A study on the value of narrow-band imaging (NBI) for the general investigation of a high-risk population of nasopharyngeal carcinoma (NPC).

BACKGROUND: This 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. METHODS: The 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. RESULTS: A 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. CONCLUSION: NBI 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.

Influence of endoscopic sinus surgery on the quality of life of patients with early nasopharyngeal carcinoma and the analysis of prognosis-related factors.

The aim of this study is investigate the influence of endoscopic sinus surgery on the quality of life and prognosis of patients with early nasopharyngeal carcinoma. Patients initially diagnosed with early nasopharyngeal carcinoma and received surgical treatment were matched with nasopharyngeal carcinoma patients who received chemoradiotherapy at a ratio of 1:1, according to the following seven factors: gender, age, T staging, N staging, clinical staging, radiotherapy options, and chemotherapy options. Patients in the surgery group received endoscopic sinus surgery plus chemoradiotherapy, while subjects in the control group received chemoradiotherapy. The quality of life of patients before and after treatment was evaluated based on the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck) and QLQ-H&N35 (Head and Neck Cancer Specific Module) questionnaires. In addition, overall survival and disease-free survival were compared between these two groups. The results showed overall survival was superior in the surgery group compared with the control group ( p = 0.007). However, the difference in disease-free survival between these two groups was not statistically significant ( p = 0.128). Furthermore, subgroup analysis revealed that for N0 patients, the effect of surgery combined with chemoradiotherapy on overall survival was superior to that of chemoradiotherapy ( p = 0.048); while for N1 patients, the difference in overall survival between these two groups was not statistically significant ( p = 0.065). For early nasopharyngeal carcinoma patients without lymph node metastasis, overall survival and disease-free survival in T1 patients were superior to those in T2 patients (χ2 = 4.403, p = 0.036; χ2 = 4.542, p = 0.033). At the end of treatment, the pain score was found to be significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.027). At 3 months and 1 year after treatment, dry mouth scores were significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.002, p = 0.026). These results demonstrated that the curative effect of surgery combined with chemoradiotherapy in the treatment of nasopharyngeal carcinoma was satisfactory and was particularly suitable for N0 patients.

Distribution and clinical significance of circulating tumor cells in nasopharyngeal carcinoma.

OBJECTIVE: Nasopharyngeal carcinoma is one of the leading malignancies with obscure etiology. Circulating tumor cells have been showed to intimately correlate with characteristics in different kinds of cancer. But links between circulating tumor cells and nasopharyngeal carcinoma were still lacking. Therefore, we explored circulating tumor cells' distribution in nasopharyngeal carcinoma and their possible associations with nasopharyngeal carcinoma. METHODS: Firstly, we found that the positive ratio of circulating tumor cells is extremely high in four stages of nasopharyngeal carcinoma. Meanwhile, positive ratios of mesenchymal circulating tumor cells were higher in early stages of nasopharyngeal carcinoma. Apart from epithelial circulating tumor cells, total, hybrid and mesenchymal circulating tumor cells were correlated with nasopharyngeal carcinoma clinical stage. RESULTS: Our results showed that hybrid and mesenchymal circulating tumor cells were associated with nasopharyngeal carcinoma metastasis (both distant and lymph node) and smoking. Meanwhile, hybrid circulating tumor cells expressed the highest Epstein-Barr virus proteins and deoxyribonucleic acid in three types of circulating tumor cells. Moreover, we found that Epstein-Barr virus proteins viral-caspid antigen-immunoglobulin A (VCA/IgA) and early antigen-immunoglobulin A (EA/IgA), but not Epstein-Barr virus-deoxyribonucleic acid, had a closed association with nasopharyngeal carcinoma metastasis. However, Epstein-Barr virus hallmarks failed to associate with other nasopharyngeal carcinoma characteristics. Furthermore, we confirmed that matrix metalloproteinase 9 existed in circulating tumor cells and expressed most in mesenchymal circulating tumor cells. In addition, matrix metalloproteinase 9-expressed extent in hybrid circulating tumor cells is somewhat different from epithelial and mesenchymal circulating tumor cells in matrix metalloproteinase 9-positive circulating tumor cells. Nevertheless, matrix metalloproteinase 9 had no relationship with other nasopharyngeal carcinoma characteristics. Finally, our results showed that circulating tumor cells were decreased in patients after therapies. CONCLUSION: Taken together, circulating tumor cells were tightly correlated with nasopharyngeal carcinoma characteristics. In addition, Epstein-Barr virus was associated with nasopharyngeal carcinoma metastasis. Of note, decreased circulating tumor cells indicated a favorable curative effect in nasopharyngeal carcinoma patients.

The Safety and Immunological Effects of rAd5-EBV-LMP2 Vaccine in Nasopharyngeal Carcinoma Patients: A Phase I Clinical Trial and Two-Year Follow-Up.

Epstein-Barr virus (EBV)-encoded latent membrane protein 2 (LMP2) promotes nasopharyngeal carcinoma (NPC) progression. Previously, we reported that the dendritic cells (DCs) transfected with EBV-LMP2 recombinant serotype 5 adenoviruses (rAd5) induced anti-tumor effect by eliciting cytotoxic T lymphocytes (CTLs)-mediated immune response in vitro and the adenoviral vaccine of EBV-LMP2 (rAd5-EBV-LMP2) stimulated antigen-specific cellular immunity in mice. However, the safety and immunological effect of rAd5-EBV-LMP2 vaccine in human still remained unknown. Here we conducted a single-center, non-randomized, open-label, single-arm phase I clinical trial to clarify this unsolved issue. A total of 24 patients with regional advanced NPC were sequentially enrolled into three dose level groups (2×10(9), 2×10(10), 2×10(11) vp). The rAd5-EBV-LMP2 vaccines were intramuscularly injected for four times within 28 d (D0, D7, D14, D28). Blood samples were harvested immediately before every vaccination, one week and one month after the last vaccination (D0, D7, D14, D28, D35, D58). All the vaccine inoculation-related toxicities presented as grade I/II adverse events. The most frequent systemic adverse reactions were fatigue (33.0%, 8/24), myalgia (29.2%, 7/24) and cough (29.2%, 7/24), while the most common regional adverse reaction was tenderness in the inoculation site (54.2%, 13/24). In addition, proportion of CD(3+)CD(4+) cells in peripheral blood was significantly increased in the high dose group (2×10(11) vp). The rAd5-EBV-LMP2 vaccine was generally well-tolerated and the high dose (2×10(11) vp) is recommended to be adopted in phase II studies. The long-term outcome of rAd5-EBV-LMP2 vaccine inoculation is required to be determined in following placebo-controlled trials.

Association between the V Leiden G1691A mutation and sudden sensorineural hearing loss in Italian population: a meta-analysis.

Epidemiological studies have reported inconsistent findings on the association between the V Leiden G1691A mutation and sudden sensorineural hearing loss (SSNHL) in Italian population. The aim of this meta-analysis was to clarify this association. PubMed, Embase, and the China National Knowledge Infrastructure (CNKI) were searched up to April 1, 2015. We used STATA12.0 to calculate summary odds ratios (ORs) with 95 % confidence intervals (CIs). Four studies including 958 patients were identified. Pooled data showed no significant association between V Leiden G1691A mutation and risk of SSNHL in Italian population: A vs. G (OR = 1.660, 95 % CI 0.428-6.446, P OR = 0.464) and AG vs. GG (OR = 1.680, 95 % CI 0.422-6.688, P OR = 0.462). The present meta-analysis suggests that V Leiden G1691A mutation is not significantly associated with increased risk of SSNHL disease in Italian population. Further large and well-designed studies are needed to confirm this association.

Vitamin C inhibits NLRP3 inflammasome activation and delays the development of age-related hearing loss in male C57BL/6 mice.

The efficacy of vitamin C in age-related hearing loss, i.e., presbycusis, remains debatable. On a separate note, inflammation induced by the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is involved in the progression of presbycusis. In this study, we investigated the effect of vitamin C on male C57BL/6 mice's presbycusis and NLRP3 inflammasome. The results showed that vitamin C treatment improved hearing, reduced the production of inflammatory factors, inhibited NLRP3 inflammasome activation, and decreased cytosolic mitochondrial DNA (mtDNA) in the C57BL/6 mouse cochlea, inferior colliculus, and auditory cortex. According to this study, vitamin C protects auditory function in male C57BL/6 presbycusis mice through reducing mtDNA release, inhibiting the NLRP3 inflammasome activation in the auditory pathway. Our study provides a theoretical basis for applying vitamin C to treat presbycusis.

Management of intractable epistaxis in patients who received radiation therapy for nasopharyngeal carcinoma.

To report clinical manifestations, bleeding point localization, and outcomes of management in 16 patients with 16 instances of intractable epistaxis after radiation therapy for nasopharyngeal carcinoma. Retrospective chart review of 16 patients with nasopharyngeal carcinoma (mean age 52.06 ± 14.37 years) with 16 instances of intractable epistaxis during the past 5 years, whose diagnosis was confirmed by angiography (n = 10) or MRI/CT imaging studies and clinical manifestations (n = 6). The mean radiation dose to the affected carotid artery was 101.37 ± 34.85 Gy. Bleeding points were detected in the internal carotid artery (n = 8) or external carotid artery (n = 8). Detachable balloons were used in one affected artery for vascular occlusion; six were treated using an absorbable gelatin sponge (n = 4) or microcoils (diameter 1 mm) (n = 2). Endovascular embolization was successful in seven radiation carotid blowout syndromes with cessation of hemorrhage. One patient underwent external carotid artery ligation and one patient recovered without treatment. The clinical follow-up was 3 months. Therapeutic endovascular embolization of intractable epistaxis is both efficient and safe. It should be considered as the primary treatment modality in intractable epistaxis of nasopharyngeal carcinoma.

Regulatory Mechanism of lncRNA CTBP1-AS2 in Nasopharyngeal Carcinoma Cell Proliferation and Apoptosis via the miR-140-5p/BMP2 Axis.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma. LncRNA CTBP1-AS2 (CTBP1-AS2) has effects on tumor cell growth. This study explored the mechanism of CTBP1-AS2 on NPC cells. METHODS: CTBP1-AS2 expressions in immortalized nasopharyngeal epithelial (NP69) and 6 human NPC cells were detected by RT-qPCR and SUNE-1/CNE-1 cells with relative high/low expressions were selected. Cell proliferation and apoptosis were detected by CCK-8, colony formation assays, and flow cytometry. The binding sites between CTBP1-AS2 and miR-140-5p and miR-140-5p and BMP2 were predicted, and the binding relationships were verified by dual-luciferase assay. BMP2 level was detected by Western blot. miR-140-5p was silenced, or BMP2 was overexpressed in SUNE-1 cells with si-CTBP1-AS2 to study the effects of miR-140-5p and BMP2 on CTBP1-AS2 silencing-inhibited malignant behaviors. RESULTS: CTBP1-AS2 was upregulated in NPC cells. CTBP1-AS2 silencing suppressed NPC cell proliferation and promoted apoptosis. CTBP1-AS2 silencing in SUNE-1 cells raised miR-140-5p expression and repressed BMP2 level. CTBP1-AS2 overexpression in CNE-1 cells suppressed miR- 140-5p expression and elevated BMP2 levels. DISCUSSION: In mechanism, miR-140-5p overexpression decreased BMP2 levels, reduced NPC cell proliferation, and promoted apoptosis. miR-140-5p knockdown or BMP2 overexpression enhanced NPC cell proliferation and inhibited apoptosis, thus restoring NPC cell malignant behaviors inhibited by silencing CTBP1-AS2. CONCLUSION: CTBP1-AS2 decreased miR-140-5p-induced BMP2 inhibition via functioning as a ceRNA of miR-140-5p and promoted BMP2 expression, thereby promoting NPC cell proliferation and suppressing apoptosis.

A Four-Gene Signature Model Improves the Prediction of Distant Metastasis in Patients with Nasopharyngeal Carcinoma: A Retrospective, Three-Center Observational Study.

Background: Similar to that in other malignant tumors, distant metastasis is one of the most important causes of poor prognosis in nasopharyngeal carcinoma (NPC). However, the genetic hallmarks and networks that regulate the distant metastasis of NPC are not fully understood. Methods: In this study, we performed high-throughput screening of mRNA expression profiles in 92 NPC samples collected from 3hospitals and detected the mRNA expression levels of 31,503 genes in these samples. Gene functional enrichment analyses were performed using gene set enrichment analysis (GSEA). Least absolute shrinkage and selection operator (LASSO) was applied to select prognostic genes and a Cox proportional hazards regression model including these genes was constructed to predict prognosis. The Kaplan-Meier curve and time-dependent receiver operating characteristic (ROC) curve were plotted to assess the performance of this model. Univariate and multivariate analyses were performed using the Cox proportion hazard model to test the independence of prognostic effect of gene model and other clinical features. Results: A total of 1837 differentially expressed genes between patients with and without distant metastasis were identified in the training cohort, including 869 upregulated genes and 968 downregulated genes. Six gene sets, including the Wnt/ß catenin signaling pathway, hedgehog (Hh) signaling pathway, Notch signaling pathway, mitotic spindle, apical surface, and estrogen response late, were enriched in patients with distant metastasis. A four-gene signature model was constructed in the training cohort, and according to the time-dependent ROC curve, this model had certain accuracy in predicting distant metastasis-free survival (DMFS) in both the training and validation cohorts. Conclusion: We developed a four-gene signature model that can evaluate the distant metastasis risk of NPC patients and may also provide novel therapeutic targets for NPC treatment in the near future.

Efficacy and Safety of Endoscopic Nasopharyngectomy Combined With Low-Dose Radiotherapy for Primary T1-2 Nasopharyngeal Carcinoma.

AIM: Intensity-modulated radiotherapy (IMRT) is a widely accepted therapy for nasopharyngeal carcinoma (NPC), but it inevitably brings out radiation-related complications and seriously affects the quality of life (QoL). Endoscopic nasopharyngectomy (ENPG) has been successfully conducted in locally recurred NPC, but few studies evaluated its application in early NPC. This study aims to assess the feasibility and safety of ENPG combined with low-dose radiotherapy (LDRT) in T1-2 NPC. PATIENTS AND METHODS: We recruited 37 newly diagnosed localized T1-2 NPC patients who voluntarily accepted ENPG +LDRT from June 2013 to September 2016. Meanwhile, the data of 132 T1-2 NPC patients treated with IMRT were collected and used as control group. The survival outcomes, QoL score and late RT-related sequelaes were compared between the 2 groups. RESULTS: After a median follow-up of 54 months, only 1 patient in ENPG+LDRT group died along with hepatic metastases. The 5-year overall survival, distant metastasis-free survival, local relapse-free survival and regional relapse-free survival in ENPG+LDRT group were 97.3%, 97.3%, 100% and 100%, which were not statistically different from the control group (97.7%, 90.2%, 95. 5%, 97.0%, respectively, all P > 0.05). In comparison with IMRT group, ENPG+LDRT exhibited better QoL and less rate of late RT-related sequlaes including hearing loss (53.8% vs 27.0%, P = 0.005), xerostomia (46.2% vs 24.3%, P = 0.023) and dysphagia (25.8% vs 8.1%, P = 0.024). CONCLUSIONS: ENPG+LDRT provided satisfactory survival outcomes, and improved the QoL and reduced the incidence of sequelae for T1-2 NPC patients.

Comparison of whole exome sequencing in circulating tumor cells of primitive and metastatic nasopharyngeal carcinoma.

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.

[Plasma resistin level in obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the changes and clinical implications of plasma resistin level in obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Plasma resistin level was measured by radioimmunoassay in 30 obese OSAHS patients (obese OSAHS group), 7 in the low apnea hypopnea index (AHI) subgroup, 9 in the medium AHI subgroup, and 14 in the high AHI subgroup, 30 obese subjects (obese group), and 28 normal healthy adults (control group). Stepwise multiple linear regression analysis was conducted to determine the correlation of plasma resistin level with body mass index (BMI), body fat percentage, waist to hip ratio (WHR), fasting blood glucose (FBG), blood lipid, AHI, and lowest arterial oxygen saturation (LSaO(2)). RESULTS: The plasma resistin levels of the obese OSAHS group and obese group were (8.48 +/- 1.44) and (7.60 +/- 1.53) microg/L respectively, both significantly higher than that of the control group [(5.78 +/- 1.62) microg/L, both P < 0.05], and that of the obese OSAHS group was significantly higher than that of the obese group (P < 0.05). The plasma resistin level of the high AHI obese OSAHS subgroup was (9.60 +/- 0.51) microg/L, significantly higher than those of the medium and low AHI obese OSAHS subgroups [(7.96 +/- 1.06) and (6.90 +/- 1.32) microg/L respectively, both P < 0.01]. Correlation analysis demonstrated that the fasting plasma resistin level was positively correlated with BMI, neck circumference, waist circumference, WHR, FBG, total cholesterol, triglyceride, and AHI (r = 0.52, 0.66, 0.74, 0.52, 0.59, 0.48, 0.46, and 0.80, all P < 0.05); and negatively correlated with high-density lipoprotein cholesterol and LSaO(2) (r = -0.52, r = -0.60, both P < 0.01). A stepwise multiple linear regression analysis showed that AHI was the most significant contributing factor for the increased plasma resistin level in the obese OSAHS group (R(2) = 0.618). CONCLUSIONS: Plasma resistin level in obese OSAHS patients are increased, and are positively correlated with AHI. It may be used as an important biological index to evaluate the severity of OSAHS.

Up-regulation of the IRX2 gene predicts poor prognosis in nasopharyngeal carcinoma.

Aberrant expression of the IRX2 gene contributes to the oncogenesis and progression of various cancers. In this study, we analyzed the clinical significance and the prognostic value of mRNA expression level of the IRX2 gene in nasopharyngeal carcinoma (NPC) patients, with the goal to find a novel prognostic biomarker for NPC. Tissue samples were collected prior to treatment from 71 NPC patients for the detection of mRNA expression level of a total of 31503 genes, with high throughput screening of the mRNA expression profile. The Kaplan-Meier curves and log-rank test were used for univariate analyses to determine if the mRNA expression level of IRX2 and other 31502 genes, as well as clinical characteristics were of prognostic value for overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS). Regularized Cox regression was performed to test the contribution of prognostic factors to OS, DMFS, and DFS of NPC patients. The Cox proportional hazard model was used to test the independence of prognostic effect of IRX2 and other clinical features. The receiver operator characteristic curve was drawn and the area under the curve (AUC) was calculated to evaluate the predictive power of IRX2 gene. Univariate analyses showed a higher mRNA expression level of the IRX2 gene correlated with shorter OS (P = 0.001), DMFS (P = 0.003), and DFS (P = 0.007). Regularized Cox regression and Cox proportional hazard model analyses further showed that ahigher mRNA expression level of the IRX2 gene in the primary NPC was an independent prognostic factor for OS (Coxnet beta = 0.03, Cox proportion hazard model P = 0.038), DMFS (Coxnet beta = 0.018, Cox proportion hazard model P = 0.01) and DFS (Coxnet beta = 0.008, Cox proportion hazard model P = 0.029). The AUC showed that the mRNA expression level of the IRX2 gene is a significant predictor for predicting the OS (AUC value = 0.7105) and DMFS (AUC value = 0.7027) of NPC patients. Our results demonstrated that the IRX2 gene may be a novel independent unfavorable prognostic factor for NPC patients.

Correlation of metastasis-associated protein expression with prognosis and chemotherapy in nasopharyngeal carcinoma.

The aim of this study was to elaborate the correlation between metastasis-associated protein (MTA) family and the occurrence, progression, prognosis and chemotherapy efficiency in nasopharyngeal carcinoma (NPC).The expression of MTA1, MTA2 and MTA3 protein were detected by immunohistochemistry in a tissue microarray (TMAs) which contains tissue samples of 152 NPC patients embedded by formalin-fixed paraffin. The MTA proteins were mainly expressed in the nuclei of NPC tissues and the correlations between MTAs expression and clinical parameters as well as prognosis of NPC patients showed ethnical differences according to statistically analysis. The results showed that in Han ethnic group, MTA1 expression was positively correlated with N staging, while the expression of MTA2 was negatively correlated with age, and the expression of MTA3 was positively correlated with gender. Patients with high MTA1 expression had poorprognosis. In Zhuang ethnic group, only MTA3 expression was positively correlated with age, recurrence and metastasis of NPC patients; neither MTA1 nor MTA2 expression had any correlation with clinical indexes. Patients with high MTA3 expression had unfavorable prognosis. In addition, our results showed that overall survival among Zhuang NPC patients with low expression of MTA2 increased significantly owing to "carboplatin + fluorouracil" chemotherapy. This therapeutic success, however, did not translate to longer overall survival among Han NPC patients. The biological function of MTA protein family in NPC patients was different among different ethnic groups. In conclusion, we demonstrated that MTAs had a certain tumor promoting function in patients with NPC, and the biological functions of MTAs might be ethnic differences, which suggesting MTAs to be important markers for guiding clinical treatment of NPC.

Stable knockdown of ZBTB7A promotes cell proliferation and progression in nasopharyngeal carcinoma.

AIMS: Although high expression of ZBTB7A is positively relative to metastasis in nasopharyngeal carcinoma (NPC) patients, the association between its low expression and metastasis of NPC remains unclear. The present study aimed to definitely identify the association. METHODS: The level of ZBTB7A was effectively knocked down by stable transfection of short hair RNA plasmid in NPC cell lines CNE2 and 5-8F (shRNA-CNE2 and shRNA-5-8F), compared with the cells that stably transfected empty plasmid (NC-CNE2 and NC-5-8F). The levels of ZBTB7A were assessed by real-time polymerase chain reaction and Western blot in the cell lines. MTT assay, colorimetric focus-formation assay, flow cytometry, wound healing assay, transwell assays, and xenograft model were performed to analyze cell vitality, proliferation, cell cycle, migration, invasion, and tumorigenicity. RESULTS: The levels of ZBTB7A were effectively reduced in shRNA-CNE2 and shRNA-5-8F. Their carcinogenicity was stronger separately than the abilities of NC-CNE2 and NC-5-8F. NC-CNE2 and shRNA-CNE2 were selected to establish the xenograft model because of their stronger tumorigenicity than NC-6-10B and shRNA-5-8F. The assay showed that shRNA-CNE2 had stronger tumorigenicity than NC-CNE2. CONCLUSIONS: The results demonstrated the reverse association between the expression of ZBTB7A and the tumorigenicity of NPC. We postulate that some oncogenic pathways, which are suppressed by ZBTB7A, will vicariously promote the proliferation and progression of NPC when ZBTB7A is decreased.

Diagnosis of nonexophytic nasopharyngeal lesion with endoscopy-guided core needle biopsy after narrow band imaging.

BACKGROUND: Due to the obstruction of the surrounding structures or stiff mucosa, the primary and recurrent nonexophytic nasopharyngeal carcinoma (NE-NPC) patients are difficult to be diagnosed histologically by traditional forceps biopsy. RESULTS: All the 15 cases had adequate biopsy for histological diagnosis. There were 5 cases of primary and 7 cases of recurrent NE-NPC, and 3 cases of inflammatory lesion. The histopathological diagnosis was consistent with the follow-up visit. The bleeding quantity during the CNB procedure ranged from 1 to 5 ml (mean 1.93 mL). The pain score during CNB were between 2 and 7 (mean 4.20). There were no serious complications. MATERIALS AND METHODS: From April 2009 to March 2016, after conventional white-light and novel narrow-band imaging, nasal endoscope-guided core needle biopsy (CNB) were performed on 15 cases of nonexophytic nasopharyngeal lesion with a semiautomatic biopsy gun. CONCLUSIONS: CNB is able to get adequate biopsy specimens and thus the diagnosis accuracy of CNB is high for NE-NPC. Nasal endoscope-guided CNB is the direct approach with a short distance in the tissue before reaching the tumor. It has the advantages of minimal trauma, short operative time, and no serious complications. It is simple, safe, and worth of application in clinic.

Clinical outcomes of residual or recurrent nasopharyngeal carcinoma treated with endoscopic nasopharyngectomy plus chemoradiotherapy or with chemoradiotherapy alone: a retrospective study.

BACKGROUND: Local 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 MATERIALS: A 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. RESULTS: The 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. CONCLUSIONS: The 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.

[The clinical experience of transnasal endoscopic approach for skull base osteoradionecrosis after radiotherapy for nasopharyngeal carcinoma].

OBJECTIVE: To investigate the method of surgical treatment via trans-nasal endoscopic approach in osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma. METHODS: Fifteen patients with osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma who underwent operation via trans-nasal endoscopic approach from 2008 to 2013 were retrospectively reviewed. The typical clinical manifestations included headache (NRS 6-9: 11 cases), foul odor (10 cases), epistaxis (4 cases), hearing loss (5 cases, 7 ears), tinnitus (4 cases, 5 ears). All patients underwent operation via trans-nasal endoscopic approach. During the operation, the diseased region was fully exposed, the necrotic tissue was resected, the necrotic bone was removed by high-speed electric drill, and the drainage was made unobstructed. The perioperative treatment and follow-up were carried out. RESULTS: After operation, all patients were diagnosed pathologically as osteoradionecrosis and mucosal chroinic inflammation, 1 case combined with fungal sphenoid sinusitis. Headache (9 cases) and foul odor (9 cases) resolved after operation. The follow-up was lasted 18-82 months, 13 cases were survival, 1 case lost to follow-up, 1 case died of cerebral hemorrhage. CONCLUSION: Surgical treatment via trans-nasal endoscopic approach is safe and effective in osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma, and is helping to improve the survival rate and survival quality.

[Treatment and outcome of recurrent cervical lymph nodes in patients with nasopharyngeal carcinoma after radiotherapy].

OBJECTIVE: To evaluate the efficacies of different treatments for recurrent cervical lymph nodes and the factors contributing to prognosis in patients with nasopharyngeal carcinoma after radiotherapy. METHODS: Clinical data of 79 patients with nasopharyngeal carcinoma after radiotherapy were retrospectively analyzed, and all cases were diagnosed as having recurrent cervical lymph nodes by pathological examination. The factors including sex, age, the interval between completion of radiotherapy and recurrence, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor in the neck were analyzed for prognosis. Kaplan-Meier curves, Log-rank test and Cox's proportional hazards regression mode were used in the statistical analysis. RESULTS: The median recurrence time was 26 months, and the 1- , 3- and 5-year overall survival rates were 77.9%, 53.4% and 39.7%. Cox's proportional hazards regression mode analysis indicated that age, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor were significantly prognostic factors. CONCLUSIONS: Neck dissection is superior to re-radiotherapy in treatment of recurrent cervical lymph nodes in nasopharyngeal carcinoma after radiotherapy. The patients younger than 45 years old, in early rN stage and for recurrence in the center region of primary tumor have a better prognosis.

Blockage of LMP1-modulated store-operated Ca(2+) entry reduces metastatic potential in nasopharyngeal carcinoma cell.

Epstein-Barr virus (EBV)-encoded latent membrane proteins (LMPs) expedite progression of EBV-relevant cancers. Of the full set of LMPs, latent membrane protein 1 (LMP1) was identified to uniquely augment store-operated Ca(2+) entry (SOCE). Previously, we reported that the suppression of SOCE exhibited inhibitory effects on cell migration and the extravasation from vasculature in EBV-negative nasopharyngeal carcinoma (NPC) cells. In this follow-up study, we aimed to expand our understanding of the modulation of SOCE by LMP1 and test the possibility that blockage of LMP1-modulated SOCE affects the LMP1-promoted metastatic potential. Here we showed that suppressions of the LMP1-boosted SOCE blunted the LMP1-promoted cell migration, VEGF-mediated angiogenesis and permeabilization in vitro. Blockage of SOCE inhibited vasculature-invasion of circulating cells and distant metastatic colonization in vivo. Notably, utilizing VEGFR2-EGFP-tag zebrafish we revealed that the LMP1-expressing cells arrested in a small-caliber vessel mobilized surrounding endothelial cells to facilitate vasculature-invasion. Thus, the LMP1-boosted SOCE promotes metastatic potential of NPC cells by solidifying their collaborations with the nearby non-cancer cells through the manipulation of oncogenic Ca(2+) signaling. Our study highlights the advantage of using both conventional mammal and transgenic zebrafish for developing a novel therapeutic strategy targeting the multiple steps of invasion-metastasis cascade.