Core D: Animal Models

核心 D：动物模型

• 批准号: 10268762
• 负责人: Saravut Weroha
• 金额: $ 21.33万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2026-08-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10268762
• 关键词: 3-Dimensional; Animal Experimentation; Animal Model; Animals; Ascites; Bioinformatics; Biometry; Breeding; Cell Line; Cells; Characteristics; Clinic; Clinical; Clinical Data; Collaborations; Collection; Communities; Complement; Data; Data Correlations; Dendritic Cell Vaccine; Development; Engraftment; Ensure; Evaluation; Female; Fostering; Funding Agency; Future; Gene Expression; Genes; Genetic; Genotype; Goals; Greater sac of peritoneum; Histologic; Human Resources; Immunocompetent; Immunocompromised Host; Individual; Injections; Laboratory Personnel; Malignant neoplasm of ovary; Mammalian Oviducts; Methods; Modeling; Molecular; Monitor; Monoclonal Antibodies; Mus; Natural Killer Cells; Operative Surgical Procedures; Outcome; Ovarian; Patients; Pharmaceutical Preparations; Pharmacotherapy; Platinum; Production; Program Research Project Grants; Reproducibility; Research Personnel; Research Project Grants; Resources; SCID Mice; Sampling; Services; Source; Standardization; TOP1 gene; Testing; Therapeutic; Tissue Banks; Translational Research; Translations; Tumor Bank; Tumor Volume; Woman; Work; Xenograft procedure; animal breeding; animal care; anticancer research; base; cancer therapy; career; clinical practice; clinically relevant; conditioning; design; drug sensitivity; experience; experimental study; genomic data; improved; in vivo; investigator training; member; nanoparticle; novel therapeutic intervention; novel therapeutics; patient derived xenograft model; patient registry; patient response; peritoneal cancer; programs; response; skills; small molecule inhibitor; taxane; three dimensional cell culture; tumor; tumor xenograft; wasting

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.

摘要 - 动物模型核心（核心D） 蛋黄酱诊所卵巢孢子的动物模型核心（核心D）的目标是提高理解 通过提供临床相关模型来增强卵巢癌的发展，并增强新疗法的发展 将是高度翻译的，从而帮助调查人员将这些治疗方法带入临床实践。根据 我们将使用大型原始患者衍生异种移植（PDX）肿瘤库开发的模型来测试新颖 四个项目中的三个中的疗法。这些模型是通过孢子，R01和 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） 腹膜腔和腹水的产生模仿患者对应物； 2）PDX对 铂/紫杉烷治疗与源患者的反应紧密平行。自从上次竞争更新以来 我们已经开发了410种新模型（累计总计661个），提高了植入效率，开发了 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 开发了体内3D培养方法。我们将继续与Core C和Biospimens合作以及 患者注册表核心（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）并扩展它们以供使用 在实验中。每个实验将包括分子样品识别对照，以确保通用 单个模型的保真度。此外，在11 - 15年中，我们将与调查人员合作进行项目1 和3提供免疫能力模型。确保所有动物实验都可以在 标准化，专家和高效的方式，核心D将作为中心资源，并与 每个项目的实验室人员将执行所有基于PDX的动物实验 项目。具体而言，核心D将：1）确保小鼠的有效计划，繁殖，购买和利用 为了最大程度地减少废物和所使用的动物数量，同时还可以减少亲身的冗余； 2）提供 动物护理，治疗和监测方面的专业知识，以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增强计划获奖者的工作， 确保所有孢子成员都可以访问可用的最高水平； 3）两个PDX 并向研究人员进行免疫能力模型，以评估新的治疗策略； 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 模型核心将继续使已建立的PDX可用于孢子研究人员和卵巢癌 整个研究社区以刺激翻译研究，以减少燃烧的目的 卵巢癌。