Emerging evidence clearly indicates that EZH2 plays a crucial role in tumor angiogenesis. However, the role of EZH2 in angiogenesis is still unknown in nasopharyngeal carcinoma (NPC). We here showed that the elevated EZH2 level was closely associated with an aggressive and poor prognostic phenotype, and was positively correlated with microvessel density (MVD) in NPC tissues. Functional studies showed that EZH2 upregulation promoted cell proliferation, migration and tubule formation of endothelial cells, and knockdown of EZH2 suppressed tumor growth, metastasis and angiogenesis in vivo. Mechanistic investigations revealed that EZH2 inhibited miR-1 transcription via promoter binding activity, leading to enhanced expression of Endothelin-1 (ET-1) which is suppressed by miR-1 targeting of ET-1 3′UTR. Furthermore, knockdown of EZH2 or overexpression of miR-1 exerted anti-angiogenic effect on NPC cells. More importantly, the neutralizing antibody against ET-1 significantly abrogated the pro-angiogenic effect of EZH2, and forced expression of ET-1 rescued the anti-angiogenic effect induced by EZH2 knockdown. In clinical specimens, ET-1 was widely overexpressed and associated with clinical stage and MVD. Taken together, our results identify a novel signaling pathway involved in NPC angiogenesis, and also suggest that EZH2-miR-1-ET-1 axis represents multiple potential therapeutic targets for NPC.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Background Although the National Comprehensive Cancer Network (NCCN) Guidelines recommend CCRT+AC and IC + CCRT as level 2A evidence for treatment of the locoregionally advanced NPC (II-IVa), IC + CCRT+AC could also be an alternative but it is seldom used because of the low completion rates. This article aimed to compare the effectiveness of the three radiotherapy regimens using a large-scale retrospective study. Methods This retrospective single center analysis enrolled 1812 diagnosed NPC patients at Nanfang Hospital from January 2005 to December 2015 and only 729 patients met the inclusion criteria and were analyzed. Patients without distant metastasis, age of 18–70 years, Karnofsky scores of at least 70,stage III-IVb, and adequate adequate bone marrow, liver and renal function. Were enrolled. Adverse events and other categorical variables were compared by Pearson chi-square test or Fishier exact test. Time-to-event data were described with the Kaplan-Meier curves, time-to-event intervals compared with the log-rank test. We did multivariable analyses with the Cox proportional hazards model to test the independent signifi cance of diff erent factors. Cox proportional hazards model was used to estimate the β regression coeffi cient, p value, and hazard ratio and its 95% CI for each of the selected risk predictors. Results The median follow-up time was 47 months. Kaplan-Meier analyses revealed no significant differences among three groups in 3-year failure-free survival (FFS, P = 0.225), 3-year overall survival (OS, P = 0.992), 3-year locoregional failure-free survival (LFFS, P = 0.549), and 3-year distant failure-free survival (DFFS, P = 0.174). Stratified survival analysis based on the risk scoring model revealed no differences in FFS, OS, LFFS, and DFFS between IC + CCRT and CCRT+AC groups for low-risk patients, however, the 3-year OS (88.3% vs. 77.6%, P = 0.049) and 3-year DFFS (84.0% vs.66.8%, P = 0.032) were respectively significantly better in IC + CCRT group compared with CCRT+AC group for high-risk patients. Conclusions Compared with CCRT+AC, IC + CCRT lowers distant metastasis rate and improves OS among patients with locally advanced NPC in high risk group.
Supported by the World Bank, the Integrated Information System for Natural Disaster Mitigation (ISNDM), including the operational service system and network telecommunication system, has been in development for three years in the Center of Disaster Reduction, Chinese Academy of Sciences, based on the platform of the GIS software Arcview. It has five main modules: disaster background information, socioeconomic information, disaster-induced factors database, disaster scenarios database, and disaster assessment. ISNDM has several significant functions, which include information collection, information processing, data storage, and information distribution. It is a simple but comprehensive demonstration system for our national center for natural disaster reduction.
Background: This study was performed to investigate whether long-term monitoring of dynamic changes in plasma Epstein-Barr virus (EBV) DNA could improve prognosis prediction of nasopharyngeal carcinoma (NPC).Methods: 1077 non-metastatic NPC patients were recruited to retrospectively analyze the prognostic value of plasma EBV DNA load pre-treatment and 3, 12, 24, and 36 months post-treatment. We also examined the prognostic value of dynamic changes in plasma EBV DNA at various time points.Results: Patients with plasma EBV DNA load above optimal pre- and post-treatment cut-offs had significantly worse five-year progression-free survival, distant metastasis-free survival, locoregional relapse-free survival, and overall survival(OS) at all time points, excluding only OS at 36 months post-treatment due to limited mortalities. Patients with persistently undetectable plasma EBV DNA at the first four time points had the best prognosis, followed by those with positive detection pre-treatment and consistently negative detection post-treatment, those with negative detection pre-treatment and positive detection at one time point post-treatment, and those with positive detection pre-treatment and at one time point post-treatment, whereas patients with positive detection at ≥2 time points post-treatment had the worst prognosis. Cox proportional hazard models identified the dynamic change pattern as an independent prognostic factor, and ROC curve analysis demonstrated that the dynamic change at four time point was more valuable than any single time point for predicting disease progression, distant metastasis, locoregional relapse, and mortality.Conclusions: Dynamic changes in plasma EBV DNA pre- and post-treatment could predict the long-term survival outcome and provide accurate risk stratification in NPC.
Purpose: To study the efficacy and safety of post-auricular injection of methylprednisolone sodium succinate plus lidocaine in the treatment of acute tinnitus, and its effect on sleep quality.Methods: Eighty acute tinnitus patients admitted to Nanfang Hospital, Southern Medical University, Guangzhou, China from January 2020 to June 2021, served as subjects for this retrospective analysis. The patients were equally assigned to a reference group given postauricular injection of lidocaine, and a research group treated with post-auricular injection of methylprednisolone sodium succinate in combination with lidocaine. Treatment efficacy values in the two groups of patients were determined and compared.Results: Total treatment effectiveness values in patients in the research group after one course of treatment, and at three months post-treatment, were significantly higher than the corresponding values in the reference group (p < 0.05). After treatment, the two groups had markedly improved Tinnitus Handicap Inventory (THI) scores, although patients in the research group had lower scores than those in reference group (p < 0.05). There were significant decreases in post-treatment pure tone threshold and Pittsburgh sleep quality index (PSQI) in the two groups of patients, with lower values in the research group than in the reference group (p < 0.05). There were no obvious adverse drug reactions during treatment and during 3-month follow-up period.Conclusion: Post-auricular injection of methylprednisolone sodium succinate and lidocaine effectively improved the clinical efficacy and the sleep quality of acute tinnitus patients. It is a simple and highly safe operation which merits clinical application.
Background Vascular mimicry is emerging as a potential target for anti-tumorigenesis.It involves the formation of microvascular channels composed of tumor cells. However, the mechanism of how tumor cells build into microvascular channels is not clear.The existence of a relationship between EMT and VM has been reported in the literature but the exact regulatory mechanism is unclear. Whether EMT regulates VM formation and its specific mechanism need to be further verified in NPC Materials and Methods We detected the relationship between EMT indicators and VM by immunohistochemical experiments. Also, the relationship between EMT indexes and VM indexes and clinical staging was analyzed. Cellular assays and immunoprotein blotting assays were used to detect EMT and VM changes in cells after addition of EGFR inhibitors. VM and EMT indices were examined after EGFR-targeted drug treatment in a subcutaneous tumorigenesis assay in nude mice. Conclusion EGFR-regulated EMT is a driver of vasculogenic mimicry in Nasopharyngeal Carcinoma.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.