ABSTRACT: The most widely used method to classify prognostic factors in cancers today is TNM. However, Oral Squamous Cell Carcinoma (OSCC) often demonstrates different behaviors in relation to aggressiveness and therapeutic response at the same TNM stage. So, in such cases biomarkers can be used to identify the biological diversity of these tumors more reliably, leading to better therapeutic strategies and disease management. The presence of inflammatory immune cells in the tumor microenvironment can have pro or antitumor effects and the investigation of the expression of inflammatory markers in OSSC can be usefulto design immunotherapeutic interventions. The Transforming Growth Factor alpha is a potent stimulator of cell migration that acts on cell proliferation, invasion and metastasis of cancer, as well as immune suppression and angiogenesis. Inflammatory cytokines, such as Interferon-gamma, mediate macrophage differentiation. Macrophages are an important component of the OSCC microenvironment. The greater amount of tumor-associated macrophages, especially the M2 phenotype, may be associated with a more aggressive biological behavior of the OSCC and, consequently, with reduced survival.

RESUMEN: El método más utilizado para clasificar los factores de pronóstico en los cánceres en la actualidad es TNM. Sin embargo, el carcinoma oral de células escamosas (COCE) a menudo muestra diferentes comportamientos en relación con la agresividad y la respuesta terapéutica en la misma etapa TNM. Entonces, en tales casos, los biomarcadores pueden usarse para identificar la diversidad biológica de estos tumores de manera más confiable, lo que lleva a mejores estrategias terapéuticas y manejo de la enfermedad. La presencia de células inmunes inflamatorias en el microambiente tumoral puede tener efectos pro o antitumorales y la investigación de la expresión de marcadores inflamatorios en COCE puede ser útil para diseñar intervenciones inmunoterapéuticas. El factor de crecimiento transformante α es un potente estimulador de la migración celular que actúa sobre la proliferación celular, la invasión y metástasis del cáncer, así como la inmunosupresión y la angiogénesis. Las citocinas inflamatorias, como el IFN-γ, median en la diferenciación de macrófagos. Los macrófagos son un componente importante del microambiente COCE. La mayor cantidad de macrófagos asociados a tumores, especialmente el fenotipo M2, puede estar asociada a un comportamiento biológico más agresivo del COCE y, en consecuencia, a una menor supervivencia.

Abstract The mechanisms that stimulate the proliferation of epithelial cells in inflammatory periapical lesions are not completely understood and the literature suggests that changes in the balance between apoptosis and immunity regulation appear to influence this process. Objective: To evaluate the expression of the epidermal growth factor (EGF), its receptor (EGFR) and of the keratinocyte growth factor (KGF), the presence of CD57+ cells, the epithelial cell proliferation index, and the expression of the Bcl-2 protein in inflammatory periapical lesions (IPL) at different stages of development. Methodology: Our sample was composed of 52 IPLs (22 periapical granulomas - PG - and 30 periapical cysts - PC), divided into three groups: PGs, small PCs, and large PCs. Specimens were processed for histopathologic and immunohistochemical analyses. Sections were evaluated according to the amount of positive staining for each antibody. Results: We found no significant differences among the groups regarding Bcl-2 (p=0.328) and Ki-67 (p>0.05) expression or the presence of CD57+ cells (p=0.748). EGF (p=0.0001) and KGF (p=0.0001) expression was more frequent in PCs than in PGs, and CD57+ cells were more frequent in IPLs with intense inflammatory infiltrates (p=0.0001). We found no significant differences in KGF (p=0.423), Bcl-2 (p=0.943), and EGF (p=0.53) expression in relation to inflammatory infiltrates or to the type of PC epithelial lining, but observed greater KGF expression (p=0.0001) in initial PCs. EGFR expression was similar among the groups (p>0.05). Conclusion: More frequent EGF and KGF expression in PCs and the greater presence of CD57+ cells in lesions with intense inflammatory infiltrates suggest that these factors influence IPL development. The greater KGF expression in initial PCs suggests its importance for the initial stages of PC formation.

Resumo Introdução Se a restauração temporária, que sela o canal radicular contra o meio bucal, falhar ou solubilizar, a medicação intracanal pode ser parcialmente removida, diminuindo a eficiência do hidróxido de cálcio (CH). Objetivo Avaliar o potencial alcalinizante e a liberação de íons cálcio de resíduos de diferentes medicações intracanal, em diferentes períodos. Material e método Incisivos humanos foram endodonticamente instrumentados e divididos aleatoriamente (n=10). Os canais radiculares foram preenchidos com: G1⎯Hidróxido de cálcio (CH); G2⎯CH com 0.4% de digluconato de clorexidina (CHC); G3⎯CH com paramonoclorofenol camforado e glicerina (HPG); G4⎯CH mantido durante todo experimento, como controle positivo (PC) e G5⎯Sem medicação intracanal, como controle negativo (NC). Os espécimes foram imersos em água destilada durante 7 dias. A medicação intracanal foi removida dos grupos experimentais com um instrumento F1 (Protaper). Os dentes foram armazenados em água destilada por 24 horas, 7, 14 e 28 dias. Os dados foram submetidos aos testes ANOVA one-way e Tukey. Resultado Todos os grupos experimentais tiveram redução no potencial alcalinizante e na liberação dos íons cálcio, quando comparados ao controle positivo (p<0.05). Não houve diferença estatisticamente significante entre os grupos experimentais, independente do período (p>0.05). Conclusão O potencial alcalinizante e a liberação de íons cálcio dos resíduos de diferentes medicações intracanal, em diferentes períodos, foram similares entre si e menores que o controle positivo, onde a medicação foi mantida dentro do canal radicular, encorajando a sua troca quando a restauração falhar.

Abstract Introduction If the restoration, that seal the root canal from oral environment, failed or solubilize, the intracanal dressing could be partially removed, decreasing the efficiency of calcium hydroxide (CH). Objective To evaluate the alkalizing potential and calcium ions release of intracanal residues from different medications, in different periods. Materials and method Human incisors were endodontically instrumented and randomly divided (n=10). The root canals were filled with: G1⎯Calcium hydroxide (CH); G2⎯CH with 0.4% chlorhexidine digluconate (CHC); G3⎯CH with camphorated paramonochlorophenol and glycerin (HPG); G4⎯CH was maintained during all experiment, as positive control group (PC) and G5⎯ No medication was performed in the negative control group (NC). The specimens were immersed in distilled water for 7 days. The intracanal dressing was removed from the experimental groups using F1 instrument (Protaper). The teeth were stored in distilled water for 24 hours, 7, 14 and 28 days. pH value and calcium ions released were evaluated and the data were submitted to ANOVA one-way and Tukey tests. Result All experimental groups presented lower alkalizing potential and calcium ions release than PC (P<0.05). No significant difference was found among the experimental groups, regardless of the period (P>0.05). Conclusion The alkalizing potential and calcium ions release of residues from different intracanal dressing, in different periods, were similar and lower than the positive control group, that the medication was maintained inside the root canal, encouraging the replacement of intracanal dressing when the restoration fail.

Abstract Objective: This study evaluated the expression of pro-inflammatory (IL-1β, IL-6, IFN-γ and TNF-α) and anti-inflammatory (IL-4 and TGF-β) cytokines in apical periodontitis lesions. Correlations between these cytokines and clinical and cone-beam computed tomographic (CBCT) data were also assessed. Material and Methods: Apical periodontitis lesions’ data were obtained from 27 patients subjected to periradicular surgery. Specimens were processed for histopathologic and immunohistochemical analysis. Sections were evaluated according to the amount of positive staining for each antibody. Expression levels of the target mediators were compared with clinical and CBCT data. Results: Twenty lesions were diagnosed as granuloma and 7 as cyst. In granulomas, IL-4 expression was significantly higher than IL-6 (p=0.001) and TNF-α (p=0.001). There was a significant relationship between high levels of TNF-α and lesions <5 mm (p=0.017). In cysts, IL-6 expression was significant lower than IL-4 (p=0.001) and IFN-γ (p=0.004). There was a significant relationship between high levels of TGF-β and endodontic treatment performed ≤4 years before (p=0.045). In general, IL-4 was the most expressed mediator in both cysts and granulomas. Conclusions: There was a balance between the expression of pro-inflammatory and anti-inflammatory cytokines associated with the chronic periradicular inflammatory process. TNF-α and TGF-β were related to some clinical and CBCT data.