Pathology

病理

• 批准号: 7991956
• 负责人: Irwin Leav
• 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/7991956
• 关键词: Aftercare; Animals; Apoptosis; Autopsy; Biological Markers; Bone neoplasms; Cell Proliferation; Disease model; Dissection; Ensure; Evaluation; Genes; Genetic Models; Goals; Harvest; Histopathology; Immunohistochemistry; Integrins; Lesion; Lung; Malignant neoplasm of prostate; Metastatic Prostate Cancer; Microscopy; Molecular; Neoplasm Metastasis; Pathologist; Pathology; Pathway interactions; Research; Research Personnel; Resolution; Rodent; Schedule; Services; Signal Pathway; Signal Transduction; Supervision; Techniques; Testing; Therapeutic; Tissue Procurements; Tissues; Tumor Markers; Tumor Tissue; Validation; angiogenesis; bone; design; experience; in vivo; inhibitor/antagonist; mitochondrial dysfunction; molecular imaging; oxidative damage; pre-clinical; preclinical study; programs; response; tissue processing; tumor; tumor growth

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.

病理学核心旨在提供三项服务，以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提供从 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 时间表相关的动物收获、尸检、组织解剖和组织处理，包括骨 病变核心C的第二个目的是提供对细胞内信号通路的组织病理学评价， 局部和转移性前列腺癌，以及骨肿瘤的相互作用后，治疗与各种 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 肿瘤标志物的定量和标准化免疫组化评价，确定参数， 细胞凋亡和细胞增殖，通过体视学方法提供肺转移的体积定量 在显微镜下观察，并检查肿瘤生长的辅助途径即血管生成的潜在调节。 第三，核心C将鉴定、表征和测试通路和靶标验证的分子生物标志物， 拟定的体内临床前研究。这将涉及分析线粒体功能障碍的标志物 和氧化损伤，项目2整合素信号转导的动态变化，以及评估一个 Runx2“基因签名”用于项目3中骨肿瘤反应的调节。核心C提供的任务 将平等地支持每个项目，并将在两名高级病理学家的监督下完成。 Drs. Core C总监欧文·利夫（Irwin Leav）和Core C联席总监钟江（Zhong Jiang）拥有丰富的 前列腺癌的组织病理学，啮齿动物的疾病模型，以及前列腺癌的分子生物标志物的评价 肿瘤反应。将形态学研究集中在核心C中将促进合作 研究人员对这一应用程序的研究，同时避免了每个项目需要单独 发展关键技术。