| Project/Area Number |
62480310
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Medical College of OITA |
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Principal Investigator |
MORI Teruaki Medical College of OITA. Associate professor, 医学部, 助教授 (60124632)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Satoru Medical College of OITA. Lecturer, 医学部, 講師 (50154498)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | TNF receptor / LDL receptor / Brain tumor / Antitumor activity / Nude mouse / 臨床治験 / TNF / 脳腫瘍 / TNF薬物動態 / brain tumor / TNFreceptor / LDLreceptor |
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| Research Abstract |
Purpose: We were examined TNF and LDL receptor on brain tumor cultured cells and antitumor activity of TNF in a experimental and clinical study. Method: In vitor study:
1. TNF and LDL receptor on three glioma cell lines were examined with ^<125>I-TNF and LDL binding assay.
2. Four glioma cell lines were exposed to 100 or1000u/ml of rrecombinant human TNF (PT-050, supplied by Dainippon Pharmaceutical Co., Ltd.) and examined for cytostatic activity and cell cycle. In vivo study:
3. Two human glioma cell lines and a rat glioma transplanted in nude mice were treated with 10,000U/0.05ml of TNF given intravenously or intratumorally 7 times daily. Subsequentry the tumors were measured and examined histologically.
4. Four dog normal brains were examined histologically after TNF intracarotidarterial (ia.)injection. In clinical study:
5. Eight cases with malignant brain tumor were treated with TNF 25-300 x10^4U/body iv. twice/week. Effect of therapy was evaluated by tumor size on CT.
6. TNF concentration in CSF and tumor tissue ofa glioblastoma was measured after TNF injection intravenously. Results:1. TNF receptors were abundant in human glioma cells and little in rat glioma cells LDL receptors were confirmed in two rat glioma cells. 2. TNF had a cytostatic effect on rat glioma cells. TNF accumlated G2+M and/ or S phase cells. 3. Human gliomas transplanted into nude mice were highly sensitive to TNF compared with rat glioma. the tumor reduction was most remarkable in the intratumoral imjection group. pathological changes were mainly due to the obstructive effect of TNF on tumor blood vessels. 4. No abnormal finding couldbe seen in the brains of dogs pathologicaly after TNF ia. injection. 5. Partial remission could be seen in two cases. side effects were hypotention , fever and liver dysfunction. but they were not so severe. 6. TNF could be detected in tumor tissue only after ia.injection.
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