Smilowitz H M, Micca P L, Nawrocky M M, Slatkin D N, Tu W, Coderre J A
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030-6125, USA.
J Neurooncol. 2000;46(3):231-40. doi: 10.1023/a:1006409721365.
Glioblastoma multiforme (GBM) is the most common primary human brain tumor. About 7000 new cases are diagnosed yearly in the USA and GBM is almost invariably fatal within a few years after it is diagnosed. Despite current neurosurgical and radiotherapeutic tumor cytoreduction methods, in most cases occult foci of tumor cells infiltrate surrounding brain tissues and cause recurrent disease. Therefore the combination of neurosurgical and radiotherapeutic debulking methods with therapies to inhibit occult GBM cells should improve prognosis. In this study we have combined boron neutron-capture therapy (BNCT), a novel binary radiotherapeutic treatment modality that selectively irradiates tumor tissue and largely spares normal brain tissue, with immunoprophylaxis, a form of active immunization initiated soon after BNCT treatment, to treat advanced, clinically relevantly-sized brain tumors in rats. Using a malignant rat glioma model of high immunogenicity, the 9L gliosarcoma, we have shown that about half of the rats that would have died after receiving BNCT debulking alone, survived after receiving BNCT plus immunoprophylaxis. Further, most of the surviving rats display immunological-based resistance to recurrent 9LGS growth six months or more after treatment. To our knowledge this study represents the first time BNCT and immunoprophylaxis have been combined to treat advanced brain tumors in rats.
多形性胶质母细胞瘤（GBM）是最常见的原发性人脑肿瘤。美国每年约有7000例新病例被诊断出来，GBM在被诊断后的几年内几乎无一例外都是致命的。尽管目前有神经外科和放射治疗的肿瘤细胞减灭方法，但在大多数情况下，肿瘤细胞的隐匿病灶会浸润周围脑组织并导致疾病复发。因此，将神经外科和放射治疗的减瘤方法与抑制隐匿性GBM细胞的疗法相结合应能改善预后。在本研究中，我们将硼中子俘获疗法（BNCT）与免疫预防相结合，用于治疗大鼠晚期、临床相关大小的脑肿瘤。BNCT是一种新型的二元放射治疗方式，能选择性地照射肿瘤组织，很大程度上使正常脑组织免受辐射；免疫预防是在BNCT治疗后不久开始的一种主动免疫形式。使用具有高免疫原性的恶性大鼠胶质瘤模型9L胶质肉瘤，我们发现，仅接受BNCT减瘤治疗后会死亡的大鼠中，约有一半在接受BNCT加免疫预防后存活了下来。此外，大多数存活的大鼠在治疗后6个月或更长时间对复发性9LGS生长表现出基于免疫的抗性。据我们所知，本研究是首次将BNCT和免疫预防相结合来治疗大鼠晚期脑肿瘤。
