Purpose: Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and dissemination. EMT occurs predominantly at the tumor edge where it is induced by cytokines, the extracellular matrix environment, or hypoxia. In the tumor cell, it is further mediated by several transcription factors and microRNAs. The aim of this study was to explore the expression of EMT-associated genes at the invasive front in colorectal cancer and to evaluate their prognostic significance.Experimental Design: We evaluated the expression of 13 EMT-associated genes at the invasion front of 30 colorectal liver metastases by quantitative real-time PCR. Immunostaining against zinc finger E-boxbinding homeobox 2 (ZEB2) was carried out on 175 primary colorectal cancer specimens and 30 colorectal liver metastases and correlated to clinical and histopathologic data. DLD-1 cells were transfected with siRNA and subjected to migration and invasion assays.Results: Gene expression analysis and immunohistochemistry showed an upregulation of ZEB2 at the invasion front in primary colorectal cancer and liver metastases. Overexpression of ZEB2 at the invasion front correlated significantly with tumor stage in primary colorectal cancer. Moreover, univariate and multivariate analysis revealed overexpression of ZEB2 at the invasion front as an independent prognostic marker for cancer-specific survival. Downregulation of ZEB2 by siRNA decreased the migration and invasion capacity of DLD-1 cells in vitro.Conclusions: Overexpression of ZEB2 at the invasion front correlates with tumor progression and predicts cancer-specific survival in primary colorectal cancer. Therefore, ZEB2 may be interesting as biomarker and potential target for treatment of colorectal cancer. Clin Cancer Res; 17(24); 7654-63. Ó2011 AACR.

Background Immunosuppressants represent an effective pharmacological treatment for the remission and management of Crohn’s disease (CD); however, it has not been well-defined if these medications are associated with an increased incidence of postoperative complications after intestinal surgery. This retrospective study evaluated the association between immunosuppressive treatment and complications following bowel resection in patients with CD. Methods A total of 426 patients with CD who underwent abdominal surgery between 2001 and 2018 were included in the study. The participants were divided into two groups. In the first group, patients were under immunosuppressive treatment at the time of surgical resection, while in the second group, patients had never received pharmacological therapy for CD before surgery. Results No statistically significant difference was found in the incidence of postoperative complications between the two groups. Double or triple immunosuppressive therapy was not associated with increased complications compared to monotherapy or no pharmacological treatment. Preoperative risk factors such as hypoalbuminemia, abscess, fistula, intestinal perforation, long duration of symptoms, and the intraoperative performance of more than one anastomosis were related to increased rates of postoperative complications. Factors affecting the occurrence of postoperative complications in the univariate analysis were included in the multivariate analysis using a stepwise logistic regression model, and these factors were also related to increased rates of postoperative surgical complications. Conclusion Immunosuppressive therapy was not associated with increased rates of postoperative complications following bowel resection in patients with CD.

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<p>PDF file - 55K, Expression fold-change of EMT-associated genes and microRNAs between the four compartments liver (L). liver invasion front (LIF). tumor invasion frot (TIF) and tumor center (Tc). All samples were normalized to 18s expression and fold change expression was calculated according to the 2-��ct method as described previously (15). P-Values (P) were assessed by using the Wilcoxon signed-rank test. (LIF vs. L: expression fold-change of target gene in liver invasion front compared to liver. LIF vs TIF: expression fold-change of target gene in liver invasion front compared to tumor invasion front. LIF vs Tc: expression fold-change of target gene in liver invasion front compared to tumor center. TIF vs L: expression fold-change of target gene in tumor invasion front compared to liver. TIF vs Tc: expression fold-change of target gene in tumor invasion front compared to tumor center. L vs Tc: expression fold-change of target gene in liver compared to tumor center).</p>

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<div>Abstract<p><b>Purpose:</b> Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and dissemination. EMT occurs predominantly at the tumor edge where it is induced by cytokines, the extracellular matrix environment, or hypoxia. In the tumor cell, it is further mediated by several transcription factors and microRNAs. The aim of this study was to explore the expression of EMT-associated genes at the invasive front in colorectal cancer and to evaluate their prognostic significance.</p><p><b>Experimental Design:</b> We evaluated the expression of 13 EMT-associated genes at the invasion front of 30 colorectal liver metastases by quantitative real-time PCR. Immunostaining against zinc finger E-box–binding homeobox 2 (ZEB2) was carried out on 175 primary colorectal cancer specimens and 30 colorectal liver metastases and correlated to clinical and histopathologic data. DLD-1 cells were transfected with siRNA and subjected to migration and invasion assays.</p><p><b>Results:</b> Gene expression analysis and immunohistochemistry showed an upregulation of ZEB2 at the invasion front in primary colorectal cancer and liver metastases. Overexpression of ZEB2 at the invasion front correlated significantly with tumor stage in primary colorectal cancer. Moreover, univariate and multivariate analysis revealed overexpression of ZEB2 at the invasion front as an independent prognostic marker for cancer-specific survival. Downregulation of ZEB2 by siRNA decreased the migration and invasion capacity of DLD-1 cells <i>in vitro</i>.</p><p><b>Conclusions:</b> Overexpression of ZEB2 at the invasion front correlates with tumor progression and predicts cancer-specific survival in primary colorectal cancer. Therefore, ZEB2 may be interesting as biomarker and potential target for treatment of colorectal cancer. <i>Clin Cancer Res; 17(24); 7654–63. ©2011 AACR</i>.</p></div>

<div>Abstract<p><b>Purpose:</b> Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and dissemination. EMT occurs predominantly at the tumor edge where it is induced by cytokines, the extracellular matrix environment, or hypoxia. In the tumor cell, it is further mediated by several transcription factors and microRNAs. The aim of this study was to explore the expression of EMT-associated genes at the invasive front in colorectal cancer and to evaluate their prognostic significance.</p><p><b>Experimental Design:</b> We evaluated the expression of 13 EMT-associated genes at the invasion front of 30 colorectal liver metastases by quantitative real-time PCR. Immunostaining against zinc finger E-box–binding homeobox 2 (ZEB2) was carried out on 175 primary colorectal cancer specimens and 30 colorectal liver metastases and correlated to clinical and histopathologic data. DLD-1 cells were transfected with siRNA and subjected to migration and invasion assays.</p><p><b>Results:</b> Gene expression analysis and immunohistochemistry showed an upregulation of ZEB2 at the invasion front in primary colorectal cancer and liver metastases. Overexpression of ZEB2 at the invasion front correlated significantly with tumor stage in primary colorectal cancer. Moreover, univariate and multivariate analysis revealed overexpression of ZEB2 at the invasion front as an independent prognostic marker for cancer-specific survival. Downregulation of ZEB2 by siRNA decreased the migration and invasion capacity of DLD-1 cells <i>in vitro</i>.</p><p><b>Conclusions:</b> Overexpression of ZEB2 at the invasion front correlates with tumor progression and predicts cancer-specific survival in primary colorectal cancer. Therefore, ZEB2 may be interesting as biomarker and potential target for treatment of colorectal cancer. <i>Clin Cancer Res; 17(24); 7654–63. ©2011 AACR</i>.</p></div>

<p>PDF file - 38K</p>