Animal Models

动物模型

基本信息

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
项目类别：
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

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

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项目摘要

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种NNAIN服务。首先，核心将监督每种饲养，维护和质量控制的前列腺癌遗传小鼠模型应用程序中的项目，包括前列腺特异性PTEN条件敲除小鼠（PTERF“'^'）和转基因流浪小鼠。这些鼠标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，以支持各种具体目标。作为核心B的联合导演，斯蒂芬·琼斯博士将确保维护，基因分型和这些小鼠应变的及时可用性以实现每个项目的实验目标。第二个核心B的任务是提供最新的分子成像，以支持对临床前评估应用程序中提出的“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），功能阻滞单克隆抗体（MAB）6.3G9至AVPE整合素（项目2），慢性发夹RNA（shRNA）的慢病毒输送到骨转移前列腺中的runx2沉默癌症，体内（项目3）。对于这些任务。核心B将对肿瘤生长的定量分析对基因设计的前列腺癌细胞类型的异种移植研究，评估肿瘤对局部和转移性疾病模型中的“网络抑制剂”，并绘制成骨细胞和整骨骨骼前列腺癌内生长期间的重塑途径，体内。 Alexei Bogdanov博士核心B将通过协调广泛的分子成像功能组合来领导这些努力，包括MRI（ICT，高分辨率X射线射线照相和生物发光。核心B将同样支持所有应用程序中的三个项目。总体而言，这些研究将提供对使用新型分子疗法治疗后的前列腺癌反应，并验证靶标和途径特异性，体内。