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[某些胃肠道疾病中紧密连接蛋白及预后因素的研究]

[Study of claudins and prognostic factors in some gastrointestinal diseases].

作者信息

Gyorffy Hajnalka

机构信息

Semmelweis Egyetem, II. sz. Patológiai Intézet, 1091 Budapest, Ulloi út 93.

出版信息

Magy Onkol. 2009 Dec;53(4):377-83. doi: 10.1556/MOnkol.53.2009.4.7.

Abstract

Gastrointestinal tumors are highly ranked regarding tumoral mortality worldwide. The development and progression of gastrointestinal (GI) diseases go hand in hand with the changes of tight junctions (TJ). Claudins (CLDN) are the main TJ proteins, showing different expression by the different tissues, with the expressed CLDN profile being representative. I. We explored the changes of CLDN expression in Barrett's esophagus and related adenocarcinoma. CLDN2 and -3 expression in Barrett's esophagus was higher than in normal foveolar epithelium. Adenocarcinoma showed higher CLDN2 and -3 expression compared with normal and Barrett's epithelia. The similar CLDN expression profile of Barrett's esophagus and adenocarcinoma supports their sequential development. II. Gastric intestinal metaplasia showed higher expression of CLDN2, -3 and -4 as compared with normal antral foveolar mucosa. Tumors of small and large bowels exhibited higher CLDN2 expression when compared with normal epithelia. Colorectal adenoma and adenocarcinoma could not be differentiated according to their CLDN profile. Intestinal metaplasias of Barrett's esophagus and stomach show similar CLDN profile to small bowel epithelium. III. Studies on duodenal mucosa in celiac disease in childhood demonstrated CLDN2 and -3 expression to be higher than in normal mucosa. The expression was significantly higher in the distal part of the duodenum samples. This and the serious histological findings suggest that the distal duodenum is more adequate for biopsy testing. IV. Beside the epithelial cells, mesenchymal tumors express intercellular junctional proteins. Expression of claudins in gastrointestinal stromal tumors (GIST) and other mesenchymal neoplasia was also studied. The CLDN profile was found to be representative to the individual tumor. GIST, angiosarcoma, hemangioma, leiomyosarcoma and leiomyoma showed expression of various CLDNs. CLDN2 was detected in all entities. CLDN1, however, was found positive in leiomyosarcoma only. Leiomyoma, on the other hand, expressed only CLDN2. GISTs and leiomyosarcomas showed CLDN2, -3, -4, -5 and -7-expression. The angiogenic tumors revealed CLDN2 and -5 expression. The similar CLDN profile observable in GIST and leiomyosarcoma is suggestive of a histogenetic relationship. Smooth muscle and vessel tumors of different dignity could also be separated from each other based on CLDN profile.

摘要

在全球范围内,胃肠道肿瘤在肿瘤死亡率方面排名很高。胃肠道(GI)疾病的发生和发展与紧密连接(TJ)的变化密切相关。紧密连接蛋白(CLDN)是主要的TJ蛋白,在不同组织中表现出不同的表达,其表达的CLDN谱具有代表性。一、我们探讨了巴雷特食管及相关腺癌中CLDN表达的变化。巴雷特食管中CLDN2和-3的表达高于正常小凹上皮。与正常上皮和巴雷特上皮相比,腺癌中CLDN2和-3的表达更高。巴雷特食管和腺癌相似的CLDN表达谱支持它们的序贯发展。二、与正常胃窦小凹黏膜相比,胃肠化生中CLDN2、-3和-4的表达更高。与正常上皮相比,小肠和大肠肿瘤中CLDN2的表达更高。结直肠腺瘤和腺癌无法根据其CLDN谱进行区分。巴雷特食管和胃的肠化生显示出与小肠上皮相似的CLDN谱。三、对儿童乳糜泻十二指肠黏膜的研究表明,CLDN2和-3的表达高于正常黏膜。在十二指肠样本的远端部分,表达明显更高。这一点以及严重的组织学发现表明,十二指肠远端更适合进行活检检测。四、除上皮细胞外,间叶组织肿瘤也表达细胞间连接蛋白。还研究了胃肠道间质瘤(GIST)和其他间叶组织肿瘤中紧密连接蛋白的表达。发现CLDN谱对个体肿瘤具有代表性。GIST、血管肉瘤、血管瘤、平滑肌肉瘤和平滑肌瘤显示出各种CLDN的表达。在所有实体中均检测到CLDN2。然而,仅在平滑肌肉瘤中发现CLDN1呈阳性。另一方面,平滑肌瘤仅表达CLDN2。GIST和平滑肌肉瘤显示出CLDN2、-3、-4、-5和-7的表达。血管生成性肿瘤显示出CLDN2和-5的表达。在GIST和平滑肌肉瘤中观察到的相似CLDN谱提示了一种组织发生学关系。不同类型的平滑肌和血管肿瘤也可以根据CLDN谱相互区分。

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