Department of Surgery and Institute of Molecular Medicine, St. James's Hospital, Trinity College Dublin, Ireland.
Department of Surgery and Institute of Molecular Medicine, St. James's Hospital, Trinity College Dublin, Ireland.
Cancer Lett. 2014 Apr 10;345(2):182-9. doi: 10.1016/j.canlet.2013.08.017. Epub 2013 Aug 27.
Esophageal adenocarcinoma (EAC) is the eighth most common cancer worldwide, and approximately 15% of patients survive 5years. Reflux disease (GERD) and Barrett's esophagus (BE) are major risk factors for the development of EAC, and epidemiologic studies highlight a strong association with obesity. The immune, inflammatory and intracellular signaling changes resulting from chronic inflammation of the esophageal squamous epithelium are increasingly well characterized. In GERD and Barrett's, an essential role for T-cells in the initiation of inflammation in the esophagus has been identified, and a balance between T-cell responses and phenotype may play an important role in disease progression. Obesity is a chronic low-grade inflammatory state, fueled by adipose tissue derived- inflammatory mediators such as IL-6, TNF-α and leptin, representing a novel area for targeted research. Additionally, reactive oxygen species (ROS) and receptor tyrosine kinase (RTK) activation may drive progression from esophagitis to EAC, and downstream signaling pathways employed by these molecules may be important. This review will explain the diverse range of mechanisms potentially driving and maintaining inflammation within the esophagus and explore both existing and future therapeutic strategies targeting the process.
食管腺癌（EAC）是全球第八大常见癌症，约有 15%的患者能存活 5 年。反流性疾病（GERD）和 Barrett 食管（BE）是 EAC 发展的主要危险因素，而流行病学研究强调了肥胖与之的强关联性。慢性食管鳞状上皮炎症导致的免疫、炎症和细胞内信号变化已得到越来越深入的研究。在 GERD 和 Barrett 食管中，T 细胞在食管炎症的发生中起着至关重要的作用，T 细胞反应和表型之间的平衡可能在疾病进展中起着重要作用。肥胖是一种慢性低度炎症状态，由脂肪组织衍生的炎症介质如 IL-6、TNF-α 和瘦素等推动，代表了一个新的靶向研究领域。此外，活性氧（ROS）和受体酪氨酸激酶（RTK）的激活可能促使食管炎向 EAC 进展，这些分子所使用的下游信号通路可能很重要。这篇综述将解释潜在的多种机制，这些机制可能在食管内驱动和维持炎症，并探讨现有的和未来针对该过程的治疗策略。
