Core D - Animal Models Core

摘要-核心D 马约诊所卵巢孢子动物模型核心的目标是提高对 卵巢癌，并通过提供临床相关模型， 高度可翻译，从而帮助研究人员将这些治疗方法从“板凳上带到床边”。到 为此，我们将采用从我们的大型患者来源的异种移植物（PDX）“活肿瘤库”中开发的模型 在四个项目中的三个项目中开发新的疗法。这些PDX模型是通过 在第1-5年期间，来自SPORE的支持，进一步称为化身，因为它们概括了 作为SCID小鼠原位模型的源患者的组织学和分子特征。而且这些 模型遍布整个腹膜腔，包括网膜，就像人类一样。在 此外，它们还概括了来源肿瘤的其他特征：1）当从 腹水患者，Avatars也有腹水; 2）Avatars对铂/紫杉烷的反应 治疗与源患者的反应密切平行。与生物标本和 生物统计学核心，我们将根据源患者（如临床参数或 种系基因型）或Avatar特征（如药物敏感性、突变或基因表达谱） 并将其扩展用于实验以评估治疗。每个实验都将包括分子样本 识别控制，以确保个体模型的遗传保真度。此外，我们还将与 第四个项目（项目8）通过育种计划提供多种免疫活性模型。这 将包括在评估树突状细胞在免疫抑制中的作用方面起作用的模型 在我们目前的资助期间（项目2）卵巢癌。为了确保所有的动物实验 以专家和有效的方式进行，并且SPORE调查人员使用标准化模型进行 不同的治疗策略-动物模型核心将作为一个中心资源， 与每个项目的实验室人员一起，将执行 项目具体而言，动物模型核心将：1）确保有效的规划，繁殖，购买和 利用小鼠进行孢子相关工作，以尽量减少浪费和使用的动物数量，同时还 减少人员冗余; 2）提供动物护理和治疗方面的专业知识，以确保高质量 翻译研究项目以及发展研究项目和职业所需的数据 发展工作，确保所有SPRE成员都能获得最高水平的技能; 3)向研究者提供患者来源的异种移植物和免疫活性模型，用于评价 卵巢癌的新治疗策略;以及4）提供监测和生物样本收集服务 进行孢子相关的实验

ABSTRACT – Core D The goals of the Animal Models Core 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 from the “bench to the bedside.” To this end, we will employ models developed from our large patient-derived xenograft (PDX) `living tumor-bank' to develop novel therapies in three of the four Projects. These PDX models, which were initiated through support from the SPORE during Years 1-5, are further referred to as Avatars, as they recapitulate the histologic and molecular features of the source patients as orthotopic models in SCID mice. Moreover, these models spread throughout the peritoneal cavity, including omentum, just like the human counterpart. In addition, they recapitulate other features of the source tumors as well: 1) When models are established from patients with ascites, the Avatars also have ascites; and 2) the responses of Avatars to platinum/taxane therapy closely parallel the responses of source patients. In collaboration with the Biospecimens and Biostatistics Cores, we will select appropriate models based on source patient (such as clinical parameters or germline genotypes) or Avatar characteristics (such as drug sensitivity, mutation or gene expression profile) and expand them for use in experiments to evaluate treatment. Each experiment will include molecular sample identification controls to assure the genetic fidelity of the individual models. In addition, we will collaborate with the fourth Project (Project 8) to provide multiple immunocompetent models through a breeding program. This will include models that have been instrumental in evaluating the role of dendritic cells in immune suppression in ovarian cancer in our current funding period (Project 2). To ensure that all animal experimentation can be performed in an expert and efficient manner—and that SPORE investigators use standardized models for their varying therapeutic strategies—the Animal Models Core will serve as a central resource, and in collaboration with the laboratory personnel from each project, will perform all the animal experimentation described in the projects. Specifically, the Animal Models Core will: 1) ensure the efficient planning, breeding, purchase and utilization of mice for SPORE related work to minimize waste and the number of animals used, while also reducing redundancies in personnel; 2) provide expertise in animal care and treatment to ensure high quality data as required for Translational Research Projects as well as Developmental Research Projects and Career Development work, ensuring that  all SPORE members will have access to the highest level of skills available; 3) provide both patient-derived xenograft and immunocompetent models to investigators for the evaluation of novel therapeutic strategies in ovarian cancer; and 4) provide monitoring and biospecimen collection services for SPORE-related experiments.