Animal Models

Animal Models Core旨在提供两个nain服务。首先，核心将监督 饲养，维护和质量控制的遗传小鼠模型的前列腺癌所利用的每一个 在申请项目中，包括前列腺特异性Pten条件性基因敲除小鼠（Pterf“^”）和转基因 TRAMP小鼠。这些小鼠模型已经在申请人的实验室中完全建立， 适当维护，并已用于生成关键的初步数据，以支持各种 明确的目标。作为核心B的联合主任，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，以支持临床前评价 在申请中提出的“网络抑制剂”，其中包括靶向Hsp90的小分子 抑制剂，加米替尼（项目1），抗avPe整联蛋白的功能阻断性单克隆抗体（mAb）6.3G9 （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 癌症，在体内（项目3）。为了这些任务。核心B将提供肿瘤生长的定量分析， 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”，并映射成骨细胞和骨细胞骨 前列腺癌胫骨内生长过程中的重塑途径。Alexei Bogdanov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工作， 包括MRI、iCT、高分辨率X射线照相术和生物发光。核心B将平等地支持所有 三个项目在应用中。总的来说，这些研究将提供一个定量和公正的评价， 前列腺癌治疗后的反应与新的分子疗法，并验证目标和途径 特异性，在体内。

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.