Kusaka Gen, Uno Kaname, Iijima Katsunori, Shimosegawa Tooru
Gen Kusaka, Kaname Uno, Katsunori Iijima, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Hospital, Sendai, Miyagi 981-8574, Japan.
World J Gastrointest Pathophysiol. 2016 Feb 15;7(1):131-7. doi: 10.4291/wjgp.v7.i1.131.
Barrett's esophagus (BE), a premalignant condition to Barrett's adenocarcinoma (BAC), is closely associated with chronic inflammation due to gastro-esophageal reflux. Caudal type homeobox 2 (CDX2), a representative marker of BE, is increased during the metaplastic and neoplastic transformation of BE. Nitric oxide (NO) has been proposed to be a crucial mediator of Barrett's carcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation of large amounts of NO generated around the gastro-esophageal junction (GEJ) by activating epithelial growth factor receptor in a ligand-independent manner. Thus, we reviewed recent developments on the role of NO in Barrett's carcinogenesis. Notably, recent studies have reported that microbial communities in the distal esophagus are significantly different among groups with a normal esophagus, reflux esophagitis, BE or BAC, despite there being no difference in the bacterial quantity. Considering that microorganism components can be one of the major sources of large amounts of NO, these studies suggest that the bacterial composition in the distal esophagus might play an important role in regulating NO production during the carcinogenic process. Controlling an inflammatory reaction due to gastro-esophageal reflux or bacterial composition around the GEJ might help prevent the progression of Barrett's carcinogenesis by inhibiting NO production.
巴雷特食管（BE）是巴雷特腺癌（BAC）的一种癌前病变，与胃食管反流引起的慢性炎症密切相关。尾型同源盒2（CDX2）是BE的代表性标志物，在BE的化生和肿瘤转化过程中表达增加。一氧化氮（NO）被认为是巴雷特癌变的关键介质。我们之前证明，通过以非配体依赖方式激活表皮生长因子受体，CDX2可能在胃食管交界处（GEJ）周围产生的大量NO刺激下直接被诱导。因此，我们综述了NO在巴雷特癌变中作用的最新进展。值得注意的是，最近的研究报道，尽管细菌数量没有差异，但在正常食管、反流性食管炎、BE或BAC组中，远端食管的微生物群落存在显著差异。考虑到微生物成分可能是大量NO的主要来源之一，这些研究表明远端食管中的细菌组成可能在致癌过程中调节NO产生方面发挥重要作用。控制胃食管反流引起的炎症反应或GEJ周围的细菌组成可能有助于通过抑制NO产生来预防巴雷特癌变的进展。
