Inflammation and the esophageal tumor microenvironment

描述(申请人提供)：食道癌在世界范围内很常见，包括两种亚型：食管鳞状细胞癌(ESCC)和食管腺癌(EAC)。不幸的是，大多数患者出现在晚期，因此使得5年生存率很低，不到5%。这一严峻的预后要求利用我们的研究团队开发的创新和独特的基因工程小鼠模型来实施功能基因组学、预防、成像和治疗的新战略。这个独特的联盟包括来自宾夕法尼亚大学、哥伦比亚大学和马萨诸塞州综合医院的食道癌领域公认的专家之间的长期合作和出版物。特别是，首席调查人员是Anil Rustgi博士(宾夕法尼亚大学)、Timothy Wang博士(哥伦比亚大学)，已经在NCI肿瘤微环境网络中，以及Umar Mahmal博士(马萨诸塞州总医院)。这项U01拨款提案的主要目标如下：(1)利用食道癌的创新模型作为一个平台，阐明肿瘤微环境中炎症和癌症之间的联系；以及(2)为转化医学的进展提供食道癌成像的新方法。这些目标将通过五个相互关联的跨学科和跨机构的具体目标来实现，并提供新的目标。我们希望Rustgi和Wang博士开发的独特的相互关联的模型可以在小鼠上内窥镜、无创成像技术和Umar Mahmod博士的分子探针(跟踪食道癌微环境中的炎症/免疫细胞)的发展促进下，在癌前和癌前病变的组织成像方面提供一个新的，未来的方向，这将对人类食道癌的早期发现产生重大影响。总体而言，这个高度成功的研究团队准备将食道癌模型转化为根除人类食道癌，这将改变美国和世界各地的临床方法。这项拟议的研究与NCI进展小组关于G1级以上癌症的报告以及NCI智库关于肿瘤微环境以及炎症和癌症的建议一致。相关性(见说明)：食道癌包括两个主要亚型，食管鳞状细胞癌(ESCC)和食管腺癌(EAC)，这两种癌症在美国和世界各地都很常见。事实上，鳞状细胞癌是世界上第五大最常见的男性癌症，在美国非洲裔美国人有很高的患病倾向。EAC是美国所有癌症中增长速度最快的。这项拟议的研究将把模型转化为改善食道癌的临床结果。

DESCRIPTION (provided by applicant): Esophageal cancer is common worldwide and comprises two subtypes: esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC). Unfortunately, most patients present at late stages, thereby making survival rates low at less than 5% at 5 years. This grim prognosis mandates the utilization of innovative and unique genetically engineered mouse models developed by our research team to implement new strategies for functional genomics, prevention, imaging and therapy. The unique consortium involves long-standing collaborations and publications between recognized experts in the field of esophageal cancer from the University of Pennsylvania, Columbia University, and Massachusetts General Hospital. In particular, the Principal Investigators are Dr. Anil Rustgi (University of Pennsylvania), Dr. Timothy Wang (Columbia University) already within the NCI Tumor Microenvironment Network, and Dr. Umar Mahmood (Massachusetts General Hospital). The overarching goals of this U01 grant proposal are the following: (1) To utilize innovative models of esophageal cancer as a platform for elucidating the link between inflammation and cancer in the tumor microenvironment; and (2) To provide new approaches in the imaging of esophageal cancer for advances in translational medicine. These goals will be pursued through five interrelated Specific Aims that are trans-disciplinary and trans-institutional, and provide new We hope that the unique interrelated models developed by Drs. Rustgi and Wang may provide a new, future direction in tissue imaging of precancerous and cancerous lesions facilitated by the development of mouse upper endoscopy, non-invasive imaging technologies and molecular probes (tracking inflammatory/immune cells in the esophageal cancer microenvironment) by Dr. Umar Mahmood, which would have a great impact upon early detection of esophageal cancer in the human. In aggregate, this highly accomplished research team is poised to translate models of esophageal cancer into the eradication of human esophageal cancer, which would alter clinical approaches in the United States and worldwide. The proposed research is in concert with the recommendations by the NCI progress group report on upper Gl cancers, and the NCI Think Tank recommendations on the Tumor Microenvironment as well as Inflammation and Cancer. RELEVANCE (See instructions): Esophageal cancer comprises two main subtypes, esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC), both common in the US and worldwide. In fact, ESCC is the 5th most common cancer amongst males worldwide and afflicts African-Americans with a high predilection in the US. EAC has the fastest rate of increase of any cancer in the US. The proposed research will translate models into improving clinical outcomes of esophageal cancers.