Mechanisms of Esophageal Carcinogenesis

这份修订后的计划项目赠款提案名为。食管癌发生机制。旨在定义和阐明食管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合作和科学核心设施的使用，该计划项目侧重于假设驱动的创新研究。 项目负责人的经验和专业知识，与核心设施提供的平台相结合，将导致研究的加强，如果项目相互独立，这是不可能的。 项目1（Rustgi，项目负责人）将重点关注表皮生长因子受体（EGFR）过表达在食管癌发生的早期或前体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-基质相互作用的相互作用，特别是EGF和TGF β受体系统，以及它们对食管癌发生的影响。 项目3（El-Deiry，项目负责人）将阐明TRAIL凋亡途径在食管癌发生中的作用。 重要的是，这些项目通过利用独特的器官型培养物和具有食管上皮特异性基因表达的基因工程小鼠进一步联合起来，这两种培养物和基因工程小鼠都是由项目负责人开发的。 三个非常成功的核心设施旨在提供食管癌特异性服务，以刺激合作研究：形态学，分子生物学/基因表达和管理。 该计划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管癌发生的分子过程的合作理解。 最后，该计划项目与NCI食管癌和胃癌进展审查小组合作。

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.