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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 | Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation显示文摘AIM To evaluate the effects of melatonin(Mel) on oxidative stress in an experimental model of bile duct ligation(BDL).METHODS Male Wistar rats(n = 32, weight ± 300 g) were allocated across four groups: CO(sham BDL), BDL(BDL surgery), CO + Mel(sham BDL and Mel administration) and BDL + Mel(BDL surgery and Mel administration). Mel was administered intraperitoneally for 2 wk, starting on postoperative day 15, at a dose of 20 mg/kg.RESULTS Mel was effective at the different standards, reestablishing normal liver enzyme levels, reducing the hepatosomatic and splenosomatic indices, restoring lipoperoxidation and antioxidant enzyme concentrations, reducing fibrosis and inflammation, and thereby reducing liver tissue injury in the treated animals.CONCLUSION The results of this study suggest a protective effect of Mel when administered to rats with secondary biliary cirrhosis induced by BDL. | Josieli Raskopf Colares Elizângela Goncalves Schemitt Renata Minuzzo Hartmann Francielli Licks Mariana do Couto Soares Adriane Dal Bosco Norma Possa Marroni | 2016 | World Journal of Gastroenterology2016，22，40： | 3 |
| 3 | N-acetylcysteine modulates angiogenesis and vasodilation in stomach such as DNA damage in blood of portal hypertensive rats显示文摘AIM: To evaluate the antioxidant effect of N-acetylcysteine(NAC) on the stomach of rats with portal hypertension.METHODS: Twenty-four male Wistar rats weighing ± 250 g were divided into four experimental groups(n =6 each): Sham-operated(SO),SO + NAC,partial portal vein ligation(PPVL),and PPVL + NAC. Treatment with NAC in a dose of 10 mg/kg(i.p.) diluted in 0.6 m L of saline solution was administered daily for 7 d starting 8 d after the surgery. Animals from the PPVL and SO group received saline solution(0.6 m L) for the same period of time as the PPVL + NAC and SO + NAC group. On the 15 th day the animals were anesthetized and we evaluated portal pressure by cannulating mesenteric artery. After,we removed the stomach for further analysis. We performed immunohistochemical analysis for endothelial nitric oxide synthase(e NOS),vascular endothelial growth factor(VEGF),and nitrotirosine(NTT) proteins in stomach. We also evaluated e NOS and VEGF by Western blot analysis and assessed DNA damage in blood samples by the comet assay.RESULTS: The portal hypertension group exhibited increases in portal pressure when compared to SO group(29.8 ± 1.8 vs 12.0 ± 0.3 mm Hg)(P < 0.001). The same was observed when we compared the e NOS(56.8 ± 3.7 vs 13.46 ± 2.8 pixels)(P < 0.001),VEGF(34.9 ± 4.7 vs 17.46 ± 2.6 pixels)(P < 0.05),and NTT(39.01 ± 4.0 vs 12.77 ± 2.3 pixels)(P < 0.05) expression by immunohistochemistry of the PPVL animals with the SO group. The expression of e NOS(0.39 ± 0.03 vs 0.25 ± 0.03 a.μ)(P < 0.01) and VEGF(0.38 ± 0.04 vs 0.26 ± 0.04 a.μ)(P < 0.01) were also evaluated by Western blot analysis,and we observed an increase of both proteins on PPVL animals. We also evaluated the DNA damage by comet assay,and observed an increase on damage index and damage frequency on those animals. NAC decreased portal pressure values in PPVL + NAC animals(16.46 ± 2 vs 29.8 ± 1.8 mm Hg)(P < 0.001) when compared to PPVL. The expression of e NOS(14.60 ± 4.1 vs 56.8 ± 3.7 pixels)(P < 0.001),VEGF(19.53 ± 3.2 vs 34.9 ± 4.7 pixels)(P < 0.05) and NTT(21.84 ± 0.7 vs 39.01 ± 4.0 pixels)(P < 0.05) evaluated by immunohistochemistry were also reduced in PPVL + NAC animals. Also,when evaluated by Western blot e NOS expression(0.32 ± 0.03 vs 0.39 ± 0.03 a.μ)(P < 0.05) and VEGF expression(0.31 ± 0.09 vs 0.38 ± 0.04 a.μ)(P < 0.01). Furthermore,NAC modulated DNA damage in PPVL + NAC animals.CONCLUSION: In view of these results,we believe NAC is able to protect the stomach from the alterations induced by the PPVL procedure. | Francielli Licks Renata Minuzzo Hartmann Camila Marques Elizangela Schemitt Josieli Raskopf Colares Mariana do Couto Soares Juliana Reys Camila Fisher Juliana da Silva Norma Possa Marroni | 2015 | World Journal of Gastroenterology2015，21，43： | 2 |
| 4 | No hmctional and transduciional signif'icanee of speeific neuropilin 1 siRNA inhibition in colon carcinoma cell lines lacking VEGF receptor 2显示文摘 | Quante M Raskopf E Stathl S | 2009 | Oncol Rep2009，21，5： | 1 |
| 5 | SiRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo显示文摘 | Raskopf E Vogt A Sauerbruch T | 2008 | J Hepatol2008，49，6： | 1 |
| 6 | Inhibition of neuropilin-1by RNA-interference and its angiostatic potential in the treatment of hepatocellular carcinoma显示文摘 | Raskopf E Vogt A Standop J | 2010 | Z Gastroenterol2010，48，1： | 1 |
| 7 | siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo显示文摘 | Raskopf E Vogt A Sauerbruch T | 2008 | J Hepatol2008，49，6： | 1 |
| 8 | Inhibition of neuropilin-1 by RNA-interferenee and its angiostatie potential in the treatment of hepatocellular carcinoma 显示文摘 | Raskopf E Vogt A Standop J | 2010 | Z Gastroenterol2010，48，1： | 1 |
| 9 | siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo显示文摘 | Esther Raskopf Annabelle Vogt Tilman Sauerbruch Volker Schmitz | 2008 | Journal of Hepatology2008，，6： | 1 |
| 10 | Accelerated orthotopic hepatocellular carcinomas growth is linked to increased expression of proangiogenic and pro-metastatic factors in murine liver fibrosis显示文摘 | Kornek M Raskopf E Tolba R | 2008 | Liver Int2008，28，4： | 1 |
| 11 | siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo显示文摘 | Raskopf E Vogt A Sauerbruch T | 2008 | J Hepatol2008，49，6： | 1 |
| 12 | Combination of systemic thioacetamide (TAA) injections and ethanol feeding accelerates hepatic fibrosis in C3 H/He mice and is associated with intrahepatic up regulation of MMP-2,VEGF and ICAM-1显示文摘 | Kornek M Raskopf E Guetgemann I | | 0，，03： | 1 |
| 13 | Plasminogen fragment K1-5 improves survival in a murine hepatocellular carcinoma model显示文摘 | Schmitz V Raskopf E Gonzalez-Carmona MA | 2007 | Gut2007，56，2： | 1 |
| 14 | Apoptotic potency of an- giostatic compounds in the treatment of cancer显示文摘 | Raskopf E Sauerbruch T Schmitz V | 2012 | Curr Pharm Biotechnoi2012，13，11： | 1 |
| 15 | Combination of Hypoxia and RNA-Interference Targeting VEGF Induces Apoptosis in Hepatoma Cells Via Autocrine Mechanisms显示文摘 | Esther Raskopf Annabelle Vogt Georges Decker Sarah Hirt Katjana Daskalow Thorsten Cramer Jens Standop Maria-Angeles Gonzalez-Carmona Tilman Sauerbruch Volker Schmitz | 2012 | Current Pharmaceutical Biotechnology2012，，11： | 1 |
| 16 | Inhibition of neuropilin-1 by RNA - interference and its angiostatic potential in the treatment of hepatocellular carcinoma显示文摘 | Raskopf E Vogt A Standop | 2010 | Zeitschrift Fur Gastroenterologie2010，48，1： | 1 |
| 17 | Effective angiostatic treatment in a murine metastatic and orthotopic hepatoma model显示文摘 | Raskopf E Dzienisowicz C Hilbert T | 2005 | Hepatology2005，41，6： | 1 |
| 18 | Plasminogen derivatives encoding kringles 1-4 and kringles 1-5 exert indirect antiangiogenic and direct antitumoral effects in experimental lung cancer显示文摘 | Schmitz V Raskopf E Gonzalez-Carmona MA | 2008 | Cancer Invest2008，25，5： | 1 |
| 19 | siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo显示文摘 | Raskopf E Vogt A Sauerbruch T | | 0，，06： | 1 |
| 20 | Effective angiostatictreatment in a murine metastatic and orthotopic hepatoma model显示文摘 | Raskopf E Dzienisowicz C Hilbert T | 2005 | Hepatology2005，41，6： | 1 |
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