Background:Epithelial–mesenchymal transition (EMT) is a crucial programme in cancer metastasis. Epidermal growth factor (EGF) is a key inducer of EMT, and Ezrin has an important role in this process. However, how Ezrin is activated and whether it mediates EGF-induced EMT in tongue squamous cell carcinomas (TSCCs) through activating NF-κB remains obscure.Methods:We used two TSCC cell lines as a cell model to study invasion and EMT in vitro, and used nude mice xenografts model to evaluate metastasis of TSCC cells. Finally, we evaluated the level of pEzrin Tyr353, nuclear p65 and EMT markers in TSCC clinical samples.Results:Ezrin Tyr353 was phosphorylated through Akt (but not ERK1/2, ROCK1) pathway, and lead to the activation of NF-κB in EGF-treated TSCC cells. Akt and NF-κB inhibitors blocked EGF-induced EMT, and suppressed invasion and migration of TSCC cells. In vivo, silencing Ezrin significantly suppressed EGF-enhanced metastasis of TSCC xenografts. Finally, high levels of expression of pEzrin Tyr353, nuclear p65, vimentin and low level of expression of E-cadherin were correlated with cancer metastasis and poor patient prognosis.Conclusion:Our data suggest that Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis inTSCC, and Ezrin may serve as a therapeutic target to reverse EMT in tongue cancers and prevent TSCC progression.
Tooth extraction is one of the most common causes of dental anxiety and pain, leading to the elevation of blood pressure (BP) and heart rate (HR). Such effects may be exaggerated and cause life-threatening accidents in patients with hypertension. Therefore, the pain and anxiety management of these patients is imperative. Virtual reality (VR) has been demonstrated to be a distraction method to relieve anxiety and pain in clinical operations. Thus, we hypothesized that VR can control the elevation of BP and HR in patients with hypertension. In this study, 96 eligible patients with controlled hypertension who needed tooth extraction were randomized to the VR or standard care group by stratified randomization of anxiety grade and gender. Their BP and HR were dynamically monitored. The corresponding systolic and diastolic BP and HR values were selected when systolic BP was at the highest point of the process. BP was converted into mean arterial pressure (MAP) for comparison per the following formula: MAP = (systolic BP + 2 × diastolic BP)/3. Statistical analyses were by intention to treat and conducted in SPSS. Nonparametric rank sum tests were used to compare the difference of ΔMAP and ΔHR between the VR and standard care groups. Multivariate linear regression was applied to evaluate the effect of VR on ΔMAP and ΔHR. The results showed that the VR technique significantly decreased the elevation of MAP ( P < 0.001) and HR ( P < 0.001), and this effect was found even after adjusting for baseline characteristics and additional surgical procedures (ΔMAP, P < 0.001, R2 = 0.276; ΔHR, P < 0.001, R2 = 0.152). VR did not increase the incidence of adverse events ( P = 0.677). In conclusion, the VR technique was effective in controlling BP and HR within an acceptable range and can help manage BP and HR during tooth extraction for patients with hypertension (Chinese Clinical Trial Registry: ChiCTR2100042132).
PurposeTo investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC).MethodsWe searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766.ResultsThe results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63–0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88–0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98–1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H.ConclusionsCompared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.Electronic supplementary materialThe online version of this article (10.1007/s10549-017-4592-y) contains supplementary material, which is available to authorized users.
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