Autochthonous Mouse Models of Cancer: Development and Use in Therapeutic Screens

本地小鼠癌症模型：开发和在治疗筛选中的应用

• 批准号: 6934162
• 负责人: PAUL F. LAMBERT
• 金额: $ 25.1万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934162
• 关键词: antineoplastics; breast neoplasms; cervix neoplasms; colon neoplasms; cooperative study; disease /disorder model; drug discovery /isolation; drug screening /evaluation; laboratory mouse; model design /development; pancreas neoplasms

Mouse models for human cancer have been crucial to our understanding of the biology of cancer, its origins and its treatment. In this project, we describe the further development of mouse models for four epithelial tumor types, that of the colon, cervix, pancreas and breast and their use in screening novel therapeutic drugs discovered in the prior projects. The mouse models that will be used have been developed and/or characterized by the co-project leaders, Drs. Dove (colon), Lambert (cervix), Sandgren (pancreas), Alexander (breast) and Moser (colon and breast). These mouse models will be further refined in the context of the proposed studies to make them more amenable to theier use in therapeutic screens. This developmental effort will include continued assessment and refinement of tumor imaging capabilities that will allow for real time imaging of tumors before, during and after treatment of animals with candidate therapeutic drugs. The tumor imaging effort will be pursued in close collaboration with Dr. Jamey Weichert, an expert in small animal imaging here at the University of Wisconsin Comprehensive Cancer Center. Once the models are fully refined, they will be used to screen a select number of candidate drugs generated under Projects 1 and 2 that have passed tissue culture based cytotoxicity and animal based pharmakinetics screens. This drug screening will be performed together with Core C. We will not only test the efficacy of drugs in reducing tumor burden, but also characterize the histopathological effects of drug treatment on multiple parameters of the different cancer types and determine the ability of the drugs to prevent recurrence.

人类癌症的小鼠模型对我们理解癌症的生物学及其起源至关重要 以及它的治疗方法。在本项目中，我们描述了四种上皮细胞小鼠模型的进一步发展 肿瘤类型、结肠、宫颈、胰腺和乳腺肿瘤及其在筛选新治疗方法中的应用 在以前的项目中发现的药物。将使用的鼠标模型已经开发和/或 由联合项目负责人Dove博士(结肠)、Lambert博士(宫颈)、Sandgren博士(胰腺)、 Alexander(乳房)和Moser(结肠和乳房)。这些鼠标模型将在上下文中进一步细化 建议的研究，使它们更容易在治疗筛查中使用。这 开发工作将包括继续评估和改进肿瘤成像能力，这将 允许在使用候选治疗性药物治疗动物之前、期间和之后对肿瘤进行实时成像 毒品。肿瘤成像工作将与Jamey Weichert博士密切合作，Jamey Weichert博士是 威斯康星大学综合癌症中心的小动物成像。一旦模特们 是完全提炼的，它们将被用于筛选项目1下产生的选定数量的候选药物 2例已通过组织培养细胞毒性和动物药代动力学筛选。这 药物筛选将与Core C一起进行。我们不仅将测试药物在减少 肿瘤负担，但也表征了药物治疗对组织病理学影响的多个参数 不同的癌症类型决定了药物预防复发的能力。