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Background and purposeActivation of the transcription factor NF-κB by proteasomes and subsequent nuclear translocation of cytoplasmatic complexes play a crucial role in the intestinal inflammation. Proteasomes have a pivotal function in NF-κB activation by mediating degradation of inhibitory IκB proteins and processing of NF-κB precursor proteins. This study aims to analyze the expression of the human proteasome subunits in colonic tissue of patients with Crohn’s disease.Materials and methodsThirteen patients with Crohn’s disease and 12 control patients were studied. The expression of immunoproteasomes and constitutive proteasomes was examined by Western blot analysis, immunoflourescence and quantitative real-time PCR. For real-time PCR, AK2C was used as housekeeping gene.ResultsThe results indicate the influence of the intestinal inflammation on the expression of the proteasomes in Crohn’s disease. Proteasomes from inflamed intestine of patients with Crohn’s disease showed significantly increased expression of immunosubunits on both protein and mRNA levels. Especially, the replacement of the constitutive proteasome subunit β1 by inducible immunosubunit β1i was observed in patients with active Crohn’s disease. In contrast, relatively low abundance of immunoproteasomes was found in control tissue.ConclusionsOur data demonstrate that in contrast to normal colonic tissue, the expression of immunoproteasomes was evidently increased in the inflamed colonic mucosa of patients with Crohn’s disease. Thus, the chronic intestinal inflammation process in Crohn’s disease leads to significant alterations of proteasome subsets.

The probability of the need for a permanent ileostomy after IPAA increases with age.

Transmembrane tyrosine-kinase Ephrin receptors promote tumor progression and/or metastasis of several malignancies including leukemia, follicular lymphoma, glioma, malignant pleural mesothelioma, papillary thyroid carcinoma, sarcomas and ovarian, breast, bladder and non-small cell lung cancers. They also drive intestinal stem cell proliferation and positioning, control intestinal tissue boundaries and are involved in liver, pancreatic and colorectal cancers, indicating involvement in additional digestive system malignancies. We investigated the role of Ephrin-B4 receptor (EPHB4), and its ligand EFNB2, in gastric and gastroesophageal junction cancers in patient cohorts through computational, mathematical, molecular and immunohistochemical analyses. We show that EPHB4 is upregulated in preneoplastic gastroesophageal lesions and its expression further increased in gastroesophageal cancers in several independent cohorts. The closely related EPHB6 receptor, which also binds EFNB2, was downregulated in all tested cohorts, consistent with its tumor-suppressive properties in other cancers. EFNB2 expression is induced in esophageal cells by acidity, suggesting that gastroesophageal reflux disease (GERD) may constitute an early triggering event in activating EFNB2-EPHB4 signaling. Association of EPHB4 to both Barrett's esophagus and to advanced tumor stages, and its overexpression at the tumor invasion front and vascular endothelial cells intimate the notion that EPHB4 may be associated with multiple steps of gastroesophageal tumorigenesis. Analysis of oncogenomic signatures uncovered the first EPHB4-associated gene network (false discovery rate: 7 3 10 290 ) composed of a five-transcription factor interconnected gene network that drives proliferation, angiogenesis and invasiveness. The EPHB4 oncogenomic network provides a molecular basis for its role in tumor progression and points to EPHB4 as a potential tumor aggressiveness biomarker and drug target in gastroesophageal cancers.Based on the GLOBOCAN recent estimates of global cancer incidence and mortality, 1 there are more than 1.4 million new cancers of the esophagus and stomach and more than 1.1 million deaths attributed to these cancers annually, thus ranking gastroesophageal cancers as the third most frequent cancers and the second leading cause of death by cancer worldwide.