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10.1038/leu.2014.93 http://scihub22266oqcxt.onion/10.1038/leu.2014.93 C4148474!4148474!24577530     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Leukemia 2014 ; 28 (10): 1960-8 Nephropedia Template TP {{tp|p=24577530|t=2014. Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity |pdf=|usr=}}{{24577530}} gab.com Text Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity JO: Leukemia http://www.kidney.de/pget.php?&tw=1&pmid=24577530 #FOAvip Identification of agents that target human leukemia stem cells (LSCs) is an important consideration for the development of new therapies. The present study demonstrates that rocaglamide and silvestrol, closely related natural products from the flavagline class of compounds, are able to preferentially kill functionally defined LSCs while sparing normal stem and progenitor cells. In addition to efficacy as single agents, flavaglines sensitize leukemia cells to several anti-cancer compounds, including front-line chemotherapeutic drugs used to treat leukemia patients. Mechanistic studies indicate that flavaglines strongly inhibit protein synthesis, leading to the reduction of short-lived anti-apoptotic proteins. Notably though, treatment with flavaglines alone or in combination with other drugs, yields a much stronger cytotoxic activity towards leukemia cells than the translational inhibitor temsirolimus. These results indicate that the underlying cell death mechanism of flavaglines is more complex than simply inhibiting general protein translation. Global gene expression profiling and cell biological assays identified Myc inhibition and the disruption of mitochondrial integrity to be features of flavaglines, which we propose contribute to their efficacy in targeting leukemia cells. Together, these findings indicate that rocaglamide and silvestrol are distinct from clinically available translational inhibitors and represent promising candidates for the treatment of leukemia. Twit Text FOAVip Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity ????Leukemia http://www.kidney.de/pget.php?&tw=1&pmid=24577530 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24577530 #FOAvip English Wikipedia <ref>{{Cite pmid|24577530}}</ref> Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity #MMPMID24577530 Callahan KP; Minhajuddin M; Corbett C; Lagadinou ED; Rossi RM; Grose V; Balys MM; Pan L; Jacob S; Frontier A; Grever MR; Lucas DM; Kinghorn AD; Liesveld JL; Becker MW; Jordan CT Leukemia 2014[Oct]; 28 (10): 1960-8 PMID24577530show ga Identification of agents that target human leukemia stem cells (LSCs) is an important consideration for the development of new therapies. The present study demonstrates that rocaglamide and silvestrol, closely related natural products from the flavagline class of compounds, are able to preferentially kill functionally defined LSCs while sparing normal stem and progenitor cells. In addition to efficacy as single agents, flavaglines sensitize leukemia cells to several anti-cancer compounds, including front-line chemotherapeutic drugs used to treat leukemia patients. Mechanistic studies indicate that flavaglines strongly inhibit protein synthesis, leading to the reduction of short-lived anti-apoptotic proteins. Notably though, treatment with flavaglines alone or in combination with other drugs, yields a much stronger cytotoxic activity towards leukemia cells than the translational inhibitor temsirolimus. These results indicate that the underlying cell death mechanism of flavaglines is more complex than simply inhibiting general protein translation. Global gene expression profiling and cell biological assays identified Myc inhibition and the disruption of mitochondrial integrity to be features of flavaglines, which we propose contribute to their efficacy in targeting leukemia cells. Together, these findings indicate that rocaglamide and silvestrol are distinct from clinically available translational inhibitors and represent promising candidates for the treatment of leukemia. äFlavaglines target primitive leukemia cells and enhance anti-leukemia (epmc).pdf DeepDyve Pubget Overpricing