Project/Area Number |
12671370
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
|
Research Institution | KUMAMOTO UNIVERSITY |
Principal Investigator |
KOCHI Masato Kumamoto University Medical School, Department of Neurosurgery, Associate Professor, 医学部, 助教授 (70178218)
|
Co-Investigator(Kenkyū-buntansha) |
USHIO Yukitaka Kumamoto University Medical School, Department of Neurosurgery, Professor, 医学部, 教授 (20028583)
西 徹 熊本大学, 医学部・附属病院, 助手 (00264309)
|
Project Period (FY) |
2000 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | malignant glioma / apoptosis / radio-chemosensitivity / subarachnoid dissemination |
Research Abstract |
1. Apoptosis-related factors and response to radio-chemotherapy of patients with anaplastic oligodendroglioma, oligoastrocytoma and astrocytoma. The p53, Bcl-2, and Bax status was assessed by immunohistochemical methods and yeast functional assay in 26 anaplastic oligodendroglial tumors and 29 anaplastic astrocytomas. There was a significant difference of the incidence of mutation of p53, and the expression of p53 and Bax between anaplastic astrocytoma and anaplastic oligodendroglial tumors. Among 43 patients who had measurable disease after surgery, all 13 anaplastic oligodendroglial tumors that expressed only Bax showed a response, as did 2 of 4 anaplastic oligodendroglial tumors that expressed both Bcl-2 and Bax. Moreover, a response was observed in 7 of 13 anaplastic astrocytomas that did, and in only 1 of 13 that did not, express Bax. Different from anaplastic astrocytomas, anaplastic oligodendroglial tumors expressed functional p53, low endogenous Bcl-2 and high endogenous Bax. This facilitates the induction of apoptosis by radio-chemotherapy. The Bax statement may be a predictor of radio-chemosensitivity in anaplastic astrocytomas. 2. Meningeal gliomatosis model and intrathecal chemotherapy. Meningeal gliomatosis model was established by inoculation of C6 or 9L cell suspension into cisterna magna of Wister rats. These rats with meningeal gliomatosis were treated with intrathecal ACNU, liposome-encapsulated ACNU or liposome-encapsulated BCNU. Liposome-encapsulated ACNU and BCNU offered survival advantage. 3. Expression of Bcl-2 in glioma cell lines and its transfection into the cells. Expression of Bcl-2 was very low in C6 or 9L by Western blotting. Bcl-2 expressing C6 or 9L cell lines were established by transfection of cDNA of Bcl-2 by liposome-mediated gene transfer method.
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