Epidermal-Growth-Factor-Receptor ELISA Kit

Brain metastasis (BM) is associated with poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutation reportedly enhances the development of BM. However, the exact mechanism of how EGFR-mutant NSCLC contributes to BM remains unknown. Herein, we found the protein WNT5A, was significantly downregulated in BM tissues and EGFR-mutant samples. In addition, the overexpression of WNT5A inhibited the growth, migration, and invasion of EGFR-mutant cells in vitro and retarded tumor growth and metastasis in vivo compared with the EGFR wide-type cells. We demonstrated a molecular mechanism whereby WNT5A be negatively regulated by transcription factor E2F1, and ERK1/2 inhibitor (U0126) suppressed E2F1's regulation of WNT5A expression in EGFR-mutant cells. Furthermore, WNT5A inhibited beta-catenin activity and the transcriptional levels of its downstream genes in cancer progression. Our research revealed the role of WNT5A in NSCLC BM with EGFR mutation, and proved that E2F1-mediated repression of WNT5A was dependent on the ERK1/2 pathway, supporting the notion that targeting the ERK1/2-E2F1-WNT5A pathway could be an effective strategy for treating BM in EGFR-mutant NSCLC.

Background Elevated pre-procedural high-sensitivity troponin T (hs-TnT) levels predict adverse outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). It is unknown whether elevated troponin levels still provide prognostic information during follow-up after successful TAVR. We evaluated the long-term implications of elevated hs-TnT levels found at 1-year post-TAVR. Methods and results The study included 349 patients who underwent TAVR for severe AS from 2010-2019 and for whom 1-year hs-TnT levels were available. Any required percutaneous coronary interventions were performed > 1 week before TAVR. The primary endpoint was survival time starting at 1-year post-TAVR. Optimal hs-TnT cutoff for stratifying risk, identified by ROC analysis, was 39.4 pg/mL. 292 patients had hs-TnT < 39.4 pg/mL (median 18.3 pg/mL) and 57 had hs-TnT >= 39.4 pg/mL (median 51.2 pg/mL). The high hs-TnT group had a higher median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, greater left ventricular (LV) mass, higher prevalence of severe diastolic dysfunction, LV ejection fraction < 35%, severe renal dysfunction, and more men compared with the low hs-TnT group. All-cause mortality during follow-up after TAVR was significantly higher among patients who had hs-TnT >= 39.4 pg/mL compared with those who did not (mortality rate at 2 years post-TAVR: 12.3% vs. 4.1%, p = 0.010). Multivariate analysis identified 1-year hs-TnT >= 39.4 pg/mL (hazard ratio 2.93, 95% CI 1.91-4.49, p < 0.001), NT-proBNP level > 300 pg/mL, male sex, an eGFR < 60 mL/min/1.73 m(2) and chronic obstructive pulmonary disease as independent risk factors for long-term mortality after TAVR. Conclusions Elevated hs-TnT concentrations at 1-year after TAVR were associated with a higher long-term mortality. [GRAPHICS] .