Computational Modelling for Electrical Impedance Spectroscopy-Based Diagnosis of Oral Potential Malignant Disorders (OPMD).

A multiscale modelling approach has been applied to the simulation of the electrical properties of oral tissue, for the purpose of informing an electrical impedance-based method of oral potential malignant disorder (OPMD) diagnosis. Finite element models of individual cell types, with geometry informed by histological analysis of human oral tissue (normal, hyperplastic and dysplastic), were generated and simulated to obtain electrical parameters. These were then used in a histology-informed tissue scale model, including the electrode geometry of the ZedScan tetrapolar impedance-measurement device. The simulations offer insight into the feasibility of distinguishing moderate dysplasia from severe dysplasia or healthy tissue. For some oral sites, simulated spectra agreed with real measurements previously collected using ZedScan. However, similarities between simulated spectra for dysplastic, keratinised and non-dysplastic but hyperkeratinised tissue suggest that significant keratinisation could cause some OPMD tissues to exhibit larger than expected impedance values. This could lead to misidentification of OPMD spectra as healthy. Sources of uncertainty within the models were identified and potential remedies proposed.

Mesenchymal stem cells participate in oral mucosa carcinogenesis by regulating T cell proliferation.

Recent evidences suggested that Mesenchymal stem cells (MSCs) may be involved in tumor formation by modulating of the tumor microenvironment, but it is still unclear the potential of MSCs in the malignant transformation of oral mucosa. Using a chemically-induced oral carcinogenesis model by 4-nitroquinoline-1-oxide (4NQO), we generated precancerous lesions and cancerous lesions in the oral cavity of rats. Flow cytometric analysis on lesions derived single cell suspension revealed an increase in the proportion of MSCs and a decreased proportion of T cell during oral mucosa malignancy. Moreover, MSCs showed increased immunosuppression capacity on T cell proliferation during mucosa malignancy. At last, we demonstrated that higher frequency of lesions resident MSCs was correlated with more Ki67 expression in the lesion, which indicated higher cellular proliferative status in the lesions. Our study demonstrated that MSCs may play an important role in oral mucosa malignant transformation through regulating T cell proliferation.

Krüppel-like factor 5 promotes the progression of oral squamous cell carcinoma via the baculoviral IAP repeat containing 5 gene.

Background: Krüppel-like factor 5 (KLF5) is highly expressed in a variety of tumors, and our study aimed to investigate the role of KLF5 in oral squamous cell carcinoma (OSCC). Methods: To explore the differential expression of KLF5, next-generation sequencing (NGS) and further analyses were conducted in paired premalignant and tumor tissues and adjacent normal mucosa. We then analyzed the mRNA expression data from The Cancer Genome Atlas (TCGA) and performed gene set enrichment analysis (GSEA) to predict the function of KLF5. Small interfering RNA (siRNA) targeting KLF5 was used to knock down its expression in cells and further evaluate the changes in cell apoptosis, proliferation, and migration. We predicted whether baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) was the potential target gene of KLF5 via the NCBI and JASPAR databases. Furthermore, we analyzed BIRC5 expression after KLF5 knockdown and explored its function in athymic BALB/c nude mice. Results: KLF5 expression in clinical samples gradually increased from normal mucosa tissues to premalignant and then to OSCC tissues. Analysis of TCGA data and GSEA also suggested that KLF5 was expressed at higher levels in OSCC and involved apoptosis and the protein 53 (P53), transforming growth factor-ß (TGF-ß), and wingless/integrated (Wnt) signaling pathways. Cell apoptosis was promoted, whereas proliferation and migration were inhibited after KLF5 knockdown. Furthermore, we found KLF5 transcription binding sites on the BIRC5 promoter and BIRC5 expression was inhibited after suppressing KLF5 in vitro and in vivo. Conclusions: Our findings indicate that KLF5 promotes the development of OSCC via BIRC5, and could be a potential diagnostic and therapeutic target for OSCC.

Epidemiological profile and clinical characteristics of oral potentially malignant disorders and oral squamous cell carcinoma: A pilot study in Bidar and Gulbarga Districts, Karnataka, India.

BACKGROUND: Clinical scenarios of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) vary between geographical districts within the same country. This could be attributed to common habits and other cultural factors, such as excessive consumption of tobacco products, leading to higher prevalence of tobacco-related lesions of the oral cavity. A better understanding of their pattern and behavior in each particular region may help in devising strategies for prevention and treatment. AIMS AND OBJECTIVES: The aim of the study is to assess the epidemiological profile and clinical characteristics of OPMD and OSCC among population in and around Bidar and Gulbarga districts of Karnataka, India. MATERIALS AND METHODS: This was a retrospective, chart review study in the districts of Bidar and Gulbarga, Karnataka, India. Medical records of patients with clinical and histopathological diagnosis of OPMD or OSCC who attended a private dental school in Bidar and 20 private dental clinics in the districts of Bidar and Gulbarga between 2010 and 2017 were included in the study. Collected data were analyzed using Statistical Package Social Sciences software, version 20.0. RESULTS: There were a total of 630 patients, with males representing 69.52% (n = 438; ratio of 2.28:1) of cases and mean age of 42.64 years. 375 (59.52%) patients had a diagnosis of OPMD with the most common subtype of oral submucous fibrosis (185/375; 49.33%) followed by leukoplakia (110/375; 29.33%) and lichen planus (80/375; 21.33%). Buccal mucosa was the most commonly affected site (33.01%). Of 630 patients, 255 (40.48%) had OSCC, with tongue being the most common site (36.86%). CONCLUSION: This study revealed for the first time that OPMD and OSCC are widespread in the districts of Bidar and Gulbarga. The available knowledge on the prevalence of these lesions could help in educating patients and implementing preventive measures by health-care providers to improve overall survival. Long-term follow-up studies are needed to better understand the disease pattern.

Oral verruciform xanthoma and erythroplakia associated with chronic graft-versus-host disease: a rare case report and review of the literature.

BACKGROUND: Oral verruciform xanthoma is an uncommon benign lesion. Although oral verruciform xanthoma occurs in healthy individuals, it has been also reported in association with some inflammatory conditions. The aim of this study is to report a case of oral verruciform xanthoma associated with chronic graft-versus-host disease and to review the literature on this topic. CASE PRESENTATION: A 47-year-old Caucasian male presented to the Sector of Oral Medicine "V. Margiotta", University Policlinic "P. Giaccone" of Palermo complaining of a mass on the gingiva. He first noticed the painless mass 1 year ago. He reported to have undergone allogenic hematopoietic stem cell transplantation 15 years ago for acute lymphoblastic leukaemia. Intraoral examination revealed a well-circumscribed, sessile yellowish and verrucous nodule upon canine, multiple yellowish and verrucous nodules on the hard palate, yellowish and verrucous nodules on left buccal mucosa. In addiction an area of white striae in a reticular pattern with erythema and ulceration was present on the dorsum of the tongue. This lesion was consistent with a known history of oral chronic graft versus host disease. Moreover, we observed a suspected area of oral erythroplakia yet on the dorsum of the tongue. In biopsy specimen of hard palate histopathological examination revealed a diagnosis of verrucous xanthoma of the oral cavity; in addiction in biopsy specimen of the dorsum of the tongue revealed the presence of erythroplakia with high grade dysplasia. CONCLUSION: Verruciform xanthoma of the oral cavity associated with chronic graft-versus-host disease is a rare condition with a usually benign clinical course but malignant transformation has been described in association with oral potential malignant disorder (e.g. chronic graft versus host disease, erythroplakia). Very rare cases showed association with oral chronic graft versus-host-disease. To date, only eight cases were published in the world literature. Therefore it could be important follow up patients also for oral verruciform xanthoma onset.