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Gene therapy for malignant brain tumor by infusion of antisense oligonucleotide

Research Project

Project/Area Number 08407043
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

FUKUI Masashi  Kyushu Univ., Neurological Institute, Dept.of Neurosurgery, Professor MD,PhD, 医学部, 教授 (10038713)

Co-Investigator(Kenkyū-buntansha) INAMURA Takanori  Kyushu Univ., Neurological Institute, Dept.of Neurosurgery, Assistant Professor, 医学部, 助手 (50274460)
IKEZAKI Kiyonobu  Kyushu Univ., Neurological Institute, Dept.of Neurosurgery, Assistant Professor, 医学部, 講師 (10145360)
NISHIO Shunji  Kyushu Univ., Neurological Institute, Dept.of Neurosurgery, Assistant Professor, 医学部, 講師 (10180580)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥39,900,000 (Direct Cost: ¥39,900,000)
Fiscal Year 1998: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1997: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1996: ¥22,900,000 (Direct Cost: ¥22,900,000)
Keywordsbradykinin / brain tumor / antisense oligonucleotide / microsatellite / apoptosis / chemotherapy / BBB / antisense / Treatment / Peameability / Brain tumor / Chemotherapy / Bradykinin / Antisease
Research Abstract

1. Genetic characterization of malignant gliomas
We recognized the microsatellite instability in the chromosome 10 in 6 out of 31 human゚Cgliomas. And rare apoptosis was recognized in malignant gliomas. These findings゚Csuggested that the genetic abnormality strongly associated with the malignant゚Ctransformation of the gliomas.
2. Establishment of quantitative measurement of antisenseoligonucleotide in the゚Corgans.
After obtaining the organs, brain, liver, and kidney, DNA fractions was extracted using centrifugation and filters. The DNA fractions were electrophorated on the acrylamide gel and trasbiotted to the membrane. A quantitative measurement of antisenseoligonucleotide was performed using RI-labeled senseoligonucleotide.
3. Selective delivery of antisenseoligonucleotide by intracarotid bradykinin infusion We injected antisenseoligonucleotide from internal carotid artery in tumor-bearing rat. The delivered oligonucleotide was measured by the methods described above. The antisenseoligonucleotide was selectively delivered into the brain tumor by 1.4 fold, compared with the control study.
3. Effect of intracarotid bradykinin infusion on vital signs in dogs.
Using 20 dogs, we examined the effect of intracarotid bradykinin infusion on vital signs. At the dose of 1 and 2.5 gamma, intracarotid bradykinin infusion did not change the vital signs significantly. On the other hand, at the dose of 5 and 10 gamma, it changed the vital signs including cerebral blood flow at the beginning of the infusion.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (57 results)

All Other

All Publications (57 results)

  • [Publications] Inamura T et al: "Experimental trials of brain tumor therapy through blood-brain barrier/blood-tumor barrier." Crit Rev Neurosurg. 6. 351-355 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kovacs Z et al: "VEGF and flt expression time kinetics in rat brain infarct." Stroke. 27. 1865-1873 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koga H et al: "Increased delivery of a new cisplatin analogue(254-S)in a rat brain tumor by an intracarotid infusion of bradykinin." Neurol Res. 18. 244-247 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsukado K et al: "Effect of calcium antagonists on regional cerebral blood flow in transplanted rat brain tumors." J Neuro Onco. 27. 1-10 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shono T et al: "Involvement of the transcription factor NF-kb in tubular morphogenesis of human microvascular endothelial cells by oxdative stress." Mol Cell Biol. 16. 4231-4239 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsukado K et al: "Enhanced tumor uptake of Carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin Analog,RMP-7." Neurosurgery. 39. 125-134 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "Radiation injury of the brain.Crit Rev Neurosurg 7:408-415,1997" Crit Rev Neurosurg. 7. 408-415 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kovacs Z et al: "A chronological evaluation of experimental brain infact by diffusion-mapping and magnetization transfer contrast imaging" Acta Neurochir Suppl.70. 43-45 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "A clinicopathologic analysis of 20 cases with reference to patient age." Acta Neurochir. 139. 336-342 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikezaki K et al: "Specificity of brain tumor capillaries and novel drug delivery system." Annals of Cancer Research and Therapy. 6. 39-44 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikezaki K et al: "Apparent diffusion coefficient(ADC) and magnetization transfer contrast(MTC)mapping of experimental brain tumor." Acta Neurochir Suppl.70. 170-172 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuba H et al: "Thiamine-deficient lactic acidosis with brain tumor treatment Report of three casees." J Neurosurg. 89. 1025-1028 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "Radiation-induced brain tumours:Potential late complications of radiation therapy for brain tumours." Acta Neurochir. 140. 763-770 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "Medulloblastoma in the first year of life:a report of five cases." J Clin Neuroscience. 5. 265-269 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizoguchi M et al: "A comparative immunohistochemical study of tissue transglutaminase and factor XIIIa in hemangioblastima." Neuropatholgy. 18. 199-205 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizoguchi M et al: "Abnomal cytoarchitecture of cortical dysplasia verified by immunohistochemistry Clin Neuropathol 17:100-109,1998" Clin Neuropathol. 17. 100-109 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "Primitive neuroectodemal tumors.Crit Rev Neurosurg 8:261-268,1998" Crit Rev Neurosurg. 8. 261-268 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inamura T et al: "Experimenta trials of brain tumor therapy through blooc-brain barrier/blood-tumor barrier." Crit Rev Neurosurg. 6. 351-355 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kovacs Z et al: "VEGF and flt expression time kinetics in rat brain infarct." Stroke. 27. 1865-1873 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koga H et al: "Increased delivery of a new cisplatin analogue (254-S) in a rat brain tumor by an intracarotid infusion of bradykinin." Neurol Res. 18. 244-247 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsukado K et al: "Effect of calcium antagonists on regional cerebral blood flow in transplanted rat brain tumors." J Neuro Once. 27. 1-10 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shono T et al: "Involvement of the transcription factor NF-kb in tubular morphogenesis of human microvascular endothelial cells by oxidative stress." Mol Cell Biol. 16. 4231-4239 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsukado K et al: "Enhanced tumor uptake of Carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin Analogy, RMP-7." Neurosurgery. 39. 125-134 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S at al: "Radiation injury of the brain." Crit Rev Neurosurg. 7. 408-415 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kovacs Z et al: "A chronological evaluation of experimental brain infact by diffusion-mapping and magnetization transfer contrast imaging." Acta Neurochir Suppl.70. 43-45 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "Thalamic gliomas : A clinicopathologic analysis of 20 cases with reference to patient age." Acta Neurochir. 139. 336-342 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikezaki K et al: "Specificity of brain tumor capillaries and novel drug delivery system." Annals of Cancer Research and Therapy. 6. 39-44 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikezaki K et al: "Apparent diffusion coefficient (ADC) and magnetization transfer contrast (MTC) mapping of experimental brain tumor." Acta Neurochir Suppl.70. 170-172 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuba H et al: "Thiamine-deficient lactic acidosis with brain tumor treatment Report of three casees." J Neurosurg. 89. 1025-1028 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "Radiation-induced brain tumours : Potential late complications of radiation therapy for brain tumours." Acta Neurochir. 140. 763-770 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "Medulloblastoma in the first year of life : a report of five cases." J Clin Neuroscience. 5. 265-269 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizoguchi M et al: "A comparative immunohistochemical study of tissue transglutaminase and factor XIIIa in hemangioblastima." Neuropatholgy. 18. 199-205 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizoguchi M et al: "Abnomal cytoarchitecture of cortical dysplasia verified by immunohistochemistry." Clin Neuropathol. 17. 100-109 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishio S et al: "Primitive neuroectodermal tumors." Crit Rev Neurosurg. 8. 261-268 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inamura T et al: "Experimental trials of brain tumor therapy through blood-brain barrier/blood-tumor barrier." Crit Rev Neurosung. 6. 351-355 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kovacs Z et al: "VEGF and flt expression time kinetics in rat brain infarct." Stroke. 27. 1865-1873 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koga H et al: "Increased delivery of a new cisplatin analogue (254-S)in a rat brain tumor by an intracarotid infusion of bradykinin." Neurol Res. 18. 244-247 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsukado K et al: "Effect of calcium antagonists on regional cerebral blood flow in transplanted rat brain tumors." J Meuro Onco. 27. 1-10 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shono T et al: "Involvement of the transcription factor NF-kb in tubular morphogenesis of human microvascular endothelial cells by oxidative stress." Mol Cell Biol. 16. 4231-4239 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsukado K et al: "Enhanced tumor uptake of Carboplatin and survival in glioma-bearing rats by intaracarotid infusion of bradykinin Analog,RMP-7." Neurosurgery. 39. 125-134 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishio S et al: "Radiation injury of the brain.Crit Rev Neurosurg 7:408-415,1997" Crit Rev Neurosurg. 7. 408-415 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kovacs Z et al: "A chronological evalution of experimental brain i nfact by diffusion-mapping and magnetization transfer contrast imaging" Acta Neurochir Suppl.70. 43-45 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishio S et al: "A clinicopathologic analysis of 20 cases with reference to patient age." Acta Neurochir. 139. 336-342 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikezaki K et al: "Specificity of brain tumor capillaries and novel drug delivery system." Annals of Cancer Research and Therapy. 6. 39-44 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikezaki K et al: "Apparent diffusion coefficient (ADC)and magnetization transfer contrast (MTC)mapping of experimental brain tumor." Acta Neurochir Suppl.70. 170-172 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuba H et al: "Thiamine-deficient lactic acidosis with brain tumor treatment Report of three cases." J Neurosurg. 89. 1025-1028 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishio S et al: "Radiation-induced brain tumours:Potential late complications of radiation therapy for brain tumours." Acta Neurochir. 140. 763-770 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishio S et al: "Medulloblastoma in the first year of life:a repor t of five cases." JClin Neuroscience. 5. 265-269 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizoguchi M et al: "A comparative immunohistochemical study of tissue transglutaminase and factor XIIIa in hemangioblastima." Neuropatholgy. 18. 199-205 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizoguchi M et al: "Abnomal cytoarchitecture of cortical dysplasia verified by immunohistochemistry Clin Neuropathol 17:100-109,1998" Clin Neuropathol. 17. 100-109 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] NIshio S et al: "Primitive neuroectodermal tumors. Crit Rev Neurosurg 8:261-268,1998" Crit Rev Neurosurg. 8. 261-268 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikezaki et al.: "Specificity of brain tumor capillaries and noveldug clelivery system" Anncls of Cancer Research and Therapy. 6. 39-44 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikezaki K: "Expression of rasular endothelial growth factor in human tumors in vivo" Brain tumor Research and Therapy. (supplent). 237-245 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koga H: "Increased delivery of a new cisplatin analogue(254-S)in a rat brain tumor by an intracarotid infusion of bradykinin" Neurological Research. 18. 244-247 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kovacs Z: "VEGF and flt Expression Time kinetics in Rat brain infarct" Stroke. 27. 1865-1873 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsukado K: "Effect of calcium antagnists on regional cerebral blood flow in transplanted rat brain tumors" Journal of Neuro-Oncology. 27. 1-10 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsukado.K: "Enhaced Tumor Uptake of Carboplatin and Survival in Glioma-bearing Rats by Intracarotid Infusion of bradykinin Analog,RMP-7" Neurosurgery. 39. 125-134 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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