Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
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Research Abstract |
Despite of the combined treatment with surgery, radiation and chemotherapy, the prognosis of patients with glioblastoma multiforme is very poor. Their median survival time (MST) is about 10 months. Therefore, we investigated the immunological condition of some patients with malignant gliomas to search their better therapeutic procedure. The brain tumor patients were examined the production of gamma interferon (IFN-gamma) from their peripheral blood lymphocytes (PBL), which was induced by co-culture with OK-432 for 3 days. The IFNgamma production of healthy subjects and brain tumor patients was 5,367 525 and 198 66 units/ml, respectively. Thus, The IFN production of brain tumor patients was impaired at a relatively early stage (Karnofsky Scale; over 70%) of these disease. ACNU, a kind of some nitrosourea derivatives, induced bone marrow suppression of brain tumor patients. It is possible that these drugs were administered once 6 to 8 weeks. Their in vitro anti-tumor efficacy was showed
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around 40% against malignant glioma cells. Seizures are sometimes the initial symptom of brain tumor patients. It is also indispensable to give them anticonvulsant agents as prophylactic anticonvulsant therapy for a long time. So, we evaluated the effects of three popular anti-convulsants (phenytoin, phenobarbital and valproate) upon the cellmediated immunity, by using normal mice. Phenytoin showed immunosuppression severely. In turn, sodium valproate never suppressed any immunological activity. No anticonvulsant agents suppressed the anti-tumor activity of LAK cells. The adoptive immunotherapy with these LAK cells had been done in twenty-four patients in whom standard therapy had failed. Eleven cases had partial responses for this therapy: the mean remission period was 16 months. The longsurvival with meningeal carcinomatosis derived from epipharyngeal cancer and has been sustained 44 months after this adoptive immunotherapy. Malignant tumor cells were eradicated from their cerebrospinal fluid in seven of twelve patients with meningeal dissemination. Eleven of 24 patients were also effective in reducing the clinical symptoms and signs. Thus, this adoptive immunotherapy is an attractive approach for the treatment of malignant brain tumors that are insensitive to several anti-cancer agents. Less
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