Advances in Brief Increased Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Barrett ' s Esophagus and Associated Adenocarcinomas 1
Advances in Brief Increased Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Barrett ' s Esophagus and Associated Adenocarcinomas 1
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发表时间：
2006
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通讯作者：
K. Wilson;Sidong;Fu;Kalathur;S. Ramanujam;Stephen;J. Meltzer
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作者：
K. Wilson;Sidong;Fu;Kalathur;S. Ramanujam;Stephen;J. Meltzer
巴雷特食管是一种恶性前病变，由慢性反流性食管炎引起。诱导型一氧化氮合酶（±NOS;NOS-2）和环氧合酶-2 （COX-2）是炎症介质和上皮细胞生长调节剂。 nos和COX-2在结直肠腺瘤和癌中表达水平较高，而COX-2在胃癌中表达水平升高。为了确定 nos和COX-2在Barrett's相关肿瘤中的作用，我们测量了这些基因在化生的Barrett's和食管腺癌中的表达。我们分别在21例患者中16例（76%）和21例患者中17例（80%）检测到Barrett粘膜中±no和COX-2 niKNA水平高于配对的胃对照组织（两种基因的/ < 0.001）。在食管腺癌中，5例中有4例和5例中分别有±no和COX-2 inKNA水平升高。此外，在10名Barrett患者中，10名患者的免疫组化染色±no和COX-2表达强烈阳性，高于匹配的胃对照组。Western blotting证实COX-2表达升高。这些发现支持了 nos和COX-2在早期和经常参与Barrett相关肿瘤进展的假设。
Barrett's esophagus is a premalignant condition arising in response to chronic reflux esophagitis. Inducible nitric oxide synthase (¡NOS;NOS-2) and cyclooxygenase-2 (COX-2) are mediators of inflammation and regu lators of epithelial cell growth. Expression levels of ¡NOSand COX-2 are high in colorectal adenomas and carcinomas, and COX-2 expression is elevated in gastric cancers. To determine the involvement of ¡NOSand COX-2 in Barrett's-associated neoplasia, we measured expression of these genes in metaplastic Barrett's and esophageal adenocarcinomas. We de tected elevated ¡NOSand COX-2 niKNA levels in Barrett's mucosa com pared with paired gastric control tissues in 16 of 21 (76%) and 17 of 21 (80%) patients, respectively (/' < 0.001 for both genes). In esophageal adenocarcinomas, ¡NOSand COX-2 inKNA levels were increased in four of five and five of five cases, respectively. Furthermore, in 10 of 10 Barrett's patients, immunohistochemical staining for ¡NOSand COX-2 expression was strongly positive and higher than in matched gastric controls. Increased COX-2 expression was confirmed by Western blotting. These findings support the hypothesis that ¡NOSand COX-2 are involved early and often in Barrett's-associated neoplastic progression.