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OBJECTIVE: To determine the predictive value of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-eosinophil ratio (LER), monocyte-to-eosinophil ratio (MER), systemic inflammatory response index (SIRI), and ratio of inflammatory cells before and after treatment for predicting survival in advanced nasopharyngeal carcinoma (NPC) and to provide a reference for treatment. METHODS: A retrospective review of 70 patients was performed. Serological indexes were obtained by drawing blood before and after systemic therapy. The cutoff values of these indexes were determined by receiver operating characteristic (ROC) curves. The prognostic value of the indexes for overall survival (OS) and distant metastasis free survival (DMFS) was evaluated. RESULTS: Survival analysis showed that a smaller pretreatment LMR value was associated with poor OS; larger pretreatment NER, LER, MER, and SIRI values were associated with poor OS; a smaller posttreatment LMR value was associated with poor OS; larger posttreatment NLR, NER, MER, and SIRI values were associated with poor OS; a smaller pretreatment LMR value was associated with poor DMFS; larger pretreatment NLR, NER, LER, and MER values were associated with poor DMFS; and larger posttreatment NLR, NER, LER, and MER values were associated with poor DMFS. Furthermore, a larger neutrophil after treatment-to-neutrophil before treatment ratio was associated with poor OS and DMFS. Logistic regression analysis showed that pretreatment MER and posttreatment NLR were independent predictors of OS in patients with advanced NPC; moreover, pretreatment and posttreatment MER and NLR were independent prognostic factors for DMFS in patients with advanced NPC. CONCLUSIONS: The NLR, NER and MER can be used to predict survival in advanced NPC patients. Eosinophils might be one of the factors for the good prognosis of NPC patients. In addition, an increased number of neutrophils after treatment may indicate a favorable prognosis.
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Neoplasias Nasofaríngeas , Neutrófilos , Humanos , Carcinoma Nasofaríngeo/patología , Neutrófilos/patología , Eosinófilos , Pronóstico , Monocitos/patología , Recuento de Linfocitos , Linfocitos/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Hypopharyngeal carcinoma is the worst type of head and neck squamous cell carcinoma. It is necessary to identify the key molecular targets related to the carcinogenesis and development of hypopharyngeal carcinoma. METHODS: Differentially expressed lncRNAs in hypopharyngeal carcinoma were selected by microarray, and lncRNA-associated proteins were found by RIP assay. Colony formation, CCK-8, wound healing and Transwell assays were performed to detect the effects of lncRNA and its associated protein on cell proliferation and migration in vitro. Downstream pathways of lncRNA and its associated protein were detected by WB. Through a subcutaneous tumor model, the effects of lncRNA and its associated protein on cell proliferation were detected. The expressions of lncRNA and its associated protein in hypopharyngeal cancer tissues were detected by qRT-PCR and immunohistochemistry assays, respectively, and survival analyses were performed by Kaplan-Meier curve. RESULTS: A total of 542 and 265 lncRNAs were upregulated and downregulated in microarrays, respectively. LncRNA NR120519 was upregulated and promoted cell proliferation and migration of hypopharyngeal carcinoma in vitro and cell proliferation in vivo. RIP and WB assays showed that KRT17 was associated with and blocked by NR120519.The silencing of KRT17 promoted cell proliferation and the migration of hypopharyngeal carcinoma in vitro and cell proliferation in vivo by activating the AKT/mTOR pathway and epithelial-mesenchymal transformation (EMT). Finally, the NR120519 high expression and KRT17 low expression groups showed shorter overall survival. CONCLUSION: NR120519 activated the AKT/mTOR pathway and EMT by blocking KRT17 to promote cell proliferation and the migration of hypopharyngeal carcinoma.
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This study aims to explore the mechanism of microRNA (miR)-101-3p-mediated SOX2/ZIC5 axis in the progression of cisplatin resistance of nasopharyngeal carcinoma (NPC). ZIC5 expression was analyzed with a bioinformatics database and detected in NPC cell lines. Cisplatin-resistant cells (HNE-1/DDP and C666-1/DDP) were transfected with sh-ZIC5, sh-SOX2, sh-SOX2 + pcDNA3.1-ZIC5, or miR-101-3p Agomir + pcDNA3.1-SOX2. MiR-101-3p, SOX2, and ZIC5 expression was assessed after transfection, and cancer associated phenotypes were evaluated after cisplatin treatment. The potential relationships among miR-101-3p, SOX2, and ZIC5 were analyzed. A xenograft mouse model of NPC was established with HNE-1 cells stably transfected or not transfected with oe-ZIC5 and subjected to tail vein injection of miR-101-3p Agomir and intraperitoneal injection of cisplatin. Overexpression of ZIC5 was found in cisplatin-resistant NPC cells. Downregulating ZIC5 in NPC cells decreased cell viability, promoted apoptosis, and reduced cisplatin resistance. SOX2 had a binding site on ZIC5, and SOX2 promoted proliferation, migration, and cisplatin resistance and inhibited cell apoptosis by up-regulating ZIC5. Mechanistically, miR-101-3p was decreased in cisplatin-resistant NPC cells and negatively targeted SOX2. Overexpression of miR-101-3p inhibited tumor growth and cisplatin resistance in xenograft mouse model, which was reversed by ZIC5 overexpression. In conclusion, the miR-101-3p/SOX2/ZIC5 axis was implicated in cancer associated phenotypes and cisplatin resistance in NPC.
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MicroARNs , Neoplasias Nasofaríngeas , Humanos , Animales , Ratones , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/genética , MicroARNs/genética , MicroARNs/metabolismo , Cisplatino/farmacología , Regulación hacia Abajo , Línea Celular Tumoral , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Proliferación Celular , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al ADN/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismoRESUMEN
OBJECTIVE: To explore the effects of exosomes loaded with circular RNA PARD3 on EBV-miR-BART4-induced stemness and resistance of cisplatin in nasopharyngeal carcinoma side population (NPC-SP) cells through the miR-579-3p/SIRT1/SSRP1 axis. METHODS: Sixty-five cancer tissues and 65 noncancerous tissues were collected from NPC patients or patients with rhinitis. The expressions of circPARD3, miR-579-3p, SIRT1, and SSRP1 were detected by qRT-PCR, western blot, or immunohistochemistry. In vivo tumor formation assay was performed in nude mice. Immunofluorescence and qRT-PCR were conducted for the determination of CD44 and CD133 expressions, and flow cytometry combined with Hoechst 33,342 dye efflux for identifying SP cells, CCK-8 and EdU assays for cell proliferation, and Transwell assay for migration and invasion. RESULTS: CircPARD3, SIRT1, and SSRP1 were upregulated while miR-579-3p was downregulated in NPC tissues and cells. CircPARD3 was positively correlated with the expressions of SIRT1 and SSRP1, and miR-579-3p was negatively correlated with circPARD3, SIRT1, and SSRP1. Exosomes loaded with circPARD3 promoted EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells, while miR-579-3p reversed the effect of exosomal circPARD3 on EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells. Additionally, miR-579-3p suppressed EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells by regulating SIRT1. SIRT1 upregulated SSRP1 expression by catalyzing H3K4 methylation and down-regulation of SSRP1 reversed the effect of SIRT1 on EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells. CONCLUSION: Exosomes loaded with circPARD3 promoted EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells through the miR-579-3p/SIRT1/SSRP1 axis. Graphical Headlights ⢠EBV-miR-BART4 induces the stemness and resistance of NPC-SP cells. ⢠CircPARD3 regulates SIRT1 by miR-579-3p. ⢠SIRT1 regulates SSRP1 expression by histone methylation. ⢠Exosomes loaded with circPARD3 promotes EBV-miR-BART4-induced NPC-SP cell stemness and resistance by the miR-579-3p/SIRT1/SSRP1 axis.
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Exosomas , MicroARNs , Neoplasias Nasofaríngeas , Animales , Ratones , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Cisplatino/farmacología , Cisplatino/uso terapéutico , MicroARNs/genética , MicroARNs/metabolismo , Células de Población Lateral/metabolismo , Células de Población Lateral/patología , Exosomas/genética , Exosomas/metabolismo , Ratones Desnudos , Sirtuina 1/genética , Sirtuina 1/metabolismo , Línea Celular Tumoral , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in Southern China. C2orf40 has been identified as a tumor suppressor gene in many cancers. However, the roles of C2orf40 in nasopharyngeal carcinoma has not been studied. METHODS: In this study, a bioinformatics analysis was performed to identify the differentially expressed genes in NPC. The quantitative methylation levels was detected using pyrosequencing. qRT-PCR, western blotting, immunohistochemistry and immunofluorescence were used to detect the expression level of related RNA and proteins. Cell proliferation was detected using CCK-8 assay, and colony formation capability was detected using colony formation assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. The apoptosis level of cells was assessed using TUNEL staining. Endogenous DNA damage and repair were assessed by the comet assay. Cell cycle analyses carried out by flow cytometry. Finally, We used a xenograft nude mouse to verify the roles of C2orf40 in chemoresistance and radioresistance in vivo. RESULTS: We found that the C2orf40 expression was significantly downregulated in NPC tissues and inversely associated with a poor prognosis. In vivo and in vitro functional experiments confirmed that overexpression of C2orf40 significantly inhibited the migration and invasion of NPC cells, and promoted their sensitivity to radiotherapy and chemotherapy of NPC cells. Mechanically, the expression level of C2orf40 was negatively correlated with the expression levels of CCNE1 and CDK1. Overexpression of C2orf40 induced cell cycle arrest of NPC cells at G/M phase. In addition, C2orf40 can down-regulated the expression levels of homologous recombination-related proteins (BRCA1, BRCA2, RAD51, and CDC25A) and inhibited the activity of the PI3K/AKT/mTOR signaling pathway. CONCLUSION: The results clarified the biological functions and mechanisms of C2orf40, as a tumor suppressor gene, in NPC, and provided a potential molecular target for improving the sensitivity of NPC to radiotherapy and chemotherapy.
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Neoplasias Nasofaríngeas , Proteínas Proto-Oncogénicas c-akt , Proteínas Supresoras de Tumor , Animales , Ciclo Celular/genética , División Celular , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Humanos , Ratones , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor worldwide with high morbidity and mortality. However, the diagnosis and molecular mechanisms of HNSCC remains poor. METHODS: Robust rank aggregation method was performed to excavate the differentially expressed genes (DEGs) in five datasets (GSE6631, GSE13601, GSE23036, GSE30784, GSE107591) from the Gene Expression Omnibus. Search Tool for the Retrieval of Interacting Genes (STRING) database extracted hub genes from the protein-protein interaction network. The expression of the hub genes was validated using expression profile from The Cancer Genome Atlas and Oncomine database. The module analysis and disease-free survival analysis of the hub genes were analyzed by Cytoscape and the Kaplan-Meier curve, respectively. The expression of hub genes was verified in clinical specimens. The functions of MMP1 which is most important in hub genes were explored in vitro and in vivo. RESULTS: Totally, 235 DEGs were identified in the present study which consists of 103 up-regulated and 132 down-regulated genes which were significantly enriched in the molecular function of calcium ion binding followed in the biological process of skin development. The mainly enriched pathways were ECM (extracellular matrix)-receptor interaction (hsa04512) and protein digestion and absorption (hsa04974). Six hub genes were screened out which showed dramatically increased expression in HNSCC samples compared with normal samples, including COL4A1, MMP1, PLAU, RBP1, SEMA3C, and COL4A2. These hub genes all showed worse disease-free survival with higher expression and were up-regulated in HNSCC clinical samples. MMP1 was proved to promote cell growth, migration, and phosphorylation of AKT in vitro and to promote liver metastasis in vivo. CONCLUSION: Bioinformatics analysis identified six key genes in HNSCC. Of these, MMP1 is the most likely biomarker. It activates the AKT pathway and promotes tumor progression.
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Neoplasias de Cabeza y Cuello , Metaloproteinasa 1 de la Matriz , Carcinoma de Células Escamosas de Cabeza y Cuello , Biomarcadores de Tumor/genética , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Humanos , Metaloproteinasa 1 de la Matriz/genética , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
BACKGROUND: Neuroimmune communication plays an important role in allergic inflammation, but the neuroimmune regulation of allergic rhinitis remains unclear. OBJECTIVE: The goal of this study was to investigate the role of CD4-positive T lymphocyte (CD4+ T cells) adhesion to D-U87 neuron-like cells in mediating allergic rhinitis CD4+ T cell differentiation. METHODS: D-U87 neuron-like cells were derived from the human glioblastoma U87 cell line. CD4+ T cells were isolated from human peripheral blood using a magnetic separation technique. In vitro coculture of D-U87 neuron-like cells and CD4+ T cells was established. The number of adherent CD4+ T cells was counted using a fluorescence microscope. The percentages of CD4+IFNγ+ and CD4+IL4+ T cells and the levels of IFNγ and IL4 cytokines in the supernatant were measured by flow cytometry. RESULTS: The results showed that the number of adherent CD4+ T cells in patients with allergic rhinitis was significantly higher than that in healthy controls. In allergic rhinitis, the percentage of CD4+IL4+ T cells was significantly increased in the adherent group compared with that in the nonadherent group. Moreover, blocking ICAM1 and E-selectin decreased the number of adherent CD4+ T cells and the percentage of CD4+IL4+ T cells in allergic rhinitis. CONCLUSION: Adhesion contributes to CD4+IL4+ T cell differentiation in the in vitro coculture system of D-U87 neuron-like cells and allergic rhinitis CD4+ T cells, which may provide new insights into therapeutic strategies for allergic rhinitis.
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Interleucina-4 , Rinitis Alérgica , Humanos , Linfocitos T CD4-Positivos/metabolismo , Diferenciación Celular , Selectina E , Molécula 1 de Adhesión IntercelularRESUMEN
With the continuous updating of head and neck surgery concepts and techniques, more and more head and neck surgeries are developing in the direction of refinement.however, the more complete the surgery, the greater the possibility of subsequent nerve exposure and injury. Even a slight perturbation of the nerve may cause serious complications, such as pressure receptor failure.It is necessary to review the mechanisms and the characteristics of baroreceptor failure syndrome after head and neck tumor surgery.
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Neoplasias de Cabeza y Cuello , Presorreceptores , Cabeza , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Cuello/cirugía , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: Hypopharyngeal cancer accounts for 2% in head and neck cancers and has a poor prognosis. Cisplatin is a widely used chemotherapeutic drug in kinds of carcinomas, concluding hypopharyngeal cancer. However, the resistance of cisplatin appeared in recent years. Cisplatin-resistance has been partly explored before, but rarely in hypopharyngeal cancer. METHODS: We cultured the hypopharyngeal cancer cell (FaDu) and induced its cisplatin-resistant cell (FaDu/DDP4). Then we tested the differentially expressed genes (DEGs) between FaDu and FaDu/DDP4. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on the DEGs, and we drew the ceRNA networks of DEGs. Finally, we chose eight miRNAs and six mRNAs for qRT-PCR to verify our microarray. RESULTS: We induced cisplatin-resistant FaDu/DDP4 and proved its chemoresistance. The resistance index (RI) of FaDu/DDP4 was 2.828. DEGs contain 2,388 lncRNAs, 1,932 circRNAs, 745 mRNAs and 202 miRNAs. These 745 mRNAs were classified into three domains and 47 secondary GO terms. In KEGG pathway enrichment, the "TNF signaling pathway", "IL-17 signaling pathway" and "JAK-STAT signaling pathway" were potentially significant signaling pathways. Then, 52 lncRNAs, 148 circRNAs, 155 mRNAs and 18 miRNAs were selected to draw the network. We noticed several potential targets (as miR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1). At last, the eight miRNAs and six mRNAs that are critical RNAs in ceRNA network were verified by qRT-PCR. CONCLUSION: The microarray helped to find DEGs in cisplatin-resistant hypopharyngeal cancer. TNF, IL-17 and JAK-STAT signaling pathways might be more significant for cisplatin-resistance. MiR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1 might be potential genes inducing resistance.
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BACKGROUND: Semaphrin3A (Sema3A) was found to play a major role in immune regulation in autoimmune diseases and to be of importance in allergic disease. However, the effect of Sema3A on allergic rhinitis (AR) is not fully clear. OBJECTIVE: We sought to elucidate the effects of Sema3A on the regulation of dendritic cells (DCs) and naive CD4+ T cells in AR. METHODS: The expression of Sema3A in nasal mucosa was measured by immunohistochemical staining and western blotting. Human peripheral blood mononuclear cells were separated by the Ficoll-Hypaque method. DCs and naive CD4+ T cells were purified by magnetic selection. A human Sema3A Fc chimera was added to DCs and naive CD4+ T cells in vitro to evaluate the effect of Sema3A on the function of DCs and T cells. Labeling T cells with CFSE was used to determine cell proliferation. Flow cytometry was used to detect the DC maturation markers (CD40 and CD83) and T helper 17 (Th17) and regulatory T cell (Treg) percentages. ELISA was used to detect the IL10, IL17, IL4, and IFNγ cytokine levels. RESULTS: The expression of Sema3A in AR inferior turbinate tissue was lower than that in healthy control tissue. Compared with healthy control DCs, AR DCs showed decreased levels of the DC maturation markers CD40 and CD83 after Sema3A treatment. Furthermore, Sema3A decreased naive CD4+ T cell proliferation in AR. In addition, Sema3A increased the percentage of Tregs but had no obvious effect on Th17 cells. Moreover, Sema3A significantly increased levels of IL10 and IFNγ, and decreased level of IL4, but had no obvious effect on level of IL17. CONCLUSION: AR presented with low expression of Sema3A in nasal mucosa, and Sema3A could decrease DC maturation, T cell proliferation, and Treg polarization.
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Rinitis Alérgica , Semaforina-3A/inmunología , Linfocitos T Reguladores/inmunología , Células Dendríticas , Humanos , Leucocitos Mononucleares , Mucosa Nasal , Rinitis Alérgica/inmunología , Semaforina-3A/genéticaRESUMEN
Aim: To investigate the role of LINC01160 in nasopharyngeal carcinoma (NPC). Materials & methods: Using NPC cells CNE-2 and HNE-2 in vitro, we performed quantitative PCR to determine mRNA expression and western blotting to determine protein expression. CCK-8, transwell, flow cytometry and wound healing assays were done to examine the function of LINC01160 and STAT1. Chromatin immunoprecipitation PCR (ChIP-PCR) confirmed that STAT1 combines with the LINC01160 promoter region. Xenograft experiments were used to verify the role of STAT1 and LINC01160 in vivo. Results: LINC01160 is upregulated in NPC and can promote a malignant cell phenotype. STAT1 is a transcription factor of LINC01160 and can promote a malignant cell phenotype through upregulating LINC01160 expression. Conclusion: STAT1 can promote a malignant cell phenotype by upregulating LINC01160.
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Regulación Neoplásica de la Expresión Génica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , ARN Largo no Codificante/genética , Factor de Transcripción STAT1/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Conjuntos de Datos como Asunto , Femenino , Humanos , Ratones , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Invasividad Neoplásica/genética , Regiones Promotoras Genéticas/genética , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Nasopharyngeal carcinoma (NPC) is an epithelial cancer emerging from the lining of nasopharyngeal mucosa, with extremely frequent occurrence in east and southeast Asia. For the purpose of exploring roles of the dysregulated long non-coding RNA (lncRNA) in NPC, we identified a novel lncRNA LINC00669 with an apparent negative correlation to the overall survival from human NPC mRNA expression profiling databases. We further performed RNA pulldown coupled with mass spectrum to find out its target protein, and applied a series of in vitro and in vivo loss-and-gain-of function assays to investigate its oncogenic roles in NPC tumor development and progression. Our results demonstrated that LINC00669 competitively binds to the key JAK/STAT signaling pathway suppressor SOCS1, and insulates it from imposing ubiquitination modification on the pathway component of STAT1, which leads to its abnormal stabilization and activation. The activated STAT1 is then transferred into the nucleus and initiates the transcription of genes related to proliferation and invasion. In summary, our study reveals that the cytoplasmic resident lncRNA LINC00669 confers malignant properties on NPC cancer cells by facilitating a persistent activation of the JAK/STAT signaling pathway. Findings in the current study shed lights on prospects for treating NPC using strategies targeting the novel regulator of the JAK/STAT signaling.
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Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Janus Quinasa 1/metabolismo , Neoplasias Nasofaríngeas/patología , ARN Largo no Codificante/genética , Factor de Transcripción STAT1/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Movimiento Celular , Proliferación Celular , Humanos , Janus Quinasa 1/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Invasividad Neoplásica , Pronóstico , Factor de Transcripción STAT1/genética , Proteína 1 Supresora de la Señalización de Citocinas/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Parasympathetic nerve hypersensitivity contributes to the severity of allergic rhinitis (AR), but the precise mechanism underlying neuroimmune regulation in patients with AR remains unclear. This study investigated the effect of cholinergic nerve inhibition on AR CD4+ T-helper (Th)2-cell polarization and the underlying regulatory mechanism in vitro. METHODS: An in-vitro neuroimmune coculture model of D-U87 cells and CD4+ T cells was established. D-U87 cells with cholinergic neuron characteristics were used as cholinergic neuron models. CD4+ T cells were derived from peripheral blood monocytes from AR patients (n = 60) and control subjects (n = 40). Th1- and Th2-cell percentages were measured by flow cytometry. Proteins involved in related signaling pathways were analyzed by protein chip assay and Western blotting. RESULTS: The Th2-cell percentage among CD4+ T cells from AR patients was significantly increased after coculture with D-U87 cells and was decreased by ipratropium bromide (IB) treatment. In contrast, the Th1-cell percentage among control CD4+ T cells was significantly increased after coculture with D-U87 cells, but was unaltered by IB treatment. Furthermore, phosphorylated Akt (p-Akt) protein levels increased in CD4+ T cells from both controls and AR patients after coculture with D-U87 cells and decreased after IB treatment. However, higher p-Akt levels were observed in cells from AR patients than in cells from control subjects. Moreover, Akt inhibition decreased Th2-cell percentage in AR patients. CONCLUSION: In-vitro cholinergic nerve inhibition with IB decreased AR CD4+ T-cell polarization into Th2 cells partially through an Akt-dependent mechanism.
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Linfocitos T CD4-Positivos/citología , Neuronas Colinérgicas/inmunología , Rinitis Alérgica/inmunología , Adolescente , Adulto , Línea Celular , Técnicas de Cocultivo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-akt/inmunología , Transducción de Señal , Adulto JovenRESUMEN
Background The prevalence of both allergic rhinitis and bronchial asthma is high throughout the world; their mutual influence on each other has been documented in many studies. However, studies regarding surgical intervention are limited. Objective To evaluate the clinical significance of endoscopic vidian neurectomy on bronchial asthma outcomes in patients with coexisting refractory allergic rhinitis and asthma. Methods A total of 109 patients with moderate to severe persistent intractable allergic rhinitis and mild/moderate asthma were allocated to the bilateral endoscopic vidian neurectomy group (group 1) or conservative medication group (group 2) according to the patients' self-selection. The Rhinoconjunctivitis Quality of Life Questionnaire, Visual Analog Scale, Asthma Quality of Life Questionnaire, Total Asthma Symptom Score, and medication scores were evaluated at six months, one year, and three years after undergoing the initial treatments. Multivariate analysis was performed to determine which triggers of asthma attacks were associated with improved asthma outcomes in patients. Results Ninety-five patients were followed up for at least three years. Postoperative scores of Rhinoconjunctivitis Quality of Life Questionnaire and Visual Analog Scale were significantly lower than preoperative scores during follow-up in group 1 and were significantly lower than those of group 2. Postoperative scores of Asthma Quality of Life Questionnaire at the three follow-up time points were higher than the preoperative scores in group 1. The Total Asthma Symptom Score was not significantly decreased in group 1. The medication scores for allergic rhinitis and asthma were gradually reduced after surgery. At the end of the follow-up, the improvement rates for allergic rhinitis and asthma were 90.6% and 45.3%, respectively. Asthma outcomes were significantly improved by controlling rhinitis symptoms in patients whose asthma attacks were induced by "rhinitis onset" or "weather change." Conclusion Controlling allergic rhinitis symptoms by bilateral endoscopic vidian neurectomy can significantly improve asthma outcomes in patients whose asthma attacks are induced by rhinitis onset and/or cold air.
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Asma/cirugía , Desnervación , Endoscopía , Rinitis Alérgica/cirugía , Adolescente , Adulto , China , Desnervación/efectos adversos , Endoscopía/efectos adversos , Femenino , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento , Escala Visual Analógica , Adulto JovenRESUMEN
Anticholinergic agent, ipratropium bromide (IB) ameliorates symptoms of allergic rhinitis (AR) using neuroimmunologic mechanisms. However, the underlying molecular mechanism remains largely unclear. In the present study, 27 mice with AR induced by ovalbumin were randomly allocated to one of three groups: Model group, model group with IB treatment for 2 weeks, and model group with IB treatment for 4 weeks. Allergic symptoms were evaluated according to symptoms scores. Differentially expressed genes [microRNAs (miRNAs) and messenger RNAs (mRNAs)] of nasal mucosa were identified by microarray analysis. The expression levels of candidate genes were measured by reverse transcriptionquantitative polymerase chain reaction (RTqPCR). The data indicates that the symptoms scores in allergic mice were significantly reduced by IB treatment. In the nasal mucosa of allergic mice with IB treatment, 207 mRNAs and 87 miRNAs were differentially expressed, when compared with the sham group. IB treatment significantly downregulated the expression levels of interleukin4Rα and prostaglandin D2 synthase, whereas the leukemia inhibitory factor, A20 and nuclear receptor subfamily 4, group A, member 1 expression levels were upregulated. Similarly, the expression levels of mmumiR1243p/5p, 133b5p, 133a3p/5p, 3843p, 181a5p, 378a5p and 30715p were significantly increased. RTqPCR data further validated these mRNA and miRNA expression levels. Thus, IB treatment regulated expression of allergic immuneassociated mRNAs and miRNAs of the nasal mucosa in allergic mice, which may be associated with ameliorated nasal allergic symptoms.
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Antagonistas Colinérgicos/farmacología , MicroARNs/genética , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/genética , Transcriptoma/efectos de los fármacos , Transcriptoma/genética , Animales , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Mucosa Nasal/efectos de los fármacos , Ovalbúmina/genética , ARN Mensajero/genéticaRESUMEN
Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of the world, but is prevalent in South China area. Besides, therapeutic outcome is still unsatisfactory for patients with refractory and relapsed NPC, even though receiving a second line of docetaxel-based chemotherapy. These reasons require a better understanding of mechanisms underlying the carcinogenesis, malignancy and chemoresistance. In the basis of our previous finding of SSRP1 over-expression in NPC cell lines, this study continuously discovered up-regulated Ets-1, phosphor-Ets-1 and Pim-3 in NPC tissues with immunohistochemistry assay and revealed a close correlation of these up-regulated proteins with NPC proliferation and invasion. Using gene-silencing technology followed by western blot and immunocytochemistry detections, SSRP1 was found to facilitate the translocation of phosphor-Ets-1 from cytoplasm to cell nucleus, but have marginal effect on Ets-1 expression and phosphorylation. Pim-3 was positively regulated by Ets-1. In NPC HNE-1 cells, all SSRP1, Ets-1 and Pim-3 knockdown diminished the cell proliferation, enhanced the apoptosis, as well as inhibited the autophagy, invasion and clonogenicity in the presence or absence of docetaxel at IC25. Exposure of HNE-1 cells to docetaxel (IC25) alone had modest effect on cell proliferation and autophagy, and was not as effective as docetaxel treatment after knockdown of SSRP1, Ets-1 or Pim-3 on induction of the apoptosis and on inhibition of the invasion and clonogenicity. Our data indicate that SSRP1/Ets-1/Pim-3 signalling is tightly associated with the proliferation, apoptosis, autophagy, invasion and clonogenicity of NPC cells, and blockage of this signalling facilitates chemosensitivity of the cells to docetaxel.
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Proteínas de Unión al ADN/genética , Proteínas del Grupo de Alta Movilidad/genética , Neoplasias Nasofaríngeas/genética , Proteínas Serina-Treonina Quinasas/genética , Proteína Proto-Oncogénica c-ets-1/genética , Proteínas Proto-Oncogénicas/genética , Transducción de Señal/genética , Taxoides/uso terapéutico , Factores de Elongación Transcripcional/genética , Autofagia/genética , Carcinoma , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Docetaxel , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Proteínas del Grupo de Alta Movilidad/metabolismo , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Nasofaringe/efectos de los fármacos , Nasofaringe/metabolismo , Nasofaringe/patología , Invasividad Neoplásica , Proteínas Serina-Treonina Quinasas/metabolismo , Proteína Proto-Oncogénica c-ets-1/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Taxoides/farmacología , Factores de Elongación Transcripcional/metabolismoRESUMEN
OBJECTIVE: To investigate the potential risk factors and management of excessive epistaxis after endoscopic endonasal surgery (EES). METHOD: Six hundred and forty-one patients who underwent EES in our hospital from December 2011 to December 2012 were reviewed retrospectively. Factors which potentially affect the incidence of excessive epistaxis after EES were analyzed with univariate and multivariate logistic regression model. RESULT: The incidence rate of excessive epistaxis after EES was 8.4% in our study. Multivariate logistic regression analysis revealed that history of previous EES, along with other four factors, correlated significantly with the occurrence of excessive epistaxis after EES. CONCLUSIONS: Previous EES, along with other three factors, may increase the chance of excessive epistaxis after EES, while pre-operative corticosteroid therapy may reduce the risk to some extent.
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Endoscopía/efectos adversos , Epistaxis/etiología , Procedimientos Quírurgicos Nasales/efectos adversos , Complicaciones Posoperatorias , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nariz/cirugía , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
CONCLUSIONS: Our study suggested that the major risk factors for postoperative bleeding after nasal endoscopic surgery (NES) included hypertension, long-term non-steroidal anti-inflammatory drugs (NSAIDs), and previous nasal surgery. The use of preoperative corticosteroids is a valuable measure for reducing postoperative bleeding after NES. OBJECTIVES: To explore risk factors for postoperative bleeding after NES and find effective measures to reduce or prevent the condition. METHODS: A total of 641 patients who underwent NES were analyzed retrospectively. Univariate analysis and logistic regression were performed to find potential risk factors. RESULTS: The incidence of postoperative bleeding after NES was 8.4%. Multivariate logistic regression analysis revealed that the occurrence of postoperative bleeding after NES was positively associated with hypertension, long-term NSAIDs, previous NES, and modified submucosal septoplasty, but negatively associated with the use of preoperative corticosteroids.