Animal Models

动物模型

• 批准号: 7991940
• 负责人: Alexei A Bogdanov
• 金额: $ 4.98万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7991940
• 关键词: Aftercare; Animal Model; Arts; Bioluminescence; Bone Remodelling Pathway; Credentialing; Data; Diagnostic radiologic examination; Disease; Disease model; Engineering; Ensure; Evaluation; Genetic; Genotype; Growth; Human; Integrins; Knockout Mice; Laboratories; Lead; Magnetic Resonance Imaging; Maintenance; Malignant neoplasm of prostate; Maps; Metastatic Prostate Cancer; Mitochondria; Molecular; Monoclonal Antibodies; Mouse Strains; Mus; Pathway interactions; Prostate; Quality Control; Resolution; Roentgen Rays; Services; Specificity; Therapeutic; Transgenic Organisms; Xenograft procedure; bone; cancer cell; cell type; design; in vivo; inhibitor/antagonist; molecular imaging; mouse model; novel; pre-clinical; preclinical evaluation; preclinical study; response; small hairpin RNA; small molecule; tumor; tumor growth; tumor progression

The Animal Models Core is designed to provide two nnain services. First, the Core will oversee the husbandry, maintenance, and quality control ofthe genetic mouse models of prostate cancer utilized by each Project in the application, including prostate-specific Pten conditional knockout mice (Pterf"'^') and transgenic TRAMP mice. These mouse models are already fully established In the applicants' laboratories, have been properly maintained, and have been used to generate critical preliminary data in support of the various specific aims. As Co-Director of Core B, Dr. Stephen Jones will ensure the maintenance, genotyping, and timely availability of these mouse strains to fulfill the experimental objectives of each Project. The second task of Core B Is to provide state-of-the-art molecular imaging in support of the preclinical evaluation of "network inhibitors" proposed In the application, which include mitochondria-targeted small molecule Hsp90 inhibitors, Gamitrinibs (Project 1), function-blocking monoclonal antibody (mAb) 6.3G9 to avPe integrin (Project 2), and lentiviral delivery of short hairpin RNA (shRNA) to silence Runx2 in bone metastatic prostate cancer, in vivo (Project 3). For these tasks. Core B will provide quantitative analysis of tumor growth in xenograft studies with genetically engineered prostate cancer cell types, evaluate tumor responses to "network inhibitors" in localized and metastatic disease models, and map osteoblastic and osteoclastic bone remodeling pathways during intratibial growth of prostate cancer, in vivo. Dr. Alexei Bogdanov, Director of Core B, will lead these efforts by coordinating an extensive portfolio of molecular imaging capabilities, including MRI, (iCT, high resolution X-ray radiography, and bioluminescence. Core B will support equally all three Projects in the application. Overall, these studies will provide a quantitative and unbiased evaluation of prostate cancer responses after treatment with novel molecular therapies, and validate target and pathway specificity, in vivo.

动物模型核心旨在提供两项服务。首先，核心将监督 每个人使用的前列腺癌遗传小鼠模型的饲养、维护和质量控制 正在申请的项目包括前列腺特异性Pten条件敲除小鼠（Pterf"'^'）和转基因 流浪老鼠。这些小鼠模型已经在申请人的实验室中完全建立，并已 妥善维护，并已用于生成关键的初步数据以支持各种 具体目标。作为 Core B 的联合主任，Stephen Jones 博士将确保维护、基因分型和 及时获得这些小鼠品系以实现每个项目的实验目标。第二个 核心 B 的任务是提供最先进的分子成像以支持临床前评估 申请中提出“网络抑制剂”，其中包括靶向线粒体的小分子Hsp90 抑制剂、Gamitrinibs（项目 1）、功能阻断单克隆抗体 (mAb) 6.3G9 to avPe 整合素 （项目 2），以及慢病毒递送短发夹 RNA (shRNA) 以沉默骨转移性前列腺中的 Runx2 体内癌症（项目 3）。对于这些任务。 Core B 将提供肿瘤生长的定量分析 使用基因工程前列腺癌细胞类型进行异种移植研究，评估肿瘤对 局部和转移性疾病模型中的“网络抑制剂”，并绘制成骨细胞和破骨细胞骨图 体内前列腺癌胫骨内生长过程中的重塑途径。阿列克谢·博格丹诺夫博士，主任 核心 B 将通过协调广泛的分子成像能力组合来领导这些努力， 包括 MRI、（iCT、高分辨率 X 射线照相术和生物发光。Core B 将同等支持所有 应用程序中的三个项目。总体而言，这些研究将为以下方面提供定量和公正的评估： 前列腺癌采用新型分子疗法治疗后的反应，并验证靶点和途径 特异性，体内。