1995 Fiscal Year Final Research Report Summary
INTRATHECAL CHEMOTHERAPY AGAINST SUBARACHNOID DISSEMINATION OF MALIGNANT BRAIN TUMORS
| Project/Area Number |
05671172
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
HAMADA Junichiro KUMAMOTO UNIVERSITY HOSPITAL DEPARTMENT OF NEUROSURGERY,INSTRUCTOR, 医学部・附属病院, 助手 (40253752)
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| Co-Investigator(Kenkyū-buntansha) |
西 徹 熊本大学, 医学部・附属病院, 助手 (00264309)
永廣 信治 熊本大学, 医学部・附属病院, 講師 (60145315)
GOTO Satoshi KUMAMOTO UNIVERSITY HOSPITAL DEPARTMENT OF NEUROSURGERY,ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (50240916)
KURATSU Junichi KUMAMOTO UNIVERSITY MEDICAL SCHOOL DEPARTMENT OF NEUROSURGERY,ASSOCIATE PROFESSO, 医学部, 助教授 (20145296)
USHIO Yukitaka KUMAMOTO UNIVERSITY MEDICAL SCHOOL DEPARTMENT OF NEUROSURGERY,PROFESSOR, 医学部, 教授 (20028583)
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| Project Period (FY) |
1993 – 1995
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| Keywords | MALIGNANT GLIOMAS / SUBARACHNOID DISSEMINATION / INTRATHECAL CHEMOTHERAPY / NITROSOUREAS / LIPOSOME |
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| Research Abstract |
1.NEUROTOXICITY AND PHARMACOKINATICS OF VENTRICULOLUMBAR PERFUSION OF MCNU IN DOGS
Ventriculolumbar perfusion of MCNU,a watersoluble nitrosourea with log P ; -0.71, was carried out in 2 dogs, oce a week, 10 consecutive weeks. No neurological and systemic symptoms were noted aftar perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma, local subependymal spongy degeneration and gliosis. The area under the drug concentration-time curve was 1152 mug*min/ml on average, significantly larger than of ACNU and the half time was 41.1 min on average, significantly longer than that of ACNU.
2.INTRATHECAL CHEMOTHERAPY OF BCNU ENCAPSULATED INTO HYBRID-LIPOSOME (LIPO-BCNU) AGAINST SUBARACHNOID DISSEMINATION OF MALIGNANT GLIOMAS
(1) A Wister rat model of meningeal gliomatosis was established by intracisternal inoculation of a 0.1 ml cell suspension containing 1*10^6 or5*10^6 viable C6 glioma cells. Two days after the inoculation, 2.5 mg/kg lipo-BCNU was administerd intracisternally. Significantly prolonged survival was obtained in 3 out of 6 experimental groups.
(2) Affer the administration of 0.1 mg lipo-BCNU or 1.0mg BCNU dissolved in 5% dextrose into cisterna magna of dogs, the cisterna magna CSF was sampled and the BCNU concentration was assayd by HPLC.The half-time of lipo-BCNU was longer than that of BCNU dissolved in 5% dextrose.
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