Experimental Glioma Animal Models Core

实验性神经胶质瘤动物模型核心

基本信息

批准号：
8299607
负责人：
G. YANCEY GILLESPIE
金额：
$ 17.54万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8299607
关键词：
Animal Experimentation Animal Model Animal Testing Animals Antibodies Aotus primate Biological Assay Biological Models Biology Bioluminescence Brain Brain Neoplasms C57BL/6 Mouse Callithrix Cell Communication Cells Clinical Clinical Trials Core Facility Correlative Study DNA Data Development Documentation Engineering Failure Gene Expression Glioma Growth Harvest Herpesvirus 1 Human Hybridomas Image Immunocompetent Immunocompromised Host Institutional Review Boards Instruction Interleukin-12 Intracranial Neoplasms Laboratories MEKs Magnetic Resonance Imaging Malignant - descriptor Malignant Glioma Malignant neoplasm of brain Mediating Modality Modeling Molecular Monitor Mus Night Monkey Normal tissue morphology Nude Mice Operative Surgical Procedures PTEN gene Pathology Patients Phase I Clinical Trials Physiology Predisposition Primary Brain Neoplasms Primates Process Production Program Research Project Grants Radiation Radiation therapy Recovery Research Personnel Rodent Safety Simplexvirus Specimen Stem cells Survival Analysis System Techniques Testing Therapeutic Therapeutic Agents Therapeutic Effect Tissues Toxic effect Training Transgenic Model Transgenic Organisms Translating Transplantation Treatment Efficacy Tumor Tissue Tumor Volume Virus Xenograft procedure animal tissue antitumor agent base clinical application comparative design efficacy testing experience improved in vivo neoplastic cell nestin protein nonhuman primate novel oncolysis preclinical efficacy preclinical evaluation preclinical safety preclinical toxicity programs receptor research study response safety study statistics success therapy design tissue processing tumor tumor xenograft virus host interaction

项目摘要

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.

核心B-实验性神经胶质瘤动物模型核心该核心设施将在该计划项目赠款中协助每个项目负责人，以测试相关动物脑肿瘤的模型，临床前的安全性和各种疗法的功效，旨在提高抗神经瘤效应我们将采用的动物模型可能确定可能采取的治疗方法来治疗恶性脑肿瘤患者。这个核心将集中与该计划相关的动物实验，标准化专家手术和动物处理技术和最小化琐碎干扰的机会可能会妨碍比较分析。在适当的情况下，将收集肿瘤体积，肿瘤质量和生存统计。正常和肿瘤组织将被收集并提交给每个研究者，或在此核心中处理基因表达或组织病理学分析。项目1将需要免疫功能低下的神经胶质瘤异种移植小鼠确定野生型HSV-1的安全性和有效性，以靶向人类恶性神经胶质瘤表达独特受体分子的细胞。表达抗CDI 33的杂交瘤将在核心中产生获取单链抗体DNA。项目2将评估AYI34.5 HSV的能力。 Express激活MEK，以促进人神经胶质瘤异种移植物中的HSV晚期基因表达裸鼠。项目3将检查人胶质瘤细胞在人神经胶质瘤中的敏感性对基因设计的HSV的异种移植，以定义病毒宿主宿主相互作用并表征和表征和表征改善HSV介导的神经胶质瘤的肿瘤。项目4将表征大脑中病毒宿主相互作用来自M032（人IL-12表达）的I期临床试验的肿瘤组织。核心将有助于动物脑肿瘤模型的开发以测试与人神经胶质瘤相关研究的发现标本。生物发光成像以监测神经胶质瘤的生长和对治疗的反应将得到协调核心。核心将有助于对HSV敏感的新World Owl Monkeys进行预开心研究（Aotus spp。）或摩尔马斯（Callithrix spp），以定义任何意外的毒性对灵长类动物的大脑核心将与8.5t/9.4t小动物NMR设施进行协调，以进行所有NMR成像研究轴承小鼠参与这些临床前评估，并将与4.7 t非人类灵长类动物坐标用于成像和光谱研究的NMR。最后，核心将继续评估串行传递人神经胶质瘤异种移植物以及用于临床前毒性和功效分析的特定转基因模型对于每一个独特的基因工程HSV，都以项目1、2和3为特征。相关性（请参阅说明）： EGAM核心是翻译实验室新颖疗法的过程的重要组成部分进行临床应用。动物测试，以高度标准化的方式通过受过训练，熟练和经验丰富的专业人员是FDA批准的先决条件，以启动IRB批准的临床试验人类。此外，我们的脑肿瘤模型在大多数方面复制了高级生物学和生理学患者的神经瘤以及因此可以预测新疗法成功或失败的可能性。