AIM: To investigate the expression and potential prognostic role of vascular endothelial growth factor (VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS:... Show moreAIM: To investigate the expression and potential prognostic role of vascular endothelial growth factor (VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: Microvessel density (MVD) in GEP-NETs was evaluated using endoglin and CD31 immunohistochemistry. In addition, tissue levels of endoglin and VEGF were determined in homogenates by ELISA. RESULTS: Endoglin was highly expressed on tumor endothelial cells. CD31 MVD in GEP-NETs was significantly higher compared to endoglin MVD (P < 0.01). Two- to four-fold higher tissue levels of endoglin and VEGF were seen in tumors compared to associated normal tissue. This increased endoglin tissue expression in tumors was significantly related to tumor size (P < 0.01), presence of metastases (P = 0.04), and a more advanced tumor stage (P = 0.02), whereas expression of VEGF was not. CONCLUSION: We suggest that endoglin is a potential marker to indicate and predict metastases, which might be useful in the post-resection therapeutic approach of patients with GEP-NETs. (C) 2011 Baishideng. All rights reserved. Show less
Introduction: Epidemiological data suggests that 5-aminosalicyclic acid (5-ASA), a nonsteroidal antiinflammatory drug used in the treatment of inflammatory bowel diseases, prevents colorectal... Show moreIntroduction: Epidemiological data suggests that 5-aminosalicyclic acid (5-ASA), a nonsteroidal antiinflammatory drug used in the treatment of inflammatory bowel diseases, prevents colorectal cancer development in these patients, although the mechanisms remain incompletely understood. Methods and Results: Here we report that 5-ASA prevents growth of several colorectal cancer cell lines by interfering in the cell cycle, i.e., an S-phase and G2/M phase arrest, dependent on 5-ASA dosage and concentration, together with an increased mitotic index. In addition, prolonged cell cycle arrest by repeated 5-ASA treatment induced apoptosis and caused abnormal spindle organization leading to mitotic catastrophe, another form of cell death. Conclusion: These observations illustrate that 5-ASA has chemopreventive and chemotherapeutic properties. Show less
The transforming growth factor-beta (TGF-beta) pathway is an important pathway in the initiation and progression of colorectal cancer. We aimed to determine the effects of 5-aminosalicylic acid (5... Show moreThe transforming growth factor-beta (TGF-beta) pathway is an important pathway in the initiation and progression of colorectal cancer. We aimed to determine the effects of 5-aminosalicylic acid (5-ASA) on TGF-beta signalling in colorectal cancer cells in vitro. 5-ASA inhibited TGF-beta 1 signalling in HCT1 16 cells and colonic fibroblasts, as judged by a TGF-beta-specific reporter gene assay, plasminogen activator inhibitor-1 mRNA and protein levels, fibroblast trans-differentiation, Smad3 phosphorylation and nuclear translocation. We conclude that 5-ASA inhibits TGF-beta 1 signalling in colorectal cancer cells, and might be a potent adjuvant therapeutic drug, interfering with aberrant TGF-beta signalling in colorectal cancer. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Show less
Kubben, F.J.G.M.; Sier, C.F.M.; Meijer, M.J.W.; Berg, M. van den; Reijden, J.J. van der; Griffioen, G.; ... ; Verspaget, H.W. 2006