CORE--EXPERIMENTAL GLIOMA TISSUE FACILITY

核心——实验性胶质瘤组织设施

• 批准号: 6324642
• 负责人: G. YANCEY GILLESPIE
• 金额: $ 21.52万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6324642
• 关键词: biomedical facility; glioma; laboratory mouse; tissue resource /registry

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.

实验性神经胶质瘤组织（EGT）核心设施将提供广泛的 一系列组织学、免疫学和体内动物测试服务 直接第二个和第三个项目以及间接第一个项目 协助基因工程疱疹的关键体内评估 单纯病毒（HSV）用于治疗人类恶性神经胶质瘤。这 目标是提供安全性的相关证据（缺乏 神经毒力）和体外选定的功效（抗肿瘤活性） 正常或严重联合免疫缺陷中的基因工程 HSV (scid) 携带同基因或异种（人）神经胶质瘤移植物的小鼠。我们将 评估注射到正常或刺伤伤者中的选定 HSV 的毒力 小鼠的脑组织，对于高度选择性的病毒，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 注射脑组织进行形态病理学检查； (c) 免疫组织化学 和使用多种免疫试剂的免疫荧光研究 如第二个和第三个项目中所述。 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神经胶质瘤模型 颅外放射激活 HSV 转导基因的表达 通过 X 射线照射启动子进行瘤内治疗。功效将被确定 使用延长颅内神经胶质瘤的生存和消退 免疫功能健全 (C57BL/6) 或免疫功能低下的小鼠或人类来源 (C.B-17 scid)小鼠。核心将有助于评估致瘤性 原位恢复的人类恶性肿瘤的潜力和病毒敏感性 神经胶质瘤细胞在 HSV 突变病毒暴露中幸存下来，如 第二个项目。目标是提高病毒产量和/或 交付以达到更有效的结果。总之，EGT 核心 将为第二个和第三个项目的研究人员提供帮助 确定选定的 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症细胞成分 移植的小鼠和人类神经胶质瘤，（b）功能检查 瘤内免疫相关细胞，以及（c）诱导和分布 转导的细胞因子表达。