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10.4161/cbt.29523 http://scihub22266oqcxt.onion/10.4161/cbt.29523 C4128863!4128863 !24921944     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24921944 &cmd=llinks): Failed to open stream: HTTP request failed! 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A human monoclonal antibody targeting the stem cell factor receptor (c-Kit) blocks tumor cell signaling and inhibits tumor growth |pdf=|usr=}}{{24921944 }} gab.com Text A human monoclonal antibody targeting the stem cell factor receptor (c-Kit) blocks tumor cell signaling and inhibits tumor growth JO: Cancer Biol Ther http://www.kidney.de/pget.php?&tw=1&pmid=24921944 #FOAvip Stem cell factor receptor (c-Kit) exerts multiple biological effects on target cells upon binding its ligand stem cell factor (SCF). Aberrant activation of c-Kit results in dysregulated signaling and is implicated in the pathogenesis of numerous cancers. The development of more specific and effective c-Kit therapies is warranted given its essential role in tumorigenesis. In this study, we describe the biological properties of CK6, a fully human IgG1 monoclonal antibody against the extracellular region of human c-Kit. CK6 specifically binds c-Kit receptor with high affinity (EC 50 = 0.06 nM) and strongly blocks its interaction with SCF (IC 50 = 0.41 nM) in solid phase assays. Flow cytometry shows CK6 binding to c-Kit on the cell surface of human small cell lung carcinoma (SCLC), melanoma, and leukemia tumor cell lines. Furthermore, exposure to CK6 inhibits SCF stimulation of c-Kit tyrosine kinase activity and downstream signaling pathways such as mitogen-activated protein kinase (MAPK) and protein kinase B (AKT), in addition to reducing tumor cell line growth in vitro. CK6 treatment significantly decreases human xenograft tumor growth in NCI-H526 SCLC (T/C% = 57) and Malme-3M melanoma (T/C% = 58) models in vivo. The combination of CK6 with standard of care chemotherapy agents, cisplatin and etoposide for SCLC or dacarbazine for melanoma, more potently reduces tumor growth (SCLC T/C% = 24, melanoma T/C% = 38) compared with CK6 or chemotherapy alone. In summary, our results demonstrate that CK6 is a c-Kit antagonist antibody with tumor growth neutralizing properties and are highly suggestive of potential therapeutic application in treating human malignancies harboring c-Kit receptor. Twit Text FOAVip A human monoclonal antibody targeting the stem cell factor receptor (c-Kit) blocks tumor cell signaling and inhibits tumor growth ????Cancer Biol Ther http://www.kidney.de/pget.php?&tw=1&pmid=24921944 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24921944 #FOAvip English Wikipedia <ref>{{Cite pmid|24921944 }}</ref> A human monoclonal antibody targeting the stem cell factor receptor (c-Kit) blocks tumor cell signaling and inhibits tumor growth #MMPMID24921944 Lebron MB ; Brennan L ; Damoci CB ; Prewett MC ; O'Mahony M ; Duignan IJ ; Credille KM ; DeLigio JT ; Starodubtseva M ; Amatulli M ; Zhang Y ; Schwartz KD ; Burtrum D ; Balderes P ; Persaud K ; Surguladze D ; Loizos N ; Paz K ; Kotanides H Cancer Biol Ther 2014[Sep]; 15 (9 ): 1208-18 PMID24921944 show ga Stem cell factor receptor (c-Kit) exerts multiple biological effects on target cells upon binding its ligand stem cell factor (SCF). Aberrant activation of c-Kit results in dysregulated signaling and is implicated in the pathogenesis of numerous cancers. The development of more specific and effective c-Kit therapies is warranted given its essential role in tumorigenesis. In this study, we describe the biological properties of CK6, a fully human IgG1 monoclonal antibody against the extracellular region of human c-Kit. CK6 specifically binds c-Kit receptor with high affinity (EC 50 = 0.06 nM) and strongly blocks its interaction with SCF (IC 50 = 0.41 nM) in solid phase assays. Flow cytometry shows CK6 binding to c-Kit on the cell surface of human small cell lung carcinoma (SCLC), melanoma, and leukemia tumor cell lines. Furthermore, exposure to CK6 inhibits SCF stimulation of c-Kit tyrosine kinase activity and downstream signaling pathways such as mitogen-activated protein kinase (MAPK) and protein kinase B (AKT), in addition to reducing tumor cell line growth in vitro. CK6 treatment significantly decreases human xenograft tumor growth in NCI-H526 SCLC (T/C% = 57) and Malme-3M melanoma (T/C% = 58) models in vivo. The combination of CK6 with standard of care chemotherapy agents, cisplatin and etoposide for SCLC or dacarbazine for melanoma, more potently reduces tumor growth (SCLC T/C% = 24, melanoma T/C% = 38) compared with CK6 or chemotherapy alone. In summary, our results demonstrate that CK6 is a c-Kit antagonist antibody with tumor growth neutralizing properties and are highly suggestive of potential therapeutic application in treating human malignancies harboring c-Kit receptor. |Animals [MESH] |Antibodies, Monoclonal/administration & dosage/pharmacology/*therapeutic use [MESH] |Antineoplastic Combined Chemotherapy Protocols/therapeutic use [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/drug effects [MESH] |Cisplatin/administration & dosage [MESH] |Dacarbazine/administration & dosage [MESH] |Etoposide/administration & dosage [MESH] |Female [MESH] |Heterografts [MESH] |Humans [MESH] |Immunoglobulin G/administration & dosage/pharmacology/*therapeutic use [MESH] |Lung Neoplasms/*drug therapy/metabolism/pathology [MESH] |Melanoma, Experimental/*drug therapy/metabolism/pathology [MESH] |Mice, Nude [MESH] |Mitogen-Activated Protein Kinase Kinases/metabolism [MESH] |Proto-Oncogene Proteins c-akt/metabolism [MESH] |Proto-Oncogene Proteins c-kit/genetics/immunology/*metabolism [MESH] |Signal Transduction [MESH]A human monoclonal antibody targeting the stem cell factor receptor (c(epmc).pdf DeepDyve Pubget Overpricing