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Effectiveness of protein kinase C (PKC) inhibitors against human malignant gliomas : anti-tumor activity of PKC inhibitors alone and in combination with cytokines

Research Project

Project/Area Number 07671554
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionTAZUKE KOFUKAI MEDICAL RESEARCH INSTITUTE.

Principal Investigator

IWASAKI Koichi  Tazuke kofukai medical reserch institute, Department III of Oncology., 医学研究所・第3研究部, 研究員 (30250062)

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: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordshuman malignant / protein kinase C inhibitors / Staurosporine / Tamoxifen / anti-tumor activity / cytokine / Tumor necrosis factor (TNF) / Interferon (IFN) / Tumor necrisis factor(TNF) / プロテインキナーゼ-C(PKC) / 悪性神経膠細胞 / PKC活性抑制物質 / タモキシフェン / TNF / IFN / 相乗効果
Research Abstract

Protein Kinase C (PKC) is a component of signal transduction system mediating a variety of cellular activities including malignant transformation PKC activity is reportedly elevated in neoplasms including malignant brain tumors. The aims of this study are to investigate the antitumor function of PKC inhibitors against malignant glial tumors prior to clinical application, and further to examine the effects of PKC inhibitors in combination with cytokines such as TNF and IFN,and analyze the underlying molecular biological mechanisms. Results : (1) All of 6 malignant glioma cell lines (including one cloned line) studied were shown to have a significantly elevated PKC activity, while a non-neoplastic astrocyte line had a normal activity. (2) In this study, we examined the effects of two reagents known to inhibit PKC activity : Staurosporine and Tamoxifen which is a clinically well-tolerated drug. It was demonstrated that both reagents inhibited proliferation and invasiveness of 5 of 6 tumor lines. but they were not toxic against a non-neoplastic astrocyte line. (3) PKC inhibitors plus TNF and/or IFN exerted synergistic or additive anti-tumor effects on human glioma cells, via mechanisms of enhancing the expression of the cytokine receptors on the tumor cells. (4) It is under examining the effects of PKC inhibitors on the expression of various oncogenesof thses glioma cells. (5) These results suggest possible therapeutic potentials of PKC lnhibitors alone and in combination with cytokines for the clinical tratment of human malignant gliomas.

Report

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

    (8 results)

All Other

All Publications (8 results)

  • [Publications] 岩崎孝一ら: "タモキシフェン(protein kinase C inhibitor)がヒト星細胞腫の増殖能と浸潤能に及ぼす効果" 北野紀要. 39. 125-129 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwasaki K,et al: "Inhibitory effects of tamoxifen and tumor necrosis factor α on human glioblastoma cells." Cancer Immunology Immunotherapy. 40. 228-234 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwasakki K, et al: "Effects of tamoxifen on proliferation and invasiveness of human astrocytoma cells" Kitano Jounal of Medicine. 39. 125-129 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwasaki K,et al: "Inhibitory effects of tamoxifen and tumor necrosis factor alpha on human glioblastoma cells" Cencer Immunology Immunotherapy. 40. 228-234 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 岩崎孝一ら: "タモキシフェン(protein kinase C inhibitor)がヒト星細胞腫の増殖能と浸潤能に及ぼす効果" 北野紀要. 39. 125-129 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwasaki K,et al: "Inhibitory effects of tamoxifen and tumor necrosis factor α on human glioblastoma cells." Cancer Immunology Immunotherapy. 40. 228-234 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 岩崎孝一ら: "タモキシフェン(protein kinasa C inhibitor)がヒト星細胞腫の増殖能と浸潤能に及ぼす効果" 北野紀要. 39. 125-129 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Iwasaki k, et al: "Inhibitory effects of tamoxifen and tumor necrosis factor α on human glioblastoma cells" Cacer Immunol Immunother. 40. 228-234 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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