Core C: Sphingolipid Cancer Animal Pathology Core

摘要 鞘脂动物癌症病理学（SACP）共享资源的总体目标是提供 本计划项目的项目负责人，具备充分有效利用知识、资源和能力 在执行研究项目时使用动物模型，并推进临床前研究。通过 SACP的核心，该项目利用基因工程小鼠模型（GEMM）的调查， 涉及致癌和转移的机制，特别是利用一组独特的动物， 鞘脂代谢基因的缺失与特异性的病理相关动物模型相结合， 癌的事实上，SACP已经成为鞘脂敲除小鼠的国家储存库， 其中几个 癌症的临床前模型，特别是动物模型，是鉴定和治疗癌症的宝贵工具。 新功能、干预、治疗靶点和生物标志物的验证。因此，核心将提供 在研究项目中利用体内模型方面具有“从头到尾”的专业知识的项目。芯会 协助i）动物模型选择; ii）生成致癌作用的动物模型，包括生成 iii）患者来源的异种移植物（PDX）的开发和使用以及人细胞的植入 体内; iv）用于未来和/或合作研究的样本生物银行;以及v）关键相关 癌症中心和/或大学附近的共享资源。SACP核心将提供 该框架的项目，以有效地进行体内研究。 具体目标1：为调查人员提供必要的资源， 实现癌症的体内模型;具体目标2：能够执行临床前和转化 具体目标3：提高对环境的影响， 通过使用共享资源，动物模型替代品和数据进行体内研究 管理 SACP核心的服务和专业知识将促进本提案中概述的体内研究，并将 提供专业知识以支持项目负责人。随着致癌模型的引入， GEMM在鞘脂中的应用，这一核心正在发展成为一个独特的和使能的核心，这是成功的关键， 计划项目及其临床前研究进展。

ABSTRACT The overall objective of the Sphingolipid Animal Cancer Pathobiology (SACP) Shared Resource is to provide the Project leaders of this Program Project with the knowledge, resources and ability to fully and efficiently utilize animal models in the execution of their research projects and to advance their preclinical studies. Through the SACP core, the projects utilize genetically engineered mouse models (GEMM) for the investigation of the mechanisms involved in carcinogenesis and metastasis, specifically utilizing a unique set of animals with deletions in genes of sphingolipid metabolism coupled with pathologically-relevant animal models of specific cancers. Indeed, the SACP has become a national repository for sphingolipid knock out mice, having generated several of them. Preclinical models, specifically animal models, of cancer are invaluable tools for the identification and validation of novel functions, interventions, therapeutic targets, and biomarkers. Therefore, the Core will provide the projects with “start-to-finish” expertise in utilizing in vivo models in their research projects. The Core will assist with i) animal model selection; ii) generation of animal models of carcinogenesis, including the generation of novel GEMM; iii) development and use of patient-derived xenografts (PDXs) and engraftment of human cells in vivo; iv) BioBanking of samples for future and/or collaborative studies; and v) access and use of critical relevant shared resources available throught the Cancer Center and/or University. The SACP Core will provide the framework for the projects to efficiently and effectively conduct in vivo resarch. To this end the SACP Core will: Specific Aim 1: Provide investigators with the necessary resources to implement in vivo models of cancer; Specific Aim 2: Enable the execution of preclinical and translational models in carcinogenesis, as well as BioBanking of samples; and Specific Aim 3: Advance the impact of in vivo research through the use of Shared Resources, animal model alternatives, and data management. The services and expertise of the SACP Core will facilitate in vivo research outlined in this proposal and will provide the expertise to support the Project Leaders. With the incorporation of carcinogenesis models and GEMM in sphingolipids, this Core is evolving as a unique and enabling Core that is critical for the success of the Program Projects and their advancement to preclinical studies.