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10.1158/0008-5472.CAN-16-1901 http://scihub22266oqcxt.onion/10.1158/0008-5472.CAN-16-1901 C5582957!5582957 !27872098     free     free     free       Cancer+Res 2017 ; 77 (2 ): 566-578 Nephropedia Template TP {{tp|p=27872098 |t=2017. Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer |pdf=|usr=}}{{27872098 }} gab.com Text Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer JO: Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=27872098 #FOAvip Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation. Medium-throughput results were scrutinized and extensively analyzed for sensitivity patterns, synergy, anticancer activity, and were validated in low-throughput experiments. Principal component analysis revealed that a fraction of all upregulated or downregulated genes of a particular targeted pathway could partly explain cell sensitivity toward agents targeting that pathway. Combination therapies deemed immediately tractable to translation included ABT-263/crizotinib, ABT-263/paclitaxel, paclitaxel/JQ1, ABT-263/XL-184, and paclitaxel/nutlin-3, all of which exhibited synergistic antiproliferative and apoptotic activity in multiple TNBC backgrounds. Mechanistic investigations of the ABT-263/crizotinib combination offering a potentially rapid path to clinic demonstrated RTK blockade, inhibition of mitogenic signaling, and proapoptotic signal induction in basal and mesenchymal stem-like TNBC. Our findings provide preclinical proof of concept for several combination treatments of TNBC, which offer near-term prospects for clinical translation. Cancer Res; 77(2); 566-78. ©2016 AACR. Twit Text FOAVip Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer ????Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=27872098 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27872098 #FOAvip English Wikipedia <ref>{{Cite pmid|27872098 }}</ref> Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer #MMPMID27872098 Wali VB ; Langdon CG ; Held MA ; Platt JT ; Patwardhan GA ; Safonov A ; Aktas B ; Pusztai L ; Stern DF ; Hatzis C Cancer Res 2017[Jan]; 77 (2 ): 566-578 PMID27872098 show ga Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation. Medium-throughput results were scrutinized and extensively analyzed for sensitivity patterns, synergy, anticancer activity, and were validated in low-throughput experiments. Principal component analysis revealed that a fraction of all upregulated or downregulated genes of a particular targeted pathway could partly explain cell sensitivity toward agents targeting that pathway. Combination therapies deemed immediately tractable to translation included ABT-263/crizotinib, ABT-263/paclitaxel, paclitaxel/JQ1, ABT-263/XL-184, and paclitaxel/nutlin-3, all of which exhibited synergistic antiproliferative and apoptotic activity in multiple TNBC backgrounds. Mechanistic investigations of the ABT-263/crizotinib combination offering a potentially rapid path to clinic demonstrated RTK blockade, inhibition of mitogenic signaling, and proapoptotic signal induction in basal and mesenchymal stem-like TNBC. Our findings provide preclinical proof of concept for several combination treatments of TNBC, which offer near-term prospects for clinical translation. Cancer Res; 77(2); 566-78. ©2016 AACR. |*Triple Negative Breast Neoplasms [MESH] |Antineoplastic Combined Chemotherapy Protocols/*pharmacology [MESH] |Blotting, Western [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/drug effects [MESH] |Drug Screening Assays, Antitumor/*methods [MESH] |Drug Synergism [MESH] |Female [MESH] |Flow Cytometry [MESH] |Humans [MESH] |Immunoprecipitation [MESH]Systematic Drug Screening Identifies Tractable Targeted Combination Th(epmc).pdf DeepDyve Pubget Overpricing