| Project/Area Number |
07671554
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | TAZUKE KOFUKAI MEDICAL RESEARCH INSTITUTE. |
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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)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| 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)
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| Keywords | human 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 |
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| 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.
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