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10.18632/oncotarget.6316 http://scihub22266oqcxt.onion/10.18632/oncotarget.6316 C4791274!4791274 !26575169     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26575169 &cmd=llinks): Failed to open stream: HTTP request failed! 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Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma |pdf=|usr=}}{{26575169 }} gab.com Text Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26575169 #FOAvip B-cell receptor (BCR) and JAK/STAT pathways play critical roles in diffuse large B-cell lymphoma (DLBCL). Herein, we investigated the anti-lymphoma activity of cerdulatinib, a novel compound that dually targets SYK and JAK/STAT pathways. On a tissue microarray of 62 primary DLBCL tumors, 58% expressed either phosphorylated SYK or STAT3 or both. SYK and STAT3 are also phosphorylated in a panel of eleven DLBCL cell lines although ABC and GCB subtypes exhibited different JAK/STAT and BCR signaling profiles. In both ABC and GCB cell lines, cerdulatinib induced apoptosis that was associated with caspase-3 and PARP cleavage. The compound also blocked G1/S transition and caused cell cycle arrest, accompanied by inhibition of RB phosphorylation and down-regulation of cyclin E. Phosphorylation of BCR components and STAT3 was sensitive to cerdulatinib in both ABC and GCB cell lines under stimulated conditions. Importantly, JAK/STAT and BCR signaling can be blocked by cerdulatinib in primary GCB and non-GCB DLBCL tumor cells that were accompanied by cell death. Our work provides mechanistic insights into the actions of cerdulatinib, suggesting that the drug has a broad anti-tumor activity in both ABC and GCB DLBCL, at least in part by inhibiting SYK and JAK pathways. Twit Text FOAVip Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26575169 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26575169 #FOAvip English Wikipedia <ref>{{Cite pmid|26575169 }}</ref> Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma #MMPMID26575169 Ma J ; Xing W ; Coffey G ; Dresser K ; Lu K ; Guo A ; Raca G ; Pandey A ; Conley P ; Yu H ; Wang YL Oncotarget 2015[Dec]; 6 (41 ): 43881-96 PMID26575169 show ga B-cell receptor (BCR) and JAK/STAT pathways play critical roles in diffuse large B-cell lymphoma (DLBCL). Herein, we investigated the anti-lymphoma activity of cerdulatinib, a novel compound that dually targets SYK and JAK/STAT pathways. On a tissue microarray of 62 primary DLBCL tumors, 58% expressed either phosphorylated SYK or STAT3 or both. SYK and STAT3 are also phosphorylated in a panel of eleven DLBCL cell lines although ABC and GCB subtypes exhibited different JAK/STAT and BCR signaling profiles. In both ABC and GCB cell lines, cerdulatinib induced apoptosis that was associated with caspase-3 and PARP cleavage. The compound also blocked G1/S transition and caused cell cycle arrest, accompanied by inhibition of RB phosphorylation and down-regulation of cyclin E. Phosphorylation of BCR components and STAT3 was sensitive to cerdulatinib in both ABC and GCB cell lines under stimulated conditions. Importantly, JAK/STAT and BCR signaling can be blocked by cerdulatinib in primary GCB and non-GCB DLBCL tumor cells that were accompanied by cell death. Our work provides mechanistic insights into the actions of cerdulatinib, suggesting that the drug has a broad anti-tumor activity in both ABC and GCB DLBCL, at least in part by inhibiting SYK and JAK pathways. |Antineoplastic Agents/*pharmacology [MESH] |Cell Line, Tumor [MESH] |Cell Survival/drug effects [MESH] |Enzyme Inhibitors/pharmacology [MESH] |Flow Cytometry [MESH] |Humans [MESH] |Immunoblotting [MESH] |Immunohistochemistry [MESH] |Intracellular Signaling Peptides and Proteins/metabolism [MESH] |Janus Kinases/metabolism [MESH] |Lymphoma, Large B-Cell, Diffuse/*pathology [MESH] |Protein-Tyrosine Kinases/metabolism [MESH] |Pyrimidines/*pharmacology [MESH] |Signal Transduction/*drug effects [MESH] |Sulfones/*pharmacology [MESH] |Syk Kinase [MESH]Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tu(epmc).pdf DeepDyve Pubget Overpricing