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10.1158/1078-0432.CCR-14-1462 http://scihub22266oqcxt.onion/10.1158/1078-0432.CCR-14-1462 C4737551!4737551 !25748087     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25748087 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Clin+Cancer+Res 2015 ; 21 (11 ): 2538-45 Nephropedia Template TP {{tp|p=25748087 |t=2015. Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy against Waldenström Macroglobulinemia |pdf=|usr=}}{{25748087 }} gab.com Text Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy against Waldenström Macroglobulinemia JO: Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=25748087 #FOAvip PURPOSE: Waldenström macroglobulinemia (WMG) is a lymphoproliferative disorder characterized by good initial responses to standard therapeutics, but only a minority of patients achieve complete remissions, and most inevitably relapse, indicating a need for novel agents. B-cell receptor signaling has been linked to clonal evolution in WMG, and Spleen tyrosine kinase (Syk) is overexpressed in primary cells, suggesting that it could be a novel and rational target. EXPERIMENTAL DESIGN: We studied the impact of the Syk inhibitor fostamatinib on BCWM.1 and MWCL-1 WMG-derived cell lines both in vitro and in vivo, as well as on primary patient cells. RESULTS: In WMG-derived cell lines, fostamatinib induced a time- and dose-dependent reduction in viability, associated with activation of apoptosis. At the molecular level, fostamatinib reduced activation of Syk and Bruton's tyrosine kinase, and also downstream signaling through MAPK kinase (MEK), p44/42 MAPK, and protein kinase B/Akt. As a single agent, fostamatinib induced tumor growth delay in an in vivo model of WMG, and reduced viability of primary WMG cells, along with inhibition of p44/42 MAPK signaling. Finally, fostamatinib in combination with other agents, including dexamethasone, bortezomib, and rituximab, showed enhanced activity. CONCLUSIONS: Taken together, these data support the translation of approaches targeting Syk with fostamatinib to the clinic for patients with relapsed and possibly even newly diagnosed WMG. Twit Text FOAVip Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy against Waldenström Macroglobulinemia ????Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=25748087 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25748087 #FOAvip English Wikipedia <ref>{{Cite pmid|25748087 }}</ref> Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy against Waldenström Macroglobulinemia #MMPMID25748087 Kuiatse I ; Baladandayuthapani V ; Lin HY ; Thomas SK ; Bjorklund CC ; Weber DM ; Wang M ; Shah JJ ; Zhang XD ; Jones RJ ; Ansell SM ; Yang G ; Treon SP ; Orlowski RZ Clin Cancer Res 2015[Jun]; 21 (11 ): 2538-45 PMID25748087 show ga PURPOSE: Waldenström macroglobulinemia (WMG) is a lymphoproliferative disorder characterized by good initial responses to standard therapeutics, but only a minority of patients achieve complete remissions, and most inevitably relapse, indicating a need for novel agents. B-cell receptor signaling has been linked to clonal evolution in WMG, and Spleen tyrosine kinase (Syk) is overexpressed in primary cells, suggesting that it could be a novel and rational target. EXPERIMENTAL DESIGN: We studied the impact of the Syk inhibitor fostamatinib on BCWM.1 and MWCL-1 WMG-derived cell lines both in vitro and in vivo, as well as on primary patient cells. RESULTS: In WMG-derived cell lines, fostamatinib induced a time- and dose-dependent reduction in viability, associated with activation of apoptosis. At the molecular level, fostamatinib reduced activation of Syk and Bruton's tyrosine kinase, and also downstream signaling through MAPK kinase (MEK), p44/42 MAPK, and protein kinase B/Akt. As a single agent, fostamatinib induced tumor growth delay in an in vivo model of WMG, and reduced viability of primary WMG cells, along with inhibition of p44/42 MAPK signaling. Finally, fostamatinib in combination with other agents, including dexamethasone, bortezomib, and rituximab, showed enhanced activity. CONCLUSIONS: Taken together, these data support the translation of approaches targeting Syk with fostamatinib to the clinic for patients with relapsed and possibly even newly diagnosed WMG. |Aminopyridines [MESH] |Apoptosis/drug effects [MESH] |B-Lymphocytes/drug effects/pathology [MESH] |Cell Cycle/drug effects [MESH] |Cell Line, Tumor [MESH] |Gene Expression Regulation, Neoplastic/drug effects [MESH] |Humans [MESH] |Intracellular Signaling Peptides and Proteins/*biosynthesis/genetics [MESH] |Morpholines [MESH] |Oxazines/*administration & dosage [MESH] |Protein-Tyrosine Kinases/*biosynthesis/genetics [MESH] |Pyridines/*administration & dosage [MESH] |Pyrimidines [MESH] |Signal Transduction/drug effects [MESH] |Syk Kinase [MESH]Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy a(epmc).pdf DeepDyve Pubget Overpricing