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10.1158/1535-7163.MCT-16-0309 http://scihub22266oqcxt.onion/10.1158/1535-7163.MCT-16-0309 C5010976!5010976!27390343     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       Mol+Cancer+Ther 2016 ; 15 (9): 2143-54 Nephropedia Template TP {{tp|p=27390343|t=2016. Direct pharmacological inhibition of ?-catenin by RNA interference in tumors of diverse origin |pdf=|usr=}}{{27390343}} gab.com Text Direct pharmacological inhibition of -catenin by RNA interference in tumors of diverse origin JO: Mol Cancer Ther http://www.kidney.de/pget.php?&tw=1&pmid=27390343 #FOAvip The Wnt/?-catenin pathway is among the most frequently altered signaling networks in human cancers. Despite decades of preclinical and clinical research, efficient therapeutic targeting of Wnt/?-catenin has been elusive. RNA interference (RNAi) technology silences genes at the mRNA level, and therefore can be applied to previously-undruggable targets. Lipid nanoparticles (LNPs) represent an elegant solution for delivery of RNAi-triggering oligonucleotides to disease-relevant tissues, but have been mostly restricted to applications in the liver. In this study, we systematically tuned the composition of a prototype LNP to enable tumor-selective delivery of a Dicer-substrate siRNA (DsiRNA) targeting CTNNB1, the gene encoding ?-catenin. This formulation, termed EnCore-R, demonstrated pharmacodynamic activity in subcutaneous human tumor xenografts, orthotopic patient-derived xenograft (PDx) tumors, disseminated hematopoietic tumors, genetically induced primary liver tumors, metastatic colorectal tumors, murine metastatic melanoma. DsiRNA delivery was homogeneous in tumor sections, selective over normal liver and independent of apolipoprotein-E binding. Significant tumor growth inhibition was achieved in Wnt-dependent colorectal and hepatocellular carcinoma models, but not in Wnt-independent tumors. Finally, no evidence of accelerated blood clearance or sustained liver transaminase elevation was observed after repeated dosing in nonhuman primates. These data support further investigation to gain mechanistic insight, optimize dose regimens and identify efficacious combinations with standard-of-care therapeutics. Twit Text FOAVip Direct pharmacological inhibition of -catenin by RNA interference in tumors of diverse origin ????Mol Cancer Ther http://www.kidney.de/pget.php?&tw=1&pmid=27390343 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27390343 #FOAvip English Wikipedia <ref>{{Cite pmid|27390343}}</ref> Direct pharmacological inhibition of ?-catenin by RNA interference in tumors of diverse origin #MMPMID27390343 Ganesh S; Koser M; Cyr W; Chopda G; Tao J; Shui X; Ying B; Chen D; Pandya P; Chipumuro E; Siddiquee Z; Craig K; Lai C; Dudek H; Monga S; Wang W; Brown BD; Abrams M Mol Cancer Ther 2016[Sep]; 15 (9): 2143-54 PMID27390343show ga The Wnt/?-catenin pathway is among the most frequently altered signaling networks in human cancers. Despite decades of preclinical and clinical research, efficient therapeutic targeting of Wnt/?-catenin has been elusive. RNA interference (RNAi) technology silences genes at the mRNA level, and therefore can be applied to previously-undruggable targets. Lipid nanoparticles (LNPs) represent an elegant solution for delivery of RNAi-triggering oligonucleotides to disease-relevant tissues, but have been mostly restricted to applications in the liver. In this study, we systematically tuned the composition of a prototype LNP to enable tumor-selective delivery of a Dicer-substrate siRNA (DsiRNA) targeting CTNNB1, the gene encoding ?-catenin. This formulation, termed EnCore-R, demonstrated pharmacodynamic activity in subcutaneous human tumor xenografts, orthotopic patient-derived xenograft (PDx) tumors, disseminated hematopoietic tumors, genetically induced primary liver tumors, metastatic colorectal tumors, murine metastatic melanoma. DsiRNA delivery was homogeneous in tumor sections, selective over normal liver and independent of apolipoprotein-E binding. Significant tumor growth inhibition was achieved in Wnt-dependent colorectal and hepatocellular carcinoma models, but not in Wnt-independent tumors. Finally, no evidence of accelerated blood clearance or sustained liver transaminase elevation was observed after repeated dosing in nonhuman primates. These data support further investigation to gain mechanistic insight, optimize dose regimens and identify efficacious combinations with standard-of-care therapeutics. äDirect pharmacological inhibition of ?-catenin by RNA interference in (epmc).pdf DeepDyve Pubget Overpricing