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Head and neck squamous cell carcinoma (HNSCC) is a kind of malignant tumor characterized by metastasis and local invasion. Its recurrence rate is high after surgery and radiotherapy, and the prognosis and quality of life are poor. In recent years, programmed death-1 (PD-1) inhibitors have been recommended in National Comprehensive Cancer Network (NCCN) guidelines for the treatment of recurrent, unresectable, and metastatic HNSCC, and their efficacy has been remarkable. PD-1 inhibitors constitute a new treatment for the patients with advanced HNSCC who are refractory to platinum-based chemotherapy and can increase the probability of surgical resection, reduce the risk of postoperative dysfunction, and improve the survival and quality of life. This article reviews the structure and mechanism of the PD-1/PD-L1 immunocheckpoint, as well as research progress on its inhibitors in the treatment of HNSCC.
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@#[Abstract] Objective: To explore the expression and regulation mechanism of Dickkopf-1 (DKK1) in head and neck squamous cell carcinoma (HNSCC) tissues. Methods: Based on the TCGA database, the relationship of DKK1 expression in HNSCC tissues and its methylation site with patients’prognosis was analyzed. GO and KEGG gene enrichment method were used to analyze the signaling pathways of DKK1 enrichment. STRING was used to analyze the interaction between DKK1 protein and other proteins. TargetScan was used to analyze the miRNAs that regulate the expression of DKK1, and the transcription factors of DKK1 were analyzed with the TRRUST website. Results: DKK1 gene was highly expressed in HNSCC tissues (P<0.01), and its expression level was significantly correlated with the HPV status, age, pathological grade, and clinical stage of patients (all P<0.05); the prognosis of HNSCC patients with high DKK1 expression was poorer than those with low DKK1 expression (P<0.01). There were 19 methylation sites in DKK1, 12 of which were significantly different between cancer tissues and normal tissues (P<0.05), and 11 sites were significantly related to the prognosis of HNSCC (P<0.05). In addition, miRNA, circRNA, lincRNA and transcription factors, etc. also participated in the regulation of DKK1. A total of 5 DKK1-related PPI networks that may involve in the occurrence, development, invasion and metastasis of HNSCC were obtained. Conclusion: DKK1 is highly expressed in HNSCC tissues and is a risk factor for poor prognosis of HNSCC patients. DKK1 plays an important role in the pathogenesis of HNSCC and is expected to become a potential target for HNSCC treatment.
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@#[Abstract] Objective: To detect the expression of CD39 in head and neck squamous cell carcinoma (HNSCC) tisseus, and to analyze its correlation with patients’clinicopathological features and its prognostic significance. Methods: Tissue specimens and case data of 85 patients with HNSCC underwent surgery at Cancer Hospital of Tianjin from May 2012 to December 2013 were collected for this study. Gene chips were obtained from Oncomine database, and HNSCC cell lines SCC15, UM1, and Cal25 were selected for this study. Online analysis was performed to compare the differential expression of CD39 in buccal mucosa (BM) tissues and HNSCC tissues, Western blotting and Immunohistochemistry (IHC) were used to detect the protein expression of CD39 in HNSCC tissues. Spearman’ s correlation analysis was used to study the correlation between the expressions of CD39 and clinicopathological features of HNSCC patients. Both Kaplan-Meier curve analysis and Log rank test were used to analyze the association between the expression of CD39 in HNSCC tissues and the survival of patients, and Cox risk proportional regression model was used to evaluate the relationship between CD39 expression and the risk of relapse. Results: The transcription level of CD39 was obviously up-regulated in HNSCC tissues than in BM tissues (P<0.01), and CD39 expression was detected in HNSCC cell lines SCC15, UM1 and Cal25. Dexamethasone (DXM) could enhance the expression of CD39 in UM1 cells in dose-dependent manner. CD39 was highly expressed in 53 (62.4%) HNSCC patients, which was positively correlated with preoperative chemotherapy (r=0.234, P<0.05). The recurrence-free survival (RFS) of patients with high CD39 expression was significantly shortened (P<0.05), and high CD39 expression was an independent relapse risk factor (HR=2.328, 95%CI=1.091-4.967; P<0.05) for patients with HNSCC. Conclusion: CD39 is DXM-inducively and constitutively expressed in HNSCC. And over-expression of CD39 is an independent predictor of poor prognosis in HNSCC patients, indicating its important role in the progression of HNSCC.
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Objective:This study aims to explore the anticancer effects and potential mechanisms of HJC0152, a novel STAT3 inhibitor, on the invasion and migration capacities of human head and neck squamous cell carcinoma (HNSCC) cell lines in vitro. Methods:Cells were divided into two groups, the dimethyl sulfoxide (DMSO) group and the HJC0152 group in which HNSCC cell lines UM-1 and SCC-15 were treated with DMSO or HJC0152 for 24 h. The total expression levels of STAT3, p-STAT3 (Tyr705/Ser727), MMP-2/9, N/E-cadherin, TWIST1, and vimentin;and the cytoplasm and nuclear expression levels of STAT3 and p-STAT3 (Tyr705/Ser727) were detected by Western blot assay. Wound healing and Transwell assays were employed to detect the invasion and migration abilities of the UM-1 and SCC-15 cells. The expression and location of N/E-cadherin were visualized by immunofluorescence staining. Results:Western blot indicated that the total expression of p-STAT3 (Tyr705), MMP-2/9, N-cadherin, TWIST1, and vimentin were significantly declined and that E-cadherin was remarkably elevated in the HJC0152 group cells compared with that of the DMSO group, with no difference in STAT3 or p-STAT3 (Ser727). Cytoplasm and nuclear STAT3 (Tyr705) were also inhibited by HJC0152. Wound healing and Transwel assays indicated that tumor invasion and migration capacities were impressively attenuated in the HJC0152 group cells compared to that of the DMSO group. Conclusion:HJC0152 suppresses the phosphorylation of STAT3 at Tyr705 in the HNSCC cell lines, leading to impair transcription activity, deplete expression levels of target genes, and subsequently inhibit migration and invasion capabilities of HNSCC.
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Objective:This study aims to explore the anticancer effects and potential mechanisms of HJC0152, a novel STAT3 inhibitor, on the invasion and migration capacities of human head and neck squamous cell carcinoma (HNSCC) cell lines in vitro. Methods:Cells were divided into two groups, the dimethyl sulfoxide (DMSO) group and the HJC0152 group in which HNSCC cell lines UM-1 and SCC-15 were treated with DMSO or HJC0152 for 24 h. The total expression levels of STAT3, p-STAT3 (Tyr705/Ser727), MMP-2/9, N/E-cadherin, TWIST1, and vimentin;and the cytoplasm and nuclear expression levels of STAT3 and p-STAT3 (Tyr705/Ser727) were detected by Western blot assay. Wound healing and Transwell assays were employed to detect the invasion and migration abilities of the UM-1 and SCC-15 cells. The expression and location of N/E-cadherin were visualized by immunofluorescence staining. Results:Western blot indicated that the total expression of p-STAT3 (Tyr705), MMP-2/9, N-cadherin, TWIST1, and vimentin were significantly declined and that E-cadherin was remarkably elevated in the HJC0152 group cells compared with that of the DMSO group, with no difference in STAT3 or p-STAT3 (Ser727). Cytoplasm and nuclear STAT3 (Tyr705) were also inhibited by HJC0152. Wound healing and Transwel assays indicated that tumor invasion and migration capacities were impressively attenuated in the HJC0152 group cells compared to that of the DMSO group. Conclusion:HJC0152 suppresses the phosphorylation of STAT3 at Tyr705 in the HNSCC cell lines, leading to impair transcription activity, deplete expression levels of target genes, and subsequently inhibit migration and invasion capabilities of HNSCC.
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Objective:To explore the role of CXCR2 in the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC).Methods:The expression of CXCR2 in HNSCC tissues of 105 cases was detected by immunohistochemical staining,the correlation between CXCR2 expression and cervical lymph node metastases of HNSCC was analysed.Then,3 stable HNSCC cell lines with CXCR2 interference were established,the effects of CXCR2 silencing on cell migration and invasion were observed by in vitro tests.Results:CXCR2 was positively expressed in 51.43% of HNSCC specimens and was statistically associated with the cervical lymph node metastases of HNSCC.CXCR2 silencing markedly inhibited the migration and invasion of HNSCC cells in vitro.Conclu-sion:CXCR2 may play a key role in the invasion and metastases of HNSCC.
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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. The molecular mechanisms involved in the development and progression of these carcinomas are not well known. Abnormalities of genomic methylation patterns have been attributed a role in carcinogenesis and local de novo methylation at tumor suppressor loci was held to be involved in silencing of tumor suppressor genes. Using Ms APPCR, we previously isolated a hypermethylated fragment corresponded to the 5'end of TPEF gene from primary liver and lung cancer cells. To confirm the inactivation of TPEF gene by hypermethylation in HNSCC, we investigated correlation between methylation pattern and expression of TPEF in 10 HNSCC cell lines. In methylation analysis such as combined-bisulfite restriction analysis(COBRA) and bisulfite sequencing, only RPMI 2650 showed none methylated pattern and another 9 cell lines showed dense methylation. The TPEF gene expression level analysis using RT-PCR showed that these 9 cell lines had not or significantly low expression levels of TPEF as compared with RPMI 2650. In addition, the increase of TPEF reexpression by 5-AzaC as demethylating agent in 9 cell lines also indicated that TPEF expression was regulated by hypermethylation. These results of this study demonstrate that epigenetic silencing of TPEF gene by aberrant methylation could play an important role in HNSCC carcinogenesis.