Immunological conditions of patients with malignant gliomas ---Therapeutic drugs and Selection of BRMs---

多形性胶质母细胞瘤虽经手术、放化疗联合治疗，但预后很差。患者的中位生存期（MST）约为10个月。因此，我们研究了一些恶性胶质瘤患者的免疫状况，以寻求更好的治疗方法。通过与OK-432共培养3天，检测脑肿瘤患者外周血淋巴细胞（PBL）产生γ干扰素（ifn - γ）的情况。健康人和脑肿瘤患者的IFNgamma产生量分别为5367 525和198 66单位/ml。因此，脑肿瘤患者IFN的产生在相对较早的阶段（Karnofsky量表，超过70%）受损。ACNU是一种亚硝基脲衍生物，可诱导脑肿瘤患者骨髓抑制。这些药物有可能每6 - 8周服用一次。体外抗肿瘤效果明显，对恶性胶质瘤细胞的抑制率约为40%。癫痫发作有时是脑肿瘤患者的初始症状。长期给予抗惊厥药物作为预防性抗惊厥治疗也是不可缺少的。因此，我们用正常小鼠评价了三种常用的抗惊厥药（苯妥英、苯巴比妥和丙戊酸）对细胞免疫的影响。苯妥英有严重的免疫抑制作用。反过来，丙戊酸钠不会抑制任何免疫活性。没有抗惊厥药物抑制LAK细胞的抗肿瘤活性。用这些LAK细胞进行过继免疫治疗已在24例标准治疗失败的患者中进行。11例患者对该疗法有部分反应：平均缓解期为16个月。这种过继性免疫治疗后，源于咽喉癌的脑膜癌患者的长期生存期持续了44个月。12例脑膜播散患者中有7例脑脊液中恶性肿瘤细胞被根除。24例患者中有11例临床症状和体征得到有效缓解。因此，这种过继免疫疗法是治疗对几种抗癌药物不敏感的恶性脑肿瘤的一种有吸引力的方法。少

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 … More 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