1995 Fiscal Year Final Research Report Summary
Histopathological and autoradiographical studies of experimental brain tumors after continuous local chemotherapy -Acute stage in rat models-
| Project/Area Number |
05671190
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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 | Nippon Medical School |
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Principal Investigator |
SHIMURA Toshiro Department of Neurosurgery Nippon Medical School, Associate, Professor, 医学部, 助教授 (90110973)
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| Co-Investigator(Kenkyū-buntansha) |
TERAMOTO Akira Department of Neurosurgery Nippon Medical School, Professor, 医学部, 教授 (60231445)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Experimental / Brain Tumor / local chemotherapy / continous / histopathology / MRI / New / Method |
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| Research Abstract |
Continuous local chemotherapy has been evaluated as being an effective administration method and as a possible adjuvant therapy in the sensitivity aspect of the cell cycle for malignant glioma. However, Neurotoxicity of anti-canser agents in the normal brain and noneffective methods for the deeper part of the tumor seems to be the most serious problems. This study was initiated to evaluate histological findings, the uptake distribution, and neurotoxicity of the continuous local administration of isotope labeled anti-cancer agents in the brain tumor of rats. The experimental brain tumor of rats and the method of continuous local chemotherapy were as follows. The tumor wos produced by intracerebralinoculation of cultured cells derived from rat brain tumor induced by using the Roussarcoma virus (Kumanishi et al. strain). One week later Fluorouracil (5-6-3H) (17.7Ci/m mol) and methotrexate (L-glutamyl 3-4-3H) (41.0Ci.m mol) were administered into the brain tumors of rats utilizing a mini o
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smotic pump (Alzet Model 2001) , respectively. We used five rats of various groups. The rats were sacrificed at various time intervals (6 hrs, 12 hrs, 24 hrs, 48hrs 72 hrs and 7 days). The tumor tissues for light microscopic autoradiography were fixed in 10% formalin for 24 hours. Sections for the light microscopic autoradiography were cut at 4 mu thick and coated with Sakura NR-M2 drips. Following exposure for one week at 4 ﾟC,the sections were stained with Konidol X.Six hours after administration, slight radioactivity was distributed in the subarachnoid space and subpial brain tissue in the vicinity of the inserted tube. Twenty four hours after adoministration high radioactivity was clearly present in many tumor cells and phagocytes at the tube tip, but no radioactivity was observed in the deeper part of the tumor or normal brain tissue. In the vicinity of necrosis foci, acute toxic inflammation was also observed. In conclusion, this experimental study shows that these anti-cancer agents are capable of direct penetration into the neoplastic cells of an intracerebral tumor following continuous local administration However, necrosis foci are small in size. The most serious side effect seemed to be the presence of acute toxic inflammation in the vicinity of necrosis foci. Less
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Research Products
(2 results)
