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10.1016/j.lungcan.2015.09.014 http://scihub22266oqcxt.onion/10.1016/j.lungcan.2015.09.014 C4619129!4619129!26410177     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Lung+Cancer 2015 ; 90 (2): 182-90 Nephropedia Template TP {{tp|p=26410177|t=2015. SMALL-MOLECULE TARGETING OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT) 3 TO TREAT NON-SMALL CELL LUNG CANCER# |pdf=|usr=}}{{26410177}} gab.com Text SMALL-MOLECULE TARGETING OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT) 3 TO TREAT NON-SMALL CELL LUNG CANCER# JO: Lung Cancer http://www.kidney.de/pget.php?&tw=1&pmid=26410177 #FOAvip Objective: Lung cancer is the leading cause of cancer death in both men and women. Non-small cell lung cancer (NSCLC) has an overall 5-year survival rate of 15%. While aberrant STAT3 activation has previously been observed in NSCLC, the scope of its contribution is uncertain and agents that target STAT3 for treatment are not available clinically. Methods: We determined levels of activated STAT3 (STAT3 phosphorylated on Y705, pSTAT3) and the two major isoforms of STAT3 (? and ?) in protein extracts of 8 NSCLC cell lines, as well as the effects of targeting STAT3 in vitro and in vivo in NSCLC cells using short hairpin (sh) RNA and two novel small-molecule STAT3 inhibitors, C188-9 and piperlongumine (PL). Results: Levels of pSTAT3, STAT3?, and STAT? were increased in 7 of 8 NSCLC cell lines. Of note, levels of pSTAT3 were tightly correlated with levels of STAT3?, but not STAT3?. Targeting of STAT3 in A549 cells using shRNA decreased tSTAT3 by 75%; this was accompanied by a 47?78% reduction in anchorage-dependent and anchorage-independent growth and a 28?45% reduction in mRNA levels for anti-apoptotic STAT3 gene targets. C188-9 and PL (@30?M) each reduced pSTAT3 levels in all NSCLC cell lines tested by ?50%, reduced anti-apoptotic protein mRNA levels by 25?60%, and reduced both anchorage-dependent and anchorage-independent growth of NSCLC cell lines with IC50 values ranging from 3.06?52.44?M and 0.86?11.66?M, respectively. Treatment of nude mice bearing A549 tumor xenografts with C188-9 or PL blocked tumor growth and reduced levels of pSTAT3 and mRNA encoding anti-apoptotic proteins. Conclusion: STAT3 is essential for growth of NSCLC cell lines and tumors and its targeting using C188-9 or PL may be a useful strategy for treatment. Twit Text FOAVip SMALL-MOLECULE TARGETING OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT) 3 TO TREAT NON-SMALL CELL LUNG CANCER# ????Lung Cancer http://www.kidney.de/pget.php?&tw=1&pmid=26410177 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26410177 #FOAvip English Wikipedia <ref>{{Cite pmid|26410177}}</ref> SMALL-MOLECULE TARGETING OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT) 3 TO TREAT NON-SMALL CELL LUNG CANCER# #MMPMID26410177 Lewis KM; Bharadwaj U; Eckols TK; Kolosov M; Kasembeli MM; Fridley C; Siller R; Tweardy DJ Lung Cancer 2015[Nov]; 90 (2): 182-90 PMID26410177show ga Objective: Lung cancer is the leading cause of cancer death in both men and women. Non-small cell lung cancer (NSCLC) has an overall 5-year survival rate of 15%. While aberrant STAT3 activation has previously been observed in NSCLC, the scope of its contribution is uncertain and agents that target STAT3 for treatment are not available clinically. Methods: We determined levels of activated STAT3 (STAT3 phosphorylated on Y705, pSTAT3) and the two major isoforms of STAT3 (? and ?) in protein extracts of 8 NSCLC cell lines, as well as the effects of targeting STAT3 in vitro and in vivo in NSCLC cells using short hairpin (sh) RNA and two novel small-molecule STAT3 inhibitors, C188-9 and piperlongumine (PL). Results: Levels of pSTAT3, STAT3?, and STAT? were increased in 7 of 8 NSCLC cell lines. Of note, levels of pSTAT3 were tightly correlated with levels of STAT3?, but not STAT3?. Targeting of STAT3 in A549 cells using shRNA decreased tSTAT3 by 75%; this was accompanied by a 47?78% reduction in anchorage-dependent and anchorage-independent growth and a 28?45% reduction in mRNA levels for anti-apoptotic STAT3 gene targets. C188-9 and PL (@30?M) each reduced pSTAT3 levels in all NSCLC cell lines tested by ?50%, reduced anti-apoptotic protein mRNA levels by 25?60%, and reduced both anchorage-dependent and anchorage-independent growth of NSCLC cell lines with IC50 values ranging from 3.06?52.44?M and 0.86?11.66?M, respectively. Treatment of nude mice bearing A549 tumor xenografts with C188-9 or PL blocked tumor growth and reduced levels of pSTAT3 and mRNA encoding anti-apoptotic proteins. Conclusion: STAT3 is essential for growth of NSCLC cell lines and tumors and its targeting using C188-9 or PL may be a useful strategy for treatment. äSMALL-MOLECULE TARGETING OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCR(epmc).pdf DeepDyve Pubget Overpricing