Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G.

BACKGROUND: To our knowledge, there is no useful and accurate prognostic biomarker or biomarkers for patients with oral squamous cell carcinoma (OSCC), a tumor with uncertain biological behavior, and unpredictable clinical progress. The purposes of this study were: a) to determine the expresión profile of Connexin 43, Bcl-2, Bax, E-cadherin, and Ki67 in patients with OSCC; b) identify the GJCA1 rs12197797 genotypic composition. MATERIAL AND METHODS: A cross-sectional study using genomic DNA and biopsy samples extracted from the oral mucosa with/without OSCC, older than 18 years, both genders, attended at Facultad de Odontología, Universidad Nacional Córdoba. Immunostaining for Cx43, Bcl-2, Bax, E-cadherin, and Ki67 and genotyping GJA1 rs12197797 by RFLP were performed. Odds Ratio (95% CI), Spearman Coefficient were estimated. Mann-Whitney test was applied to analyze immunostaining between controls/cases (p <0.05 was set for statistical significance). RESULTS: GG (mutant) was the most frequent genotype in patients with OSCC diagnosis (53.2%) in relation to CC "healthy" genotype (p=0.00487; OR=7.33; CI95% [1.1-54.7]). And, the allele G (mutant) had a presence in 75.5% of OSCC patients. However, no significant association was observed between alleles C/G and diagnosis (p=0.0565). The heterozygous genotype was the most frequent in the patients of both groups Cx43 and E-cadherin markers were lower in OSCCs in relation to controls. Ki67 and Bcl-2 immunolabeling were high on OSCC, and Bax immunomarker was diminished in OSCC. CONCLUSIONS: We hypothesized that the oral epithelium losses Connexin 43 and E-cadherin in the membrane, which modifies cell differentiation. The Ki67 and Bcl2 overexpression would increase the cell density in the tissue, by promoting proliferation and decreasing apoptosis. And, this study shows evidence that patients who carry on allele G of GJA1rs12197797 could be at risk of developing OSCC.

Tumorigenic effect mediated by ROS/eicosanoids and their regulation on TP53 expression in a murine mammary gland adenocarcinoma.

The aim of this study was to investigate the in vivo and in vitro effects of dietary ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) and their derivatives on the expression of TP53 and their relationship with cellular proliferation and death in a murine mammary adenocarcinoma model. BALB/c mice were divided in three diet groups: chia oil (ChO) rich in ω-3, corn oil (CO) rich in ω-6/ω-3 and safflower oil (SO) rich in ω-6 and subcutaneously inoculated with LMM3 mammary tumor cell line. Results demonstrated that diets with higher concentration of omega-6 PUFAs induced an increment of linoleic and arachidonic acid on tumor cell membranes increasing ROS liberation, 12(S)-HHT generation, TP53, Ki67 expression and cell proliferation. However, diets enriched with high content in omega-3 PUFAs induced higher tumor cell apoptosis and tumor infiltration of CD3+ lymphocytes, lowest cell viability and proliferation. Dietary omega-3 PUFAs nutritional intervention can be used as a potential preventative strategy to inhibit the molecular signaling pathways involved in the mammary tumor growth process as the TP53.

Clinical and Immunohistochemical epithelial profile of non-healing chronic traumatic ulcers.

BACKGROUND: Chronic wounds were previously related to cancer. Chronic Traumatic Ulcers (CTU) are lesions caused by chronic mechanical irritation (CMI) frequently diagnosed in Oral Medicine. Although these conditions may reflect a benign nature, some authors have proposed its relationship with malignant transformation. Currently, there are scarce investigations that evaluate biomarkers within CTU. The aim of this study was to evaluate cell differentiation and proliferation biomarkers patterns of CTU and OSCC through recognized markers such as cytokeratin 19 and Ki67 and correlate it with clinical features of both groups of patients. MATERIAL AND METHODS: A Cross-sectional study of adult patients (n=79), both sexes, attended at Oral Medicine Department, Facultad de Odontología, Universidad Nacional de Córdoba. The patients were classified into two groups: CTU (n=41), and OSCC (n=38). A subset of specimens were immunolabeled with Ki67 and Ck19. RESULTS: The population consisted of 51.9% male and 48.1% female, with an average of 57.0 ± 13.9. years (OSCC group) and 60.9 ± 14.9 years (CTU group). OSCC group presented higher scores for both biomarkers (Ki67 and Ck19), but only there were differences statistically significant for Ki67 (p=0.032). 25% of non-healing CTU were positive with medium scores of Ck19 and showed an immunohistochemical profile similar to OSCC. The lateral tongue was the most frequent site in both groups. CONCLUSION: The altered immunohistochemical pattern found in many specimens of CTU was also observed in OSCC. The tongue border presents physiological conditions that could offer a suitable environment for the development of neoplastic events associated with CMI. Further studies are needed to understand the underlying mechanisms that could link oral non-healing ulcers with early malignant changes.

Oral cancer associated with chronic mechanical irritation of the oral mucosa.

BACKGROUND: Most of the studies dealing with Chronic Mechanical Irritation (CMI) and Oral Cancer (OC) only considered prosthetic and dental variables separately, and CMI functional factors are not registered. Thus, the aim of this study was to assess OC risk in individuals with dental, prosthetic and functional CMI. Also, we examined CMI presence in relation to tumor size. MATERIAL AND METHODS: A case-control study was carried out from 2009 to 2013. Study group were squamous cell carcinoma cases; control group was patients seeking dental treatment in the same institution. RESULTS: 153 patients were studied (Study group n=53, Control group n=100). CMI reproducibility displayed a correlation coefficient of 1 (p<0.0001). Bivariate analysis showed statistically significant associations for all variables (age, gender, tobacco and alcohol consumption and CMI). Multivariate analysis exhibited statistical significance for age, alcohol, and CMI, but not for gender or tobacco. Relationship of CMI with tumor size showed no statistically significant differences. CONCLUSIONS: CMI could be regarded as a risk factor for oral cancer. In individuals with other OC risk factors, proper treatment of the mechanical injuring factors (dental, prosthetic and functional) could be an important measure to reduce the risk of oral cancer.

Cell apoptosis and proliferation in salivary glands of Sjögren's syndrome.

BACKGROUND: Sjögren's syndrome (SS) occurs associated with parotid neoplasm, non-Hodgkin's B-cell lymphoma, which could impair the condition or be life-threatening for patients. The aim of this work was to analyze cell proliferation and apoptosis modifications in acinar, ductal and inflammatory infiltrate in salivary glands (SG) in patients with Sjögren Syndrome, keratoconjunctivitis, or stomatitis sicca or in healthy subjects, to establish parameters that indicate the likelihood of malignancy of the disease in populations at risk. METHODS: A study was performed with n = 58 histological samples of lower lip SG from patients diagnosed with SS, keratoconjunctivitis, or stomatitis sicca (SICCA) and from healthy subjects (C). Ki67 and caspase-3 immunolabeling were performed. RESULTS: The most important result was significant differences between the three study groups in Ki67 and caspase-3 markers (P < 0.0001) in infiltrated lymphocytes. CONCLUSION: The results of this work are indicative of a high degree of proliferation (85%) in infiltrated lymphocytes (IL) associated with SS which, according the literature, could be considered a risk. Furthermore, the markers used in this work are widely known and represent a lower cost than others and can be used to determine risk groups within the population of SS patients, enabling their follow-up.

The effects of ω-6 and ω-3 fatty-acids on early stages of mice DMBA submandibular glands tumorigenesis.

The aim of this work was: to assess the impact of diets enriched in polyunsaturated fatty acids ω-3 and ω-6 families on the lipid profile of cell membrane and their effect on cycle regulation and apoptosis, evaluated by TP53 and Ki-67 expression in 9,10-dimethyl-1,2-benzanthracene (DMBA) induced tumor development in submandibular glands (SMG) in murine models. To generate tumorigenic changes, SMG mice in the experimental group were injected with 50µl of 0.5% of DMBA. Both control (no DMBA) and experimental groups of BALB/c mice were fed with: chia oil (ChO), rich in ω-3 fatty acid; corn oil (CO), rich in ω-6/ω-3 fatty acid; and safflower (SO) oil, rich in ω-6fatty acid. Results demonstrate novel differential effects of ω-3 and ω-6 PUFAs on the regulation of early tumorigenesis events in murine SMG injected with DMBA. This knowledge may help to develop chemoprotective treatments, therapeutic agents and health promotion and prevention activities in humans.

Simple predictive model for Early Childhood Caries of Chilean children.

INTRODUCTION: Early Childhood Caries (ECC), in both industrialized and developing countries, is the most prevalent chronic disease in childhood and it is still a health public problem, affecting mainly populations considered as vulnerable, despite being preventable. OBJECTIVE: The purpose of this study was to obtain a simple predictive model based on risk factors for improving public health strategies for ECC prevention for 3-5 year-old children. METHODS: Clinical, environmental and psycho-socio-cultural data of children (n=250) aged 3-5 years, of both genders, from the Health Centers, were recorded in a Clinical History and Behavioral Survey. RESULTS: 24% of children presented behavioral problems (bizarre behavior was the main feature observed as behavioral problems). The variables associated to dmf ?4 were: bad children temperament (OR=2.43 [1.34, 4.40]) and home stress (OR=3.14 [1.54, 6.41]). It was observed that the model for male gender has higher accuracy for ECC (AUC= 78%, p-value=0.000) than others. CONCLUSIONS: Based on the results, we proposed a model where oral hygiene, sugar intake, male gender, and difficult temperament are main factors for predicting ECC. This model could be a promising tool for cost-effective early childhood caries control.

Introducción: Las caries temprana de la infancia (CTI), a pesar de ser una enfermedad prevenible, permanece como uno de los problemas de salud pública, tanto en países industrializados como en los que están en vías de desarrollo, afectando principalmente a poblaciones vulnerables. Objetivo: el objetivo de este trabajo fue generar un modelo sencillo basado en factores de riesgo que sea predictivo del riesgo de CTI en niños de 3-5 años de edad a fin de mejorar las estrategias preventivas a nivel de salud pública. Métodos: Se recolectaron datos clínicos, del hogar y psico-socio-cultural de niños (n=250) de ambos sexos que concurren a centros de salud en la región del Bio Bio ­ Chile mediante historia clínica y encuesta de comportamiento. Resultados: 24% de los niños presentó problemas de comportamiento (un comportamiento extraño fue la principal característica observada como problema de comportamiento). Las variables asociadas a ceo ?4 fueron: mal temperamento del niño (OR=2,43 [1,34; 4,40]) y estrés del hogar (OR=3,14 [1,54; 6,41]). Se observe que el modelo estratificado por género masculino fue el que presentó la mayor precisión diagnóstica de CTI (AUC= 78%, p-valor=0.000); además Conclusiones: Proponemos un modelo donde la higiene oral, el consumo de azúcar, el género masculino y el mal temperamento son los principales factores de predictivos de CTI. Este modelo podría ser una herramienta promisoria para el costo-efectividad del control de caries temprana.

Risk genes in head and neck cancer: a systematic review and meta-analysis of last 5 years.

The aim of this work was to identify risk genes related to the development and progression of squamous cell carcinoma head and neck (SCCHN) and do a meta-analysis of available estimates. Eligible gene/polymorphism studies were identified by electronic searches. Individual participant data of 8540 patients with HNC and 9844 controls from 19 genetic studies were analyzed, yielding adjusted (tobacco, gender, age and alcohol) odds ratios (OR) and 95% confidence intervals (CIs) comparing cases with controls. A meta-analysis was done on the studies that applied fixed and random models. People have an increase of polymorphism expression related to inflammation (NFKB1-294-ATTG, TNFα308-A2A2/A2A1, and TNFß252- B2B2/B2B1) or carcinogenic metabolism (GSTM1 null, and CYP1A1 m1/m1), representative of malignancy development. Furthermore, the increased expression of genes associated with the stabilization and repair of the cellular (OGG1-Asp267Asn, Ser279Gly Ile253Phe, 1578A>T, 1582C>T Ala399Glu (1542C>A) 1582insG 1543_1544delCT), and genes associated with the regulation of proliferation, apoptosis or tumor survival (miRNA499-CT/CC, CRYABC802G-CG/GG) are considered as risk factors. In this scheme, only the polymorphisms of ADH7A92G-GG and DEC1606-T/C genes are protective against malignancy transformation. The TP53, GSTM1 and CYPA1genes have been evaluated in more than one study and analyzed for homogeneity in each genotype. The meta-analysis showed no significant association between different allelic variants of Arg72Pro rs1042522 and SCCHN risk. In a model of tumorigenesis, an increased risk of SCCHN is associated with DNA repair and DNA stabilization genes. In addition, the polymorphisms involved in inflammation and carcinogenic metabolism processes represent an increased risk of SCCHN.

Simple predictive model for early childhood caries of chilean children / Simple predictive model for early childhood caries of chilean children.

INTRODUCTION: Early Childhood Caries (ECC), in both industrialized and developing countries, is the most prevalent chronic disease in childhood and it is still a health public problem, affecting mainly populations considered as vulnerable, despite being preventable. Objective The purpose of this study was to obtain a simple predictive model based on risk factors for improving public health strategies for ECC prevention for 3-5 year-old children. Methods - Clinical, environmental and psycho-socio-cultural data of children (n=250) aged 3-5 years, of both genders, from the Health Centers, were recorded in a Clinical History and Behavioral Survey. Results-24

of children presented behavioral problems (bizarre behavior was the main feature observed as behavioral problems). The variables associated to dmf ?4 were: bad children temperament (OR=2.43 [1.34, 4.40]) and home stress (OR=3.14 [1.54, 6.41]). It was observed that the model for male gender has higher accuracy for ECC (AUC= 78

, p-value=0.000) than others.Conclusions- Based on the results, we proposed a model where oral hygiene, sugar intake, male gender, and difficult temperament are main factors for predicting ECC. This model could be a promising tool for cost-effective early childhood caries control.

Concentración de proteínas totales en saliva de jóvenes consumidores sociales de alcohol / Total protein concentration in saliva alcohol social young consumers

La concentración de proteínas salivales, así como el flujo salival, puede ser afectada por el consumo crónico de alcohol a través de la alteración estructural que éste produce en las glándulas secretoras. Aunque existen antecedentes acerca de una modificación en la concentración de proteínas salivales como consecuencia de la ingesta aguda de etanol, no se hallaron referencias sobre los efectos del consumo social del mismo. Por ello, el objetivo del presente estudio fue analizar la concentración de proteínas totales en saliva de jóvenes consumidores sociales de alcohol, las cuales son imprescindibles para mantener el estado de salud de los tejidos dentarios y peridentarios. Participaron treinta estudiantes universitarios de ambos sexos, de 18-25 años de edad, clínicamente sanos, con y sin antecedentes de consumo de alcohol. Los mismos respondieron a un cuestionario referido al consumo de alcohol y tabaco, administración de medicamentos y presencia de enfermedades sistémicas. Se obtuvieron muestras de saliva mixta no estimulada, en condiciones de ayuno y mediante la técnica de expectoración. Luego de centrifugar las muestras, la concentración de proteínas fue analizada por Lowry modificado y el perfil de proteínas por SDS PAGE 12 por ciento. El consumo de alcohol se encontró estadísticamente correlacionado con el hábito de fumar (p=0,0001) y el sexo masculino (p=0,01). La concentración de proteínas totales salivales (g/l) fue significativamente diferente entre los grupos de consumidores y no consumidores de alcohol (p=0.04), con una mayor concentración promedio en el grupo de no consumidores en relación a las variables sexo, tabaco y medicación. Los resultados del presente estudio permiten concluir que el consumo social de alcohol modifica la concentración de proteínas totales de la saliva

The concentration of salivary proteins, as well as the salivary flow, may be affected by the chronic alcohol intake through the structural changes it induces in the secretory glands. Although the modification in salivary protein concentration as a result of acute alcohol intake has been reported, no references were found on the effects of its social intake. Thus, the main purpose of this study was to analyze the concentration of total proteins in saliva of young social alcohol consumers, which are necessary to maintain the healthy condition of dental and peridental tissues. Thirty University students of both sexes, age range18-25 years old, apparently healthy, with and without (control) background of alcohol intake, participated in the study. They answered a questionnaire referred to the alcohol intake and tobacco smoking, medicine intake and presence of systemic diseases. Non-stimulated mixed saliva was obtained in fast condition and through the expectoration technique. After centrifuging the samples, the protein concentration was analyzed by modified Lowry and protein profile by electrophoresis 12 percent SDS PAGE. The alcohol intake was statistically correlated to tobacco smoking (p=0,0001) and masculine sex (p=0,01). The concentration of total salivary proteins was significantly different between the consumer and non-consumer groups (p=0.04), the highest mean concentration found in the second group in relation to sex, tobacco smoking and medicine intake. The results of the present study allow to conclude that the social alcohol intake modify the concentration of total salivary proteins