CORE--ANIMAL FACILITIES

核心——动物设施

基本信息

批准号：
6203243
负责人：
GAIL T COLBERN
金额：
$ 20.68万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-08-01 至 2002-11-30
项目状态：
已结题

项目摘要

The Animal Research Core is an integral unit for the SPORE - Bay Area Breast Cancer Translational Research Program. The translational nature of the research involved in this program frequently requires animal studies prior to clinical application. The centralized nature of the Core and interaction with all SPORE investigators allows maximal usage of this valuable research asset of an animal model for human breast cancer. The use of a single facility for this research reduces equipment duplication and costs and allows coordination of animal work to achieve volume discounts. The primary goal of the Animal Research Core is maintenance and refinement of the xenogeneic animal model for human breast cancer. Immune deficient mice, hormone supplemented if required, are inoculated with human breast cancer cell lines in Matrigel. Tumor-bearing mice are then supplied to investigators in the SPORE Projects and Developmental Projects. Animals are treated within the Core at the direction of the investigator. Animals or harvested tumor or tissues are then supplied to the investigator for analysis. Project 1 will utilize animals with HER2/neu expressing tumors from BT474, MDA453, MKN7 and transfected MCF7 (clone 18) cell lines to determine the efficacy and toxicity of immunoliposomes encapsulating specific chemotherapy agents. Project 2 will use doxorubicin chemoresistant tumors developed in animals for analysis using comparative genomic hybridization (CGH) to determine copy number abnormalities at one or a few chromosomal regions associated with chemoresistance. Project 4 will use cell lines transfected with the Luciferase reporter gene to sensitively examine the effect of urokinase plasminogen activator inhibitors on metastatic activity. The Animal Research Core has conducted one extensive study through a SPORE Developmental Project (In vivo drug resistance of breast cancer cell lines due to HER2/neu oncogene) and has consulted on several other projects awaiting funding. Refinement of the animal model system occurs continuously in the Core and pilot studies are conducted as necessary to support the SPORE Projects and Developmental Projects. In addition to growth of breast cancer cell lines as tumors, the Animal Research Core is growing primary human breast cancers in the mouse model system. In vitro culture of these tissues has been difficult and has routinely resulted in selection of the diploid population of tumor cells, very different from the original aneuploid tumor. Recent inoculations and serial passages of animal tumors from primary human breast tumors have yielded tumor tissue for analysis and studies are pending for use of this new tissue source.

动物研究核心是 SPORE 的一个组成部分 - 湾区乳腺癌转化研究计划。翻译的本质该计划涉及的研究经常需要动物研究临床应用前。核心的集中化性质与所有 SPORE 调查员的互动可以最大限度地利用这一点人类乳腺癌动物模型的宝贵研究资产。这本研究使用单一设施可减少设备重复和成本，并允许协调动物工作以达到产量折扣。动物研究核心的主要目标是维护和人类乳腺癌异种动物模型的完善。免疫缺陷小鼠，如果需要补充激素，接种基质胶中的人类乳腺癌细胞系。那么荷瘤小鼠提供给 SPORE 项目和发展研究人员项目。动物在核心内按照主管人员的指示接受治疗研究者。然后将动物或收获的肿瘤或组织提供给调查员进行分析。项目 1 将利用动物来自 BT474、MDA453、MKN7 和转染的 MCF7 的 HER2/neu 表达肿瘤（克隆18）细胞系，以确定功效和毒性封装特定化疗药物的免疫脂质体。项目2将使用动物体内开发的阿霉素耐药肿瘤进行分析使用比较基因组杂交 (CGH) 确定拷贝数与以下相关的一个或几个染色体区域的异常化学耐药性。项目 4 将使用转染的细胞系荧光素酶报告基因可灵敏地检查尿激酶的作用纤溶酶原激活剂抑制剂对转移活性的影响。动物研究核心通过 SPORE 进行了一项广泛的研究开发项目（乳腺癌细胞系的体内耐药性由于 HER2/neu 致癌基因）并为其他几个项目提供了咨询等待资金。动物模型系统的完善必要时持续进行核心研究和试点研究支持 SPORE 项目和发展项目。此外乳腺癌细胞系作为肿瘤的生长，动物研究核心是在小鼠模型系统中生长原发性人类乳腺癌。体外这些组织的培养一直很困难，并且通常会导致肿瘤细胞二倍体群体的选择，与原始非整倍体肿瘤。最近的接种和连续传代原发性人类乳腺肿瘤的动物肿瘤已产生肿瘤组织正在等待对这种新组织来源的使用进行分析和研究。