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Gene Therapy for the Childhood Brain Tumors

Research Project

Project/Area Number 07670904
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionJikei University School of Medicine

Principal Investigator

MATSUSHIMA Hiroshi  Jikei University School of Medicine, Department of Pediatrics, Assistant Professor, 医学部, 講師 (70190460)

Co-Investigator(Kenkyū-buntansha) HAMANO Shinichiro  Jikei University School of Medicine, Dept.of Pediatrics, Assistant, 医学部, 助手 (80208595)
NAKAE Yoichiro  Jikei University School of Medicine, Dept.of Pediatrics, Assistant, 医学部, 助手 (40188876)
MAEKAWA Kihei  Jikei University School of Medicine, Dept.of Pediatrics, Professor, 医学部, 教授 (80056613)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsGene Therapy / Brain Tumor / Nerve Growth Factor / Nerve Growth Factor Receptor / Signal Transduction / 神経腫瘍 / 神経成長因子受容体 / シグナル伝達路
Research Abstract

The human trkA cDNA was transfected into a human neuronal cell line to investigate the possibility of the gene therapy for childhood brain tumors. Trasfectants expressing the trkA mRNA and surface-bound receptors transcriptionally activate immediate-early genes folowing NGF stimulation. Long-term NGF treatment of the transfectants induces growth arrest as well as down regulation of the amplified N-myc gene. Subcutaneous treatment of the transfectants-bearing mice with NGF induces neuronal and glial differentiation. Thus, trkA expression in immature neuronal cells is sufficient to generate a functional NGF receptor complex that leads to growth arrested and differentiated mature neurons in vitro and in vivo in the presence of NGF.Hence, NGF/NGF-receptor cascade may be useful for the gene therapy to the childhood brain tumors that are thought to be developed from the immature neuroblasts. Furthermore, we investigated the regulatory mechanisms of the NGF/NGF-receptor cascade expression.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(12 results)

All Other

All Publications (12 results)

  • [Publications] H.Matsushima: "Constitutive N-myc gene expression inhibits trkA mediated neuronal differentiation" Oncogene. 10. 1915-1925 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Maekawa: "Identification of three novel mutations in the Niemann-Pick disease type A and B" Hum.Mutat.7. 65-68 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Maekawa: "Clinical and genetic studies of five fatal cases of Japanese Gaucher disease type 1" Acta Paediatr. Jpn.38. 233-236 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Hamano: "Interstitital duplication 8q22-q24" American Journal of Medical Genetics. 65. 36-39 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 松島宏: "神経細胞への遺伝子導入" 小児科臨床. 49. 2617-2624 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiroshi Matsushima: "Constitutive N-myc gene expression inhibits trkA mediated neuronal differentiation." Oncogene. 10. 1915-1925 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihei Maekawa: "Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B." Human Mutation. 7. 65-68 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihei Maekawa: "Clinical and genetic studies of five fatal cases of Japanese Gaucher disease type 1." Acta Paediatr.Jpn.338. 233-236 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinichiro Hamano: "Interstitital duplication 8q22-24 : Report of a case proven by FISH with mapped cosmid probes." Am.J.of Med.Genet.65. 36-39 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 松島宏: "神経細胞への遺伝子導入" 小児科臨床. 49. 2617-2624 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsushima, H.: "Constitutive N-myc gene expression blocks NGF/trkA mediated neuronal differentiation." Neurochemical Res.20. 372 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsushima, H.: "Constitutive N-myc gene expression inhibits trkA mediated neuronal differentiation." Oncogene. 10. 1915-1925 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-03-31   Modified: 2016-04-21  

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