PRECLINICAL MOUSE MODELS: CENTRAL NERVOUS SYSTEM CANCERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 星形细胞胶质瘤是人类最常见的原发脑肿瘤。很少对标准的肿瘤治疗有反应，它是人类最致命的肿瘤之一。Van Dyke实验室最近开发了转基因小鼠星形细胞瘤模型，方法是使Rb通路失活，而Rb通路发生在90%的人类对应物中。这个模型非常类似于人类胶质瘤的病理和分子途径(见出版物)。无论是在人类病例中还是在我们的模型中，对致癌病变在不同的脑微环境中诱导的星形胶质细胞的特性了解很少。这个项目的目的是解决与正常和肿瘤相关的星形胶质细胞的形态、分布和分子组成的不同问题。我们建议使用NCMIR开发的技术来研究1肿瘤相关和瘤周星形细胞的形态，2星形细胞在肿瘤内的分布和边界，以及3与肿瘤相关的分子成分与正常周围区域的分布差异。16年来，国际癌症研究所的特里·范戴克博士一直在使用鼠标操纵策略来研究癌症。在分析肿瘤抑制基因p53和pRb的过程中，她的实验室使用转基因和基因敲除策略建立了几个肿瘤模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Astrocytic glioma is the most prevalent primary brain tumor in human. Rarely responding to standard tumor therapies, it is one of the most deadly human tumors. The Van Dyke lab recently developed trangenic mouse model for astrocytoma by inactivating the Rb pathway, which occurred in 90% of the human counterpart. This model closely resembles the pathology and molecular pathways of human glioma (see publication). Little is understood about the properties of astrocytes elicited by cancer-promoting lesions in distinct brain microenvironments either in human cases or in our model. The aim of this project is designed to address distinct questions about the morphology, distribution and molecular constituents associated with normal,and tumor-associated astrocytes. We propose to use the techniques devloped in NCMIR to investigate 1 tumor-associated and peritumoral astrocytic morphology, 2 astrocytic distribution and boundaries within tumors and 3 differences in distribution of molecular constituents associated with tumor and normal surrounding areas by large scale mapping. The PI, Dr. Terry Van Dyke has utilized mouse manipulation strategies to study cancer for 16 years. In the course of analyzing the tumor suppressors p53 and pRb, her lab has established several tumor models using transgenic and knock-out strategies.