CORE--EXPERIMENTAL GLIOMA TISSUE FACILITY

实验胶质瘤组织（EGT）核心设施将提供广泛的 一系列组织学、免疫学和体内动物试验服务， 第二、三个项目直接和第一个项目间接 以协助基因工程疱疹的关键体内评价 单纯疱疹病毒（HSV）用于治疗人类恶性神经胶质瘤。的 目的是提供安全性（缺乏 神经毒力）和功效（抗肿瘤活性）的体外选择的 基因工程HSV在正常或严重联合免疫缺陷中的应用 （SCID）携带同基因或异种（人）胶质瘤移植物的小鼠。我们将 评价将选定的HSV注射到正常或刺伤中的毒力 小鼠的脑组织，以及对于高度选择的病毒，亚人灵长类动物的脑组织 （Aotus猴）通过（a）临床监测（B）显微镜检查 注射的脑组织用于形态病理学;（c）免疫组织化学 以及使用多种免疫试剂的免疫荧光研究 如第二和第三个项目所述。EGT核心设施将 我还负责开发和验证一种新的颅内 神经胶质瘤模型，可用于测试联合治疗， 颅外照射激活HSV转导基因的表达 通过X-照射促进剂进行肿瘤内给药。将确定疗效 使用延长颅内胶质瘤的生存期和消退， 免疫活性（C57 BL/6）或免疫功能低下的小鼠或人源 （C.B-17 scid）小鼠。核心将有助于评估肿瘤发生 原位回收的人类恶性肿瘤的潜在和病毒易感性 已经在HSV突变体病毒暴露中存活的神经胶质瘤细胞，如 第二个项目。目标是提高病毒产量和/或 以实现更有效的结果。总而言之，EGT核心 将为第二和第三个项目的调查人员提供协助 确定所选HSV突变体在体内产生的抗肿瘤作用 通过（a）病毒的免疫组织化学/免疫荧光鉴定， 肿瘤细胞和宿主免疫相关的炎性细胞成分， 移植的鼠和人神经胶质瘤，（B）功能检查 肿瘤内免疫相关细胞的分布，和（c）诱导的和 转导的细胞因子表达。

The Experimental Glioma Tissue (EGT) Core Facility will provide a wide range of histologic, immunologic and in vivo animal testing services to the second and third Projects directly and to the first Project indirectly to assist in critical in vivo evaluation of genetically engineered herpes simplex viruses (HSV) for the treatment of human malignant gliomas. The objective will be to provide correlative evidence of both safety (lack of neurovirulence) and efficacy (anti-tumor activity) of in vitro selected genetically engineered HSV in normal or severe combined immune deficiency (scid) mice bearing syngeneic or xenogeneic (human) glioma grafts. We will evaluate virulence of selected HSV injected into normal or stab-wounded brain tissue of mice and, for highly selected viruses, subhuman primates (Aotus monkeys) by (a) clinical monitoring (b) microscopic examination of injected brain tissue for morphologic pathology; (c) immunohistochemical and immunofluorescent studies using a wide variety of immunologic reagents as described in the second and third Projects. The EGT core facility will also be responsible for developing and validating a new intracranial glioma model that can be used to test combined therapy involving extracranial radiation to activate expression of HSV-transduced genes intratumorally via x-irradiation promoters. Efficacy will be determined using prolongation of survival and regression of intracranial gliomas of mouse or human origin in immunocompetent (C57BL/6) or immunocompromised (C.B-17 scid)mice. The core will assist in assessment of tumorigenic potential and viral susceptibility of in situ recovered human malignant glioma cells that have survived HSV mutant virus exposure as described in the second Project. The goal will be to improve viral production and/or delivery to achieve a more efficacious result. In summary, the EGT Core will provide assistance to investigators in the second and third Projects to define the anti-tumor effects produced in vivo by selected HSV mutants by (a) immunohistochemical/immunofluorescent identification of viral, tumor cell and host immune related inflammatory cell components with engrafted murine and human gliomas, (b) functional examination of intratumoral immune-related cells, and (c) distribution of induced and transduced cytokine expression.