Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil

Abstract This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Efeito dos tratamentos com ácido acetilsalicílico e celecoxibe na expressão de citocinas e no comportamento de linhagens celulares de carcinoma epidermoide de boca / Effect of treatment with aspirin and celecoxib on the expression of cytokines and behavior of cell lines of squamous cell carcinoma

Quatro décadas de pesquisas mostraram que muitos mecanismos inflamatórios estão intrinsecamente ligados ao desenvolvimento e manutenção do câncer, e ainda, que as citocinas inflamatórias exercem papel primordial nessa relação. Os anti-inflamatórios não esteroides (AINEs) podem reduzir o desenvolvimento neoplásico por afetar a produção de citocinas inflamatórias pelas células neoplásicas. No entanto, até o momento não foi bem definido se o tratamento com AINEs é capaz de modular a expressão de citocinas inflamatórias por células do carcinoma epidermoide oral (CEO). O objetivo deste trabalho foi avaliar a expressão de citocinas inflamatórias em linhagens celulares de CEO após tratamento com ácido acetilsalicílico (AAS) e celecoxibe (CLX). Foi realizado screening da expressão de 84 citocinas e quimiocinas, através de PCR array, das linhagens SCC4, 9 e 25 tratadas com doses de AAS e CLX próximas às concentrações plasmáticas dos fármacos em humanos. Os resultados mostraram que AAS e CLX modularam a expressão de citocinas e que as linhagens responderam de maneira diferente aos tratamentos. Observou-se aumento de expressão de citocinas pró-inflamatórias como a IL-1?, IL-8 e TNF na SCC9 e 25, assim como diminuição de expressão de ACKR4 e CXCL10 na SCC4 e 9.

Four decades of research have shown that many inflammatory mechanisms are intrinsically linked to the development and maintenance of cancer and that inflammatory cytokines play pivotal role in this association. Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce neoplastic growth on affecting the production of inflammatory cytokines by the neoplastic cells. So far, it is not well established if the treatment with NSAIDs can modulate the expression of inflammatory cytokines by OSCC cells. The objective of this study was to evaluate the expression of inflammatory cytokines by OSCC cell lines after treatment with acetylsalicylic acid (ASA) and celecoxib (CLX). Eighty-four cytokines and chemokines mRNA expression were screened by PCR array on SCC4, 9 and 25 cell lines treated with ASA and CLX at plasma concentrations in humans. The results showed that ASA and CLX modulate the expression of cytokines with all cell lines responding differently to the treatments. Increased expression of proinflammatory cytokines such as IL-1?, IL-8 and TNF in SCC9 and 25, and reduced expression of ACKR4 and CXCL10 in SCC4 and 9, was observed. Thus it follows that the treatments of lines SCC4, SCC9 and SCC25 with ASA and CLX at the next plasma concentrations in humans are able to modulate the gene expression of inflammatory cytokines.

Efeito dos tratamentos com ácido acetilsalicílico e celecoxibe na expressão de citocinas e no comportamento de linhagens celulares de carcinoma epidermoide de boca / Effect of treatment with aspirin and celecoxib on the expression of cytokines and behavior of cell lines of squamous cell carcinoma

Quatro décadas de pesquisas mostraram que muitos mecanismos inflamatórios estão intrinsecamente ligados ao desenvolvimento e manutenção do câncer, e ainda, que as citocinas inflamatórias exercem papel primordial nessa relação. Os anti-inflamatórios não esteroides (AINEs) podem reduzir o desenvolvimento neoplásico por afetar a produção de citocinas inflamatórias pelas células neoplásicas. No entanto, até o momento não foi bem definido se o tratamento com AINEs é capaz de modular a expressão de citocinas inflamatórias por células do carcinoma epidermoide oral (CEO). O objetivo deste trabalho foi avaliar a expressão de citocinas inflamatórias em linhagens celulares de CEO após tratamento com ácido acetilsalicílico (AAS) e celecoxibe (CLX). Foi realizado screening da expressão de 84 citocinas e quimiocinas, através de PCR array, das linhagens SCC4, 9 e 25 tratadas com doses de AAS e CLX próximas às concentrações plasmáticas dos fármacos em humanos. Os resultados mostraram que AAS e CLX modularam a expressão de citocinas e que as linhagens responderam de maneira diferente aos tratamentos. Observou-se aumento de expressão de citocinas pró-inflamatórias como a IL-1?, IL-8 e TNF na SCC9 e 25, assim como diminuição de expressão de ACKR4 e CXCL10 na SCC4 e 9.

Four decades of research have shown that many inflammatory mechanisms are intrinsically linked to the development and maintenance of cancer and that inflammatory cytokines play pivotal role in this association. Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce neoplastic growth on affecting the production of inflammatory cytokines by the neoplastic cells. So far, it is not well established if the treatment with NSAIDs can modulate the expression of inflammatory cytokines by OSCC cells. The objective of this study was to evaluate the expression of inflammatory cytokines by OSCC cell lines after treatment with acetylsalicylic acid (ASA) and celecoxib (CLX). Eighty-four cytokines and chemokines mRNA expression were screened by PCR array on SCC4, 9 and 25 cell lines treated with ASA and CLX at plasma concentrations in humans. The results showed that ASA and CLX modulate the expression of cytokines with all cell lines responding differently to the treatments. Increased expression of proinflammatory cytokines such as IL-1?, IL-8 and TNF in SCC9 and 25, and reduced expression of ACKR4 and CXCL10 in SCC4 and 9, was observed. Thus it follows that the treatments of lines SCC4, SCC9 and SCC25 with ASA and CLX at the next plasma concentrations in humans are able to modulate the gene expression of inflammatory cytokines.

Immunolocalization of FGF-10 in murine incisors and molar germs / Imunolocalização de FGF-10 em germes de incisivos e molares murinos

Objective: The aim of this study was to identify the presence of FGF-10 in mouse dental germs by means of the immunohistochemical technique, fromthe initial development phase through to the more advanced phases. Methods: Fetuses of five mice, on days 15.5, 16.5, 17.5, 18.5 and 19.5 of pregnancy, respectively, were collected. At time intervals of 0.5, 1.5, 2.5 and 3.5 days after birth, the mouse offspring were sacrificed. The heads of all the specimens were fixed and submitted to histotechnique and3?m thick sections were obtained. The presence of FGF-10 was detected by means of the avidin-biotin-peroxidase immunohistochemistry technique.Results: Immunostaining was detected in both epithelium and ectomesenchyme with intensity and spatial-temporal differences. A reduction in the presence of FGF-10 was observed in the cervical loop area, on the lingual side of the incisor crowns, and both sides of the molar crowns. With the increase in enamel matrix deposition, immunostaining on the secretory pole of ameloblasts also increased. Conclusion: FGF-10 immunostaining could be related to cell proliferation in epithelium and cell differentiation in epithelium and ectomesenchyme. This could be related to morphological determination in intercuspal areas of molar germs and to continuous growth of the incisor crown. Decrease in FGF-10 in the cervical loop could be related to the termination of crown formation. Increase in FGF-10 expression in ameloblasts suggests a relationship with active enamel production. The results suggest the inclusion of the pattern of the presence of FGF-10 in future investigations into the cause of morphological anomalies, such as palato-gingival groove.

Objetivo: Identificar a presença de FGF-10 em germes dentários de rato pela técnica de imunohistoquímica. Métodos: Os fetos de cinco ratos, nos dias 15,5; 16,5; 17,5; 18,5; 19,5, respectivamente, de gravidez, foram coletados. Em intervalos de tempo de 0,5; 1,5; 2,5 e 3,5 dias após o nascimento, as proles de ratas foram sacrificadas. As cabeças de todos os exemplares foram fixadas e submetidas à histotécnica e cortes com 3?m de espessura foram obtidos. A presença de FGF-10 foi detectada pela técnica de imunohistoquímica da avidinabiotina-peroxidase. Resultados: A imunomarcação foi detectada no epitélio e no ectomesênquima com intensidade e diferenças espaço-temporais. Uma redução da presença de FGF-10 foi observada na área da alça cervical, no lado lingual de coroas de incisivo e em ambos os lados das coroas de molares. Com o aumento da deposição de matriz de esmalte, a imunomarcação no pólo secretor de ameloblastos também aumentou.Conclusão: a presença de FGF-10 parece estar relacionada com a proliferação de células no epitélio e diferenciação de células no epitélio e ectomesênquima. Isso pode estar relacionado à determinação morfológica nas áreas intercuspídeas de germes dos molares e ao crescimento contínuo da coroa nos incisivos. A diminuição do FGF-10 em áreas alça cervical parece estar relacionada com o término de formação da coroa. O aumento de FGF-10 em ameloblastos parece estar relacionada com a produção ativa de esmalte.