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| 1 | VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab显示文摘AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metastases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab. | Markus Moehler Christian Frings Annett Mueller Ines Gockel Carl C Schimanski Stefan Biesterfeld Institute of Pathology Johannes Gutenberg University Mainz 55101 Germany Peter R Galle Martin H Holtmann | 2008 | World Journal of Gastroenterology2008，14，26： | 15 |
| 2 | Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?显示文摘AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma. METHODS: The (co-)expression pattern of VEGFR1-3,PDGFRα/b and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition,IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS: The majority of samples revealed a VEGFR1 (98%),VEGFR2 (80%),VEGFR3 (67%),PDGFRα (82%) and PDGFRβ(82%) expression,whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells,accompanied by an additional nuclear staining for VEGFR3 ,EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes,which also depicted a PDGFRα expression.receptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy. | Daniel Drescher Markus Moehler Ines Gockel Kirsten Frerichs Annett Müller Friedrich Dünschede Thomas Borschitz Stefan Biesterfeld Martin Holtmann Thomas Wehler Andreas Teufel Kerstin Herzer Thomas Fischer Martin R Berger Theodor Junginger Peter R Galle Carl C Schimanski | 2007 | World Journal of Gastroenterology2007，13，26： | 4 |
| 3 | Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis显示文摘 | Ralf Kiesslich Johannes Fritsch Martin Holtmann Heinz H. Koehler Manfred Stolte Stephan Kanzler Bernhard Nafe Michael Jung Peter R. Galle Markus F. Neurath | 2003 | Gastroenterology2003，，4： | 2 |
| 4 | Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis显示文摘 | Ralf Kiesslich Johannes Fritsch Martin Holtmann Heinz H. Koehler Manfred Stolte Stephan Kanzler Bernhard Nafe Michael Jung Peter R. Galle Markus F. Neurath | 2003 | Gastroenterology2003，，4： | 1 |
| 5 | Current concept of pathophysiological understanding and natural course of ulcerative colitis显示文摘 | Martin H. Holtmann Peter R. Galle | 2004 | Langenbeck’s Archives of Surgery2004，，5： | 1 |
| 6 | 18 F-Fluorodeoxyglucose Positron-Emission Tomography (PET) Can Be Used to Assess Inflammation Non-invasively in Crohn’s Disease显示文摘 | Martin H. Holtmann Manuela Uenzen Andreas Helisch Anja Dahmen Jonas Mudter Martin Goetz Mathias Schreckenberger Peter R. Galle Peter Bartenstein Markus F. Neurath | 2012 | Digestive Diseases and Sciences2012，，： | 1 |
| 7 | Treatment of patients with Crohn’s disease and concomitant chronic hepatitis C with a chimeric monoclonal antibody to TNF显示文摘 | Martin H Holtmann Peter R Galle Markus F Neurath | 2003 | The American Journal of Gastroenterology2003，，2： | 1 |
| 8 | Long-Term Effectiveness of Azathioprine in IBD Beyond 4 Years: A European Multicenter Study in 1176 Patients显示文摘 | Martin H. Holtmann Frank Krummenauer Christina Claas Kristina Kremeyer Dirk Lorenz Olivia Rainer Iris Vogel Ulrich B?cker Stephan B?hm Carsten Büning Rainer Duchmann Guido Gerken Hans Herfarth Norbert Lügering Wolfgang Kruis Max Reinshagen Jan Schmidt And | 2006 | Digestive Diseases and Sciences2006，，9： | 1 |
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