Core 1: Animal and Cell Model Core

核心1：动物和细胞模型核心

• 批准号: 10605252
• 负责人: Guido Erwin Michael Eibl
• 金额: $ 28.57万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605252
• 关键词: Animal Euthanasia; Animal Model; Animals; Area; Backcrossings; Biological; Biometry; Blood; Breeding; Calories; Cell Culture Techniques; Cell model; Chemoprevention; Collaborations; Comprehensive Cancer Center; Data; Data Collection; Development; Diet; Dietary Component; Digestive System Disorders; Drug or chemical Tissue Distribution; Ensure; Environment; Evaluation; Fatty acid glycerol esters; Flow Cytometry; Formalin; Generations; Genetic; Genetically Engineered Mouse; Genotype; Human; Human Resources; Individual; Institution; Intervention; Intervention Studies; KRASG12D; Laboratories; Laboratory Research; Leptin deficiency; Logistics; Malignant neoplasm of pancreas; Medical center; Modeling; Monitor; Mus; Obesity; Organoids; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Diseases; Pancreatic Intraepithelial Neoplasia; Paraffin; Pathology; Phase; Preparation; Primary Cell Cultures; Procedures; Process; Random Allocation; Randomized; Research Personnel; Resource Sharing; Resources; Sampling; Sampling Studies; Services; Standardization; Tissue Banks; Tissue Harvesting; Tissues; Tumor Promotion; Work; animal care; animal facility; animal imaging; animal tissue; cost; design; diet-induced obesity; dietary control; experimental group; experimental study; innovation; member; mouse model; novel; pancreatic cancer model; programs; square foot; three dimensional cell culture; tissue processing; training project; tumor

PROJECT SUMMARY The main objective of the Animal and Cell Model (ACM) Core is to provide animal and innovative cell culture models to the Project investigators and to coordinate and standardize the shared use of the models. Integrated into the ACM Core is the Pathology Sub-Core, which will process animal tissues to meet the needs for the individual projects. The impact of obesity on PDAC will be investigated in KC mice with diet-induced obesity (DIO) or genetically-induced obesity, which will allow to distinguish direct tumor promoting effects of dietary components from true obesity effects. For the DIO model, animals will be randomly allocated to either a control diet or a high fat, high calorie diet (HFCD) and the effect on tumor development assessed. For the genetically- induced obesity model, KC mice will be crossed into the leptin deficient ob/ob background (KCO). The ACM Core will carry out in collaboration with all three projects the main interventional study, in which KC mice are treated with statins. Tissues from this large study will be shared among and analyzed by all three projects. In addition to the main animal study, the ACM Core will conduct Project-specific interventions and will back-cross the KC model into additional genetic backgrounds. The main objectives of the Core are 1) to provide animal- related services and novel cell culture models to all Projects, 2) to minimize duplication of effort and reduce costs by coordinating experiments (shared animal and tissue use), and 3) to reduce variability introduced by different environments and husbandry and to ensure consistency in animal handling and data collection (concentration of resources and expertise). Services that the ACM Core provides for each Project include: obtaining and maintaining institutional approval, designing the animal studies in terms of logistics and statistical power calculations (together with Project PI's and Biostatistics Sub-Core), maintaining animal strains and setting up breeding pairs, genotyping of all animals, randomization of animals to experimental groups, preparation and administration of experimental diets or interventions, daily monitoring and animal care, euthanasia of animals, harvest of tissues and blood at sacrifice, processing tissue, e.g. fixing in formalin and embedding in paraffin, and sectioning (together with the Pathology Sub-Core), histopathological evaluation of tissue sections (together with the Pathology Sub-Core), generation of primary cell cultures (PanINs and murine pancreatic cancer), generating the murine and human pancreatic organoid cultures, storage of raw data, central banking of tissues and biological samples, distribution of tissues to individual Projects, discussion of results with Project Leaders, and training of Project investigators in animal procedures (if desired).

项目总结 动物和细胞模型(ACM)核心的主要目标是提供动物和创新细胞培养 向项目调查员提供模型，并对模型的共享使用进行协调和标准化。集成 进入ACM核心的是病理学分核心，它将处理动物组织以满足 个别项目。肥胖对饮食诱导肥胖的KC小鼠的PDAC的影响将被研究 (Dio)或遗传导致的肥胖，这将允许区分饮食的直接促癌作用 来自真正的肥胖效应的成分。对于DIO模型，动物将被随机分配到一个对照组 评估饮食或高脂肪、高卡路里饮食(HFCD)对肿瘤发展的影响。对于基因上的- 诱导肥胖模型后，KC小鼠将进入瘦素缺乏ob/ob背景(KCO)。ACM CORE将与所有三个项目合作开展主要的干预性研究，其中KC小鼠 用他汀类药物治疗。这项大型研究的组织将在所有三个项目之间共享和分析。在……里面 除了主要的动物研究，ACM核心将进行特定于项目的干预，并将回交 将KC模型转化为额外的遗传背景。核心的主要目标是1)提供动物- 为所有项目提供相关服务和新颖的细胞培养模式，2)最大限度地减少重复工作并降低成本 通过协调实验(共享动物和组织使用)，以及3)减少不同 环境和畜牧业，并确保动物处理和数据收集的一致性(集中 资源和专业知识)。ACM核心为每个项目提供的服务包括：获取和 保持机构认可，从后勤和统计权力的角度设计动物研究 计算(连同PI项目和生物统计学分核心)，维持动物品系和建立 配对繁殖，所有动物的基因分型，动物随机分组，准备和 管理实验饲料或干预措施、日常监测和动物护理、动物安乐死、 在牺牲时采集组织和血液，处理组织，例如用福尔马林固定和石蜡包埋，以及 切片(与病理分核心一起)、组织切片的组织病理学评价(与 病理亚核)，原代细胞培养(Panins和小鼠胰腺癌)，生成 小鼠和人胰腺器官培养、原始数据存储、组织和生物的中央银行 样本，向个别项目分发组织，与项目负责人讨论结果，以及培训 动物程序方面的项目调查员(如果需要)。