Mechanisms of Esophageal Carcinogenesis

这份修订后的计划项目拨款建议书题为。食道癌的发生机制。旨在定义和阐明食道鳞状细胞癌发生的分子机制，并最终转化为诊断和治疗的新策略。基于项目负责人之间的历史互动协作和对科学核心设施的使用，该计划项目专注于创新的假设驱动的研究。项目负责人的经验和专门知识与核心设施提供的平台相配合，将有助于加强研究，而如果这些项目彼此独立，这是不可能的。项目1(Rustgi，项目负责人)将侧重于表皮生长因子受体(EGFR)过度表达在食道癌发生的早期或早期阶段的生物学作用及其功能后果。项目2(Herlyn，项目负责人)将强调上皮-间质相互作用，特别是EGF和TGFbeta受体系统的相互作用，以及它们对食道癌发生的影响。项目3(El-Deary，项目负责人)将阐明TRAIL凋亡通路在食道癌发生中的作用。重要的是，这些项目通过利用独特的器官类型培养和具有食道上皮特异性基因表达的基因工程小鼠而进一步团结起来，这两个都是由项目负责人开发的。三个非常成功的核心设施旨在为促进合作研究提供针对食道癌的特定服务：形态学、分子生物学/基因表达和管理。该项目得到了宾夕法尼亚大学癌症中心和医学院的明确支持，因此将促进跨学科研究，从而导致对形成和调节食道癌发生的分子过程的合作理解。最后，该计划项目是与NCI食道癌和胃癌进展审查小组合作的。

This revised Program Project grant proposal entitled. Mechanisms of Esophageal Carcinogenesis. seeks to define and elucidate the molecular mechanisms underlying squamous cell carcinogenesis in the esophagus with eventual translation to new strategies in diagnosis and therapy. Based upon historical interactive collaborations between the Project Leaders and usage of the Scientific Core Facilities, this program project focuses upon hypothesis-driven research that is innovative. The experience and expertise of the Project Leaders, in concert with the platforms provided by the Core Facilities, will result in enhancement of the research that would not be possible if the projects were independent of each other. Project 1 (Rustgi, Project Leader) will focus upon the biological roles of epidermal growth factor receptor (EGFR) overexpression in the early or precursor stages of esophageal carcinogenesis and their functional consequences. Project 2 (Herlyn, Project Leader) will emphasize the interplay of epithelial-stromal interactions, especially the EGF and TGFbeta receptor systems, and their influence on esophageal carcinogenesis. Project 3 (El-Deiry, Project Leader) will elucidate the role of the TRAIL apoptotic pathway in esophageal carcinogenesis. Importantly, the projects are further united by their utilization of unique organotypic cultures and genetically engineered mice that have esophageal epithelial specific gene expression, both developed by the Project Leaders. Three highly successful Core facilities are designed to provide esophageal cancer-specific services for the stimulation of collaborative research: Morphology, Molecular Biology/Gene Expression and Administrative. This Program Project has the unequivocal support of the University of Pennsylvania Cancer Center and Medical School and as such will foster interdisciplinary research that leads to a cooperative understanding of the molecular processes that form and regulate esophageal carcinogenesis. Finally, the Program Project is in concert with the NCI Progress Review Group for esophageal and stomach cancers.