in adult nude mouse brain, NT2 cells stop dividing and differentiate into postmitotic mature neurons. To determine if this phenomenon is developmentally regulated, we transplanted NT2 cells into the mouse brain at postnatal days (P)0-21 (P0-P21). Transplantation of NT2 cell into the CP of neonatal brain at P0-P4 resulted in the rapid formation of bulky tumors and most of the grafted mice died within 5-40 weeks after implantation. Although older neonatal (P7, P12) mice with similar CP grafts of NT2 cells survived longer than P0-P4 mice, NT2 cells still were tumorigenic in these older mice. These neonatal mice under P12 had bulky tumor located in subarachnoid space and ventricle. In contrast, NT2 cells transplanted into the CP of pups at P14, P16 and P21 behaved like NT2 cell grafts in the adult mouse CP. BrdU-positive NT2 cell was stained in dark on the nuclei. The BrdU-labeling index (BrdU-LI) of NT2 cells, cocultured with the CP, arachnoid membrane, neocortex, and cerebellum of mice, was 42.14±5.22 (mean ± standard deviation), 47.20±8.26, 44.08±11.8 and 41.74±3.54 respectively. No significant differences were observed among them. On the other hand, that of the control was 42.77 ア 5.12. No significant differences were observed between them compared with the control. Statistical analysis was not much differences among the different region, however, the Brd-U LI of NT2 cells cocultured with arachnoid menbrane was higher than other region. These data suggest that developmentally regulated factors exist in the adult mouse CP but not neonatal mouse brain.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] 宮園正之: "左側脳室三角部に主座を置く巨大異型性髄膜腫の1手術例"脳神経外科速報. 11. 901-906 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Amano T: "Effect of single low dose irradiation on subventricular zone cells in juvenile rat brain"Neurol Res. 24. 809-816 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Amano T: "Tumorigenic potential of transplanted human embryonal carcinoma (NTera 2) cells is regulated by the developmental stage of the mouse brain"Neurol Res. (in submission).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazono M. et al.: "Surgical treatment of a giant intraventricular atypical meningioma situated in the trigone (Atrium) : case report"Neurosurg Lett. 11(12). 901-906 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Amano T. et al.: "Effects of single low dose irradiation on subventricular zone cells in juvenile rat brain"Neurol Res. 24. 809-816 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Amano T. et al.: "Tumorigenic potential of transplanted human embryonal carcinoma (NTera 2) cells is regulated by the developmental stage of the mouse brain"Neurol Res. (in submission). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Amano T, Inamura T, Wu CM, Kura S, Nakamizo A, Inoha S, Miyazono M, Ikezaki K: "Effect of single low dose irradiation on subventricular zone cells in juvenile rat brain"Neurol Res. 24. 809-816 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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