Core D: Animal Models

摘要-动物模型核心（核心D） 马约诊所卵巢孢子动物模型核心（核心D）的目标是提高对 通过提供临床相关模型， 将是高度可翻译的，从而帮助研究人员将这些治疗方法应用于临床实践。因此，委员会认为， 我们将使用从我们的大型原位患者来源的异种移植（PDX）肿瘤库开发的模型来测试新的 在四个项目中的三个项目中进行治疗。这些模型是在SPORE、R 01和 第1-10年期间的其他资金来源，并概括了来源的组织学和分子特征 SCID小鼠的肿瘤。重要的是，它们还概括了源肿瘤的关键临床特征：1）扩散， 腹膜腔和腹水的产生模拟患者对应物;和2）PDX对 铂/紫杉烷治疗与源患者的反应密切平行。自从上次竞争性续约以来， 我们已经开发了410种新型号（累计661种），提高了植入效率， 将研究数据无缝传输到生物统计学和生物信息学核心（核心C）的方法，并成功地 开发了离体3D培养方法。我们将继续与核心C和生物标本合作， 患者登记核心（核心B），根据源患者选择适当的模型（例如，临床参数 或种系基因型）或PDX特征（例如，药物敏感性、基因表达）并将其扩增以供使用 在实验中。每个实验都将包括分子样品鉴定对照，以确保遗传 个人模型的真实性。此外，在11-15年级，我们将与研究人员合作开展项目1 和3提供免疫活性模型。为了确保所有动物实验都能在 核心D将作为一个中心资源，并与 每个项目的实验室人员将执行 项目具体而言，核心D将：1）确保小鼠的高效规划、繁育、采购、利用 尽量减少废物和使用的动物数量，同时减少人员冗余; 2）提供 动物护理、治疗和监测方面的专业知识，确保转化研究的高质量数据 项目，发展研究计划项目和职业提升计划获奖者的工作， 确保所有SPORE成员都能获得最高水平的技能; 3）提供PDX 和免疫活性模型，以研究人员评估新的治疗策略;和4）提供 用于离体3D培养实验的PDX肿瘤。在行政核心的指导下，动物 Models Core将继续向SPORE研究人员和卵巢癌研究人员提供已建立的PDX。 研究社区，以促进翻译研究，以减轻负担的目标， 卵巢癌

ABSTRACT – ANIMAL MODELS CORE (CORE D) The goals of the Animal Models Core (Core D) of the Mayo Clinic Ovarian SPORE are to improve understanding of ovarian cancer and enhance the development of novel therapies by providing clinically relevant models that will be highly translatable, thereby helping investigators bring these treatments into clinical practice. Accordingly, we will use models developed from our large orthotopic patient-derived xenograft (PDX) tumor bank to test novel therapies in three of four projects. These models were initiated through support from the SPORE, an R01, and other funding sources during Years 1-10, and recapitulate the histologic and molecular features of the source tumors in SCID mice. Importantly, they also recapitulate key clinical features of the source tumors: 1) spread in the peritoneal cavity and production of ascites mimic the patient counterpart; and 2) the responses of PDXs to platinum/taxane therapy closely parallel the responses of source patients. Since the last competitive renewal, we have developed 410 new models (for a cumulative total of 661), improved engraftment efficiency, developed methods to seamlessly transfer study data to Biostatistics and Bioinformatics Core (Core C), and successfully developed ex vivo 3D culture methods. We will continue collaborating with Core C and the Biospecimens and Patient Registry Core (Core B) to select appropriate models based on source patient (e.g., clinical parameters or germline genotypes) or PDX characteristics (e.g., drug sensitivity, gene expression) and expand them for use in experiments. Each experiment will include molecular sample identification controls to assure the genetic fidelity of the individual models. In addition, in Years 11-15, we will collaborate with investigators on Projects 1 and 3 to provide immunocompetent models. To ensure that all animal experimentation can be performed in a standardized, expert and efficient manner, Core D will serve as a central resource and, in collaboration with the laboratory personnel from each project, will perform all the PDX-based animal experimentation described in the projects. Specifically, Core D will: 1) Ensure the efficient planning, breeding, purchasing, and utilization of mice to minimize waste and the number of animals used, while also reducing redundancies in personnel; 2) provide expertise in animal care, treatment, and monitoring to ensure high quality data for Translational Research Projects, Developmental Research Program projects and Career Enhancement Program awardees’ work, ensuring that all SPORE members will have access to the highest level of skills available; 3) provide both PDX and immunocompetent models to investigators for the evaluation of novel therapeutic strategies; and 4) provide PDX tumors for ex vivo 3 D culture experiments. Under the direction of the Administrative Core, the Animal Models Core will continue to make established PDXs available to SPORE investigators and the ovarian cancer research community at large in order to stimulate translational research with the goal of reducing the burden of ovarian cancer.