Surgical and Animal Core

外科和动物核心

• 批准号: 8299770
• 负责人: Dai Fukumura
• 金额: $ 43.77万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8299770
• 关键词: Abdomen; Aerobic Bacteria; Animal Experiments; Animal Model; Animals; Antibiotics; Backcrossings; Biomedical Engineering; Blood Vessels; Boston; Brain; Brain Neoplasms; Breeding; CXCR4 gene; Cancer Model; Caring; Cephalic; Characteristics; Clinical; Colon; Colonic Neoplasms; Colorectal Cancer; Cost Savings; Development; Engineering; Ensure; Environment; Foundations; Functional disorder; Gene Expression; Generations; Genes; Genetically Engineered Mouse; Glial Fibrillary Acidic Protein; Gnotobiotic; Goals; Immunocompetent; Implant; In Situ; Infection; Instruction; Knock-out; Knockout Mice; Laboratories; Leadership; Liver; Liver neoplasms; Lung; Maintenance; Malignant neoplasm of brain; Malignant neoplasm of liver; Malignant neoplasm of pancreas; Methods; Modeling; Molecular; Monitor; Mus; Neoplasm Metastasis; Operative Surgical Procedures; Organ; Organism; Pancreas; Parasites; Physiological; Pre-Clinical Model; Preparation; Procedures; Process; Production; Program Research Project Grants; Pump; Quality Control; Role; Savings; Sentinel; Services; Site; Solid Neoplasm; Techniques; Texas; Therapeutic Agents; Time; Tissue Banks; Tissue Sample; Transgenic Mice; Vendor; Virus; angiogenesis; animal colony; animal facility; animal model development; base; controlled release; cost; cost effectiveness; effective therapy; high standard; implantation; improved; in vivo; innovation; interest; intravital microscopy; meetings; mouse model; novel; operation; pancreatic neoplasm; pathogen; pathogenic bacteria; programs; research study; response; sample collection; tumor

A hallmark of our laboratory is the development of novel and innovative in vivo tumor models that allow us to study barriers in the delivery of therapeutic agents. This is only possible because of the outstanding surgical expertise and unique animal facility available in the Steele Laboratory since its inception in 1975. This Core will continue to serve two major functions: (i) the surgical support, including novel animal model development, and (ii) the breeding and maintenance of mice, including genetically engineered mice (GEM). Both are vital for successful completion of all Program Project Grant (PPG) goals. Thus, Core C is a cornerstone of this PPG. This Core will continue to develop or improve and provide sophisticated orthotopic tumor models - syngeneic tumor grafts (all four Projects) - as well as cranial window (Projects 1), lung window (Project 2), liver tumor preparation (Project 2, 3) and abdominal window (Project 4). These will enable in vivo time-course monitoring of molecular, cellular, anatomical, and functional parameters in the orthotopic organ environment of brain, colon, liver and pancreatic tumors and their metastases. In addition, this Core will significantly expand maintenance and provision of GEM models in this revised PPG in order to meet a surge of GEM demand from all 4 Projects to study the role of the host microenvironment in response to treatment in spontaneous tumors. Through his leadership of the operation of Cox-7 gnotobiotic animal facility. Dr. Huang will continue to ensure that all experimental animals are of uniform quality and free of murine viruses, pathogenic bacteria, and parasites. This will enable the PPG team to carry out all experimental procedures without the use of antibiotics. These studies are extremely difficult and more costly elsewhere. Currently 26 defined-flora genetically engineered mouse lines are available in the Cox-7 facility. Based on the need of all 4 Projects, additional mouse lines will also be engineered or rederived, bred, and produced within the facility. Tumors that are screened and free of mouse pathogens will be serially passaged in vivo and implanted into experimental animals within the colony. In vivo tumors will not be passaged beyond the fifth generation (F5) to avoid changes in tumor characteristics. This assures tight control of the quality of animals and tumors. Core C will continue to provide standard animal procedures such as controlled-release pump implantation, vascular line placement, post-surgical care and tissue collection.

我们实验室的一个标志是开发新颖和创新的体内肿瘤模型，使我们能够研究治疗药物输送中的障碍。这之所以成为可能，是因为斯蒂尔实验室自 1975 年成立以来拥有出色的外科专业知识和独特的动物设施。该核心将继续发挥两大功能：(i) 外科支持，包括新型动物模型开发，以及 ( ii) 小鼠的繁殖和饲养，包括基因工程小鼠（GEM）。两者对于成功完成所有计划项目拨款 (PPG) 目标都至关重要。因此，Core C 是这个 PPG 的基石。该核心将继续开发或改进并提供复杂的原位肿瘤模型 - 同基因肿瘤移植物（所有四个项目） - 以及颅窗（项目 1）、肺窗（项目 2）、肝肿瘤制备（项目 2、3）和腹窗（项目 4）。这些将使体内时程监测脑、结肠、肝脏和胰腺肿瘤及其转移的原位器官环境中的分子、细胞、解剖和功能参数成为可能。此外，该核心将在修订后的 PPG 中显着扩大 GEM 模型的维护和提供，以满足所有 4 个项目对 GEM 需求的激增，以研究宿主微环境在自发性肿瘤治疗中的作用。通过他领导 Cox-7 无菌动物设施的运营。黄博士将继续确保所有实验动物品质统一，不含鼠类病毒、病原菌、寄生虫。这将使 PPG 团队能够在不使用抗生素的情况下进行所有实验程序。这些研究在其他地方极其困难且成本更高。目前，Cox-7 设施中有 26 个特定菌群的基因工程小鼠品系。根据所有 4 个项目的需要，还将在该设施内设计或重新衍生、培育和生产更多小鼠品系。经过筛选且不含小鼠病原体的肿瘤将在体内连续传代并植入群体内的实验动物中。体内肿瘤不会传代超过第五代（F5），以避免肿瘤特征发生变化。这确保了对动物和肿瘤质量的严格控制。 Core C 将继续提供标准动物程序，例如控释泵植入、血管导管放置、术后护理和组织收集。