Epstein-Barr virus (EBV)-

BackgroundTo explore the upstream signal transduction mechanisms responsible for the imbalanced expression of glucocorticoid receptor (GR) isoforms in chronic rhinosinusitis (CRS) mucosa.MethodsAn in vitro model of Glucocorticoid resistance was established by inducing nasal polyp tissue with IL-1β. Changes in the protein and mRNA expression of GRα, GRβ and the key enzymes in the p38 MAPK and JNK signal pathways were measured, respectively, before and after being induced with different doses of IL-1β and specific inhibitors of p38 MAPK, JNK, ERK, PI3K and PKC. The Glucocorticoid sensitivity was measured using in vitro Glucocorticoid binding assay. Analysis of variance (ANOVA) was used to analyze the data.ResultsThe mRNA and protein expression levels of GRα, GRβ and key enzymes of the p38 MAPK and JNK pathways increased both in time- and concentration-dependent manners in IL-1β-induced nasal polyp tissue. The expression of GRβ increased more significantly than that of GRα, and the GRα/GRβ ratio decreased in time- and concentration-dependent manners. Statistically significant differences were found in the GRα/GRβ ratio and the mRNA expression of phospho-p38 MAPK and phospho-JNK between the IL-1β-induced groups and the control groups (P < 0.05). Either a specific inhibitor of the p38 MAPK pathway or a specific inhibitor of the JNK pathway increased the GRα/GRβ ratio and the Glucocorticoid affinity. None of the specific inhibitors of ERK, PI3K or PKC had any influence on the expression of GR isoforms.ConclusionOur results demonstrated that the imbalanced expression of GR isoforms in nasal polyp tissue induced by IL-1β in vitro is mediated through the p38 MAPK and JNK signal pathways.

BackgroundLocal residual and recurrent nasopharyngeal carcinoma (NPC) generally shows treatment failure after standard radiotherapy with or without concurrent chemotherapy. Whether endoscopic nasopharyngectomy might provide an additional therapeutic advantage remains controversial. Therefore, we retrospectively compared the clinical prognoses of patients with residual or recurrent NPC treated with endoscopic nasopharyngectomy combined with chemoradiotherapy (CRT) with those of patients treated with CRT alone.Methods and MaterialsA total of sixty-two patients with local residual or recurrent NPC were studied retrospectively: 36 patients received endoscopic nasopharyngectomy combined with CRT, whereas 26 patients who refused the surgery or had surgical contraindications received CRT alone. Serum Epstein-Barr virus (EBV) DNA levels were measured pre- and post-treatment. The differences in prognosis between the two treatment regimens and the pre- and post-treatment changes in EBV-DNA levels were analyzed.ResultsThe median follow-up time was 31 months, with a 3-year overall survival (OS) of 51.40% and a 3-year disease-free survival (DFS) of 46.86%. The surgery + CRT group had a better OS than the CRT alone group did (χ2 = 4.054, P = 0.044). The pretreatment EBV-DNA levels showed a positive correlation with the clinical staging of recurrent NPC (χ2 = 11.674, P = 0.009). Patients with negative pretreatment serum EBV-DNA levels showed a superior OS to those of patients who tested positive for EBV-DNA (>0 copy/mL) (χ2 = 9.833, P = 0.002). The post-treatment EBV-DNA levels, compared with the pretreatment levels, decreased significantly in the surgery + CRT group (Z =  − 3.484, P = 0.000). In contrast, the EBV-DNA levels after CRT alone did not decrease significantly (Z =  − 1.956, P = 0.051). Multivariate analysis indicated that local staging, pretreatment EBV-DNA load, and the treatment method were independent risk factors for OS. Subgroup analysis indicated that the patients who tested negative for EBV-DNA before the treatment and those who received surgery + CRT showed a better OS than those who received CRT alone.ConclusionsThe pretreatment serum EBV-DNA level was associated with disease prognosis. The combination therapy preceded by surgery can effectively decrease the copy number of EBV-DNA. Patients with local intermediate- and late-stage NPC, especially those negative for EBV-DNA, may consider opting for surgery followed by post-operative adjuvant radiotherapy or chemotherapy.

Background Nasopharyngeal carcinoma (NPC) is one of the most common cancers. To investigate the gene mutation profile of NPC patients, we performed whole exome sequencing (WES) in tumor cells, peripheral blood cells, and circulating tumor cells (CTCs) of primitive and metastatic NPC patients, and explored its clinical significance. Methods Primitive tumor cells, white blood cells, and CTCs of patients were collected and hybridized with probes targeting whole exons. Mutational signatures, signaling pathways, and cancer associated genes from CTCs cells of two primitive and two metastatic patients were analyzed using gene ontology (GO) method. Results The mutational landscape of four primitive tumors showed that there were more MSH2 alterations in more non-silent mutation number patients Additionally, BAP1 gene mutation only occurred in metastatic patients. The most frequently mutated genes among the primitive tumor and CTC samples were CFAP74, MOB3C , PDE4DIP , IGFN1 , CYFIP2 , NOP16 , SLC22A1 , ZNF117 , and SSPO . Interestingly, only PMS1 , BRIP1 , DEE , OR2T12 , CPN2 , MLXIPL , BAIAP3 , IGSF3 , SIN3B , and ZNF880 alterations occurred in primary tumors of metastatic patients. Primitive and metastatic NPC had significantly distinct mutational signatures. GO analysis revealed that each patient had his own mutational signaling pathways. Non-silent single nucleotide variations (non-silent SNVs) and insertion-deletion mutations (INDELs) in CTCs were more dramatic than in primitive tumor cells. Conclusions These changes are strongly relevant to their clinical characteristics and therapeutic strategy.

BackgroundThis study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients.MethodsThe positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated.ResultsA total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = − 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode.ConclusionNBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects.