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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 | Estimation of linear functionals on Sobolev spaces with applications to Fourier transforms and spline interpolation显示文摘 | Bramble J H Hilbert S R | 1974 | SIAM J Numer Anal1974，7，： | 2 |
| 3 | Estimation of Linear Functionals on Sobolev Spaces with Application to Fourier Trans- forms and Spline Interpolation显示文摘 | BRAMBLE J H HILBERT S R | 1970 | SIAM J Numer Anal1970，7，1： | 1 |
| 4 | Complete se- quence analysis of the genome of the bacterium Mycoplasma pneumoniae显示文摘 | Himmelreich R Hilbert H Plagens H | 1996 | Nucleic Acids Res1996，24，22： | 1 |
| 5 | Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae显示文摘 | Hilbert H Plagens H | 1996 | Nucleic Acids Research1996，24，： | 1 |
| 6 | Collocation, dissipation and ' Over- shoot' for time integration schemes in structural dy- namics显示文摘 | Hilbert H M | 1978 | EESD1978，6，1： | 1 |
| 7 | Acoustic analog to quantum mechanical level splitting显示文摘 | Hilbert S Batelaan H | 2007 | American Journal of Physics2007，75，11： | 1 |
| 8 | Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae显示文摘 | Himmelreich R Hilbert H Plagens H Herrmann R | 1996 | Nucleic Acids Res1996，24，22： | 1 |
| 9 | Sedation during non - invasive ventilation 显示文摘 | Hilbert G Clouzeau B Nam Bui H | 2012 | Minerva Anestesiol2012，78，7： | 1 |
| 10 | A specific collagen type Ⅱ gene(COL2A1) mutation presenting as spondyloperipheral dysplasia显示文摘 | Zabel B Hilbert K Stoss H | 1996 | Am J Med Genet1996，63，1： | 1 |
| 11 | Complete se- quence analysis of the genome of the bacterium Mycoplasma pneumoniae显示文摘 | Himmelreieh R Hilbert H Plagens H | 1996 | Nucleic Acids Res1996，24，22： | 1 |
| 12 | Comparative analysis of the genomes of bacteria Mycoplasma pneumoniae and Mycoplasma genitalium显示文摘 | HIMMELREICH R PLAGENS H HILBERT H | 1997 | Nucleic Acid Res1997，25，4： | 1 |
| 13 | Separation of metal- lic from semiconducting single-walled carbon nanotubes显示文摘 | Ralph K Frank H Hilbert V L | 2003 | Science2003，301，： | 1 |
| 14 | Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae显示文摘 | Himmelreich R Hilbert H Plagens H | 1996 | Nucleic Acids Res1996，24，22： | 1 |
| 15 | Attenuation of apoptosis underlied B lymphocyte stimulator enhancement of humoral immune responses 显示文摘 | Do Rk Hatada E Lee H Tourigny MR Hilbert D Chen-Kiang S | 2000 | J Exp Med2000，192，7： | 1 |
| 16 | Comparative analysis of the genomes of the bacteria Mycoplasma pneumoniae and Mycoplasma genitalium显示文摘 | Himmelreich R Plagens H Hilbert H | 1997 | Nucleic Acids Res1997，25，： | 1 |
| 17 | The genome structure of Pseudomonas putida: high-resolution mapping and microarray analysis显示文摘 | Stjepandic D Weinel C Hilbert H | 2002 | Environ Microbiol2002，，12： | 1 |
| 18 | Comparison of Bmode ultrasound and computed tomography in the diagnosis of maxillary sinusitis in mechanically ventilated patients显示文摘 | Vargas F Tomath H | 2001 | Crit Care Med2001，29，7： | 1 |
| 19 | Human cryopreserved homografts: electron microscopic analysis of cellular injury 显示文摘 | Crescenzo D G Hilbert S L Messier R H | 1993 | Ann Thorac Surg1993，55，： | 1 |
| 20 | Collocation, dissipation and ‘overshoot' for time integration schemes in structural dynamics 显示文摘 | Hilbert H M | 1978 | EESD1978，6，1： | 1 |
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