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10.1002/pbc.26218 http://scihub22266oqcxt.onion/10.1002/pbc.26218 C5584632!5584632!27555605     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27555605&cmd=llinks): Failed to open stream: HTTP request failed! 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Initial Testing (Stage 1) of Tazemetostat (EPZ-6438), a Novel EZH2 Inhibitor, by the Pediatric Preclinical Testing Program |pdf=|usr=}}{{27555605}} gab.com Text Initial Testing (Stage 1) of Tazemetostat (EPZ-6438), a Novel EZH2 Inhibitor, by the Pediatric Preclinical Testing Program JO: Pediatr Blood Cancer http://www.kidney.de/pget.php?&tw=1&pmid=27555605 #FOAvip Background: Tazemetostat (EPZ-6438) is a selective inhibitor of the histone methyltransferase EZH2, currently in clinical development for non-Hodgkin lymphoma and genetically defined tumors. Procedures: Tazemetostat was tested against the PPTP solid tumor xenografts using a dose of 400 mg/kg administered twice-daily by oral gavage for 28 days. H3K27me3:H3 ratios were determined in control and treated tumors. Results: Tazemetostat induced significant differences in event free survival (EFS) distribution compared to control in 9 of 30 (30%) of the xenografts studied. Significant differences in EFS distribution were observed in 5 of 7 (71%) rhabdoid tumor xenograft lines compared to 4 of 23 (17%) non-rhabdoid xenograft lines [chi square (?2) test p=0.006]. Tazemetostat induced tumor growth inhibition meeting criteria for intermediate and high EFS treated to control (T/C) activity in 2 of 25 (8%) and 1 of 25 (4%) xenografts, respectively. Intermediate and high activity for the EFS T/C metric was observed exclusively among rhabdoid tumor xenografts (3 of 5 rhabdoid tumor versus 0 of 22 non-rhabdoid tumors (?2 test p<0.001). One rhabdoid tumor xenograft (G401) showed stable disease. For one rhabdoid tumor (G401), delayed tumor regression to tazemetostat was noted following 1 week of tumor growth. Tazemetostat induced significant reduction of H3K27me3 levels in the majority of tumors compared to controls. Conclusions: Tazemetostat demonstrated significant antitumor activity in rhabdoid tumor models, but showed no consistent activity against any other histology. Tazemetostat reduced H3K27me3 levels irrespective of tumor response. Further preclinical testing to evaluate tazemetostat in combination with other anticancer agents is warranted. Twit Text FOAVip Initial Testing (Stage 1) of Tazemetostat (EPZ-6438), a Novel EZH2 Inhibitor, by the Pediatric Preclinical Testing Program ????Pediatr Blood Cancer http://www.kidney.de/pget.php?&tw=1&pmid=27555605 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27555605 #FOAvip English Wikipedia <ref>{{Cite pmid|27555605}}</ref> Initial Testing (Stage 1) of Tazemetostat (EPZ-6438), a Novel EZH2 Inhibitor, by the Pediatric Preclinical Testing Program #MMPMID27555605 Kurmasheva RT; Sammons M; Favours E; Wu J; Kurmashev D; Cosmopoulos K; Keilhack H; Klaus CR; Houghton PJ; Smith MA Pediatr Blood Cancer 2017[Mar]; 64 (3): ä PMID27555605show ga Background: Tazemetostat (EPZ-6438) is a selective inhibitor of the histone methyltransferase EZH2, currently in clinical development for non-Hodgkin lymphoma and genetically defined tumors. Procedures: Tazemetostat was tested against the PPTP solid tumor xenografts using a dose of 400 mg/kg administered twice-daily by oral gavage for 28 days. H3K27me3:H3 ratios were determined in control and treated tumors. Results: Tazemetostat induced significant differences in event free survival (EFS) distribution compared to control in 9 of 30 (30%) of the xenografts studied. Significant differences in EFS distribution were observed in 5 of 7 (71%) rhabdoid tumor xenograft lines compared to 4 of 23 (17%) non-rhabdoid xenograft lines [chi square (?2) test p=0.006]. Tazemetostat induced tumor growth inhibition meeting criteria for intermediate and high EFS treated to control (T/C) activity in 2 of 25 (8%) and 1 of 25 (4%) xenografts, respectively. Intermediate and high activity for the EFS T/C metric was observed exclusively among rhabdoid tumor xenografts (3 of 5 rhabdoid tumor versus 0 of 22 non-rhabdoid tumors (?2 test p<0.001). One rhabdoid tumor xenograft (G401) showed stable disease. For one rhabdoid tumor (G401), delayed tumor regression to tazemetostat was noted following 1 week of tumor growth. Tazemetostat induced significant reduction of H3K27me3 levels in the majority of tumors compared to controls. Conclusions: Tazemetostat demonstrated significant antitumor activity in rhabdoid tumor models, but showed no consistent activity against any other histology. Tazemetostat reduced H3K27me3 levels irrespective of tumor response. Further preclinical testing to evaluate tazemetostat in combination with other anticancer agents is warranted. äInitial Testing (Stage 1) of Tazemetostat (EPZ-6438), a Novel EZH2 Inh(epmc).pdf DeepDyve Pubget Overpricing