Pathology

病理核心旨在提供三种服务来支持本计划的实验目标 项目申请。首先，核心将确保及时和可靠地获得从以下来源收集的肿瘤组织 每个项目中使用的前列腺癌遗传模型的临床前研究。这将涉及到 依赖时间表的动物收获、身体解剖、组织解剖和组织处理，包括骨骼 损伤。核心C的第二个目标是提供对脑内信号通路的组织病理学评估 局限性和转移性前列腺癌，以及骨-肿瘤相互作用的治疗后，不同的 在项目1、2和3中测试的“网络抑制剂”。完成这些任务。核心C将支持 肿瘤标记物的定量和标准化免疫组织化学评价，确定参数 细胞凋亡和细胞增殖，提供肺转移的体视学定量 显微镜下观察，并检测肿瘤生长的辅助途径的潜在调节，即血管生成。 第三，核心C将识别、表征和测试途径和靶标验证的分子生物标记物 建议的临床前研究，活体内。这将涉及分析线粒体功能障碍的标志物。 和项目1的氧化损伤，项目2的整合素信号的动态变化，以及对 Runx2“基因签名”用于调节项目3中的骨肿瘤反应。 将平等地支持每个项目，并将在两名资深病理学家的监督下完成。 CORE C董事欧文·利夫博士和CORE C联席董事钟江博士在 前列腺癌的组织病理学、啮齿类动物的疾病模型以及前列腺癌分子生物标志物的评价 肿瘤反应。C核心的形态研究的集中化将促进合作 调查人员对此应用程序的研究，同时消除了每个项目单独 研发关键技术。

The Pathology Core is designed to provide three services to support the experimental aims of this Program Project application. First, the Core will ensure timely and reliable availability of tumor tissues collected from the preclinical studies with genetic models of prostate cancer used in each Project. This will involve schedule-dependent animal harvesting, necropsy, tissue dissection, and tissue processing, including bone lesions. The second objective of Core C is to provide histopathological evaluation of signaling pathways in localized and metastatic prostate cancer, as well as bone-tumor interplay after treatment with the various "network inhibitors" tested in Projects 1, 2, and 3. To accomplish these tasks. Core C will support quantitative and standardized immunohistochemical evaluation of tumor markers, determine parameters of apoptosis and cell proliferation, provide volumetric quantification of lung metastasis by stereologic microscopy, and examine a potential modulation of ancillary pathways of tumor growth, i.e. angiogenesis. Third, Core C will identify, characterize and test molecular biomarkers of pathway and target validation for the proposed preclinical studies, in vivo. This will involve analysis of markers of mitochondrial dysfunction and oxidative damage for Project 1, dynamic changes in integrin signaling for Project 2, and evaluation of a Runx2 "gene signature" for modulation of bone-tumor responses in Project 3. The tasks provided by Core C will support equally each Project, and will be accomplished under the supervision of two senior pathologists. Drs. Irwin Leav, Director of Core C, and Zhong Jiang, Co-Director of Core C, have extensive experience in histopathology of prostate cancer, disease models in rodents, and evaluation of molecular biomarkers of tumor responses. The centralization of the morphologic studies in Core C will facilitate collaborative research among the investigators on this application, while obviating the need for each Project to individually develop key techniques.