| Project/Area Number |
07457319
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | SAGA MEDICAL SCHOOL |
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Principal Investigator |
TABUCHI Kazuo SAGA MEDICAL SCHOOL,NEUROSURGERY,PROFESSOR, 医学部, 教授 (50116480)
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| Co-Investigator(Kenkyū-buntansha) |
MINETA Toshihiro SAGA MEDICAL SCHOOL,NEUROSURGERY,CLINICAL INSTRUCTOR, 医学部, 助手 (20264187)
FUKUYAMA Kouzou SAGA MEDICAL SCHOOL,NEUROSURGERY,CLINICAL INSTRUCTOR, 医学部, 助手 (60238516)
TODA Keisuke SAGA MEDICAL SCHOOL,NEUROSURGERY,CLINICAL INSTRUCTOR, 医学部, 助手 (80274588)
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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 |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | Brain tumor / apoptsis / TUNEL / Fas / Fas ligand / ICE / Bcl-2 / OK-432 / 養子免疫療法 / ICE inhibitor / p53 / p16 / p21 / Bcl-x |
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| Research Abstract |
1. We detected the internucleosomal DNA fragmentation by modified TUNEL staining and analyzed the expression of apoptosis-related gene products in cultured glioma cells and biopsied brain tumor specimens. The fragmented and condensed nuclei were clearly stained for TUNEL and the percentages of stained nuclei (apoptotic index) were ranging from 0% to 8.9%. Fas, Bcl-2 families (Bcl-2, Bcl-x and Bax) and ICE families (ICE,Ich-1) were found to be involved in tumorigenesis of certain brain tumors.
2. We investigated the role of the Fas ligand-Fas system in human glioblastoma cell lines (T98G,U251 and A172).
Immunohistochemical and flow cytometrical analyzes revealed that all three cell lines expressed Fas highly, however, apoptotic changes such as nuclear fragmentation, the DNA ladder pattern on gel electrophoresis, and reduction of viable cells were observed only in T98G cells by treatment of Fas mAb (50ng/ml).
3. We have been applying an adoptive immunotherapy protocol to patients with malignant brain tumors using OK-432-activated peripheral blood mononuclear cells (OK-MCs). To elucidate the mechanism of OK-MCs' cytotoxicity, we examined the cytocidal activity of OK-MCs against Fas expressing T98G glioma cells.
Apoptosis of T98G cells induced by treatment with OK-MCs was unequivocally inhibited by the treatment of T98G cells with ZB4 monoclonal antibody, which binds to Fas and blocks the binding of Fas ligand to Fas. These results indicate that the cytotoxic activity of OK-MCs via apoptosis seems to be partly mediated by the Fas ligand/Fas system.
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