Animal Models

动物模型核心的设计是为了提供两个NNAN服务。首先，核心将监督 各自利用的前列腺癌遗传性小鼠模型的饲养、维护和质量控制 应用中的项目，包括前列腺特异性Pten条件基因敲除小鼠(Pterf“‘^’)和转基因 捉弄老鼠。这些老鼠模型已经在申请者的实验室中完全建立起来，已经 维护得当，并已用于生成关键的初步数据，以支持各种 明确的目标。作为Core B的联席主任，Stephen Jones博士将确保维护、基因分型和 及时提供这些小鼠品系，以实现每个项目的实验目标。第二 核心B的任务是提供最先进的分子成像技术，以支持临床前评估 申请中提出的“网络抑制剂”，包括线粒体靶向的小分子Hsp90 抑制剂，Gamitrinibs(项目1)，针对avPe整合素的功能阻断单抗(MAb)6.3G9 (项目2)，以及慢病毒传递短发夹状RNA(ShRNA)以沉默骨转移前列腺癌中的Runx2 癌症，活体(项目3)。来完成这些任务。核心B将提供#年肿瘤生长的定量分析 用基因工程前列腺癌细胞类型进行的异种移植研究，评估肿瘤对 局部和转移疾病模型中的“网络抑制物”，以及成骨细胞和破骨细胞骨的图谱 前列腺癌体内生长过程中的重塑途径。阿列克谢·博格丹诺夫博士 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， 包括磁共振成像、信息通信技术、高分辨率X射线照相和生物发光。核心B将平等地支持所有 应用程序中的三个项目。总体而言，这些研究将提供对 前列腺癌新分子疗法治疗后的反应，并验证靶点和途径 特异性，活体内。

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.