We also replicated associations with rs4148737 in the ATP-binding cassette subfamily B member 1 (ABCB1) gene (discovery: HR = 2.96, 95% CI = 1.08-8.10, P = 0.034; replication: HR = 1.60, 95% CI = 1.05-2.44, P = 0.029), which we have previously found to be associated with poorer OS in pediatric osteosarcoma patients, and rs11188147 in cytochrome P450 family 2 subfamily C member 8 gene (CYP2C8) (discovery : HR = 2.49, 95% CI = 1.06-5.87, P = 0.037; replication: HR = 1.77, 95% CI = 1.06-2.96, P = 0.030), an enzyme involved in the oxidative metabolism of the ES chemotherapeutic agents cyclophosphamide and ifosfamide.
Overexpression of HER2 was present in 32% of OS and 16% of ES and was significantly associated with the increased expression of P-glycoprotein, a surface molecule responsible for multidrug resistance.
Given the poor outcomes of many patients with Ewing sarcoma and the well-established ARA-C safety profile, clinical trials testing ARA-C are warranted.
A four-step methodology was designed.First, the 2007-2015 ACS-NSQIP database was examined to identify all ES patients using the "emergent" variable and CPT codes for "digestive system".
A four-step methodology was designed.First, the 2007-2015 ACS-NSQIP database was examined to identify all ES patients using the "emergent" variable and CPT codes for "digestive system".
This morphology, along with a polyphenotypic immunoprofile, including the expression of vimentin/CD99/cytokeratins/alpha-smooth muscle actin and vimentin/CD99/S-100 protein in case 1 and case 2, respectively, suggested the possibility of Ewing sarcoma (EWS)/PNET.
Herein, we show that ADAMTS4 mRNA was expressed in all primary EWS samples and all EWS-derived cell lines examined, while its expression was detected only in small subpopulations of other solid tumors.
Since ES cells are susceptible to an increased oxidative stress to reduce cell viability, here we demonstrate that administration of β3-ARs antagonist, SR59230A, improves the apigenin effect on cell death, identifying β3-AR as a potential discriminating factor that could address the use of apigenin in ES.
Using a combination of AGO2 pull-down experiments by PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) and of RNAseq upon miRNA depletion by ectopic sponge expression, we aimed to identify the targetome of miR-17-92 in Ewing sarcoma.
Taken together, our results suggest that IGF1R and the downstream PI3K/AKT/mTOR kinase cascade mediate intrinsic resistance to BET inhibitors in Ewing sarcoma.
Molecular examination reveals that the action of ezrin in Ewing's sarcoma is dependent on the AKT/mTOR signal transduction cascade, but not MAP Kinase.
Repression of autocrine IGF1 by BET inhibitors led to significant inhibition of the IGF1R/AKT pathway critical to Ewing sarcoma cell proliferation and survival.
Normal ALK protein expression is restricted to the nervous systems of adult mammals, but the aberrant expression of ALK has been observed in a variety of pediatric cancers, including glioma and Ewing sarcoma.
Cell lines established from solid tumors of ectodermal origin, including melanoma and breast carcinoma, exhibited widespread mRNA expression of the ALK receptor at a broad range (53/64), an association which was found to be strongest in cell lines derived from neuroblastoma (6/6), glioblastoma (8/8) as well as in cell lines established from Ewing sarcoma (4/4) and retinoblastomas (2/2).