| spelling |
Maria Cássia Ferreira de Aguiarhttp://lattes.cnpq.br/6698384703955708Vanessa de Fátima BernardesManoela Domingues MartinsSílvia Ferreira de SousaMartinho Campolina Rebelo HortaFelipe Paiva Fonsecahttp://lattes.cnpq.br/5040404733798846Lauren Frenzel Schuch2019-12-17T18:00:02Z2019-12-17T18:00:02Z2019-11-20http://hdl.handle.net/1843/31602O câncer de boca corresponde a cerca de 4% das doenças neoplásicas, e o carcinoma de células escamosas representa o tipo mais frequente, englobando cerca de 90 a 95% dos casos. O cigarro é o principal fator etiológico para o câncer de boca, causando danos ao DNA e mutações que se não reparadas levam ao surgimento de lesões. O dano ao DNA associado ao cigarro tem sido estudado em diferentes tipos de câncer, mas ainda pouco explorado em relação ao câncer de boca. Checkpoint kinase 2 (CHK2) e P53 são proteínas que estão envolvidas no processo de checagem do ciclo celular, sendo responsáveis pelo reparo ao dano ao DNA. A proteína H2AX é uma histona nuclear que sofre fosforilação em resposta aos danos ao DNA, principalmente às quebras da dupla cadeia. O objetivo deste estudo foi avaliar a resposta a danos no DNA através da expressão de CHK2, γH2AX e TP53 entre fumantes e não fumantes com carcinoma de células escamosas de boca (CCEB). Além disso, foram analisadas associações entre imuno-expressão das proteínas estudadas, dados clínico-patológicos e classificação histopatológica. Foram incluídos 35 indivíduos (18 não fumantes e 17 fumantes) com CCEB de língua e soalho bucal. Reação imuno-histoquímica foi realizada para γH2AX para identificação de quebras de fita dupla, CHK2 e TP53 para avaliação da indução de parada do ciclo celular. Análises descritivas e estatísticas foram realizadas. A pesquisa foi composta por 22 homens (62,8%) e 13 mulheres (37,2%), com idade média de 63,9 anos. Entre os não fumantes, 50% apresentaram tumores bem diferenciados, enquanto que fumantes mostraram maior número em moderadamente diferenciados e pouco diferenciados (35,3% cada). No geral, 31 (88,6%) casos foram positivos para CHK2, 27 (77,2%) foram positivos para γH2AX e 23 (65,7%) foram positivos para TP53. Não foi observada associação entre essas proteínas com hábitos de fumar e não fumar (p> 0,05). Semelhanças entre os padrões imuno-histoquímicos de CHK2, γH2AX e TP53 em fumantes e não fumantes com CCEB foram observadas neste estudo, assim como entre os parâmetros clínico-patológicos. De forma geral, os resultados indicaram expressão positiva para essas proteínas no CCEB. Este estudo fornece informaçaões sobre o dano ao DNA na carcinogênese oral.Oral cancer accounts for about 4% of neoplastic diseases, and squamous cell carcinoma is the most common type, accounting for about 90 to 95% of cases. Cigarette smoking is the main etiological factor for oral cancer, causing DNA damage and mutations that, if not repaired, lead to lesions. Cigarette-associated DNA damage has been studied in different cancers, but is still poorly explored in relation to oral cancer. Checkpoint kinase 2 (CHK2) and P53 are proteins that are involved in the cell cycle checking process and are responsible for repairing DNA damage. The H2AX protein is a nuclear histone that undergoes phosphorylation in response to DNA damage, especially double strand breaks. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), γH2A histone family member X (γH2AX) and TP53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). In addition, associations amongst immunoexpression of studied proteins, clinicopathologic data and histopathological grading were analyzed. Thirty-five individuals (18 nonsmokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry was carried out for γH2AX for identification of double-strand breaks, CHK2 and P53 for evaluation of the induction of cell cycle arrest. Descriptive and statistical analyses were performed. The survey consisted of 22 males (62.8%) and 13 females (37.2%), with a mean age of 63.9 years. Fifty percent of non-smokers OSCC were well-differentiated tumors, whereas for smokers, OSCC were moderately differentiated and poorly differentiate tumors, equally (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.2%) were γH2AX-positive and 23 (65.7%) were TP53-positive. No association among these proteins with smoking and non-smoking habits was observed (p>0.05). Similarities in the CHK2, γH2AX and P53 immunohistochemical staining pattern were observed between smokers and non-smokers with OSCC in this survey, and the immunoexpression was not associated with clinicopathologic parameters. Overall, the results indicated consistent expression of these proteins in OSCC. This study provides information about the DNA damage in oral carcinogenesis.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em OdontologiaUFMGBrasilODONTO - FACULDADE DE ODONTOLOGIADano ao DNAQuinase do ponto de checagem 2Proteína supressora de tumor p53Neoplasias bucaisTabacoDano ao DNACHK2Gama-H2AXP53Câncer oralTabacoExpressão das proteínas CHK2, γH2AX e TP53 em carcinoma de células escamosas de boca de indivíduos fumantes e não fumantesExpression of CHK2, γH2AX and TP53 proteins in smokers and non-smokers oral squamous cell carcinomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALdissertaçao completa.pdfdissertaçao completa.pdfapplication/pdf14461602https://repositorio.ufmg.br/bitstream/1843/31602/3/dissertac%cc%a7ao%20completa.pdf017a356c73a3feb87ff675fde56271e4MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-82119https://repositorio.ufmg.br/bitstream/1843/31602/4/license.txt34badce4be7e31e3adb4575ae96af679MD54TEXTdissertaçao completa.pdf.txtdissertaçao completa.pdf.txtExtracted texttext/plain117544https://repositorio.ufmg.br/bitstream/1843/31602/5/dissertac%cc%a7ao%20completa.pdf.txtbc0a7fa01936cb89501ea6c937cc5199MD551843/316022019-12-18 03:24:00.408oai:repositorio.ufmg.br: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Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2019-12-18T06:24Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
|