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http://scihub22266oqcxt.onion/ C4741801!4741801!26378050     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26378050&cmd=llinks): Failed to open stream: HTTP request failed! 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Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration |pdf=|usr=}}{{26378050}} gab.com Text Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26378050 #FOAvip The use of BCR-ABL1 tyrosine kinase inhibitors (TKI) has led to excellent clinical responses in patients with chronic phase chronic myeloid leukemia (CML). However these inhibitors have been less effective as single agents in the terminal blast phase (BP). We show that pyrvinium, a FDA-approved anthelminthic drug, selectively targets BP-CML CD34+ progenitor cells. Pyrvinium is effective in inducing apoptosis, inhibiting colony formation and self-renewal capacity of CD34+ cells from TKI-resistant BP-CML patients, while cord blood CD34+ are largely unaffected. The effects of pyrvinium are further enhanced upon combination with dasatinib, a second generation BCR-ABL1 TKI. In a CML xenograft model pyrvinium significantly inhibits tumor growth as a single agent, with complete inhibition in combination with dasatinib. While pyrvinium has been shown to inhibit the Wnt/?-catenin signalling pathway via activation of casein kinase 1?, we find its activity in CML is not dependent on this pathway. Instead, we show that pyrvinium localizes to mitochondria and induces apoptosis by inhibiting mitochondrial respiration. Our study suggests that pyrvinium is a useful addition to the treatment armamentarium for BP-CML and that targeting mitochondrial respiration may be a potential therapeutic strategy in aggressive leukemia. Twit Text FOAVip Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26378050 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26378050 #FOAvip English Wikipedia <ref>{{Cite pmid|26378050}}</ref> Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration #MMPMID26378050 Xiang W; Cheong JK; Ang SH; Teo B; Xu P; Asari K; Sun WT; Than H; Bunte RM; Virshup DM; Chuah C Oncotarget 2015[Oct]; 6 (32): 33769-80 PMID26378050show ga The use of BCR-ABL1 tyrosine kinase inhibitors (TKI) has led to excellent clinical responses in patients with chronic phase chronic myeloid leukemia (CML). However these inhibitors have been less effective as single agents in the terminal blast phase (BP). We show that pyrvinium, a FDA-approved anthelminthic drug, selectively targets BP-CML CD34+ progenitor cells. Pyrvinium is effective in inducing apoptosis, inhibiting colony formation and self-renewal capacity of CD34+ cells from TKI-resistant BP-CML patients, while cord blood CD34+ are largely unaffected. The effects of pyrvinium are further enhanced upon combination with dasatinib, a second generation BCR-ABL1 TKI. In a CML xenograft model pyrvinium significantly inhibits tumor growth as a single agent, with complete inhibition in combination with dasatinib. While pyrvinium has been shown to inhibit the Wnt/?-catenin signalling pathway via activation of casein kinase 1?, we find its activity in CML is not dependent on this pathway. Instead, we show that pyrvinium localizes to mitochondria and induces apoptosis by inhibiting mitochondrial respiration. Our study suggests that pyrvinium is a useful addition to the treatment armamentarium for BP-CML and that targeting mitochondrial respiration may be a potential therapeutic strategy in aggressive leukemia. �Pyrvinium selectively targets blast phase-chronic myeloid leukemia thr(epmc).pdf DeepDyve Pubget Overpricing