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Development of chemokine-cocktail therapy against hyman malignant gliomas using lymphocyte-specific chemokines

Research Project

Project/Area Number 13671451
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TAKESHIMA Hideo  Kagoshima University, Medical Hospital, Assistant Professor, 医学部附属病院, 講師 (70244134)

Co-Investigator(Kenkyū-buntansha) HIRANO Hirofumi  Kagoshima University, Medical Hospital, Assistant Professor, 医学部附属病院, 講師 (00264416)
KURATSU Jun-ichi  Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (20145296)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsChemokine / Glioma / LARC / TARC / Immunotherapy / LARK
Research Abstract

Lymphocytes are frequently observed in human malignant glioma, the mechanism(s) underlying their appearance is not fully understood. To clarify tumor immunity in malignant gliomas, we analyzed the expression of 8 novel lymphocyte-specific chemokines in human glioma cell lines and glioma tissues by RT-PCR, Northern blot, immunoblot and immunohistochemistry, and examined the correlation with the infiltration of various subsets of lymphocytes. For the 8 chemokines examined (LARC, TARC, ELC, SLC, PARC, LEC, HCC-2, and SCM-1a), expression of LARC was clearly detectable in all 12 glioma cell lines by RT-PCR. Additionally, expression of TARC and SCM-1a was detectable in the majority of glioma cell lines. However, the expression level of most chemokines was low, so that Northern blot analysis could not demonstrate their expression with the exception of LARC in 2 cell lines. Expression of LARC mRNA and LARC protein was strongly induced by phorbol myristate ester in U87 MG cells. The production of LARC protein was demonstrated in 4 of 8 glioblastoma tissues by immunoblot, and 9 of 33 samples (27.3%) by immunohistochemistry. Interestingly, the positivist of LARC staining was significantly correlated with the infiltration of CD8-, CD4-, and CD45R0-positive cells (p<0.001).
Although the constitutive expression level of LARC is low, certain stimulations could strongly induce its expression, and play a crucial role in the tumor immunity of human malignant glioma.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kino T, Takeshima H, et al.: "Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannaoma"Genes Cells. 6. 441-454 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura T, Takeshima H, et al.: "Intratumoral delivery of interleukin 12 expression plasmids with in vivo electroporation is effective for colon and renal cancer"Hum Gene Ther. 12. 1265-1276 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamahata H, Takeshima H, et al.: "The role of thrombin in the neo-vascularization of malignant gliomas : An intrinsic modulator for the up-regulation of vascular endothelial growth factor"Int J Oncol. 20. 921-928 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimura T, Takeshima H, et al.: "Expression of lymphocyte-specific chemokines in human malignant glioma : Essential role of LARC in cellular immunity of malignant glioma"Int J Oncol. 21. 707-715 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyanohara O, Takeshima H, et al.: "Diagnostic significance of soluble c-kit in the cerebrospinal fluid of patients with germ cell tumors"J Neurosurg. 97. 177-183 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obara S, Takeshima H, et al.: "Inhibition of migration of human glioblastoma cells by cerivastatin in association with focal adhesion kinase(FAK)"Cancer Lett. 185. 153-161 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kino T, Takeshima H, et al.: "Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannoma"Genes Cells. 6. 441-454 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura T, Takeshima H, et al.: "Intratumoral delivery of interleukin 12 expression plasmids with in vivo electroporation is effective for colon and rectal cancer"Hum Gene Ther. 12. 1265-1276 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamahata H, Takeshima H, et al.: "The role of thrombin in the neo-vascularization of malignant gliomas: An intrinsic modulator for the up-regulation of vascular endothelial growth factor"Int J Oncol. 20. 921-928 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimura T, Takeshima H, et al.: "Expression of lymphocyte-specific chemokines in human malignant glioma: Essential role of LARC in cellular immunity of malignant glioma"Int J Oncol. 21. 707-715 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyanohara O, Takeshima H, et al.: "Diagnostic significance of soluble c-kit in the cerebrospinal fluid of patients with germ cell tumors"J Neurosurg. 97. 177-183 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obara S, Takeshima H, et al.: "Inhibition of migration of human glioblastoma cells by cerivastatin in association with focal adhesion kinase (FAK)"Cancer Lett. 185. 153-161 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kino T, Takeshima H, et al.: "Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannoma"Genes Cells. 6. 441-454 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamura T, Takeshima H, et al.: "Intratumoral delivery of interleukin 12 expression plasmids with in vivo electroporation is effective for colon and renal cancer"Hum Gene Ther. 12. 1265-1276 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamahata H, Takeshima H, et al.: "The role of thrombin in the neo-vascularization of malignant gliomas : An intrinsic modulator for the up-regulation of vascular endothelial growth factor"Int J Oncol. 20. 921-928 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kimura T, Takeshima H, et al.: "Expression of lymphocyte-specific chemokines in human malignant glioma : Essential role of LARC in cellular immunity of malignant glioma"Int J Oncol. 21. 707-715 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyanohara O, Takeshima H, et al.: "Diagnostic significance of soluble c-kit in the cerebrospinal fluid of patients with germ cell tumors"J Neurosurg. 97. 177-183 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Obara S, Takeshima H, et al.: "Inhibition of migration of human glioblastoma cells by cerivastatin in association with focal adhesion kinase (FAK)"Cancer Lett. 185. 153-161 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanioka, K. et al.: "Biological role of thymidine phosphorylase in human astrocytic tumors"Oncology Rep. 8. 491-496 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kino, T. et al.: "Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannoma"Genes Cells. 6. 441-454 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamura, T. et al.: "Intratumoral delivery of interleukin 12 expression plasmids with in vivo electroporation is effective for colon and renal cancer"Hum Gene Ther. 12. 1265-1276 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamahata H, et al.: "The role of thrombin neo-vascularization of malignant gliomas : An intrinsic modulator for the up-regulation of vascular endothelial growth factor"Int J Oncol. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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

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