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Reconstruction of Impaired CNS Pathway using Adenovirus Vector

Research Project

Project/Area Number 10470293
Research Category

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

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

Principal Investigator

ARITA Kazunori  Hiroshima Univ., Dept. of Neurosurgery, Associate Professor, 医学部, 助教授 (90212646)

Co-Investigator(Kenkyū-buntansha) KAWAGUCHI Saburo  Kyoto Unvi., Graduate School of Medicine, Faculty of Medicine, Dept. of Integrative Brain Science, Professor, 大学院・医学研究科, 教授 (70024635)
TOMINAGA Atsushi  Hiroshima Univ., Dept. of Neurosurgery, Research Associate, 医学部, 助手 (60274049)
KURISU Kaoru  Hiroshima Univ., Dept. of Neurosurgery, Professor, 医学部, 教授 (70201473)
INOUE Tatsushi  Hiroshima Univ., Dept. of Neurosurgery, Research Associate, 医学部・附属病院, 助手 (80304434)
HEIKE Yuji  National Shikoku Cancer Center, Research Assistant, 厚生技官(研究職)
平家 勇司  国立病院四国がんセンター, 厚生技官(研究職)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1998: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsCNS / Regeneration / Axon / Adenovirus vector / Tumor suppression genne / Brain injcoy / Neural repair / Adenovirus vector / Axonal guidance / Axonal regeneration / Neural cell death / ラット / 神経再生 / 脊髄損傷モデル / 神経栄養因子
Research Abstract

It has been widely believed the mammalian CNS does not regenerate. But our laboratory demonstrated that marked regeneration is possible under the favorable condition. The condition mainly depends on the formation of glial scar. We have set up the hypothesis that tumor suppressor gene trasfer using adenovirus vector into the CNS traumatic lesion would inhibit the subsequent formation of gliosis and lead to induction of marked axonal regenaration. We selected NBS1 as candidate, which is reported to be mutated or deleted in Nijmegen breakage syndrome, presenting B-cell lymphoma with a high incidence.In contrary to our expect, our data did not showed correlation between NBS1 and malignant lymphoma.
We tested the adenovirus vector as a tool for gene delivery, using Wistar strain rat. Two to 28 days after the adenovirus injection into the local spinal cord, the distribution of lacZ was examined. It was detected not only in injection site (spinal cord) but also in choroid plexus, basal ganglia, dura etc. There was no pareplegic or fatal animal. Thus we confirmed the usefulness an d safety of adenoviurus as a deliver of gene in the treatment of CNS injury.
This study elucidates the therapeutic breakthrough in the spinal cord injury, cerebral apoplexy, and CNS degenerative disease if appropriate gene candidate is obtained.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report

Research Products

(30 results)

All Other

All Publications (30 results)

  • [Publications] 井上辰志,栗栖薫: "中枢神経伝導路の再生"別冊・医学の歩み・神経疾患. 97-100 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 井上辰志,栗栖薫: "哺乳動物中枢神経伝導路の再生"Equilibrium Res. 58. 573-581 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seiji Hama, et al: "Absence of Mutations in the NBS1 Gene in B-cell Malignant Lymphoma Patients"ANTICANCER RESEARCH. 20. 1897-1900 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fumiyuki Yamasaki, et al: "Recurrece of Meningiomas"Cancer. 89. 1102-1110 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroyuki Yoshioka, et al: "Transformation of rat glioma cells with the M-CSF gene inhibits tumorigenesis in vivo."Journal of Neoro-Oncology. 40. 197-204 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hama Seiji, et al: "Adenovirus-mediated P16 gene transfer prevents drug-induced cell death through G1 arrest in human glioma cells."Int.J.Cancer. 77. 47-54 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tatsushi Inoue, et al : "Spontaneous regeneration of the pyramidal tract after transection in young rats"Neuroscience Letters. 247. 151-154 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroyuki Yoshioka: "Peritumoral brain edema in meningiomas-Influence of vascular endothelial growth factor (VEGF) expression and vascular supply"Cancer. 86. 936-944

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seiji Hama: "Symptomatic Rathke′s cleft cyst coexisting with central Diabetes inspidus"Endcrine Journal. 46. 187-192

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada Kunyu, et al: "Telomerase activity in central nervous system malignant lymphoma."Cancer. 86. 1050-1055 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroyuki Yoshioka, Seiji Hama, Takashi Sadatomo, Eiji taniguchi, Kunyu Harada, Kazuhiko Sugiyama, Fumihiro Kimura, Kazuo Motoyoshi, Kaoru Kurisu: "Transformation of rat glioma cells with the M-CSF gene inhibits tumorigenesis in vivo."Journal of Neoro-Oncology. 40. 197-204 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hama Seiji, Heike Yuji, Naruse Ichiro, Takahashi Minako, Yoshioka Hiroyuki, Arita Kazunori, Kurisu Kaoru, Goldman K Corey, Curiel T David, Saijo Nagahiro: "Adenovirus-mediated P16 gene transfer prevents drug-induced call death through G1 arrest in human glioma cells."Int.J.Cancer. 77. 47-54 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue Tatsushi, Kawaguchi Saburo and Kurisu Kaoru: "Spontaneous regeneration of the pyramidal tract after transection in young rats"Neuroscice letters. 247. 151-154 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue Tatsushi and Kurisu Kaoru: "Regeneration of the Mammalian CNS Pathway"Equilibrium Res. 58. 573-581 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue Tatsushi and Kurisu Kaoru: "Regeneration of the CNS pathway"IGAKU-NO-AYUMI SHINKEI-SIKKAN -state of arts. 97-100 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroyuki Yoshioka, Seiji Hama, Eiji Taniguchi, Kazuhiko Sugiyama, Kazunori Arita, Kaoru Kurisu: "Peritumoral brain edema in meningiomas-Influence of vascular endothelial growth factor (VEGF) expression and vascular supply"Cancer. 85. 936-944 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seiji Hama: "Symptomatic Rathke's cleft cyst coexisting with central Diabetes inspidus"Endcrine Journal. 46. 187-192 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada Kunyu, Kurisu Kaoru, Arita Kazunori, Sadatomo Takashi, Tahara Hidetoshi, Tahara Eiji, Ide Toshinori, Uozumi Tohru: "Telomerase activity in central nervous system malignant lymphoma."Cancer. 86. 1050-1055 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshioka Hiroyuki, Kurisu Kaoru, Arita Kazunori: "Cytokine in the cental nervous system."IYAKU Journal. 36. 124-129 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seiji Hama, Shinya Matsuura, Hiroshi Taushi, Jyunko Sawada, Chikage Kato, Fumiyuki Yamasaki, Hiroyuki Yoshioka, Kazuhiko Sugiyama, Kazunori Arita, Kaoru Kurisu: "Absence of Mutations in the NBS1 Gene in B-cell Malignant Lymphoma Patients."ANTICANCER RESEARCH. 20. 1897-1900 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fumiyuki Yamasaki, Hiroyuki Yoshioka, Seiji Hama, Kazuhiko Sugiyama, Kazunori Arita, Kaoru Kurisu: "Recurrece of Meningiomas."Cancer. 89. 1102-1110 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] SEIJI HAMA et al: "Absence of Mutations in the NBS1 Gene in B-Cell Malignant Lymphoma Patients"ANTICANCER RESEARCH. 20. 1897-1900 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉岡宏幸 ら: "中枢神経疾患におけるサイトカイン"医薬ジャーナル. 36. 124-129 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 井上辰志: "哺乳動物中枢神経伝導路の再生"Equilibrium Res. 58・6. 573-581 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tatsushi Inoue: "Spontaneous regeneration of the pyramidal tract after transection in young rats"Neuroscuence Letters. 247. 151-154 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 井上辰志: "中枢神経伝導路の再生"神経疾患-state of arts. 97-100 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] SEIJI HAMA: "Symptomatic Rathke'S Cleft Cyst Coexisting with Central Diabetes Insipidus and Hypophysitis:Case Report"Endocrine Journal. 46・1. 187-192 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] SEIJI HAMA: "Absence of Mutations in the NBSI Gene in B-cell Malignant Lymphoma Patients"Anticancer research. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Seiji Hama: "Adenovirus-mediated P16gene transfer prevents uting induced Cell death through G1 arrest in human gliorna Cells" International journal of cancer. 77(1). 47-54 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroyuki Yoshioka: "Peritumoral Brain Edena Associated with Menirgioma" GANCER. 85(4). 936-944 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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