| Project/Area Number |
14571323
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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 | Kagoshima University |
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Principal Investigator |
HIRANO Hirofumi Kagoshima University, Faculty of Medicine and Dentistry, Assistant Professor, 歯学部附属病院, 講師 (00264416)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAYAMA Tetsuya Kagoshima University, Graduate School of Medical and Dental Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (40336334)
TAKESHIMA Hideo Kagoshima University, University Hospital, Faculty of Medicine and Dentistry, Assistant Professor, 歯学部附属病院, 講師 (70244134)
KURATSU Jun-ichi Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (20145296)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | macrophage / docosahexaenoic acid / glioblastoma / apoptosis / 5-FU / Macrophage |
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| Research Abstract |
We took notice of macrophages infiltrating into malignant glioma.These macrophages express thymidine phosphorylase(TP), which convert 5-FU prodrug into active form.In order to estimate the anti-tumor effects of macrophages and 5-FU prodrug therapy for malignant glioma, we analyzed immunoactivity of macrophages in glioblastoma and metabolism of5-FU.
The macrophages induced from peripheral blood cells showed anti-tumor effects to glioma cell line U251GM cells by MTT assay, 51Cr releasing assay.Analysis of free fatty acids in glioblastoma specimens demonstrated that a large amount of docosahexaenoic acid(DHA)was contained in the necrosis.We evaluated the influence of DHA on macrophages and proved that the DHA suppressed the anti-tumor effects of macrophages.Microbeads assay showed that the DHA inhibited phagocytotic activity of macrophages.The influence of DHA on glioma cells, U25 1MG cells as well as cultured cells from surgery, and macrophages were evaluated by flow cytometry.The experiment clarified that DHA easily induced apoptosis to macrophages, while the glioma cells were hardly influenced by DHA.According to these results, there is a possibility that the DHA included in necrosis, which is histopathological feature of glioblastoma, suppresses the anti-tumor immunity of macrophages.
Additionally the activity of dihydropyrimidine dehydrogenase, rate-determining enzyme in degradation of 5-FU, and thymidylate synthetase, the target enzyme of 5-FU were analyzed on previous glioma cells.The results suggested that increased activity of these enzymes caused the resistance of 5-FU therapy.
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