jte-013 has been researched along with Bone-Neoplasms* in 1 studies
1 other study(ies) available for jte-013 and Bone-Neoplasms
Article | Year |
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Modulating sphingosine-1-phosphate receptors to improve chemotherapy efficacy against Ewing sarcoma.
Tumor vasculature is innately dysfunctional. Poorly functional tumor vessels inefficiently deliver chemotherapy to tumor cells; vessel hyper-permeability promotes chemotherapy delivery primarily to a tumor's periphery. Here, we identify a method for enhancing chemotherapy efficacy in Ewing sarcoma (ES) in mice by modulating tumor vessel permeability. Vessel permeability is partially controlled by the G protein-coupled Sphinosine-1-phosphate receptors 1 and 2 (S1PR1 and S1PR2) on endothelial cells. S1PR1 promotes endothelial cell junction integrity while S1PR2 destabilizes it. We hypothesize that an imbalance of S1PR1:S1PR2 is partially responsible for the dysfunctional vascular phenotype characteristic of ES and that by altering the balance in favor of S1PR1, ES vessel hyper-permeability can be reversed. In our study, we demonstrate that pharmacologic activation of S1PR1 by SEW2871 or inhibition of S1PR2 by JTE-013 caused more organized, mature and functional tumor vessels. Importantly, S1PR1 activation or S1PR2 inhibition improved antitumor efficacy. Our data suggests that pharmacologic targeting of S1PR1 and S1PR2 may be a useful adjuvant to standard chemotherapy for ES patients. Topics: Animals; Antibiotics, Antineoplastic; Bone Neoplasms; Capillary Permeability; Cell Line, Tumor; Doxorubicin; Endothelial Cells; Humans; Mice, Nude; Oxadiazoles; Pyrazoles; Pyridines; Sarcoma, Ewing; Sphingosine 1 Phosphate Receptor Modulators; Sphingosine-1-Phosphate Receptors; Thiophenes; Treatment Outcome; Xenograft Model Antitumor Assays | 2020 |