Core D - Animal Models Core

核心 D - 动物模型核心

• 批准号: 9149467
• 负责人: PAUL HALUSKA
• 金额: $ 13.88万
• 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: 2009-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9149467
• 关键词: Abdominal Cavity; Animal Experimentation; Animal Model; Animal Testing; Animals; Ascites; Biological Assay; Biostatistics Core; Breeding; Characteristics; Chromosomes; Clinic; Clinical; Collaborations; Collection; Complement; Complex; DNA Sequence; Data Quality; Dendritic Cells; Development; Disease; Ensure; Evaluation; Fingerprint; Fostering; Funding; Gene Expression Profile; Gene Targeting; Genetic; Genotype; Goals; Greater sac of peritoneum; Histologic; Human; Human Resources; Immune system; Immunocompetent; Immunosuppression; Individual; Intestinal Obstruction; Investigation; Laboratory Personnel; Life; Malignant neoplasm of ovary; Methods; Modeling; Molecular; Monitor; Mus; Mutation; Neoplasm Metastasis; Omentum; Outcome; Ovarian; Patients; Phenotype; Platinum; Publications; Quality Control; Reproducibility; Research; Research Personnel; Research Project Grants; Resistance; Resources; Role; SCID Mice; Sampling; Services; Source; Therapeutic; Tissues; Translational Research; Tumor Bank; Validation; Work; Writing; Xenograft Model; Xenograft procedure; actionable mutation; animal breeding; animal care; avatar models; base; bench to bedside; career development; clinically relevant; comparative genomic hybridization; drug sensitivity; experience; forging; improved; in vivo; member; novel therapeutics; programs; research study; response; skills; taxane; tumor; wasting

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.

抽象-核心D 梅奥诊所卵巢孢子动物模型核心的目标是提高对 并通过提供临床相关的模型来促进新疗法的开发 具有高度的可译性，从而帮助调查人员将这些治疗方法从“替补席上带到床边”。至 为此，我们将使用从我们的大型患者来源的异种移植(PDX)‘活的肿瘤库’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型号是通过 在1-5年间来自孢子的支持，进一步被称为化身，因为它们概括了 来源患者作为SCID小鼠原位模型的组织学和分子特征。此外，这些 模型遍布整个腹膜腔，包括大网膜，就像人类的对应模型一样。在……里面 此外，它们还概括了来源肿瘤的其他特征：1)当模型从 有腹水的患者，替身也有腹水；2)替身对铂/紫杉烷的反应 治疗与原始患者的反应密切相关。与生物质学家和 生物统计学核心，我们将根据源患者选择合适的模型(如临床参数或 生殖系基因类型)或阿凡达特征(如药物敏感性、突变或基因表达谱) 并将其扩展到用于评估治疗的实验中。每个实验将包括分子样本 身份识别控制，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能力模型。这 将包括有助于评估树突状细胞在免疫抑制中的作用的模型 在我们目前的资助期(项目2)，在卵巢癌方面取得进展。以确保所有动物实验都能 以专业和高效的方式进行-孢子调查人员使用标准化模型进行他们的 不同的治疗策略-动物模型核心将作为中心资源，并进行合作 与来自每个项目的实验室人员一起，将执行 项目。具体地说，动物模型核心将：1)确保高效的规划、繁殖、购买和 利用老鼠进行与孢子有关的工作，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，确保所有孢子成员都能获得现有的最高水平的技能； 3)向研究人员提供患者来源的异种移植和免疫活性模型，以评估 卵巢癌的新治疗策略；以及4)提供监测和生物样品收集服务 进行与孢子有关的实验。