Endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma.

BACKGROUND: Loco-regional spread of disease causes high morbidity and is associated with the poor prognosis of malignant oral tumors. Better understanding of mechanisms underlying the establishment of lymph node metastasis is necessary for the development of more effective therapies for patients with oral cancer. The aims of this work were to evaluate a possible correlation between endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma (OSCC), and to study signaling pathways that regulate Bcl-2 expression in lymphatic endothelial cells. METHODS: Endothelial cells were selectively retrieved from paraffin-embedded tissue sections of primary human OSCC from patients with or without lymph node metastasis by laser capture microdissection. RT-PCR was used to evaluate Bcl-2 expression in tumor-associated endothelial cells and in tumor cells. In vitro, mechanistic studies were performed to examine the effect of vascular endothelial growth factor (VEGF)-C on the expression of Bcl-2 in primary human lymphatic endothelial cells. RESULTS: We observed that Bcl-2 expression is upregulated in the endothelial cells of human oral tumors with lymph node metastasis as compared to endothelial cells from stage-matched tumors without metastasis. VEGF-C induced Bcl-2 expression in lymphatic endothelial cells via VEGFR-3 and PI3k/Akt signaling. Notably, OSCC cells express VEGF-C and induce Bcl-2 in lymphatic endothelial cells. CONCLUSIONS: Collectively, this work unveiled a mechanism for the induction of Bcl-2 in lymphatic endothelial cells and suggested that endothelial cell Bcl-2 contributes to lymph node metastasis in patients with oral squamous cell carcinoma.

Oral lymphatic malformations: A multicenter study of 208 cases and literature review.

BACKGROUND: To evaluate the frequency and analyze demographic and clinical characteristics of individuals with a histopathological diagnosis of oral lymphatic malformations (OLMs). METHODS: A multicenter study was performed, collecting biopsy record data from a consortium of Brazilian Oral and Maxillofacial Pathology Centers. A review was also conducted to compare this data with cases already available in the literature. RESULTS: This study retrieved 208 cases of OLM in the multicenter study and 1035 cases in the literature review. In both, OLMs affected male and female individuals equally, with the most affected site being the tongue. Individuals ≥60 years of age were uncommonly affected. Symptomatic and larger lesions were more commonly reported in the literature review. CONCLUSIONS: This study comprises the largest sample of OLMs to date. OLMs are rare conditions, without sex predilection. The elderly proved to be less frequently affected, and the tongue is the most commonly affected site.

Prevalence of oral mucosal lesions in population-based studies: A systematic review of the methodological aspects.

OBJECTIVES: To conduct a systematic review of the literature to evaluate the methodological aspects of population-based studies on the prevalence of oral mucosal lesions (OMLs). METHODS: Two reviewers independently conducted a literature search in three databases (PubMed, Web of Science and Scopus) and extracted data using a standardized form. Data on the following characteristics of the included studies were collected: sample size; age of participants; references used to define the diagnostic criteria, training of the examiners, and data collection; type, grouping and characteristics of the lesions; and lesions excluded and measures of agreement between examiners. Data were analysed descriptively, and data synthesis was performed for each of the studies included in the analysis. A quality analysis of the studies was conducted, and the risk of bias was evaluated. RESULTS: A total of 29 studies were included in the analysis. Most of the published studies on the prevalence of OMLs were performed in Asian countries. The sample sizes ranged from 255 to 39 206. The World Health Organization guidelines were followed by most of the studies, in terms of design, examiner training and data collection. Approximately 25% of the studies did not determine inter-examiner reliability. Moreover, almost half of the studies included did not report the response rate nor did they present the results with the appropriate confidence intervals. CONCLUSIONS: Several important points need to be improved in population-based studies focusing on the prevalence of OMLs. In particular, these studies should adequately report the response rate and findings, and to a lesser extent, the diagnostic criteria and training of the examiners. We encourage more research in this field and reinforce the importance of standardized studies to facilitate the comparison of different findings. PROSPERO registration number: CRD42018099386.

Pulp responses to the application of a self-etching adhesive in human pulps after controlling bleeding with sodium hypochlorite.

OBJECTIVE: To evaluate the pulp response to direct capping with self-etching adhesive systems using sodium hypochlorite as a hemostatic agent. METHOD AND MATERIALS: Twenty-six human third molars scheduled for extraction were selected from undergraduate students of dentistry. Class I cavities with pulp exposures were performed. To control bleeding, 2.5% sodium hypochlorite was used for 20 seconds, followed by washing with saline solution. The pulp exposures were capped with calcium hydroxide (n = 10) or adhesive system (n = 16). All cavities were restored with adhesive system and composite resin. Half of the samples of each capping material were extracted after 30 days and the remaining after 90 days. The samples were prepared for histological analysis (hematoxylin-eosin) and bacterial detection (Brown & Hopps) and evaluated according to standard ranking. Data were submitted to statistical analysis (Mann-Whitney test). RESULTS: There was a significant difference (P <.05) only in relation to dentin barrier formation. Pulps dressed with calcium hydroxide showed dentin barrier formation in all specimens, obliterating the exposure site. No inflammatory response was associated with material. In the experimental group, after 30 days, there was an attempt for healing with reparative dentin deposition, presenting a mild to moderate inflammatory infiltrate. Similar findings were found after 90 days, decreasing the inflammatory response. Bacteria were not detected in any specimen evaluated. Sodium hypochlorite was effective for hemostatic control. CONCLUSION: Calcium hydroxide produced better biological performance than the self-etching adhesive, and sodium hypochlorite did not interfere with the pulp repair.

Telomeres and tissue engineering: the potential roles of TERT in VEGF-mediated angiogenesis.

Telomeres are protective structures located at the end of eukaryotic chromosomes which are shortened after each cell division, leading to senescence. Telomerase activity prevents telomere shortening by reverse transcription catalyzed by the subunit called TERT (telomerase reverse transcriptase). TERT expression has shown interesting cellular properties, which may be appealing for tissue engineering, such as the enhancement of cell proliferation and differentiation abilities in vitro. Despite some evidence for playing these roles in VEGF (vascular endothelial growth factor)-mediated angiogenesis, it is still unclear whether TERT can contribute to this essential event to generate functional organs. This review suggests a hypothesis that TERT and VEGF potentially regulates the transcriptional expression of each other, which would give new perspectives in the roles of telomerase in regulating several cellular processes, and also contributing for a better comprehension of the molecular mechanisms underlying VEGF signaling (both paracrine and autocrine). In general, based on the literature revised, it is possible to conclude that TERT is a potential VEGF enhancer; however, it is necessary to elaborate methodological approaches to explore this potential and to assess the potential benefits on tissue engineering approaches.

An image processing software applied to oral pathology.

This study presents the development and evaluation of an image processing software for computer-assisted cellular structure counting. The proposed software consists of a set of processing and analytical tools which allows its use in several applications of cell and cellular structure counting. A particular application in AgNOR quantitative analysis is presented. The knowledge obtained from experienced pathologists has been codified in a sequence of processing steps in order to allow automatic estimation of the mean number of AgNORs per cell in ameloblastomas. The performance of the presented software in such application was verified by comparing the data provided by visual analysis, by two observers previously calibrated and under supervision of two experienced specialists (Group 1) and by the computer program (Group 2). No statistical difference was observed (p<0.05) between the two groups. The use of the proposed method in AgNOR applications permitted attainment of accurate and precise data without the difficulties frequently found in the traditional visual analysis method (time, training and subjectivity). The developed software is an interesting tool as an aid in the study (estimation of the number of cells and cellular structures) of malignant and benign neoplasms.

Immunohistochemical expression of fibronectin and tenascin after direct pulp capping with calcium hydroxide.

The aim of this study was to investigate the expression of 2 extracellullar matrix glycoproteins, fibronectin (FNC) and tenascin (TNC), following direct pulp capping with calcium hydroxide (CH). Third molars scheduled for extraction were used. Standardized class I cavities with pulp exposures were prepared. After control of bleeding, CH powder was applied in the exposure sites, which were covered with CH cement (Dycal; Dentsply) and the cavities were filled with zinc oxide-eugenol cement. Three teeth were extracted at each post-treatment period (1, 7, 14, and 30 days). Demineralized and paraffin-embedded specimens were stained for histologic technique (hematoxylin-eosin) and for immunohistochemical analysis. Anti-TNC and anti-FNC monoclonal antibodies were used with the streptavidin-biotin complex method. Generally, similar patterns of immunohistochemical expression were observed for TNC and FNC in the pulp tissue as a whole. In the exposure site, TNC immunostaining increased over time, exhibiting a thicker immunostaining pattern within 30 days. The imunohistochemical technique showed expression of both glycoproteins during pulp healing process.