| Project/Area Number |
11671406
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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 | Fukuoka University |
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Principal Investigator |
YAMAMOTO Masaaki Sch.of Med.Fukuoka University, Assist.Prof., 医学部, 講師 (80240125)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | malignant astrocytoma / uPA / gelatinase / IRP / NF-kB / invasion / TNF-alpha / RAP / 蛋白分解酵素 / NF-kB |
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| Research Abstract |
In this study, we investigated that the role of NF-kB for regulation of the expression of urokinase-type plasminogen activator (uPA) and signal transduction in tumor necrosis factor-α (TNF-α)-induced cytotoxicity. We found that NF-kB (p50 and p65 subunits) is activated in human astrocytomas in vivo and in vitro, which contributed the overexpression of uPA.Activation of nuclear factor-κB (NF-κB) protects against TNF-α-induced apoptosis in human glioblastoma cells in vitro. The results of zymography and in vitro invasion assay showed that NF-kB inhibitors (steroid, aspirin and pentoxyfiline) suppressed the expression of uPA and invasiveness of human glioblastoma cells in vitro. This effect was accelerated by BB-94, gelatinase inhibitor. Combined with NF-kB inhibitors and recombinant human TNF-alpha, the invasive potential of human glioblastoma cells decreased and induced apoptosis in glioblastoma cells. Our results suggest that the constitutive activation of NF-κB subunits in malignant astrocytoma is realistic traget for malignant astrocytomas therapy modifying the serine and matrix metalloproteinase activities.
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