CEACAM1 increased the lymphangiogenesis through miR-423-5p and NF- kB in Non-Small Cell Lung Cancer.

Background: Lung cancer causes significant mortality, with invasion and metastasis being the main features that cause most cancer deaths. Lymph node metastasis is the primary metastatic route in non-small cell carcinoma (NSCLC) and influences the staging and prognosis of NSCLC. Cumulative studies have reported that Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the progression of various cancers. However, few studies have discussed the function of CEACAM1 in lymphangiogenesis in NSCLC. Here, we examined how CEACAM1 influences lymphangiogenesis in NSCLC. Methods: A total of 30 primary squamous cell carcinoma (LUSC) patients diagnosed with LN metastasis were prospectively selected. LUSC tumor tissues, para-cancerous tissues, and positive lymph node tissues were harvested. The expression and subcellular location of CEACAM1, CD31, and LVYE1 in clinical samples were detected by immunohistochemistry. Next, the CEACAM1 and hsa-miR-423-5p expressions were detected by qPCR. The protein expression of lymphangiogenesis-associated proteins and critical cytokines of the NF-κB pathway in HDLECs was detected by Western blot. A tube formation assay was performed to detect the lymphangiogenesis in different groups. The interaction between CEACAM1 and hsa-miR-423-5p was verified using a dual luciferase assay. Results: CEACAM1 was found to be a potential gene associated with lung cancer prognosis. It was positively correlated with angiogenesis and lymphangiogenesis. Then, we detected the function of CEACAM1 in lymphangiogenesis and found that CEACAM1 promoted lymphangiogenesis. hsa-miR-423-5p overexpression inhibited lymphangiogenesis via targeting CEACAM1. Finally, we observed that CEACAM1 can activate the NF-κB pathway and, therefore, promote lymphangiogenesis. Conclusion: We found that CEACAM1 enhanced lymphangiogenesis in NSCLC via NF-kB activation and was repressed by miR-423-5p. This suggests the value of CEACAM1 as a new therapeutic marker in NSCLC.

Angiogenesis in nasopharyngeal carcinoma: insights, imaging, and therapeutic strategies.

Nasopharyngeal carcinoma (NPC) is a highly prevalent head and neck malignancy in southern China frequently diagnosed at advanced stages owing to subtle early symptoms and associated metastasis. Angiogenesis emerges as a pivotal factor in NPC progression, with numerous angiogenesis-related factors showing aberrant expression and contributing to increased neovascularization within NPC tumors. These abnormal vessels not only nourish tumor growth but also facilitate metastasis, culminating in unfavorable patient outcomes. Multiple studies have demonstrated the applicability of various imaging techniques for assessing angiogenesis in NPC tumors, thus serving as a foundation for personalized treatment strategies and prognostic assessments. Anti-angiogenic therapies have exhibited significant potential for inhibiting NPC angiogenesis and exerting anti-tumor effects. To enhance efficacy, anti-angiogenic drugs are frequently combined with other treatment modalities to synergistically enhance anti-tumor effects while mitigating the side effects associated with single-agent therapies, consequently improving patient prognosis. Identifying the potential mechanisms and key targets underlying NPC angiogenesis and exploring more effective detection and treatment approaches holds promise for shaping the future of NPC diagnosis, treatment, and prognosis, thereby offering new avenues and perspectives for research and clinical practice.

HOXA13 promotes the proliferation, migration, and invasion of nasopharyngeal carcinoma HNE1 cells by upregulating the expression of Snail and MMP-2.

Homeobox A13 (HOXA13) has been verified as an oncogen in some malignancies. However, its role in nasopharyngeal carcinoma (NPC) is still unclear. This study aims to explore the role of HOXA13 in NPC and its underlying mechanism. The mRNA expression of HOXA13 in NPC was obtained from the GSE53819 and GSE64634 datasets in the Gene Expression Omnibus (GEO) database. MTT, colony formation and transwell assays and xenograft tumour models were used to investigate the effects of HOXA13 on NPC HNE1 cells in vitro and in vivo. The expression of HOXA13, epithelial-mesenchymal transition-transcription factor (EMT-TF) Snail and matrix metalloproteinase 2 (MMP-2) was detected by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The results showed that HOXA13 was upregulated in NPC. Silencing HOXA13 suppressed the proliferation, migration, and invasion of HNE1 cells, which inhibited tumour growth, while overexpression of HOXA13 induced the opposite effects. In addition, the expression of Snail and MMP-2 at the transcriptional and protein levels was associated with the expression of HOXA13. In summary, our results suggest that HOXA13 plays a role as a cancer-promoting gene in NPC. The underlying mechanism may be related to the upregulation of Snail and MMP-2.

Long non-coding RNA HOTTIP exerts an oncogenic function by regulating HOXA13 in nasopharyngeal carcinoma.

BACKGROUND: The long non-coding RNA HOXA transcript at the distal tip (HOTTIP) and homeobox A13 (HOXA13) have been identified as oncogenes that play a pivotal role in tumorigenesis. However, their specific mechanisms of action in nasopharyngeal carcinoma (NPC) progression remain unclear. METHODS AND RESULTS: In the present study, RT-qPCR was employed to quantify RNA expression in NPC cells and tissues. Flow cytometry, MTT, CCK8 and colony formation assays were utilized to assess cell apoptosis and proliferation. Transwell assay was conducted to evaluate migration and invasion while Western blotting was performed for protein expression analysis. Our findings revealed that the expression of HOTTIP was significantly upregulated in NPC cell lines. Inhibition of HOTTIP could induce apoptosis and suppress proliferation, clonogenicity, invasion and metastasis in NPC cells. Knockdown of HOTTIP led to downregulation of HOXA13 expression, which subsequently inhibited the proliferation and metastasis in NPC cells. The inhibitory effects on cell proliferation and metastasis caused by HOTTIP silencing were rescued by HOXA13 overexpression. Additionally, there was a significant positive correlation between HOTTIP and HOXA13, which were found to be elevated in NPC tissues compared to normal tissues. CONCLUSIONS: We have determined that LncRNA HOTTIP facilitates tumorigenesis by modulating the expression of HOXA13 in NPC cells. Targeting HOTTIP/HOXA13 may be a promising therapeutic strategy for NPC.

Combination of smoking and Epstein-Barr virus DNA is a predictor of poor prognosis for nasopharyngeal carcinoma: a long-term follow-up retrospective study.

BACKGROUND: This retrospective study was performed to determine the prognostic potential of smoking and its combination with pre-treatment plasma Epstein-Barr virus (EBV) DNA levels in patients with nasopharyngeal carcinoma (NPC). METHODS: Medical records of 1080 non-metastatic NPC patients who received intensity-modulated radiotherapy were reviewed. Male patients were categorized as never and ever smokers, and the smoking amount, duration, and cumulative consumption were used to evaluate dose-dependent effects. Survival outcomes were assessed using Kaplan-Meier survival analysis and the multivariate Cox regression analysis. Propensity score matching (PSM) was constructed. RESULTS: The 5-year overall survival (OS) was worse for ever smokers than never smokers, and significantly decreased with the increase of smoking amount, duration, and cumulative consumption. Compared with never smokers, the multivariate-adjusted hazard ratio (HR) of death was higher in ever smokers (HR = 1.361, P = 0.049), those smoked ≥20 cigarettes/day (HR = 1.473, P = 0.017), those smoked for ≥30 years (HR = 1.523, P = 0.023), and those cumulative smoked for ≥30 pack-years (HR = 1.649, P = 0.005). The poor prognostic effects of smoking was also confirmed in the PSM analysis. The combination of cumulative smoking consumption and pre-treatment EBV DNA levels was proven to be an independent poor prognostic factor for male NPC, and the risk of death, progression, and distant metastases gradually increased with both factors (P < 0.001). CONCLUSIONS: Combination of smoking and pre-treatment EBV DNA levels as a predictor of poor prognosis could further improve the risk stratification and prognostication for NPC.

Development of a Radiotherapy Localisation Computed Tomography-Based Radiomic Model for Predicting Survival in Patients With Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy Following Induction Chemotherapy.

BACKGROUND: Our purpose is to develop a model combining radiomic features of radiotherapy localisation computed tomography and clinical characteristics that can be used to estimate overall survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy following induction chemotherapy. METHODS: We recruited 145 patients with pathologically confirmed nasopharyngeal carcinoma between February 2012 and April 2015. In total, 851 radiomic features were extracted from radiotherapy localisation computed tomography images for the gross tumour volume of the nasopharynx and the gross tumour volume of neck metastatic lymph nodes. The least absolute shrinkage and selection operator algorithm was applied to select radiomics features, build the model and calculate the Rad-score. The patients were divided into high- and low-risk groups based on their Rad-scores. A nomogram for estimating overall survival based on both radiomic and clinical features was generated using multivariate Cox regression hazard models. Prediction reliability was evaluated using Harrell's concordance index. RESULTS: In total, seven radiomic features and one clinical characteristic were extracted for survival analysis, and the combination of radiomic and clinical features was a better predictor of overall survival (concordance index = .849 [confidence interval: .782-.916]) than radiomic features (concordance index = .793 [confidence interval: .697-.890]) or clinical characteristics (concordance index = .661 [confidence interval: .673-.849]) alone. CONCLUSION: Our results show that a nomogram combining radiomic features of radiotherapy localisation computed tomography and clinical characteristics can predict overall survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy following induction chemotherapy more effectively than radiomic features or clinical characteristics alone.

Integrating pre- and post-treatment Plasma Epstein-Barr Virus DNA levels for better prognostic prediction of Nasopharyngeal Carcinoma.

Background: Pre- and post-treatment plasma Epstein-Barr virus (EBV) DNA are important biomarkers for the prognosis of nasopharyngeal carcinoma (NPC). This study was performed to determine the prognostic potential of integrating EBV DNA levels in plasma measured pre-treatment (pre-EBV) and 3 months post-treatment (3 m-EBV). Materials and methods: A total of 543 incident non-metastatic NPC patients treated with intensity-modulated radiotherapy, with or without chemotherapy, were reviewed. Patients were divided into four subgroups based on pre-EBV and 3 m-EBV status. The data for pre-EBV and 3 m-EBV samples were integrated, and the predictability of the survival of patients with NPC was analyzed. Results: There were significant differences in the 5-year progression-free survival, distant metastasis-free survival, locoregional relapse-free survival, and overall survival among the four patient subgroups (P<0.001). Patients who tested negative for both pre-EBV and 3 m-EBV had the best prognosis, followed by patients who tested positive for pre-EBV and negative for 3 m-EBV, and those who tested negative for pre-EBV and positive for 3 m-EBV; however, patients who tested positive for both pre-EBV and 3 m-EBV had the poorest chances of survival. Multivariate analyses demonstrated that integration of pre-EBV and 3 m-EBV data was an independent predictor of NPC progression in patients. Receiver operating characteristic curve analysis further confirmed that the combination of pre-EBV and 3 m-EBV had a greater prognostic value than pre-EBV or 3 m-EBV alone. Conclusions: Integrating pre-EBV and 3 m-EBV data could provide more accurate risk stratification and better prognostic prediction in NPC.

High VCAM-1 Predicts Poor Prognosis and is Associated with Chemotherapy Resistance in Nasopharyngeal Carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) is a malignant tumor endemic in southern China and Southeast Asia with a poor prognosis. Vascular cell adhesion protein 1 (VCAM-1) is highly expressed in NPC; however, it is unclear whether VCAM-1 is correlated with chemotherapy resistance and prognosis in NPC. PATIENTS AND METHODS: To further explore the role of VCAM-1 in chemotherapy resistance and prognosis in NPC, we examined the expression of VCAM-1, the sensitivity of chemotherapy drugs, and clinical follow-up data from 73 patients with NPC. Then, the results of VCAM-1 expression were analyzed in response to chemotherapy drugs, progression-free survival (PFS), and overall survival (OS). RESULTS: The expression of VCAM-1 protein in NPC was significantly higher than that in chronic inflammatory tissue. No significant differences in the expression of VCAM-1 among gender, age, pathologic classification, tumor classification, lymph node status, metastasis status, and overall clinical stage were found. The periods of PFS and OS in patients with high VCAM-1 expression were significantly shorter than those in patients with low VCAM-1 expression. The sensitivity rates of NPC to eight chemotherapy drugs were different; carboplatin and docetaxel showed the highest chemotherapy sensitivity and resistance rates, respectively. The resistance rates to paclitaxel were different between the patients with high VCAM-1 expression and those with low VCAM-1 expression. CONCLUSION: Our data indicated that VCAM-1 was highly expressed in NPC. Patients with high VCAM-1 expression were more prone to shorter periods of PFS and OS. VCAM-1 could be a prognostic marker of NPC patients. The detection of VCAM-1 expression in NPC may be valuable for chemotherapy drug evaluation and management of patients with NPC in the clinic.

Long-term monitoring of dynamic changes in plasma EBV DNA for improved prognosis prediction of nasopharyngeal carcinoma.

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). MATERIALS AND METHODS: About 1077 nonmetastatic NPC patients were recruited to retrospectively analyze the prognostic value of plasma EBV DNA load pretreatment and 3, 12, 24, and 36 months posttreatment. 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 posttreatment 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 posttreatment 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 pretreatment and consistently negative detection posttreatment, those with negative detection pretreatment and positive detection at one time point posttreatment, and those with positive detection pretreatment and at one time point posttreatment, whereas patients with positive detection at ≥2 time points posttreatment had the worst prognosis. Cox proportional hazard models identified the dynamic change pattern as an independent prognostic factor, and receiver operating characteristic 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 posttreatment could predict the long-term survival outcome and provide accurate risk stratification in NPC.

FANCD2 knockdown with shRNA interference enhances the ionizing radiation sensitivity of nasopharyngeal carcinoma CNE-2 cells.

Fanconi anemia complementation group D2 (FANCD2) has been associated with the sensitivity of tumor cells to DNA crosslinking damaging agents in certain solid tumors. However, its role in nasopharyngeal carcinoma (NPC) is still unclear. In the present study, the role of FANCD2 in the response of NPC CNE-2 cells to radiation was investigated. A CNE-2 cell model with stable FANCD2 silencing was constructed by lentiviral transfection. Fluorescence quantitative PCR and western blotting were used to evaluate FANCD2 expression in CNE-2 cells. The biological impact of FANCD2 silencing on the response of CNE-2 cells to radiation was investigated in vitro and in vivo. The microarray technology, western blotting, and immunohistochemistry were used to analyze the proteins involved in related pathways after irradiation to investigate the underlying mechanism. Lentivirus-mediated shRNA interference stably silenced the FANCD2 gene in CNE-2 cells. In vitro, in the FANCD2-silenced group, cell proliferation was significantly inhibited, apoptosis was increased, and the cell cycle was arrested at the G2/M phase after irradiation. In vivo, FANCD2 silencing slowed tumor growth, as the volume and weight of the xenograft tumors were significantly decreased. Both in vitro and in vivo, the differentially expressed genes NUPR1, FLI1, and FGF21 were downregulated in the FANCD2-silenced group. Our results show that FANCD2 silencing affected the sensitivity of CNE-2 cells to ionizing radiation by regulating cell proliferation, apoptosis, and cell cycle distribution. The mechanism might be associated with changes in NUPR1, FLI1, and FGF21 protein expression due to the FANCD2 silencing. This study provides a promising target for NPC radiotherapy.

Effect of Blocking the OX40/OX40L Signaling Pathway by siRNA Interference on Animal Experimental Study of Allergic Rhinitis.

BACKGROUND: The identification of new approaches and intervention targets for the treatment of AR is urgently needed. We aimed to investigate the effect of blocking the OX40/OX40L signaling pathway by small interfering RNA (siRNA) on ovalbumin (OVA)-induced AR in a mouse model. METHODS: After establishment of the AR model, the mice were interfered by siRNA-OX40L (experimental group), siRNA-C (negative control group), or PBS (control group). Nose scratching, sneezing and nasal discharge were observed. OX40L mRNA and protein and the IL-5, TNF-α, regulatory T cell (Treg) -specific marker Foxp3, and eosinophil (EOS) levels were analyzed. RESULTS: The numbers of nose scratching and sneezing were significantly lower in the siRNA-OX40L-treated group (p <0.05). After the intervention of siRNA-OX40L, OX40L mRNA and protein levels were significantly inhibited (p <0.05), but the Foxp3 level was significantly increased in the experimental group (p <0.05). The IL-5 and TNF-α levels were significantly lower in the experimental group (p <0.05), and the reduction was more evident for the Th2-type cytokine IL-5 than for the Th1-type cytokine TNF-α. Few or no EOSs were found in the nasal mucosal epithelium of the experimental group (p <0.05), whereas EOS infiltration was significant in the other two groups. CONCLUSIONS: Blockage of the OX40/OX40L signaling pathway with siRNA-OX40L interference can inhibit allergic reactions and relieve allergic symptoms in AR mice. The underlying mechanism may be related to correcting Th2 immune deviation, inducing immune tolerance, and promoting Treg production.

Expression of FANCD2 is associated with prognosis in patients with nasopharyngeal carcinoma.

The relationship between Fanconi anemia complementation group D2 (FANCD2) and early diagnosis, pathogenesis, recurrence, and prognosis in patients with nasopharyngeal carcinoma (NPC) was investigated in a retrospective case-control study. The clinicopathological data of patients with NPC were collected. The results showed that FANCD2 was significantly higher in poorly differentiated squamous cell carcinoma than in moderately and well differentiated carcinoma. FANCD2 was significantly lower in recurrent NPC tissues than in NPC tissues before treatment. FANCD2 was markedly higher in T1-2, stage I-II NPC tissues with a duration of disease shorter than 6 months than in T3-4, stage III-IV NPC tissues with a duration of disease longer than 6 months. Moreover, compared with patients with cervical lymph node metastases, FANCD2 was elevated in tissues from patients without cervical lymph node metastases. Furthermore, the NPC patients in the high-FANCD2-expression group exhibited a higher recurrence rate than the patients in the low-FANCD2-expression group. Finally, the disease-free survival rate of the high-expression group was significantly lower than it was in the low-expression group. Therefore, FANCD2 is associated with the occurrence, differentiation, and cervical lymph node metastasis of NPC. With the development of NPC, FANCD2 is down-regulated. FANCD2 may be a molecular marker for the early diagnosis and prognosis of NPC.

Dynamic Changes in Plasma MicroRNAs Have Potential Predictive Values in Monitoring Recurrence and Metastasis of Nasopharyngeal Carcinoma.

Although circulating microRNAs (miRNAs) have already proven to be useful as diagnostic and prognostic biomarkers in nasopharyngeal carcinoma (NPC), the potential of these molecules to monitor patients over time has been less explored. This study aimed to analyze dynamic changes in plasma miRNAs before and after treatment and explore their clinical significance in monitoring recurrence and metastasis of NPC. Candidate miRNAs were screened by microarray analysis and validated by real-time quantitative polymerase chain reaction (RT-qPCR). In the follow-up cohort including 102 patients, blood samples (plasma) were collected before the treatment initiation, 3 months, 6 months, and 12 months after treatments, and at the time of any recurrence or metastasis. Among these plasma miRNAs, miR-9-3p, miR-124-3p, miR-892b, and miR-3676-3p were significantly upregulated (P = 0.018, P = 0.039, P = 0.001, and P = 0.01, resp.) after treatment compared with pretreatment, and the four plasma miRNAs were downregulated again at recurrence or metastasis (P < 0.001, P = 0.015, P = 0.003, and P = 0.026, resp.). The dynamic changes in plasma miRNAs after treatment reflect the outcome of the disease and have the potential to monitor recurrence and metastasis in patients with NPC.

Detailed analysis of inflammatory cell infiltration and the prognostic impact on nasopharyngeal carcinoma.

BACKGROUND: One of the most striking characteristics of nasopharyngeal carcinoma (NPC) is the presence of a very abundant immune cells infiltrate containing mainly T-lymphocytes. The purpose of this study was to present our analysis providing a comprehensive characterization of antitumor inflammatory response in NPC. METHODS: The densities of 9 types of inflammatory cells were assessed in 197 patients with NPC, including CD3 + T-lymphocytes, CD8 + cytotoxic T-lymphocytes, CD20 + B-lymphocytes, CD56 + natural killer (NK) cells, FOXP3 + regulatory T-lymphocytes, CD1a + immature dendritic cells, CD83 + mature dendritic cells, neutrophil elastase + neutrophils, and tryptase + mast cells. We characterized the inflammatory infiltrate in relation to clinical stage and patient survival. The expression of programmed death-1 (PD-1) on tumor-infiltrating lymphocytes (TILs) was also detected. The correlations between PD-1 expression and clinical characteristics and posttreatment outcome were analyzed. RESULTS: The patients with NPC with a low density of tumor-infiltrating FOXP3+, CD8 + T-lymphocytes, neutrophils, and mast cells showed a significantly longer overall survival (OS) and progression-free survival (PFS). However, patients with a high density of NK cells showed a better OS and PFS. The densities of NK cells and mast cells could be served as biomarkers for predicting recurrence or distant metastasis in patients with NPC. Moreover, PD-1 positivity predicted poor prognosis in patients with NPC. CONCLUSION: The densities of inflammatory cells are correlated with the prognosis of patients with NPC.

MicroRNA-92b inhibits epithelial-mesenchymal transition-induced migration and invasion by targeting Smad3 in nasopharyngeal cancer.

Increasing studies reports that aberrant miRNAs contribute to nasopharyngeal carcinoma (NPC) development and progression. However, the role of miR-92b in NPC remains unclear. In present research, we found that a reduced miR-92b expression in NPC tissues and cell lines. The clinical data showed that the down-regulated miR-92b expression was obviously associated with adverse prognostic characteristic. Furthermore, we confirmed that miR-92b was a novel independent prognostic symbol for predicting 5-year survival of NPC patients. MiR-92b overexpression inhibited cell migration, invasion and EMT progress, while down-regulated miR-92b reversed the effect. Besides, miR-92b could modulate Smad3 by directly binding to its 3'-UTR. In clinical samples of NPC, miR-92b inversely correlated with Smad3. Alternation of Smad3 expression at least partially abrogated the migration, invasion and EMT progress of miR-92b on NPC cells. In summary, our results indicated that miR-92b functioned as a tumor suppressor gene in regulating the EMT and metastasis of NPC via targeting Smad3, and may represent a novel potential therapeutic target and prognostic marker for NPC.

Improved Sodium-Ion Storage Performance of Ultrasmall Iron Selenide Nanoparticles.

Sodium-ion batteries are potential low-cost alternatives to current lithium-ion technology, yet their performances still fall short of expectation due to the lack of suitable electrode materials with large capacity, long-term cycling stability, and high-rate performance. In this work, we demonstrated that ultrasmall (∼5 nm) iron selenide (FeSe2) nanoparticles exhibited a remarkable activity for sodium-ion storage. They were prepared from a high-temperature solution method with a narrow size distribution and high yield and could be readily redispersed in nonpolar organic solvents. In ether-based electrolyte, FeSe2 nanoparticles exhibited a large specific capacity of ∼500 mAh/g (close to the theoretical limit), high rate capability with ∼250 mAh/g retained at 10 A/g, and excellent cycling stability at both low and high current rates by virtue of their advantageous nanosizing effect. Full sodium-ion batteries were also constructed from coupling FeSe2 with NASICON-type Na3V2(PO4)3 cathode and demonstrated impressive capacity and cycle ability.

M2-polarized tumour-associated macrophages in stroma correlate with poor prognosis and Epstein-Barr viral infection in nasopharyngeal carcinoma.

OBJECTIVES: To assess the relationships between CD163 expression, localization of CD163+ macrophages, clinicopathological features and prognosis of NPC. METHODS: A total of 110 cases of NPC specimens and 80 cases of nasopharyngitis specimens were analysed for CD163 expression by immunohistochemistry and EBERs expression in situ hybridization. RESULTS: CD163 + macrophages in the tumour stroma were positively correlated with the tumour and nodal stage. Higher expression of Epstein-Barr virus-encoded RNAs (EBERs) in the nuclei of tumour cells was associated with higher density of CD163 + macrophages in the tumour stroma. More importantly, greater infiltration of CD163 + macrophages in the tumour stroma was associated with poor overall survival (OS) and poor progression-free survival (PFS). Multivariate analysis revealed that the density of CD163+ macrophages in the tumour stroma may be an independent risk factor for NPC prognosis. CONCLUSIONS: Increased infiltration of CD163+ macrophages in the tumour stroma correlates with worse outcomes and with Epstein-Barr virus (EBV) infection status of tumour cells in nasopharyngeal carcinoma (NPC).

Silencing of FANCD2 enhances the radiosensitivity of metastatic cervical lymph node-derived head and neck squamous cell carcinoma HSC-4 cells.

Fanconi anemia complementation group D2 (FANCD2) is involved in the key steps of the Fanconi anemia (FA) pathway, which plays a role in the repair of DNA crosslink damage. However, the role of FANCD2 during radiotherapy for head and neck squamous cell carcinoma (HNSCC) is unclear. In this study, the HNSCC cell line HSC-4 was used. Western blotting was used to evaluate the expression of the FANCD2 in HSC-4 cells. We investigated the impact of FANCD2 on the radiosensitivity of HSC-4 cells in vitro and in vivo. TUNEL, western blotting and immunohistochemistry were used to analyze the apoptosis and proteins involved in apoptosis-related pathways after radiotherapy to investigate the relevant mechanism. The present study showed that shRNA interference could effectively and stably silence FANCD2 expression in HSC-4 cells. In vitro, the silencing of FANCD2 inhibited cell proliferation, decreased the survival rate, increased apoptosis and induced S phase arrest in HSC-4 cells after radiotherapy. In vivo, the silencing of FANCD2 could prolong the tumor-forming time and slow tumor growth. In addition, the tumor volume was significantly reduced, the weight was deceased, and the tumor inhibition rate was increased after radiotherapy. TUNEL showed that the silencing of FANCD2 significantly increased apoptosis in HSC-4 cells induced by radiotherapy. Both in vitro and in vivo esperiments revealed that the expression of the Bax and p-p38 proteins in HSC-4 cells, in which FANCD2 had been silenced, was increased after radiotherapy, whereas the expression of the p38 and Bcl2 proteins was decreased. Our results suggested that the silencing of FANCD2 enhanced the radiosensitivity of HSC-4 cells, and its mechanism involves the activation of the p38 MAPK signaling pathway and the regulation of the expression of Bax and Bcl2 proteins. This study provides a novel candidate target for HNSCC therapy.

Highly active and durable methanol oxidation electrocatalyst based on the synergy of platinum-nickel hydroxide-graphene.

Active and durable electrocatalysts for methanol oxidation reaction are of critical importance to the commercial viability of direct methanol fuel cell technology. Unfortunately, current methanol oxidation electrocatalysts fall far short of expectations and suffer from rapid activity degradation. Here we report platinum-nickel hydroxide-graphene ternary hybrids as a possible solution to this long-standing issue. The incorporation of highly defective nickel hydroxide nanostructures is believed to play the decisive role in promoting the dissociative adsorption of water molecules and subsequent oxidative removal of carbonaceous poison on neighbouring platinum sites. As a result, the ternary hybrids exhibit exceptional activity and durability towards efficient methanol oxidation reaction. Under periodic reactivations, the hybrids can endure at least 500,000 s with negligible activity loss, which is, to the best of our knowledge, two to three orders of magnitude longer than all available electrocatalysts.

[Distribution and prognostic significance of tumor-infiltrating mast cells in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the infiltration and prognostic significance of tumor-infiltrating mast cells (TIMs) in nasopharyngeal carcinoma (NPC). METHODS: Immunohistochemistry for tryptase was performed on 154 NPC specimens. The median value of TIM density was used as a cutoff point to separate the patient cohort into two groups with either low or high TIM infiltration. The associations between TIM and clinicopathological factors were analyzed by Mann-Whitney U text. Survival curves were plotted according to the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Log-rank test and the Cox proportional hazard models, respectively. P<0.05 was considered statistically significant. All statistical analyses were conducted using SPSS 13.0. RESULTS: TIM was mainly in the stroma of NPC and detected in all specimens. The median value of TIM density (25.60/high power field) was used as a cutoff point to separate the patient cohort into two groups with either low or high TIM infiltration. The density of TIM was positively correlated with N stage (Z=-2.193, P<0.05) and clinical stage (Z=-2.551, P<0.05). The 3-year overall survival (OS) and progression-free survival (PFS) of patients were 64.4% and 55.7% in the high TIM density group; 78.3% and 77.0% in the low TIM density group. For survival evaluation, high density of TIM was associated with worse OS and PFS (P<0.05). Multivariate Cox regression model analysis showed TIM infiltration was an independent risk factor for both OS and PFS. CONCLUSIONS: The density of TIM in NPC increased with tumor stage. High TIM infiltration was associated with poor overall survival and progression-free survival.