Experimental Glioma Animal Models Core

核心B-实验性脑胶质瘤动物模型核心 该核心设施将帮助本计划中的每个项目负责人在相关动物身上进行测试 脑肿瘤模型、临床前安全性和各种治疗方法的有效性 抗胶质瘤作用我们将使用的动物模型可能会确定其毒性和疗效 可能会被推进到治疗恶性脑瘤患者的治疗方式。这个核心将 集中与该计划相关的动物实验，使外科和动物专家标准化 处理技术和最大限度地减少可能阻碍比较的琐碎干扰的机会 分析。将在适当的时候收集肿瘤体积、肿瘤质量和生存统计数据。正常和 肿瘤组织将被收集并提交给每个研究人员，或者将在这个核心中进行基因处理 表达或组织病理学分析。项目1将要求在免疫低下的情况下移植胶质瘤 小鼠靶向人脑恶性胶质瘤野生型HSV-1的安全性和有效性研究 表达独特受体分子的细胞。表达抗CDI33的杂交瘤将在核心中产生 获得单链抗体DNA。项目2将评估AYI34.5 HSV的能力 表达活化的MEK促进人脑胶质瘤移植瘤中HSV晚期基因的表达 裸鼠。项目3将检测人脑胶质瘤前体细胞在人脑胶质瘤中的敏感性 基因工程单纯疱疹病毒的异种移植以确定病毒与宿主细胞的相互作用并表征和 改善HSV介导的脑胶质瘤溶瘤作用。项目4将描述大脑中病毒与宿主的相互作用 来自M032(表达人IL-12)的I期临床试验的肿瘤组织。核心将协助 动物脑瘤模型的建立及与人脑胶质瘤的相关性研究 标本。监测胶质瘤生长和治疗反应的生物发光成像将协调进行 被核心。该中心将协助对HSV敏感的新世界猫头鹰猴子进行IND前安全性研究 (Aotus spp.)或绒猴(Callithrix Spp)来确定对灵长类大脑的任何意想不到的毒性 核心将与8.5T/9.4T小型动物核磁共振设备协调，进行所有肿瘤的核磁共振成像研究- 有生育能力的小鼠参与了这些临床前评估，并将与4.7T非人类灵长类动物协调 用于成像和光谱研究的核磁共振。最后，核心将继续评估连续通过 用于临床前毒性和疗效分析的人脑胶质瘤异种移植瘤和特异性转基因模型 对于由项目1、2和3开发和/或表征的每一种独特的基因工程HSV。 相关性(请参阅说明)： EGAM核心是从实验室转化新疗法的过程中必不可少的组成部分 到临床应用。动物试验，以高度标准化的方式进行，由训练有素、熟练的 经验丰富的专业人员是FDA批准启动IRB批准的临床试验的先决条件 人类。此外，我们的脑瘤模型在大多数方面复制了高级别的生物学和生理学 患者中的胶质瘤可以预测新疗法的成功或失败的可能性。

Core B - Experimental Glioma Animal Models Core This core facility will assist each Project Leader in this Program Project Grant to test, in relevant animal models of brain tumors, preclinical safety and efficacy of various therapies designed to achieve an improved anti-glioma effect The animal models we will employ are likely to identify both toxicity and efficacy of therapeutic modalities that might be advanced to treat patients with malignant brain tumors. This core will centralize animal experimentation associated with this Program, standardizing expert surgical and animal handling techniques and minimizing chances for trivial interferences that could hamper comparative analyses. Tumor volume, tumor mass and survival statistics will be collected where appropriate. Normal and tumor tissues will be collected and submitted to each investigator or will be processed in this core for gene expression or histopathologic analyses. Project 1 will require glioma xenografts in immunocompromised mice to determine the safety and efficacy of wild-type HSV-1 engineered to target human malignant glioma cells expressing unique receptor molecules. Hybridomas expressing anti-CDI 33 will be produced in the Core to acquire single chain antibody DNA. Project 2 will evaluate the capacity of a AYI34.5 HSV engineered to express activated MEK to facilitate HSV late gene expression in human glioma xenografts in the brains of nude mice. Project 3 will examine the susceptibility of human glioma progenitor cells in human glioma xenografts to genetically engineered HSV to define virus-host cell interactions and to characterize and improve HSV-mediated oncolysis of gliomas. Project 4 will characterize virus-host interactions in brain tumor tissues from a Phase I clinical trials with M032 (human IL-12 expressing). The Core will assist with development of animal brain tumor models to test findings from these correlative studies with human glioma specimens. Bioluminescence imaging to monitor glioma growth and response to therapy will be coordinated by the Core. The Core will assist with pre-IND safety studies in HSV-sensitive New-World owl monkeys (Aotus spp.) or marmosets (Callithrix spp) conducted to define any unanticipated toxicities to primate brain The Core will coordinate with the 8.5T/9.4T Small Animal NMR Facility for all NMR imaging studies of tumor- bearing mice involved in these preclinical evaluations and will coordinate with the 4.7T nonhuman primate NMR for imaging and spectroscopic studies. Finally, the Core will continue to evaluate serially passaged human glioma xenografts as well as specific transgenic models for preclinical toxicity and efficacy analyses for each ofthe unique genetically engineered HSV developed and/or characterized by Projects 1, 2 and 3. RELEVANCE (See instructions): The EGAM Core is an essential component to the process of translating novel therapies from the laboratory to clinical application. Animal testing, performed in a highly standardized fashion by trained, skilled and experienced professionals, is a prerequisite for FDA approval to initiate-IRB approved clinical trials in humans. Moreover, our brain tumor models replicate, in most ways, the biology and physiology of high grade gliomas in patients and as such can be predictive of the likelihood of success or failure of novel therapies.