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| 1 | AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma显示文摘Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a signifi cant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways. | KJ Schmitz H Lang J Wohlschlaeger GC Sotiropoulos H Reis KW Schmid HA Baba | 2007 | World Journal of Gastroenterology2007，13，48： | 8 |
| 2 | Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice显示文摘AIM: Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor (VEGF) via stimulating endothelial cell proliferation, migration, and survival. Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities. Here, we tested a recombinant adenovirus, AdsFIt1-3, that encodes an antagonistically acting fragment of the VEGF receptor 1 (Flt-1), for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice. METHODS: Murine colorectal carcinoma cells (CT26) were inoculated subcutaneously into Balb/c mice for in vivo studies. Tumor size and survival were determined. 293 cell line was used for propagation of the adenoviral vectors. Human lung cancer line A549 and human umbilical vein endothelial cells were transfected for in vitro experiments. RESULTS: Infection of tumor cells with AdsFlt1-3 resulted in protein secretion into cell supernatant, demonstrating correct vector function. As expected, the secreted sFlt1-3 protein had no direct effect on CT26 tumor cell proliferation in vitro, but endothelial cell function was inhibited by about 46% as compared to the AdLacZ control in a tube formation assay. When AdsFlt1-3 (5×109 PFU/animal) was applied to tumor bearing mice, we found a tumor inhibition by 72% at d 12 after treatment initiation. In spite of these antitumoral effects, the survival time was not improved. According to reduced intratumoral microvessel density in AdsFIt1-3-treated mice, the antitumor mechanism can be attributed to angiostatic vector effects. We did not detect increased systemic VEGF levels after AdsFlt1-3 treatment and liver toxicity was low as judged by serum alanine aminotransferase determination. CONCLUSION: In this study we confirmed the value of a systemic administration of AdsFIt1-3 to block VEGF signaling as antitumor therapy in an experimental metastatic colorectal carcinoma model in mice. | Volker Schmitz Miroslaw Kornek Tobias Hilbert Christian Dzienisowicz Esbher Raskopf Christian Rabe Tilman Sauerbruch Cheng Qian Wolfgang H Caselmann | 2005 | World Journal of Gastroenterology2005，11，28： | 4 |
| 3 | Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer显示文摘AIM:To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer.METHODS:Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals.Allelic discrimination was performed by quantitative real-time polymerase chain reaction.Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression.RESULTS:Thirty-nine(32%) patients displayed a CC genotype,57(46.7%) a CT genotype and 26(21.3%) a TT genotype.The frequency of the C allele(fC) in the patient group was 0.55,which was not signif icantly different from that of healthy blood donors.The distribution was compatible with the Hardy-Weinberg equilibrium.Analysis of clinicopathological parameters did not show any signif icant correlation of the T393C genotype with gender(P=0.50),differentiation(P=0.29),pT-category(P=0.19),pN-category(P=0.30),pM-category(P=0.25),R-category(P=0.95),the classifications according to WHO(P=0.34),Laurén(P=0.16),Goseki(P=1.00) and Ming(P=0.74).Dichotomization between C+(CC+CT) and C-genotypes(TT),however,revealed signif icantly more advanced tumor stages(P=0.023) and lower survival rates(P=0.043) for C allele carriers.CONCLUSION:The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers. | Hakan Alakus Stefan P Mnig Ute Warnecke-Eberz Gül Alakus Günther Winde Uta Drebber Klaus J Schmitz Kurt W Schmid Kathrin Riemann Winfried Siffert Elfriede Bollschweiler Arnulf H Hlscher Ralf Metzger | 2009 | World Journal of Gastroenterology2009，15，48： | 3 |
| 4 | Assimilation and metabolism of formaldehyde by leaves appear unlikely to be of value for indoor air purification显示文摘 | SCHMITZ H HILGERS U WEIDNER M | 2000 | New Phytologist2000，147，2： | 1 |
| 5 | How does insertion in global value chains affect upgrading in industrial clusters 显示文摘 | Humphrey J Schmitz H | 2002 | Regional Studies2002，36，9： | 1 |
| 6 | Activation of extracellular regulated kinases (ERK1/2) but not AKT predicts poor prognosis in colorectal carcinoma and is associated with k-ras mutations显示文摘 | Schmitz KJ Wohlschlaeger J Alakus H | 2007 | Virchows Arch2007，450，2： | 1 |
| 7 | 2001, Governance in Global Value Chains 显示文摘 | Humphrey J Schmitz H | 2001 | IDS Bulletin2001，32，3： | 1 |
| 8 | Assimilation and metabolism of formaldehyde by leaves appear unlikely to be of value for indoor air purification 显示文摘 | Schmitz H Hilgers U Weidner M | 2000 | New Phytologist2000，147，2： | 1 |
| 9 | How does insertion in global value chains affect upgrading in industrial clusters?显示文摘 | Humphrey J Schmitz H | 2002 | Regional Studies2002，36，9： | 1 |
| 10 | Three-dimensional relativistic calculation of strong-field photoionization by the phase-space-averaging method显示文摘 | SCHMITZ H BOUCKE K KULL H J | 1998 | Physical Review A1998，57，1： | 1 |
| 11 | How does insertion in glob- al value chains affect upgrading in industrial clusters 显示文摘 | HUMPHREY J SCHMITZ H | 2002 | Regional Studies2002，，36： | 1 |
| 12 | Postoperative pain management in orthopaedic patients: no differences in pain score,but improved stress control by epidural anaesthesia显示文摘 | Adams H A Saatweber P Schmitz C S | 2002 | Eur J Anaesthesiol2002，19，9： | 1 |
| 13 | Long-distance transport of sulfur in Nicotiana tabacum 显示文摘 | Rennenberg H Schmitz K Bergmann L | 1979 | Planta1979，147，： | 1 |
| 14 | Duodenal biopsies of HIV-infected patients with diarrhrea exhibit epithelial barrier defects but no active secretion显示文摘 | Stockmann M Fromm M Schmitz H | 1998 | AIDS1998，12，1： | 1 |
| 15 | How does insertion in global valuechains affect upgrading in industrial clusters? 显示文摘 | HUMPHREY J SCHMITZ H | 2002 | Regional Studies2002，36，9： | 1 |
| 16 | Collective efficiency:growth path for small-scale industry显示文摘 | Schmitz H | | 0，，04： | 1 |
| 17 | Governance in Global Value Chains显示文摘 | Humphrey J Schmitz H | | 0，，： | 1 |
| 18 | Delivery of peptide and protein drugs over the blood-brain barrier显示文摘 | Brasnjevic I Steinbusch H W Schmitz C | 2009 | Prog Neurobiol2009，87，4： | 1 |
| 19 | Rho5p downregulates the yeast cell integrity pathway 显示文摘 | Schmitz H P Huppert S Lorberg A | 2002 | Journal of Cell Science2002，115，15： | 1 |
| 20 | Small shoemakers and Fordist giants : Tale of a supercluster 显示文摘 | Schmitz H | 1995 | World Development1995，23，1： | 1 |
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