Core D: Animal Models

核心 D：动物模型

• 批准号: 10705042
• 负责人: Saravut Weroha
• 金额: $ 23.14万
• 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 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705042
• 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 care; anticancer research; cancer therapy; career; clinical practice; clinically relevant; conditioning; design; drug sensitivity; experience; experimental study; forging; 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） Mayo Clinic 卵巢孢子动物模型核心（核心 D）的目标是增进理解 卵巢癌的研究并通过提供临床相关模型来促进新疗法的开发 将具有高度可转化性，从而帮助研究人员将这些治疗方法应用于临床实践。因此， 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 四个项目中的三个的疗法。这些模型是在 SPORE、R01 和 第 1-10 年的其他资金来源，并概括来源的组织学和分子特征 SCID 小鼠体内的肿瘤。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与患者的情况相似； 2) PDX 的反应 铂/紫杉烷治疗与来源患者的反应非常相似。自上次竞争更新以来， 我们开发了410个新模型（累计661个），提高了植入效率，开发了 方法将研究数据无缝传输到生物统计和生物信息学核心（核心 C），并成功 开发了离体 3D 培养方法。我们将继续与 Core C 和 Biospecimen 合作 患者注册核心（核心 B）根据来源患者（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本识别控制，以确保遗传 各个模型的保真度。此外，在 11-15 年级，我们将与项目 1 的研究人员合作 3提供免疫活性模型。确保所有动物实验都能在 以标准化、专业和高效的方式，Core D 将作为中央资源，并与 来自每个项目的实验室人员将执行项目中描述的所有基于 PDX 的动物实验 项目。具体而言，核心D将： 1）确保小鼠的高效规划、饲养、采购和利用 最大限度地减少浪费和使用的动物数量，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）同时提供PDX 和免疫活性模型，供研究人员评估新的治疗策略； 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 Models Core 将继续向 SPORE 研究人员和卵巢癌提供已建立的 PDX 整个研究界，以刺激转化研究，以减轻研究人员的负担 卵巢癌。