Purpose: Epithelial to mesenchymal transitions are vital for tumor growth and metastasis.Several inducers of epithelial to mesenchymal transition are transcription factors that repress E-cadherin expression, such as Snail, Slug, and Twist. In this study, we aimed to examine the expression of these transcription factors in pancreatic cancer. Experimental Design: The expression of Snail, Slug, and Twist was detected by immunohistochemistry in tissue samples from patients with pancreatic ductal adenocarcinoma. Five human pancreatic cancer cell lines (AsPC-1, Capan-1, HPAF-2, MiaPaCa-2, and Panc-1) were analyzed by reverse transcription-PCR, real-time PCR, and Western blotting. An orthotopic nude mouse model of pancreatic cancer was applied for in vivo experiments. Results: Seventy-eight percent of human pancreatic cancer tissues showed an expression of Snail, and 50% of the patients displayed positive expression of Slug. Twist showed no or only weak expression. Snail expression was higher in undifferentiated cancer cell lines (MiaPaCa-2 and Panc-1) than in more differentiated cell lines (Capan-1, HPAF-2, AsPC-1). Expression of Slug was detected in all cell lines with different intensities. Twist was not expressed. After exposure to hypoxia, theTwist gene was activated in all five pancreatic cancer cell lines. Conclusions:The transcription factors Snail and Slug are expressed in pancreatic cancer but not in normal tissue, suggesting a role in the progression of human pancreatic tumors.Twist, activated by hypoxia, may play an important role in the invasive behavior of pancreatic tumors.Pancreatic cancer is the fifth leading cause of cancer-related death in industrial western countries. It is an aggressive disease with <5% survival after 5 years (1, 2). This is largely attributable to late clinical presentation and limitations in diagnostic methods. More than 80% of patients are diagnosed with pancreatic cancer at a locally advanced or metastatic stage, which excludes a curative surgical resection (3). The response to conventional therapies, such as radiotherapy and chemotherapy, is poor and has little effect on the natural progress of this malignancy (4). Understanding the molecular biology of pancreatic cancer and metastasis may provide insight for the development of novel tumor markers or new therapeutic strategies.Epithelial to mesenchymal transition (EMT) is a key step during embryonic morphogenesis and is involved in the progression of primary tumors toward metastasis (5). During EMT, cells undergo a developmental switch from a polarized, epithelial phenotype to a highly motile fibroblastoid or mesenchymal phenotype (6). Tumor cells begin to grow invasive, enter into systemic circulation (''intravasation''), move from the circulatory system into a new host tissue (''extravasation''), and proliferate and grow to a secondary tumor. The cell adhesion molecules E-cadherin and N-cadherin, members of the classic cadherin family, are regarded as inducers of EMT (7,8). E-cadherin is required for the formation o...

Pouchitis is characterized by a selective change of tight junction proteins in favor of opening the epithelial tight junction and, thus, the paracellular pathway, which contributes to the inflammatory process. This resembles changes in inflammatory bowel disease (IBD) and indicates IBD recurrence in pouchitis.

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.

Colorectal cancer is one of the leading causes of cancer-related death worldwide. Molecular biomarkers could help to predict patient outcome and to identify patients who benefit from adjuvant therapy. Pontin and Reptin are ATPases which are involved in transcriptional regulation, DNA damage repair and regulation of cell proliferation. Many interaction partners of Pontin and Reptin such as β-catenin and c-myc are important factors in carcinogenesis. We hypothesized that Pontin and Reptin expression may be a negative predictor for survival in colorectal carcinoma. Specimens from 115 patients with primary colon adenocarcinomas UICC stage III and primary rectal adenocarcinomas UICC stage II and III curatively resected at the Department of Surgery, Charité Berlin, were evaluated. Clinical follow-up data were complete and mean follow-up time of patients was 51.8 months. We evaluated the expression of Pontin, Reptin and Ki-67 by immunohistochemistry. Patients with Pontin-positive carcinomas showed no differences in recurrence-free survival (p=0.109) and overall survival (p=0.197). There were no differences in Reptin-positive carcinomas and Ki-67-positive carcinomas in recurrence-free survival (p=0.443 and p=0.160) and overall survival (p=0.477 and p=0.687). Patients with Pontin-positive colorectal carcinomas receiving adjuvant therapy had a significantly worse recurrence-free survival (p=0.008) and overall survival (p=0.011) than Pontin-negative patients with adjuvant therapy. In UICC stage III, Pontin-positive colorectal carcinomas had a significantly worse recurrence-free survival (p=0.028). Pontin-positivity seems to be a negative predictor for response to adjuvant therapy in colorectal cancer patients and may help to identify patients with adverse outcome in advanced tumor stages.