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10.1002/hep.26790 http://scihub22266oqcxt.onion/10.1002/hep.26790 C3966948!3966948!24242874     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Hepatology 2014 ; 59 (4): 1435-47 Nephropedia Template TP {{tp|p=24242874|t=2014. Differential effects of sorafenib on liver versus tumor fibrosis mediated by SDF1?/CXCR4 axis and Gr-1+ myeloid cell infiltration in mice |pdf=|usr=}}{{24242874}} gab.com Text Differential effects of sorafenib on liver versus tumor fibrosis mediated by SDF1 /CXCR4 axis and Gr-1+ myeloid cell infiltration in mice JO: Hepatology http://www.kidney.de/pget.php?&tw=1&pmid=24242874 #FOAvip Sorafenib?a broad kinase inhibitor?is a standard therapy for advanced hepatocellular carcinoma (HCC), and has been shown to exert anti-fibrotic effects in liver cirrhosis, a precursor of HCC. However, the effects of sorafenib on tumor desmoplasia?and its consequences on treatment resistance ? remain unknown. We demonstrate that sorafenib has differential effects on tumor fibrosis versus liver fibrosis in orthotopic models of HCC in mice. Sorafenib intensifies tumor hypoxia, which increases stromal-derived factor 1? (SDF1?) expression in cancer and stromal cells, and subsequently Gr-1+ myeloid cell infiltration. The SDF1?/CXCR4 pathway directly promotes hepatic stellate cell (HSC) differentiation and activation via MAP kinase pathway. This is consistent with the association between SDF1? expression with fibrotic septa in cirrhotic liver tissues as well as with desmoplastic regions of human HCC samples. We demonstrate that after treatment with sorafenib, SDF1? increased the survival of HSCs and their ?-SMA and Collagen I expression, thus increasing tumor fibrosis. Finally, we show that Gr-1+ myeloid cells mediate HSC differentiation/activation in a paracrine manner. CXCR4 inhibition using AMD3100 in combination with sorafenib treatment prevents the increase in tumor fibrosis?despite persistently elevated hypoxia?in part by reducing Gr-1+ myeloid cell infiltration, and inhibits HCC growth. Similarly, antibody blockade of Gr-1 reduces tumor fibrosis and inhibited HCC growth when combined with sorafenib treatment.Conclusion: Blocking SDF1?/CXCR4 or Gr-1+ myeloid cell infiltration may reduce hypoxia-mediated HCC desmoplasia and increase the efficacy of sorafenib treatment. Twit Text FOAVip Differential effects of sorafenib on liver versus tumor fibrosis mediated by SDF1 /CXCR4 axis and Gr-1+ myeloid cell infiltration in mice ????Hepatology http://www.kidney.de/pget.php?&tw=1&pmid=24242874 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24242874 #FOAvip English Wikipedia <ref>{{Cite pmid|24242874}}</ref> Differential effects of sorafenib on liver versus tumor fibrosis mediated by SDF1?/CXCR4 axis and Gr-1+ myeloid cell infiltration in mice #MMPMID24242874 Chen Y; Huang Y; Reiberger T; Duyverman AM; Huang P; Samuel R; Hiddingh L; Roberge S; Koppel C; Lauwers GY; Zhu AX; Jain RK; Duda DG Hepatology 2014[Apr]; 59 (4): 1435-47 PMID24242874show ga Sorafenib?a broad kinase inhibitor?is a standard therapy for advanced hepatocellular carcinoma (HCC), and has been shown to exert anti-fibrotic effects in liver cirrhosis, a precursor of HCC. However, the effects of sorafenib on tumor desmoplasia?and its consequences on treatment resistance ? remain unknown. We demonstrate that sorafenib has differential effects on tumor fibrosis versus liver fibrosis in orthotopic models of HCC in mice. Sorafenib intensifies tumor hypoxia, which increases stromal-derived factor 1? (SDF1?) expression in cancer and stromal cells, and subsequently Gr-1+ myeloid cell infiltration. The SDF1?/CXCR4 pathway directly promotes hepatic stellate cell (HSC) differentiation and activation via MAP kinase pathway. This is consistent with the association between SDF1? expression with fibrotic septa in cirrhotic liver tissues as well as with desmoplastic regions of human HCC samples. We demonstrate that after treatment with sorafenib, SDF1? increased the survival of HSCs and their ?-SMA and Collagen I expression, thus increasing tumor fibrosis. Finally, we show that Gr-1+ myeloid cells mediate HSC differentiation/activation in a paracrine manner. CXCR4 inhibition using AMD3100 in combination with sorafenib treatment prevents the increase in tumor fibrosis?despite persistently elevated hypoxia?in part by reducing Gr-1+ myeloid cell infiltration, and inhibits HCC growth. Similarly, antibody blockade of Gr-1 reduces tumor fibrosis and inhibited HCC growth when combined with sorafenib treatment.Conclusion: Blocking SDF1?/CXCR4 or Gr-1+ myeloid cell infiltration may reduce hypoxia-mediated HCC desmoplasia and increase the efficacy of sorafenib treatment. äDifferential effects of sorafenib on liver versus tumor fibrosis media(epmc).pdf DeepDyve Pubget Overpricing