Tyrosine sulphation of CXCR4 induces the migration of fibroblast in OSF.

Oral submucous fibrosis (OSF) caused by areca nut chewing is a prevalent fibrotic disease in Asia-Pacific countries. Arecoline-induced migration of fibroblasts (FBs) plays a vital role in the development of OSF. However, the specific molecular mechanisms involved remain unclear. Many studies have shown that tyrosine sulphation of chemokines can influence cell migration. Herein, we demonstrated that arecoline stimulates tyrosine sulphation of the chemokine receptor 4 (CXCR4) through the tyrosylprotein sulphotransferase-1 (TPST-1) to enhance the migration ability of FBs. Moreover, by RNA-Seq analysis, we found that the most significantly altered pathway was the EGFR pathway after the arecoline stimulation for FBs. After the knockdown of arecoline-induced EGFR expression, the tyrosine sulphation of CXCR4 was significantly decreased by the inhibition of TPST-1 induction. Finally, in human OSF specimens, TPST-1 expression was directly correlated with the expression of CXCR4. These data indicate that the arecoline-induced tyrosine sulphation of CXCR4, which is regulated by TPST-1, might be a potential mechanism that contributes to FB migration in OSF.

Lateral approach is a more aesthetical option for radical resection of BSCC: assessment of its surgical, oncological, functional, and aesthetic outcomes.

BACKGROUND: The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. METHODS: This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. RESULTS: Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. CONCLUSION: The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.

Application of a chimeric ALT perforator flap with vastus lateralis muscle mass in the reconstruction of the defects after radical resection of a buccal carcinoma: A retrospective clinical study.

BACKGROUND AND OBJECTIVES: Aggressive resection of buccal cancer simultaneously leaves both oral and lateral facial defects. It is unknown whether a perforator-based chimeric anterolateral thigh (ALT) flap, with a muscular component, is suitable for the reconstruction of these complicated defects. METHODS: In this retrospective study, 48 patients with a buccal carcinoma (T2 N0-1 M0), who underwent extensive surgical resection, were enrolled. Twenty-seven cases underwent reconstruction using the classical ALT perforator flap (classical group), and 21 cases used the chimeric ALT perforator flap with vastus lateralis muscle mass (chimeric group). The incidence of wound infection, lower limb extremity function, facial appearance, survival curves, and quality of life were compared between groups. RESULTS: The incidence of wound infection or effusion was lower in the chimeric group than in the classical group. The aesthetic result achieved in the chimeric group was better than in the classical group. Meanwhile, there was no significant difference in the function of the donor site between groups. CONCLUSIONS: The chimeric ALT perforator flap, with a muscular component, can reconstruct both the oral and lateral face defects accurately. It sustains the profile of the lateral face and decreases the incidence of wound infection.

TCGA based integrated genomic analyses of ceRNA network and novel subtypes revealing potential biomarkers for the prognosis and target therapy of tongue squamous cell carcinoma.

OBJECTIVES: The study aimed to investigate the ceRNA network in biological development of Tongue Squamous Cell Carcinoma (TSCC) and to identify novel molecular subtypes of TSCC to screen potential biomarkers for target therapy and prognosis by using integrated genomic analysis based on The Cancer Genome Atlas (TCGA) database. MATERIAL AND METHODS: Data on gene expressions were downloaded from TCGA and GEO database. Differentially expressed RNAs(DERNAs) were shown by DESeq2 package in R. Functional enrichment analysis of DEmRNAs was performed using clusterprofilers in R. PPI network was established by referring to String website. Survival analysis of DERNAs was carried out by survival package in R. Interactions among mRNAs, miRNAs and lncRNAs were obtained from Starbase v3.0 and used to construct ceRNA network. Consensus Cluster Plus package was applied to identify molecular subtypes. All key genes were validated by comparing them with GEO microarray data. Statistical analyses of clinical features among different subtypes were performed using SPSS 22.0. RESULTS: A total of 2907 mRNAs (1366 up-regulated and 1541 down-regulated), 191miRNAs (98 up-regulated and 93 down-regulated) and 1831 lncRNAs (1151 up-regulated and 680 down-regulated) were identified from tumor and normal tissues. A ceRNA network was successfully constructed and 15 DEmRNAs, 1 DEmiRNA, 2 DElncRNAs associated with prognosis were employed. Furthermore, we firstly identified 2 molecular subtypes, basal and differentiated, and found that differentiated subtype consumed less alcohol and was related to a better overall survival. CONCLUSION: The study constructed a ceRNA network and identified molecular subtypes of TSCC, and our findings provided a novel insight into this intractable cancer and potential therapeutic targets and prognostic indicators.

Pathogenesis investigation of miR-199-5p in oral submucous fibrosis based on bioinformatics analysis.

OBJECTIVES: Fibrosis diseases are one of the leading causes of suffering and death. However, no systematic investigation has been carried out on fibrosis-related genes. MATERIALS AND METHODS: By querying PubMed using keywords "fibrosis" and "gene" or "protein," we identified fibrosis-related genes in the last decade. Bioinformatics analysis was performed by MAS 3.0 software. Key miRNA was selected to assess its relationship with oral submucous fibrosis (OSF) and fibroblast functions. RESULTS: A total of 1,310 genes related to fibrosis were identified. TGF-ß1, CTGF, MMP9, HSP47, and S1P were found to be associated with mainly fibrotic organs. In total, 244 cellular components terms, 595 molecular function terms, 1,816 cellular component terms, and 136 KEGG pathway annotations were predicted. miR-199-5p was selected as the key miRNA, which has higher level in OSF. Upregulated miR-199-5p was significantly related to OSF duration and OSF histological grade (p = 0.028 and 0.012, respectively). Overexpressive miR-199-5p reduced proliferation and induced apoptosis in buccal fibroblasts. Additionally, expression levels of collagen I (COL I) and III (COL III) were promoted by overexpressive miR-199-5p in buccal fibroblasts. CONCLUSION: These results indicate that fibrosis-related genes are related to a series of complex mechanisms. The characteristics of miR-199-5p may supply important clues for developing therapeutic strategy for OSF.

A squamous odontogenic tumor following an orthodontic micro-screw: A rare case report and review of the literature.

We reported a very rare case of squamous odontogenic tumor(SOT) in a 23-year-old female. The tumor arose after an implanting operation of an orthodontic micro-screw, and was definitely diagnosed by the histopathological examination. Based on the case report and a review of the literature, we discussed about the general features, differential diagnosis and pathogenesis of SOT.

CD73 as a novel marker for poor prognosis of oral squamous cell carcinoma.

Ecto-5'-nucleotidase [cluster of differentiation (CD)73] has important functions in several types of cancer, however, its expression in squamous cell carcinoma (SCC) remains unknown. The present study was designed to investigate CD73 expression in SCC. CD73 expression was assessed by immunohistochemistry in 113 patients with oral SCC (OSCC). The association between CD73 expression and clinicopathological features, overall survival (OS) and disease-free survival (DFS) times of patients were statistically analyzed. CD73 expression was detected in 58.4% (66/113) of OSCC patients, with the immunostaining predominantly localized in the cytomembrane and a little in the cytoplasm. Statistical analysis revealed that CD73 expression was more frequently detected in patients with larger tumors (P=0.021). The overexpression of CD73 was significantly associated with clinical stage (P=0.047). Furthermore, immunohistochemical staining showed that overexpression of CD73 was inversely correlated with DFS (P=0.002) and OS (P=0.002) times. Multivariate Cox regression analysis revealed that CD73 expression was an independent prognostic factor for poor DFS (P=0.018) and OS (P=0.021). The current study is the first to evaluate the clinical significance and prognostic value of CD73 in patients with OSCC. The findings suggest that CD73 is a potential prognostic marker for OSCC.

Synergistic effects of betel quid chewing, tobacco use (in the form of cigarette smoking), and alcohol consumption on the risk of malignant transformation of oral submucous fibrosis (OSF): a case-control study in Hunan Province, China.

OBJECTIVES: Oral submucous fibrosis (OSF) is a potentially malignant disorder, wherein 7% to 13% of patients with OSF develop oral squamous cell carcinoma (OSCC) at clinically coincident sites established to have OSF. We aimed at investigating the lifestyle-related risk factors for malignant transformation of OSF. STUDY DESIGN: A case-control study was conducted among 80 cases with OSF-associated OSCC and 80 controls with OSF but without clinically or histopathologically evident OSCC, recruited from January 2012 to October 2014 in the Xiangya Hospital, Hunan Province, Mainland China. RESULTS: The odds ratios (OR) for OSCC were 13.3 (95% confidence interval [95% CI]: 3.1-56.4) and 45.1 (95% CI: 9.6-212.9) at the highest exposure of betel quid (BQ) chewing, by duration and frequency, respectively. Higher risks were also found to be associated with the consumption of cigarette (OR = 5.0, 95% CI: 1.7-14.8) and alcohol (OR = 3.1, 95% CI: 1.1-8.6). Adjusted ORs increased substantially among patients who consumed BQ and cigarette or alcohol simultaneously, which were 26.1 (95% CI: 4.0-172.6) and 55.-(95% CI: 1.8-1742.8) at the longest duration, and 160.3 (95% CI: 18.7-11371.2) and 58.1 (95% CI: 2.4-1434.9) at the highest dose, respectively. CONCLUSIONS: The use of BQ, cigarette, and alcohol were identified as risk factors for malignant transformation of OSF in the Hunan province, Mainland China. Synergistic effects between BQ chewing and cigarette or alcohol consumption were revealed.

Enhanced anticancer activity of a protein phosphatase 2A inhibitor on chemotherapy and radiation in head and neck squamous cell carcinoma.

The aim of this study is to eliminate more cancer cells by promoting them from quiescence into cell cycle or by changing their molecular events, leading them to be sensitive to radiation or chemotherapy. Protein phosphatase 2A plays an important role in many cellular functions and regulates various biological processes. It is unclear that LB1, which is an inhibitor of protein phosphatase 2A, has enhanced anticancer activity on chemotherapy (cisplatin and 5-fluorourcil) and radiation in head and neck squamous cell carcinoma (HNSCC). Herein, we performed both in vitro and in vivo studies to determine the anticancer activity of LB1 on chemotherapy and radiation in HNSCC, with detection of p53 expression, AKT and MDM2 phosphorylation. In vitro studies indicated that, LB1 could significantly enhance the cytotoxicity of cisplatin, 5-fluorourcil, and radiation; LB1 could also significantly enhance the treatment effect of cisplatin in nude mice. The anticancer activity of LB1 was mediated by increased AKT phosphorylation and decreased p53 expression with increased MDM2 phosphorylation, especially when combined with cisplatin. Our data suggest a strategy of improving treatment effect through the enhanced anticancer activity of LB1 on cisplatin-based chemotherapy and radiation in HNSCC.

Novel genetic biomarkers for susceptibility to oral submucous fibrosis: cytochrome P450 3A.

Oral submucous fibrosis (OSF) is a chronic and insidious oral mucosal disease, which always carries high risk of transition to oral cancer. Mainly based on genetic predisposition in pharmacokinetics for toxic substances of betel quid, there are obviously variable responses to betel quid among chewers. But the key genes resulting in interindividual variability in OSF development are still obscure. The cytochrome P450 3A (CYP 3A) gene family plays major roles in the oxidative metabolism of active endogenous and xenobiotic substrates, which is generally found polymorphic with variant alleles in different individuals and regarded as a major determinant of the interindividual variability in chemicals pharmacokinetics. Based on the specific property of CYP 3A, we consider this polymorphically expressed genotype could be a predictor of OSF susceptibility. Betel-quid chewers with lower level of CYP 3A expression might be more susceptible to toxicity of betel quid, resulting in higher risk of OSF lesion. Meanwhile, individuals at genetically high risk of OSF could be screened according to the genetic polymorphisms in some exclusive regions of the CYP 3A genes. By analyzing the polymorphisms of CYP 3A genes, we could differentiate interindividual variability for pharmacokinetics of betel-quid chewers, and then guide OSF therapy.