BackgroundFor early‐stage oral squamous cell carcinoma (OSCC), there is no existing risk‐stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer‐specific mortality.MethodsA total of 568 early‐stage OSCC patients who had surgery only and also with available 5‐year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT‐PCR. The final 5‐plex prognostic marker panel was utilized to generate a cancer‐specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts.ResultsThe risk score from the 5‐plex marker panel consisting of miRNAs‐127‐3p, 4736, 655‐3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low‐risk group, the high‐risk group had 23‐fold increased mortality risk (hazard ratio 23, 95% confidence interval 13‐42), with a median time‐to‐recurrence of 6 months and time‐to‐death of 11 months (vs >60 months for each among low‐risk patient; p < .001).ConclusionThe miRNA‐based 5‐plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early‐stage OSCC.
Clin Invest Med 2010; 33 (3): E189-E195. AbstractPurpose: Recurrent aphthous stomatitis (RAS) is one of the most common ulcers of the oral cavity with a reported prevalence of 5-50%. There is still no definitive treatment for RAS; however, immunosuppressive and immunomodulant agents have been proposed. In this study, we compared the therapeutic effects of 5 mg/d prednisolone with 0.5 mg/ d colchicine in the treatment of RAS. Methods: In a double-blind randomized clinical trial, 34 patients with RAS were randomly divided into two groups for treatment with prednisolone or colchicine. All patients took the medication for three months and were assessed at two weeks intervals. The groups were compared for size and number of lesions, severity of pain and burning sensation, duration of pain-free episodes and any side effects of the prescribed medicines. Both colchicine and prednisolone treatments significantly reduced RAS (p<0.001). No significant differences in size and number of lesions, recurrence and severity of pain and duration of pain-free period were seen between the two treatment groups. Colchicine (52.9%) had significantly more side effects than prednisolone (11.8%). Conclusion: Low dose prednisolone and colchicine were both effective in treating RAS. Given that the two therapies had similar efficacy, yet colchicine was associated with more side effects, , 5mg/d of prednisolone seems to be a better alternative in reducing the signs and symptoms of the disease.Recurrent aphthous stomatitis (RAS) is one of the most common ulcers of the oral cavity with a reported prevalence of 5-50%. 1-3 Several etiologies have been proposed for RAS but the exact cause still remains unknown. According to severity and location of the lesions, different types of topical or systemic treatments have been used, but none of them have shown ORIGINAL RESEARCH
Exosomes are membrane vesicles with a diameter of 40–100 nm that are secreted by many cell types into the extracellular milieu. Exosomes are found in cell culture supernatants and in different biological fluids and are known to be secreted by most cell types under normal and pathological conditions. Considerable research is focusing on the exploitation of exosomes in biological fluids for biomarkers in the diagnosis of disease. More recently, exosomes are being exploited for their therapeutic potential. Exosomes derived from dendritic cells, tumor cells, and malignant effusions demonstrate immunomodulatory functions and are able to present antigens to T-cells and stimulate antigen-specific T-cell responses. Exosomes have also been examined for their therapeutic potential in the treatment of infections such as toxoplasmosis, diphtheria, tuberculosis and atypical severe acute respiratory syndrome as well as autoimmune diseases. Attempts to find practical applications for exosomes continue to expand with the role of exosomes as a drug delivery system for the treatment of autoimmune/inflammatory diseases and cancers.
Objectives Methyltransferase‐like 14 (METTL14) plays an epigenetic role in various cancer through N6‐methyladenosine (m6A) modification. This study sought to analyze the mechanism of METTL14 in oral squamous cell carcinoma (OSCC) cell proliferation. Methods Expression levels of METTL14, lncRNA metastasis associated with lung adenocarcinoma transcript 1 (lncRNA MALAT1), microRNA (miR)‐224‐5p, and histone lysine demethylase 2A (KDM2A) in OSCC tissues (N = 40), and cell lines (FaDu, SCC‐25, CAL‐27, and SCC‐15) were detected. Cell viability and colony formation capacity were assessed. m6A level, stability, and subcellular localization of lncRNA MALAT1 were determined. Nude mouse xenograft tumor assay was performed to confirm the role of METTL14 in vivo. Results METTL14 and lncRNA MALAT1 were upregulated, and miR‐224‐5p was downregulated in OSCC tissues and cells. Silencing METTL14 repressed OSCC cell viability and colony formation. Overexpression of MALAT1 and KDM2A or miR‐224‐5p downregulation reversed the inhibition of silencing METTL14 on OSCC cell proliferation. METTL14 induced m6A modification of MALAT1 to upregulate MALAT1. MALAT1 is comparatively bound to miR‐224‐5p to promote KDM2A transcription. In vivo, METTL14 promoted tumor growth via regulating MALAT1/miR‐224‐5p/ KDM2A. Conclusions Overall, our findings verified the therapeutic role of silencing METTL14 in OSCC treatment through the MALAT1/miR‐224‐5p/KDM2A axis.
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