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| 1 | 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 |
| 2 | Identification of PDE iso-zymes in human pulmonary artery and effect of selective PDE inhibitors显示文摘 | Tenor H Dent G | 1994 | Am J Physiol1994，266，： | 1 |
| 3 | Global strategy for thed iagnosis,m anagem ent and prevent ion of chron ic obstructivepu lm onary d isease:GOLD execu tive summ ary显示文摘 | Rabe KF H urd S An zueto A | 2007 | Am J Resp ir C rit C areM ed2007，9，6： | 1 |
| 4 | Gene rearrangements in radiation-induced thyroid carcinogenesis 显示文摘 | Rabes H M | 2001 | Med Pediatr Oncol2001，36，： | 1 |
| 5 | A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants 显示文摘 | Rabe H Wacker A Hulskamp G | 2000 | Eur J Pediatr2000，159，： | 1 |
| 6 | Incipient polyploid spoeiation in tbe maid- enbair fern (Adiantum pedatum ; Adiantaceae) 显示文摘 | Rabe E W Hanfler C H | 1992 | American Jour- nal of Botany1992，79，： | 1 |
| 7 | Epitaxial BiFe03 multiferroic thin film heterostructures 显示文摘 | WANG J NEATON J B ZHENG H NAGARAJAN V OGALE S B LID B VIEHLAND D VAITHYANAATHAN V SCHLOM D G WAGHMARE U V SPALDIN N A RABE K M WUTTIG M RAMESH R | 2003 | Science2003，299，： | 1 |
| 8 | A systematic review and meta-analysis of a brief delay in clamping the umbilical cord of preterm infants 显示文摘 | Rabe H Reynolds G Diaz-Rossello J | 2008 | Neonatology2008，93，： | 1 |
| 9 | Effect of timing ofumbilical cord clamping and other strategies to influence placentaltransfusion at preterm birth on maternal and infant outcomes 显示文摘 | Rabe H Diaz -Rossello JL Duley L | 2012 | Cochrane Database Syst Rev2012，8，00： | 1 |
| 10 | Early versus delayed cord clamping in preterm infants显示文摘 | Rabe H Reynolds G Diaz-Rossello J | 2004 | Cochrane Database Syst Rev2004，4，00： | 1 |
| 11 | Ferroelectricity at the nanoscale: Local polarization in oxide thin films and heterostructures显示文摘 | Ahn C H Rabe K M Triscone J M | 2004 | Science2004，303，5657： | 1 |
| 12 | DCC mediated axon guidance of spinal interneurons is essential for normal locomotor central pattern generator function显示文摘 | Rabe Bernhardt N Memic F Gezelius H | | 0，，： | 1 |
| 13 | Photoaging: mechanisms and repair 显示文摘 | Rabe J H Mamelak A J Mcelgunn P J S | 2006 | J Am Acad Dermatol2006，55，1： | 1 |
| 14 | Bioindication of air pollution by chlorophyllde-struetion in plant leaves显示文摘 | RABE R KREEB K H | 1980 | Oikos1980，34，2： | 1 |
| 15 | photoaging: mechanism and repair 显示文摘 | Jessica H Rabe Adam J Mamelak Patrick J S Mcelgunn | 2006 | Am Acad Dermatol2006，55，： | 1 |
| 16 | Giant cavernous haemangioma with Kasabach-Merritt syndrome: a case report and review显示文摘 | Frevel T Rabe H Uckert F | 2002 | Eur J Pediatr2002，161，5： | 1 |
| 17 | Identification of PDE isozymes in human pulmonary artery and effect of selec-tive PDE inhibi- tors显示文摘 | Rabe KF Tenor H Dent G | 1994 | Am J Physio1994，266，5： | 1 |
| 18 | Effect of timing of umbilical cord clamping and other strategies to influence placentM transfusion at preterm birth on maternal and infant outcomes显示文摘 | Rabe H Diaz-Rossello JL Duley L Dowswell T | 2012 | Cochrane Database Syst Rev2012，8，00： | 1 |
| 19 | Effect of the PGE1 methyl analog Misoprostol on the pregnant uterus in the first trimester显示文摘 | Rabe T Basse H Thuro H | 1987 | Geburtshilfe Frauenheilkd1987，47，5： | 1 |
| 20 | Voltage-gated sodium and potassium channels in radial glial cells of trout optic tectum studied by patch clamp analysis and single cell RT-PCR显示文摘 | Rabe H Koschorek E Nona S N | 1999 | Glia1999，26，3： | 1 |
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