Role of nitric oxide in the pathogenesis of Barrett's-associated carcinogenesis.
Role of nitric oxide in the pathogenesis of Barrett's-associated carcinogenesis.
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DOI：
10.4291/wjgp.v7.i1.131
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
G. Kusaka;K. Uno;K. Iijima;T. Shimosegawa
中科院分区：
文献类型：
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作者：
G. Kusaka;K. Uno;K. Iijima;T. Shimosegawa
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。尾部型同源盒2（CDX2）是BE的代表性标志物，在BE的化生和肿瘤转化过程中增加。一氧化氮 (NO) 被认为是巴雷特癌发生的关键介质。我们之前证明，CDX2可能是在胃食管连接处（GEJ）周围产生的大量NO刺激下通过以配体无关的方式激活上皮生长因子受体而直接诱导的。因此，我们回顾了 NO 在 Barrett 癌发生中的作用的最新进展。值得注意的是，最近的研究表明，尽管细菌数量没有差异，但正常食管、反流性食管炎、BE或BAC组中远端食管的微生物群落存在显着差异。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成分可能在致癌过程中调节NO的产生中发挥重要作用。控制胃食管反流或胃食管结合部周围细菌成分引起的炎症反应可能有助于通过抑制一氧化氮的产生来防止巴雷特癌的进展。
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.