Oral lichen planus (OLP) is a chronic inflammatory disease, which has been clinically associated with development to oral cancer. A double immunofluorescence labeling study found that 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulated in oral epithelium in OLP and oral squamous cell carcinoma (OSCC) biopsy specimens, whereas little or no immunoreactivity was observed in normal oral mucosa. Colocalization of 8-nitroguanine and inducible nitric oxide synthase (iNOS) was found in oral epithelium of OLP and OSCC. Immunoreactivity of 3-nitrotyrosine, which is formed by protein tyrosine nitration and is considered to be a biochemical marker for inflammation, was also observed in oral epithelial cells and colocalized with 8-nitroguanine. Accumulation of p53 was more strongly observed in oral epithelium in OSCC than OLP, whereas there was no p53 accumulation in normal oral mucosa. Our findings demonstrate that iNOS-dependent DNA damage in OLP may lead to p53 accumulation in not only OLP but also OSCC. We conclude that the formation of potentially mutagenic DNA lesions including 8-nitroguanine and 8-oxodG may contribute to the development of oral cancer from OLP.

Our study exhibited that TNF-alpha may be associated with the immunopathogenesis of OLP in Thai patients and FAO 0.1% had an effect on the reduction of TNF-alpha expression.

Altered expression of TFFs in saliva and gingival tissues was detected in patients with CP. The results suggest that TFF3 may be involved in the pathogenesis of periodontal disease.

Medicine, Indianapolis, Indiana, USA and a unifying hypothesis of pathogenesis Chaiyarit P, Kafrawy AH, Miles DA, Zunt, SL, Van Dis ML, Gregory RL: Oral lichen planus: an immunohistochemical study of heat shock proteins (HSPs) and cytokeratins (CKs) and a unifying hypothesis of pathogenesis. J Oral Pathol Med 1999; 28: 210-5. C Munksgaard, 1999.The expression of heat shock proteins HSP60 and HSP70 and cytokeratins CK1/ 10 and CK7/18 were compared in epithelium of oral lichen planus (OLP) lesions and oral fibromas using an avidin-biotin-peroxidase complex (ABC) immunohistochemical method. An immunostaining intensity distribution (IID) index was developed to assess staining intensity and the proportion of positively stained Key words: avidin-biotin-peroxidase complex cells in different layers of the epithelium. The expression of HSP60 in the basal (ABC); cytokeratins (CKs); heat shock proteins (HSP); immunostaining intensity layer was significantly higher in OLP than in fibromas. No difference in HSP70 distribution (IID); oral lichen planus (OLP) expression was evident between OLP and fibromas. The expression of CK1/10 in the epithelial basal and suprabasal layers was significantly higher in OLP than in A. H. Kafrawy, Department of Oral Surgery, fibromas. There was no demonstrable staining for CK7/18 in either OLP or fibro-Medicine and Pathology, Indiana University School of Dentistry, 1121 West Michigan mas. A significant correlation was evident between the expression of HSP60 andStreet, Room 106, Indianapolis, Indiana CK1/10 in the basal epithelial cells in OLP. The findings support a role for HSP60 46202-5186, USA in the pathogenesis of OLP. A unifying hypothesis of the pathogenesis of OLP, involving two sequential immune reactions, is proposed.

Previously established ELISA assays can be employed for measurement of trefoil peptides in saliva and cervical mucus. TFF3 was the predominant trefoil peptide in both saliva and cervical mucus, and TFF3 in cervical mucus represents the highest concentration measured in a biological fluid to date.

Background Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct epithelial cell lining. The misdiagnosis of CCA and other biliary diseases may occur due to the similarity of clinical manifestations and blood tests resulting in inappropriate or delayed treatment. Thus, an accurate and less-invasive method for differentiating CCA from other biliary diseases is inevitable. Methods We quantified methylation of OPCML , HOXA9 , and HOXD9 in serum cell-free DNA (cfDNA) of CCA patients and other biliary diseases using methylation-sensitive high-resolution melting (MS-HRM). Their potency as differential biomarkers between CCA and other biliary diseases was also evaluated by using receiver operating characteristic (ROC) curves. Results The significant difference of methylation levels of OPCML and HOXD9 was observed in serum cfDNA of CCA compared to other biliary diseases. Assessment of serum cfDNA methylation of OPCML and HOXD9 as differential biomarkers of CCA and other biliary diseases showed the area under curve (AUC) of 0.850 (0.759–0.941) for OPCML which sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 80.00%, 90.00%, 88.88%, 81.81%, and 85.00%, respectively. The AUC of HOXD9 was 0.789 (0.686–0.892) with sensitivity, specificity, PPV, NPV, and accuracy of 67.50%, 90.00%, 87.09%, 73.46%, and 78.75%, respectively. The combined marker between OPCML and HOXD9 showed sensitivity, specificity, PPV, and NPV of 62.50%, 100%, 100%, and 72.72%, respectively, which may be helpful to prevent a misdiagnosis between CCA and other biliary diseases. Conclusions Our findings suggest the application of serum cfDNA methylation of OPCML and HOXD9 for differential diagnosis of CCA and other biliary diseases due to its less invasiveness and clinically practical method which may benefit the patients by preventing the misdiagnosis of CCA and avoiding unnecessary surgical intervention. Electronic supplementary material The online version of this article (10.1186/s13148-019-0634-0) contains supplementary material, which is available to authorized users.

Arecoline, the major alkaloid of areca nut, is known to induce oral carcinogenesis, however, its mechanism is still needed to elucidate. This study investigated the effects of arecoline on cell viability and cell-cycle progression of oral squamous cell carcinoma (OSCC) cells as well as a relevant cellular gene expression. The results showed that a low concentration of arecoline (0.025 μg/ml) increased OSCC cell viability, proportion of cells in G2/M phase and cell proliferation. Simultaneously, it induced IL-6, STAT3 and c-Myc expression. Interestingly, c-myc promoter activity was also induced by arecoline. MiR-22 expression in arecoline-treated OSCC cells was suppressed and comparable to an upregulated c-Myc expression. In arecoline-treated OSCC cells, oncostatin M (OSM) expression was significantly upregulated and inversely correlated with miR-22 expression. Likewise, OSM expression and its post-transcriptional activity were significantly decreased in miR-22-transfected OSCC and 293FT cells. This result demonstrated that miR-22 directly targeted OSM. Interestingly, miR-22 played an important role as a tumor suppresser on suppressing cell proliferation, migration and cell-cycle progression of OSCC cells. This result suggested the effect of arecoline to promote cell proliferation and cell-cycle progression of OSCC cells might be involved in induction of c-Myc expression and reduction of miR-22 resulting in OSM upregulation.

These findings suggest the clinical significance of TFF2 and TFF3 molecules as negative markers of tumor progression in OSCC. Quantification of TFF levels in saliva may not be optimal in terms of diagnostic or predictive value for OSCC derived from oral mucosa.