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10.1038/ncomms9499 http://scihub22266oqcxt.onion/10.1038/ncomms9499 C4608384!4608384 !26465273     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 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 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26465273 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Nat+Commun 2015 ; 6 (ä): 8499 Nephropedia Template TP {{tp|p=26465273 |t=2015. STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody |pdf=|usr=}}{{26465273 }} gab.com Text STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=26465273 #FOAvip Drug resistance is a major impediment in medical oncology. Recent studies have emphasized the importance of the tumour microenvironment (TME) to innate resistance, to molecularly targeted therapies. In this study, we investigate the role of TME in resistance to cixutumumab, an anti-IGF-1R monoclonal antibody that has shown limited clinical efficacy. We show that treatment with cixutumumab accelerates tumour infiltration of stromal cells and metastatic tumour growth, and decreases overall survival of mice. Cixutumumab treatment stimulates STAT3-dependent transcriptional upregulation of IGF-2 in cancer cells and recruitment of macrophages and fibroblasts via paracrine IGF-2/IGF-2R activation, resulting in the stroma-derived CXCL8 production, and thus angiogenic and metastatic environment. Silencing IGF-2 or STAT3 expression in cancer cells or IGF-2R or CXCL8 expression in stromal cells significantly inhibits the cancer-stroma communication and vascular endothelial cells' angiogenic activities. These findings suggest that blocking the STAT3/IGF-2/IGF-2R intercellular signalling loop may overcome the adverse consequences of anti-IGF-1R monoclonal antibody-based therapies. Twit Text FOAVip STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=26465273 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26465273 #FOAvip English Wikipedia <ref>{{Cite pmid|26465273 }}</ref> STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody #MMPMID26465273 Lee JS ; Kang JH ; Boo HJ ; Hwang SJ ; Hong S ; Lee SC ; Park YJ ; Chung TM ; Youn H ; Mi Lee S ; Jae Kim B ; Chung JK ; Chung Y ; William WN Jr ; Kee Shin Y ; Lee HJ ; Oh SH ; Lee HY Nat Commun 2015[Oct]; 6 (ä): 8499 PMID26465273 show ga Drug resistance is a major impediment in medical oncology. Recent studies have emphasized the importance of the tumour microenvironment (TME) to innate resistance, to molecularly targeted therapies. In this study, we investigate the role of TME in resistance to cixutumumab, an anti-IGF-1R monoclonal antibody that has shown limited clinical efficacy. We show that treatment with cixutumumab accelerates tumour infiltration of stromal cells and metastatic tumour growth, and decreases overall survival of mice. Cixutumumab treatment stimulates STAT3-dependent transcriptional upregulation of IGF-2 in cancer cells and recruitment of macrophages and fibroblasts via paracrine IGF-2/IGF-2R activation, resulting in the stroma-derived CXCL8 production, and thus angiogenic and metastatic environment. Silencing IGF-2 or STAT3 expression in cancer cells or IGF-2R or CXCL8 expression in stromal cells significantly inhibits the cancer-stroma communication and vascular endothelial cells' angiogenic activities. These findings suggest that blocking the STAT3/IGF-2/IGF-2R intercellular signalling loop may overcome the adverse consequences of anti-IGF-1R monoclonal antibody-based therapies. |*Drug Resistance, Neoplasm [MESH] |*Tumor Microenvironment [MESH] |Animals [MESH] |Antibodies, Monoclonal, Humanized [MESH] |Antibodies, Monoclonal/pharmacology/therapeutic use [MESH] |Cell Line, Tumor [MESH] |Cellular Reprogramming [MESH] |Human Umbilical Vein Endothelial Cells [MESH] |Humans [MESH] |Insulin-Like Growth Factor II/*metabolism [MESH] |Interleukin-8/metabolism [MESH] |Mice [MESH] |Mice, Inbred BALB C [MESH] |Mice, Inbred NOD [MESH] |Mice, Nude [MESH] |Mice, SCID [MESH] |Neoplasm Invasiveness [MESH] |Neoplasms, Experimental/drug therapy/*metabolism [MESH] |Neovascularization, Pathologic [MESH] |Paracrine Communication [MESH] |Receptor, IGF Type 1/*antagonists & inhibitors [MESH] |Receptor, IGF Type 2/metabolism [MESH]STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits (epmc).pdf DeepDyve Pubget Overpricing