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http://scihub22266oqcxt.onion/ C4791224!4791224!26657731     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Oncotarget 2015 ; 6 (41): 43172-81 Nephropedia Template TP {{tp|p=26657731|t=2015. Epigenetic effects of RRx-001: a possible unifying mechanism of anticancer activity |pdf=|usr=}}{{26657731}} gab.com Text Epigenetic effects of RRx-001: a possible unifying mechanism of anticancer activity JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26657731 #FOAvip RRx-001 is a novel aerospace-derived compound currently under investigation in several ongoing Phase II studies. In a Phase I trial, it demonstrated anti-cancer activity and evidence of resensitization to formerly effective therapies in heavily pre-treated patients with relapsed/refractory solid tumors. RRx-001 generates reactive oxygen and nitrogen species (ROS and RNS) and nitric oxide (NO), elicits changes in intracellular redox status, modulates tumor blood flow, hypoxia and vascular function and triggers apoptosis in cancer cells. We investigated the effect of RRx-001 on the epigenome of SCC VII cancer cells. RRx-001 at 0.5 and 2 ?M significantly decreased global DNA methylation, i.e., 5-methylcytosine levels, in SCC VII cells. Consistently, 0.5-5 ?M RRx-001 significantly decreased Dnmt1 and Dnmt3a protein expression in a dose- and time-dependent manner. In addition, global methylation profiling identified differentially methylated genes in SCC VII cells treated with 0.5, 2, and 5 ?M RRx-001 compared to control cells. Twenty-three target sites were hypomethylated and 22 hypermethylated by >10% in the presence of at least two different concentrations of RRx-001. Moreover, RRx-001 at 2 ?M significantly increased global acetylated histone H3 and H4 levels in SCC VII cells after 24 hour treatment, suggesting that RRx-001 regulates global acetylation in cancer cells. These results demonstrate that, in contrast to the traditional ?one drug one target? paradigm, RRx-001 has multi(epi)target features, which contribute to its anti-cancer activity and may rationalize the resensitization to previously effective therapies observed in clinical trials and serve as a unifying mechanism for its anticancer activity. Twit Text FOAVip Epigenetic effects of RRx-001: a possible unifying mechanism of anticancer activity ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26657731 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26657731 #FOAvip English Wikipedia <ref>{{Cite pmid|26657731}}</ref> Epigenetic effects of RRx-001: a possible unifying mechanism of anticancer activity #MMPMID26657731 Zhao H; Ning S; Scicinski J; Oronsky B; Knox SJ; Peehl DM Oncotarget 2015[Dec]; 6 (41): 43172-81 PMID26657731show ga RRx-001 is a novel aerospace-derived compound currently under investigation in several ongoing Phase II studies. In a Phase I trial, it demonstrated anti-cancer activity and evidence of resensitization to formerly effective therapies in heavily pre-treated patients with relapsed/refractory solid tumors. RRx-001 generates reactive oxygen and nitrogen species (ROS and RNS) and nitric oxide (NO), elicits changes in intracellular redox status, modulates tumor blood flow, hypoxia and vascular function and triggers apoptosis in cancer cells. We investigated the effect of RRx-001 on the epigenome of SCC VII cancer cells. RRx-001 at 0.5 and 2 ?M significantly decreased global DNA methylation, i.e., 5-methylcytosine levels, in SCC VII cells. Consistently, 0.5-5 ?M RRx-001 significantly decreased Dnmt1 and Dnmt3a protein expression in a dose- and time-dependent manner. In addition, global methylation profiling identified differentially methylated genes in SCC VII cells treated with 0.5, 2, and 5 ?M RRx-001 compared to control cells. Twenty-three target sites were hypomethylated and 22 hypermethylated by >10% in the presence of at least two different concentrations of RRx-001. Moreover, RRx-001 at 2 ?M significantly increased global acetylated histone H3 and H4 levels in SCC VII cells after 24 hour treatment, suggesting that RRx-001 regulates global acetylation in cancer cells. These results demonstrate that, in contrast to the traditional ?one drug one target? paradigm, RRx-001 has multi(epi)target features, which contribute to its anti-cancer activity and may rationalize the resensitization to previously effective therapies observed in clinical trials and serve as a unifying mechanism for its anticancer activity. äEpigenetic effects of RRx-001: a possible unifying mechanism of antica(epmc).pdf DeepDyve Pubget Overpricing