CORE--EXPERIMENTAL GLIOMA TISSUE FACILITY

实验性胶质瘤组织(EGT)核心设施将提供广泛的 组织学、免疫学和活体动物检测服务范围 第二和第三个项目直接和间接到第一个项目 协助对基因工程疱疹进行关键的体内评估 单纯疱疹病毒(HSV)治疗人类恶性胶质瘤。这个 目标是提供两种安全性的相关证据(缺乏 神经毒性)和体外药效(抗肿瘤活性) 正常或严重联合免疫缺陷的基因工程单纯疱疹病毒 (SCID)携带同基因或异种(人)胶质瘤移植物的小鼠。我们会 选择的HSV对正常和刺伤患者的毒力评价 小鼠的脑组织，对于高度选择的病毒，亚人灵长类动物 (A)临床监测(B)显微镜检查 注射脑组织作形态病理学检查；(C)免疫组织化学 以及使用多种免疫试剂进行的免疫荧光研究 如第二和第三个项目所述。EGT核心设施将 还负责开发和验证新的颅内 可用于测试联合治疗的脑胶质瘤模型 颅外照射激活HSV转导基因的表达 通过x-射线促进剂瘤内注射。疗效将会被确定 脑胶质瘤延长生存期和消退的临床应用 小鼠或人类来源的免疫活性(C57BL/6)或免疫受损 (C.B-17)小鼠。该核心将协助评估肿瘤的致癌性 原位修复人恶性肿瘤的潜在性和病毒易感性 在HSV突变病毒暴露下幸存下来的胶质瘤细胞 第二个项目。目标将是提高病毒产量和/或 交付，以达到更有效的效果。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 筛选HSV突变体体内抗肿瘤作用的研究 通过(A)免疫组织化学/免疫荧光鉴定病毒， 肿瘤细胞和宿主免疫相关炎症细胞成分 (B)小鼠和人脑胶质瘤移植瘤的功能检查 瘤内免疫相关细胞，以及(C)诱导和 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.