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1.
Braz J Otorhinolaryngol ; 90(3): 101410, 2024.
Article in English | MEDLINE | ID: mdl-38490010

ABSTRACT

OBJECTIVE: Our aim in this study is to identify the core genes of chronic rhinosinusitis with nasal polyps and analyze the correlations between it and inflammation-related genes. METHODS: GSE72713 dataset containing gene expression data of ECRSwNP, nonECRSwNP and healthy samples was obtained from Gene Expression Omnibus (GEO) and filtered by limma to identify DEGs among three groups, then the functions and correlated pathways of DEGs were analyzed using GO and KEGG. The core DEGs were selected by the intersection of DEGs and the PPI network was constructed via STRING. The correlations between the expression levels of CRSwNP core gene and inflammation-related genes were analyzed via the Mann-Whitney U test. RESULTS: The DEGs among ECRSwNP, nonECRSwNP, and CTRL were filtered respectively, and enrichment analysis showed they were associated with olfaction and/or immune responses. The PPI network was constructed by 7 core DEGs obtained via the intersection among three groups, and ALOX15 was confirmed as the core gene in the network. Subsequently, the correlations between the expression levels of ALOX15 and inflammation-related genes were illustrated. CONCLUSION: In this study, the core gene ALOX15 was selected from the DEGs among ECRSwNP, nonECRSwNP, and CTRL. IL5, IL1RL1, and IL1RAP were found to exhibit a significant positive correlation with ALOX15. LEVEL OF EVIDENCE: Level 3.


Subject(s)
Inflammation , Nasal Polyps , Rhinitis , Sinusitis , Nasal Polyps/genetics , Humans , Sinusitis/genetics , Rhinitis/genetics , Chronic Disease , Inflammation/genetics , Arachidonate 15-Lipoxygenase/genetics , Gene Expression Profiling , Protein Interaction Maps/genetics , Case-Control Studies , Rhinosinusitis
2.
J Transl Med ; 20(1): 505, 2022 11 03.
Article in English | MEDLINE | ID: mdl-36329529

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors are promising tools in combating several cancers, including head and neck squamous cell carcinoma (HNSCC). However, a substantial portion of HNSCC patients do not respond to PD-L1 antibody. Here we describe a photodynamic therapeutic (PDT) approach to enhance anti-tumor effects of the anti-PD-L1 antibody. METHODS: Phototoxicity of PDT was confirmed using fluorescence microscopy, Cell Counting Kit-8 (CCK-8), Enzyme Linked Immunosorbent Assay (ELISA) and flow cytometry analyses. Phenotypic and functional maturation of immature DCs (imDCs) induced by PDT were measured using flow cytometry and ELISA. A mouse model was established using the HNSCC line, SCC7, and was used to evaluate therapeutic effects of PDT-DC vaccine in facilitating anti-tumor immunity of PD-L1 antibody. RESULTS: Immunogenic cell death (ICD) of SCC7 cells was induced by PDT with 0.5 µM of m-THPC and the 5 J/cm2 of light dose. ICD of SCC7 cells stimulated imDCs maturation. In vivo assays suggested that PDT-DC vaccine and anti-PD-L1 mAb synergistically induced anti-tumor immunity and suppressed tumor progression. CONCLUSION: PDT-DC vaccine enhances therapeutic effects of PD-L1 antibody, which might provide a novel approach for HNSCC immunotherapy.


Subject(s)
Head and Neck Neoplasms , Immune Checkpoint Inhibitors , Mice , Animals , Squamous Cell Carcinoma of Head and Neck/therapy , Disease Models, Animal , B7-H1 Antigen/metabolism , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Head and Neck Neoplasms/therapy , Dendritic Cells
3.
Ann N Y Acad Sci ; 1518(1): 299-314, 2022 12.
Article in English | MEDLINE | ID: mdl-36303271

ABSTRACT

The pathogenesis of chronic rhinosinusitis (CRS) is largely unknown, but accumulating evidence supports the role of the airway epithelium in its pathophysiology. In our study here, we evaluated whether epidermal growth factor (EGF) regulates a hypoxia-inducible factor 1α (HIF-1α)-microRNA-21 (miR-21)-aquaporin 4 (AQP4) axis in nasal epithelial cells from CRS patients. We found that, compared with normal sinus mucosa, EGF, HIF-1α, and miR-21 were upregulated and AQP4 was downregulated in sinus mucosa from patients with CRS and in a CRS mouse model. It was established that EGF upregulated HIF-1α and miR-21 expression, that HIF-1α regulated miR-21 transcription, and that the AQP4 gene was a target of miR-21. Knockdown of EGF and HIF-1α mRNAs and of miR-21, or overexpression of AQP4 mRNA, inhibited proliferation and promoted apoptosis of hypoxia-exposed human nasal epithelial cells, effects that were associated with reduced levels of α-SMA, fibronectin, and vimentin, as well as promoted caspase-3 activity and E-cadherin levels. In the mouse CRS model, EGF elevation increased in vivo production of inflammatory IL-4 and IFN-γ to promote CRS, which was reversed by AQP4 elevation. Collectively, EGF upregulates HIF-1α and miR-21 expression to inhibit AQP4 expression, thereby promoting the proliferation of nasal epithelial cells and the development of CRS.


Subject(s)
MicroRNAs , Sinusitis , Animals , Humans , Mice , Aquaporin 4/genetics , Epidermal Growth Factor/metabolism , Hypoxia , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , MicroRNAs/metabolism , RNA, Messenger , Sinusitis/genetics , Sinusitis/metabolism
4.
Sci Rep ; 10(1): 20627, 2020 Nov 20.
Article in English | MEDLINE | ID: mdl-33219266

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

5.
Stem Cell Res Ther ; 11(1): 151, 2020 04 09.
Article in English | MEDLINE | ID: mdl-32272958

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by persistent symptomatic inflammation of the nasal passage and sinus mucosa. Various microRNAs (miRs) have been implicated in CRS. Hence, the current study was conducted to explore the effect of microRNA-761 (miR-761) on remodeling of nasal mucosa and epithelial-mesenchymal transition (EMT). METHODS: Bioinformatics analysis was initially performed to predict the differentially expressed genes (DEGs) associated with CRS. Gene targeting relationship between miR-761 and lipocalin 2 (LCN2) was analyzed by bioinformatics analysis and verified using dual-luciferase reporter gene assay. Histopathological analyses of the nasal mucosa tissues were conducted via hematoxylin-eosin (HE) and alcian blue (AB)-periodic acid Schiff (PAS) staining. ELISA was employed to determine the IL-8 and MMP-9 levels. To define downstream pathway of miR-761, levels of proteins related to LCN2/Twist1 signaling pathway were assessed. Additionally, the effects of miR-761 on EMT, proliferation, and apoptosis were determined. RESULTS: LCN2 was highly expressed in CRS. LCN2 was a target of miR-761. miR-761 overexpression or LCN2 silencing decreased IL-8 and MMP-9 levels and morphological changes in nasal epithelial tissue from CRS mice. Overexpressed miR-761 or silenced LCN2 decreased the expression of LCN2 and Twist1, indicating LCN2/Twist1 signaling pathway was inactivated. Moreover, miR-761 overexpression or LCN2 silencing reduced the expression of N-cadherin and vimentin, while increased that of E-cadherin, suggesting inhibition of EMT. Furthermore, miR-761 overexpression or LCN2 silencing promoted cell proliferation and inhibited cell apoptosis in CRS. CONCLUSION: Taken together, miR-761 suppressed the remodeling of nasal mucosa through inhibition of LCN2 and the LCN2/Twist1 signaling pathway.


Subject(s)
Epithelial-Mesenchymal Transition , MicroRNAs , Animals , Cell Proliferation , Lipocalin-2/genetics , Mice , MicroRNAs/genetics , Nasal Mucosa
6.
Clin Transl Sci ; 13(1): 169-178, 2020 01.
Article in English | MEDLINE | ID: mdl-31794148

ABSTRACT

As an extremely prevalent disease worldwide, allergic rhinitis (AR) is a condition characterized by chronic inflammation of the nasal mucosa. To identify the finer molecular mechanisms associated with the AR susceptibility genes, differentially expressed genes (DEGs) in AR were investigated. The DEG expression and clinical data of the GSE19187 data set were used for weighted gene co-expression network analysis (WGCNA). After the modules related to AR had been screened, the genes in the module were extracted for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, whereby the genes enriched in the KEGG pathway were regarded as the pathway-genes. The DEGs in patients with AR were subsequently screened out from GSE19187, and the sensitive genes were identified in GSE18574 in connection with the allergen challenge. Two kinds of genes were compared with the pathway-genes in order to screen the AR susceptibility genes. Receiver operating characteristic (ROC) curve was plotted to evaluate the capability of the susceptibility genes to distinguish the AR state. Based on the WGCNA in the GSE19187 data set, 10 co-expression network modules were identified. The correlation analyses revealed that the yellow module was positively correlated with the disease state of AR. A total of 89 genes were found to be involved in the enrichment of the yellow module pathway. Four genes (CST1, SH2D1B, DPP4, and SLC5A5) were upregulated in AR and sensitive to allergen challenge, whose potentials were further confirmed by ROC curve. Taken together, CST1, SH2D1B, DPP4, and SLC5A5 are susceptibility genes to AR.


Subject(s)
Gene Regulatory Networks/immunology , Genetic Predisposition to Disease , Rhinitis, Allergic/genetics , Biomarkers/analysis , Computational Biology/methods , Datasets as Topic , Dipeptidyl Peptidase 4/analysis , Dipeptidyl Peptidase 4/genetics , Gene Expression Profiling/statistics & numerical data , Gene Expression Regulation/immunology , Humans , Nasal Mucosa/immunology , Nasal Mucosa/pathology , Oligonucleotide Array Sequence Analysis/statistics & numerical data , Predictive Value of Tests , ROC Curve , Rhinitis, Allergic/epidemiology , Rhinitis, Allergic/immunology , Rhinitis, Allergic/pathology , Risk Assessment/methods , Salivary Cystatins/analysis , Salivary Cystatins/genetics , Symporters/analysis , Symporters/genetics , Transcription Factors/analysis , Transcription Factors/genetics
7.
Sci Rep ; 9(1): 11823, 2019 08 14.
Article in English | MEDLINE | ID: mdl-31413263

ABSTRACT

Choline phosphate-based delivery systems can target the acidic tumor microenvironment. In this study, we set out to evaluate the diagnostic value of Choline phosphate cytidylyltransferase-α (CCTα) in laryngeal squamous cell cancer (LSCC). The expression of CCTα was detected using immunohistochemistry in 50 LSCC patients' tissues and 16 vocal polyps as control group. Then, clinical data was collected and we used receiver operating characteristic curve (ROC) to estimate the potential of CCTα as diagnostic biomarker. We found CCTα levels to be significantly high in the tissues derived from LSCC patients, (p < 0.001). Further, we observed a positive correlation of CCTα with tumor size (p < 0.001), TNM stage (p < 0.001), lymph node metastasis (p < 0.001) as well as the grade of LSCC malignancy (p < 0.001). Furthermore, AUC was determined to be 0.939 by ROC, and the optimal cutoff value 3.100, with 76.0% sensitivity and 100% specificity. We also found an epigenetic basis of CCTα over-expression in LSCC tissues with significantly reduced methylation of CCTα in LSCC tissues, compared to vocal polyps (p < 0.001). These results support epigenetically-induced over-expression of CCTα as a potential diagnostic marker for LSCC.


Subject(s)
Biomarkers, Tumor/metabolism , Choline-Phosphate Cytidylyltransferase/metabolism , Laryngeal Neoplasms/diagnosis , Squamous Cell Carcinoma of Head and Neck/diagnosis , Aged , Case-Control Studies , Female , Humans , Laryngeal Neoplasms/pathology , Male , Middle Aged , Prognosis , Squamous Cell Carcinoma of Head and Neck/pathology , Tumor Microenvironment
8.
Acta Otolaryngol ; 139(10): 890-894, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31452425

ABSTRACT

Background: Allergic rhinitis combined with chronic rhinosinusitis with nasal polyps (ARwCRSwNP) is very common clinically. Conventionally, the treatment for these patients is surgical method for CRSwNP followed by treatment with a nasal steroid spray or other antiallergic drugs to control AR. In recent years, some rhinologists introduced vidian neurectomy (VN) or posterior nasal neurectomy (PNN) into endoscopy to treat refractory AR and reported an encouraging outcome. Furthermore, we explore the control of recurrence of nasal polyps and improvement in symptoms after endoscopic PNN for the treatment of ARwCRSwNP. Objective: To investigate the control of recurrence of nasal polyps and improvement in symptoms after endoscopic PNN for the treatment of ARwCRSwNP. Methods: Eighty-five patients with ARwCRSwNP who were admitted to our hospital from November 2016 to July 2018 were enrolled in two groups. Group A underwent conventional functional endoscopic sinusitis surgery (FESS) combined with PNN; group B underwent conventional FESS alone. VAS, RQLQ, SNOT-22 and postoperative nasal endoscopy were used to evaluate the improvement in symptoms and the recurrence of nasal polyps. Results: The experimental group had better control of sneezing (p < .05) and rhinorrhea (p < .01) than the control group. For those who underwent surgery more than 6 months prior in both groups, the recurrence rate was 29.6% (8/27) in the experimental group and 44.4% (8/18) in the control group, and there was no significant difference (χ2 = .483, p = .487). Conclusion: FESS combined with PNN can improve the symptoms of sneezing and rhinorrhea caused by ARwCRSwNP more obviously than FESS alone, but there is no clear statistical advantage of this procedure for improving the overall symptoms and controlling the recurrence of nasal polyps.


Subject(s)
Denervation , Endoscopy , Nasal Polyps/surgery , Rhinitis, Allergic/complications , Rhinitis, Allergic/surgery , Sinusitis/surgery , Adult , Chronic Disease , Female , Humans , Male , Middle Aged , Nasal Polyps/complications , Paranasal Sinuses/innervation , Sinusitis/complications , Treatment Outcome
9.
Inflammation ; 42(4): 1370-1382, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31028575

ABSTRACT

Chronic rhinosinusitis (CRS) is a common disease characterized by inflammation of the nose and paranasal sinuses lasting over 12 weeks. This study aims to evaluate the effect of desmoglein 3 (DSG3) on inflammatory response and goblet cell mucin secretion in a mouse model of CRS. The CRS-related differentially expressed genes and disease genes were screened using microarray-based gene expression analysis. Subsequently, CRS mouse models were established. The levels of pro-inflammatory factors TNF-α, IL-6, and IL-8 were measured by ELISA. In addition, loss-of-function experiment was conducted using siRNAs targeting DSG3 and ß-catenin. The secretion of mucins MUC5B and MUC5AC in goblet cells was detected, and the apoptosis of goblet cells was assessed. The regulatory effect of DSG3 on the Wnt/ß-catenin signaling pathway was analyzed by determining the mRNA and protein levels of DSG3, Wnt, ß-catenin, and GSK3ß. DSG3 was identified to be an upregulated gene in CRS, which was further documented in CRS mice models. Elevated inflammation and mucin production were noted in CRS mice models. Also, it was found that DSG3 or ß-catenin silencing could decrease the levels of TNF-α, IL-6, and IL-8, and the positive rates of MUC5B and MUC5AC while enhancing goblet cell apoptosis. The Wnt/ß-catenin signaling pathway was blocked by DSG3, evidenced by downregulated Wnt and ß-catenin as well as upregulated GSK3ß mRNA and protein levels. Overall, this study provides evidence that silencing DSG3 could inhibit the activation of the Wnt/ß-catenin signaling pathway, thus alleviating CRS.


Subject(s)
Desmoglein 3/genetics , Goblet Cells/drug effects , Inflammation/drug therapy , Rhinitis/metabolism , Sinusitis/metabolism , Wnt Signaling Pathway/drug effects , Animals , Chronic Disease , Desmoglein 3/pharmacology , Disease Models, Animal , Gene Silencing , Goblet Cells/metabolism , Mice , Mucins/drug effects , Mucins/metabolism , Rhinitis/drug therapy , Sinusitis/drug therapy , beta Catenin/drug effects , beta Catenin/metabolism
10.
J Cell Physiol ; 234(2): 1442-1451, 2019 02.
Article in English | MEDLINE | ID: mdl-30132853

ABSTRACT

Human dental pulp stem cells (hDPSCs) are primarily derived from the pulp tissues of permanent third molar teeth. They were widely used in human bone tissue engineering. It was previously indicated that microRNA (miR) expressions are closely associated with hDPSCs development. However, the specific effect of miR-488 on hDPSCs still remains unclear. In this study, we aimed to investigate effects of miR-488 on the differentiation of hDPSCs into odontoblast cells through the p38 mitogen-activated protein kinases (MAPK) signaling pathway by binding to MAPK1. The hDPSCs were isolated and cultured in vitro. Dual-luciferase reporter gene assay was performed to test the relationship between MAPK1 (p38) and miR-488. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expressions of p38 MAPK signaling pathway-related genes (MAPK1, Ras, and Mitogen-activated protein kinase kinase 3/6 [MKK3/6]), along with expressions of dentin Sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteonectin (OCN). ALP staining and alizarin red staining were conducted to detect ALP activity and degree of mineralization. Initially, we found that MAPK1 was the target gene of miR-488. Besides, downregulation of miR-488 was observed to stimulate the p38 MAPK signaling pathway and to increase the messenger RNA and protein expressions of DSPP, ALP, and OCN. Furthermore, ALP activity and formation of a mineralized nodule in hDPSCs were enhanced upon downregulation of miR-488. The aforementioned findings provided evidence supporting that downregulation of miR-488 promotes odontoblastic differentiation of hDPSCs through the p38 MAPK signaling pathway by targeting MAPK1, paving the basis for further study about hDPSCs.


Subject(s)
Cell Differentiation , Dental Pulp/enzymology , MicroRNAs/metabolism , Odontoblasts/enzymology , Stem Cells/enzymology , Tooth Calcification , p38 Mitogen-Activated Protein Kinases/metabolism , Dental Pulp/cytology , Down-Regulation , Enzyme Activation , HEK293 Cells , Humans , MicroRNAs/genetics , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Signal Transduction
11.
Pathol Oncol Res ; 25(4): 1437-1443, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30361911

ABSTRACT

To study the expression of programmed death-ligand 1 (PD-L1), and its effects on CD8+ tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) in human laryngeal squamous cell carcinoma. Sixty-nine patients with laryngeal carcinoma and 10 with vocal cord leukoplakia received tumor resection at Neck Surgery Department in the Second Affiliation Hospital of Jilin University (Changchun, Jilin) from Jan. 2010 to Dec. 2015. The expressions of PD-L1, CD8, CD16 and CD206 in laryngeal carcinoma, paracancerous and vocal cord leukoplakia tissues were detected with immunohistochemistry. The associations between PD-L1 expression and clinicopathologic features, expression of TAMs and CD8+ T cell infiltration were analyzed. Expression of PD-L1 is significantly higher in laryngeal carcinoma than in paracancerous or leukoplakia tissue. The expression of PD-L1 is closely associated with stage of laryngeal cancer, histological differentiation and neck lymphatic metastasis. PD-L1 expression is negatively correlated with the number of CD8+ TILs and CD16+ cells (M1 type TAMs), while is positively associated with CD206+ (M2 type TAMs). PD-L1 is highly expressed in the laryngeal cancer with the tumor microenvironment immunosuppression.


Subject(s)
B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Squamous Cell/immunology , Laryngeal Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Tumor Microenvironment/immunology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/secondary , Female , Follow-Up Studies , Humans , Laryngeal Neoplasms/metabolism , Laryngeal Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged
12.
Wideochir Inne Tech Maloinwazyjne ; 13(4): 533-538, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30524626

ABSTRACT

INTRODUCTION: This is a novel minimally invasive surgical method for maxillary sinus mucoceles and antrochoanal polyps. AIM: To describe a modified technique of inferior meatal fenestration with a mucosal flap for maxillary sinus diseases and to present a case series of subjects who underwent this procedure. The novel surgical technique and indications for this approach are also discussed. MATERIAL AND METHODS: The authors analyzed data from 32 cases involving patients who underwent resection of maxillary sinus mucoceles and antrochoanal polyps via modified endoscopic inferior meatal fenestration with a mucosal flap in the period from January, 2011 to January, 2016. The group included 19 men and 13 women, and the patients' mean age was 36.2 years (range: 11-56 years). Preoperative and postoperative imaging studies were available in all cases and were reviewed. RESULTS: Thirty-two cases are included in this study. The appearance of nasal and (or) maxillary sinus mucosa was observed in the follow-up at 1 month, 3 months and 6 months using endoscopes. Postoperative computed tomography was performed for only 9 patients in this study. The mean follow-up period was 56 (range: 10-82) months in these cases. All patients had an uneventful post-operative period. Postoperative symptoms were relieved gradually for 1 to 2 weeks after the operation. No patients experienced recurrent symptoms related to the mucocele. Mucocele and polyps recurrence was not observed. No patient showed re-stenosis and obstruction of the nasal cavity, facial pain or numbness during follow-up. CONCLUSIONS: Maxillary sinus mucoceles and antrochoanal polyps are completely excised via modified endoscopic inferior meatal fenestration with a mucosal flap. It could keep the nasal lateral wall intact.

13.
Cancer Cell Int ; 18: 110, 2018.
Article in English | MEDLINE | ID: mdl-30123088

ABSTRACT

BACKGROUND: The aim of the study was to investigate the effect associated with the protein expression of VEGF, JAK2 and STAT3 on the clinicopathologic characteristics and prognosis in the development and progression of nasopharyngeal carcinoma (NPC). METHODS: Fifty NPC patients in addition to 20 patients with chronic nasopharyngitis (CNP) were recruited for the purposes of the study. Western blotting and immunohistochemistry methods were employed to evaluate the protein expressions of JAK2, STAT3 and VEGF in the NPC and CNP tissues, with their respective correlations with the clinicopathologic characteristics of NPC patients subsequently analyzed. Spearman's rank correlation coefficient and Kaplan-Meier method were conducted to evaluate the respective correlations of JAK2, STAT3 and VEGF with NPC as well as the survival rates of patients with NPC. Cox regression analyses was performed in determine the prognostic NPC factors. RESULTS: Compared with the CNP tissues, the NPC tissues exhibited elevated levels of JAK2, STAT3 and VEGF which were subsequently determined to share a positive correlation with T stages, lymph node metastasis (LNM), N stages and clinical stages, while a negative correlation with survival rates were observed in the NPC patients. Positive correlations between the expressions of JAK2, STAT3 and VEGF were detected among the NPC tissues. NPC patients survival time with negative expressions of JAK2, STAT3 and VEGF were observed to be longer than that of NPC patients with positive expressions of JAK2, STAT3 and VEGF. T stage, LNM, N stage, clinical stage. The expressions of JAK2, STAT3 and VEGF were discovered to be independent risk factors associated with the prognosis of patients with NPC. CONCLUSION: The results obtained from the present study support the notion that higher expressions of JAK2, STAT3 and VEGF may be correlated with the clinicopathologic characteristics and prognosis of patients suffering from NPC.

14.
Cancer Biomark ; 23(1): 107-123, 2018.
Article in English | MEDLINE | ID: mdl-29991129

ABSTRACT

OBJECTIVE: Accumulating studies have revealed that microRNAs (miRs) play a critical role in the development and progression of nasopharyngeal carcinoma (NPC), which is a disease with a remarkable racial and geographical distribution. In our study, through the alteration in the expression of microRNA-185 (miR-185) in NPC cells by microarray-based gene expression profiling, we subsequently evaluated its ability to influence NPC cells and associated mechanism. METHODS: The expressions of miR-185 and HOXC6 in NPC and paracancerous tissues collected from patients with NPC were detected. The CNE-2 cells with the lowest miR-185 among the five NPC cell lines (CNE-1, CNE-2, HNE-1, HNE-2, and 5-8F) were selected and transfected with a series of mimic or inhibitor of miR-185, or shRNA-against HOXC6. The Kaplan-Meier method was used to analyze the survival of patients. Besides, the reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to determine the levels of related genes/proteins. By means of cell counting kit-8 (CCK-8) assay, transwell assay, flow cytometry, and AO staining, the influences miR-185 has on the processes associated with NPC, including cell proliferation, invasion, apoptosis and autophagy were evaluated. RESULTS: NPC was observed to decrease miR-185 but increase HOXC6. Dual luciferase reporter gene assay demonstrated that HOXC6 is a target gene of miR-185. Increased mRNA and protein levels of Bax, caspase-3, LC3 and Beclin1 and reduced levels of HOXC6, TGF-ß1, mTOR, Cyclin D1, PCNA, Bcl-2 were found by overexpression of miR-185. High expression of miR-185 and low expression of HOXC6 had longer survival time of NPC patients. Overexpressed miR-185 enhanced cell apoptosis and autophagy, and reduced cell proliferation and invasion, while miR-185 inhibitor was observed to have induced effects on the CNE-2 cells. CONCLUSION: Overall, the data show that miR-185 could negatively target HOXC6 to suppress cell proliferation, promotes apoptosis and autophagy through inhibiting TGF-ß1/mTOR axis in NPC. Thus, miR-185 is useful strategy for the treatment of NPC.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma/genetics , Homeodomain Proteins/genetics , MicroRNAs/genetics , Nasopharyngeal Neoplasms/genetics , Adult , Apoptosis/genetics , Autophagy/genetics , Carcinoma/pathology , Caspase 3/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/antagonists & inhibitors , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/pathology , Neoplasm Proteins , Neoplasm Staging , RNA, Messenger/genetics , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , TOR Serine-Threonine Kinases/genetics , Transforming Growth Factor beta1/genetics
15.
J Craniofac Surg ; 28(6): 1534-1536, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28692517

ABSTRACT

A 50-year-old woman presented with gradually increasing right-sided facial numbness. Neuroimaging revealed a lesion in the right cavernous sinus mimicking meningioma. The resection of the right cavernous sinus neoplasm was implemented via endoscopic endonasal approach under general anesthesia. Histological examination of the surgical specimen revealed adenoid cystic carcinoma. Adenoid cystic carcinoma in the cavernous sinus is extremely rare as a primary lesion and challenging to manage. Little data exist to guide treatment when this tumor extends to involve the structure of cavernous sinus. Our study illustrates that endoscopic endonasal approach is a good choice for resection of the tumor in the cavernous sinus.


Subject(s)
Carcinoma, Adenoid Cystic , Cavernous Sinus , Nose/surgery , Skull Base Neoplasms , Cavernous Sinus/pathology , Cavernous Sinus/surgery , Female , Humans , Middle Aged
16.
Cancer Biomark ; 16(2): 291-300, 2016.
Article in English | MEDLINE | ID: mdl-26756620

ABSTRACT

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common head and neck cancer with an incidence of 10-30 cases per 100,000 in southern China. Although primary treatment includes radiation therapy, prognosis is still unsatisfactory. OBJECTIVE: In this study, we examined the role of HNF1A-AS in NPC progression in vitro and in vivo. METHODS: Relative levels of long non-coding RNA (LncRNA), HNF1A-AS, were evaluated in tumor tissues from 20 patients with NPC as well as from cultured NPC cell lines. Lentivirus-mediated HNF1A-AS knockdown was conducted in NPC cell lines, CNE-2 and SUNE-1. Cell migration and invasion abilities were estimated in vitro by colony-formation, wound-healing, and transwell assays. Cell cycle analysis was used to further examine the role of HNF1A-AS in cell proliferation. The tumor size of 24 male mice with or without HNF1A-AS knockdown was monitored once a week. The underlying mechanism of HNF1A-AS-mediated cell proliferation was studied by western blot analysis. RESULTS: Lentivirus-mediated HNF1A-AS knockdown suppressed cell proliferation and migration abilities. In mice injected with CNE-2 and SUNE-1, depletion of HNF1A-AS caused inhibition of tumor growth, whereas cell cycle analysis showed that HNF1A-AS-knockdown resulted in cell accumulation in the G0/G1 phase. Moreover, HNF1A-AS was found to be associated with epithelial to mesenchymal transition. CONCLUSIONS: Overall, our results suggest that LncRNA, HNF1A-AS potentially regulates NPC tumorigenesis. This could help in development of new strategies for NPC diagnosis and treatment.


Subject(s)
Gene Expression Regulation, Neoplastic , Hepatocyte Nuclear Factor 1-alpha/genetics , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , RNA, Long Noncoding , Animals , Carcinoma , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Disease Models, Animal , Epithelial-Mesenchymal Transition/genetics , Gene Knockdown Techniques , Heterografts , Humans , Male , Mice , Nasopharyngeal Carcinoma , Neoplasm Metastasis , RNA, Small Interfering/genetics , Tumor Burden , Tumor Stem Cell Assay , Up-Regulation
17.
Article in Chinese | MEDLINE | ID: mdl-26665457

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the safety and effectiveness of balloon sinuplasty, and to summarize the main points of its use. METHOD: Fifteeen patients (41 sinuses) were offered treatment with a new technique of balloon sinuplasty and followed for 3 to 6 months after surgery, including "balloon-only" patients and "hybrid" patients. Effectiveness was evaluated by endoscopic examination and computed tomographic (CT) scan. The effect of the operation was tested by the Lund-Mackay CT scores, and the patient's subjective symptoms were tested by the sino-nasal outcome test-20 (SNOT-20) to evaluate postoperative condition. RESULT: Fifteeen patients (41 sinuses) were followed after surgery, including 9 "balloon-only" patients and 6 "hybrid" patients. No unanticipated adverse effects were noted in any patients. Endoscopic examination showed the sinus ostium was opening well, and CT scan showed the lesions apparently disappeared. Lund-Mackay CT scores showed that all patients postoperative scores were significantly improved from baseline at 3 months and 6 months. SNOT-20 showed that all patients postoperative scores were significantly improved from baseline at 3 months and 6 months. There was no significant difference between the "balloon-only" patients and "hybrid" patients. Operation curative effect is very confirmed, and subjective symptoms improved significantly. CONCLUSION: Balloon sinuplasty can not only open nasal sinus effectively, but also preserve normal tissue structure and mucous membrane of nasal cavity and nasal sinus. Balloon sinuplasty appears to be a safe, effective and minimally invasive treatment option to relieve sinus ostial obstruction. Patients who received balloon catheter sinusotomy in endoscopic sinus surgery had significant improvement after surgery. Balloon sinuplasty can also be combined with the endoscopic sinus surgery to achieve a better therapeutic effect. It is worth of clinical promotion and application.


Subject(s)
Endoscopy , Nasal Surgical Procedures/methods , Paranasal Sinus Diseases/surgery , Paranasal Sinuses/surgery , Airway Obstruction , Humans , Postoperative Period , Tomography, X-Ray Computed , Treatment Outcome
18.
Cell Biochem Biophys ; 71(1): 261-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25241082

ABSTRACT

The objective of this study is to investigate the chemoresistance of CD133(+) cancer stem cells in Hep-2 cells of laryngeal cancer and detect the expression mRNA and protein levels of BMI-1 in CD133(+) cells and CD133(-) cells. The response of Hep-2 cells to different chemotherapeutic agents was investigated, and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133, and the CD133(+) subset of cells was separated and analyzed chemotherapy resistance. Colony formation assays were studied and cells were injected subcutaneously into axillary fossa of node mice to measure the tumor-forming ability. RT-PCR and Western blot analyses were used to detect the expression levels of BMI-1 in the different subpopulation cells. It was concluded that chemotherapy enriched the CD133(+) subpopulation 2-fourfold, relative to the untreated cells. 1.55 ± 0.28% of Hep-2 cells were observed to be CD133(+) cells. Flow cytometric analysis revealed that after the treatment with these chemotherapeutic agents, the expression of CD133 was up to 5.16 ± 0.86%, 4.94 ± 0.58%, 3.66 ± 0.59%. After 5-FU treatment, the expression of CD133 was 6.7 ± 1.6% relative to the untreated mice 2.6 ± 0.96% by nude mice tumor xenograft model. CD133(+) cancer stem cells were more resistant to chemotherapy; the proliferation capability and tumor-forming ability were no difference after chemotherapy. Semi-quantitative RT-PCR and Western blot analyses provided strong evidence that BMI-1 expression in CD133(+) cells is different from CD133(-) cells remarkably. Taken together, it was confirmed that CD133(+) cancer stem cells were chemoresistant and BMI-1 was highly expressed in these CD133(+) cells.


Subject(s)
Laryngeal Neoplasms/pathology , Neoplastic Stem Cells/metabolism , Polycomb Repressive Complex 1/metabolism , AC133 Antigen , Animals , Antigens, CD/metabolism , Carboplatin/pharmacology , Carcinogenesis/drug effects , Cell Line, Tumor , Docetaxel , Drug Resistance, Neoplasm , Fluorouracil/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Glycoproteins/metabolism , Humans , Mice , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/pathology , Peptides/metabolism , Polycomb Repressive Complex 1/genetics , Taxoids/pharmacology
19.
Asian Pac J Trop Med ; 7(11): 867-72, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25441985

ABSTRACT

OBJECTIVE: To explore the inhibitive and apoptosis inductive effect of IL-24 genes on CD133(+) laryngeal cancer cells in Hep-2 line. METHODS: Human peripheral blood monocytes were isolated. The total RNA was extracted by using Trizol method and reverse transcripted into cDNA using RT-PCR method. Primers P1 and P2 was designed for the amplification of human IL-24 genes. After confirmation of agarose gel electrophoresis tests, TA was cloned into pMD19-T simple vector. Nhe I and Xho I double digesting human IL-24 and pIRES2-ZsGreen1 and eukaryotic expression vector were used to establish the pIRES2-ZsGreen1-hIL-24 vector, and detected by enzyme digestion and gene sequencing methods. Flow cytometry (FCM) was used to isolate CD133(+) cells from Hep-2 cells. CD133(+) cells were transfected with pIRES2-ZsGreen1-hIL-24 through liposome 2000. After detection, MTT and FCM were used to observe the effect of IL-24 gene on CD133(+) laryngeal cancer Hep-2 cells. RESULTS: Lipotin mediated transfection of recombinant pIRES2-ZsGreen1-hIL-24 plasmid into CD133(+) Hep-2 could expressed IL-24 gene in cells stably. MTT results showed that IL-24 transfected group was significantly suppressed compared to empty vector group and control group (P<0.05); FCM results showed that the apoptosis rate of experimental group increased significantly compared to empty vector group and control group (P<0.05). CONCLUSIONS: IL-24 gene expressions can inhibit proliferation of CD133(+) laryngeal cells in Hep-2 line and promote their apoptosis.

20.
Int J Clin Exp Med ; 7(10): 3305-12, 2014.
Article in English | MEDLINE | ID: mdl-25419362

ABSTRACT

Endoscopy is essential for the diagnosis and treatment of cancers derived from the larynx. However, a laryngoscope with conventional white light (CWL) has technical limitations in detecting small or superficial lesions on the mucosa. Narrow band imaging especially combined with magnifying endoscopy (ME) is useful for the detection of superficial squamous cell carcinoma (SCC) within the oropharynx, hypopharynx, and oral cavity. A total of 3675 patients who have come to the outpatient clinic and complained of inspiratory stridor, dyspnea, phonation problems or foreign body sensation, were enrolled in this study. We describe the glottic conditions of the patients. All 3675 patients underwent laryngoscopy equipped with conventional white light (CWL) and NBI system. 1149 patients received a biopsy process. And 1153 lesions were classified into different groups according to their histopathological results. Among all the 1149 patients, 346 patients (312 males, 34 females; mean age 62.2±10.5 years) were suspected of having a total of 347 precancerous or cancerous (T1 or T2 without lymphnode involvement) lesions of the larynx under the CWL. Thus, we expected to attain a complete vision of what laryngeal lesions look like under the NBI view of a laryngoscope. The aim was to develop a complete description list of each laryngeal conditions (e.g. polyps, papilloma, leukoplakia, etc.), which can serve as a criteria for further laryngoscopic examinations and diagnosis.

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