Head and neck squamous cell carcinomas (HNSCCs) most commonly develop in older patients (≥60 years of age) with a history of tobacco and alcohol use. However, young individuals (≤45 years of age) can also develop HNSCC, often without common risk factors. Increasing evidence shows that Human Papillomavirus (HPV) infection is associated with particular HNSCC sites (e.g. oropharynx). We assessed the Roche Linear Array HPV Genotyping Test in several lesions and then examined the prevalence of HPV in HNSCCs from young and older patients. HPV infection was most prevalent in oropharyngeal cancers (16/22, 73%), rarely found in oral cavity cancers (2/53, 4%), and other head and neck sites (1/17, 6%). HPV positive tumors were associated with patients that were >40 and <60 years old (p=0.02). The absence or shortened time of carcinogen exposure from common risk factors and the development of oral squamous cell carcinoma (OSCC) at an early age suggest aberrant genetic events that are different than those in OSSCs from older patients. We used Affymetrix SNP 6.0 arrays to genomically profile oral tumors from young and older patients. Tumors from young patients showed different regions/genes of copy number alterations than those from older patient tumors. An increase of regions of loss of heterozygosity (LOH) in tumors from older patients was observed, and there was a high prevalence of copy number neutral LOH on chromosome 9 in tumors from young and older patients. These data suggest different genetic mechanisms in these patient groups. We have previously shown that HNSCCs from younger patients exhibited a high incidence of microsatellite instability (MSI), a marker of defective mismatch repair (MMR). Deregulated mRNA levels of hPMS1, hPMS2 and hMLH1 were observed and absent/low expression of hPMS1, hPMS2 and hMLH1 protein levels were observed in >50% of OSCCs. No mutations were observed in hPMS1 and hPMS2 and no significant differences of MSI or LOH were observed across genomic loci between tumors of young and older patients. The role of these genetic mechanisms in oral cancer appears complex; studies such as ours should further improve our knowledge of the molecular mechanisms leading to early-onset oral carcinomas.

Head and neck squamous cell carcinomas (HNSCCs) most commonly develop in older patients (≥60 years of age) with a history of tobacco and alcohol use. However, young individuals (≤45 years of age) can also develop HNSCC, often without common risk factors. Increasing evidence shows that Human Papillomavirus (HPV) infection is associated with particular HNSCC sites (e.g. oropharynx). We assessed the Roche Linear Array HPV Genotyping Test in several lesions and then examined the prevalence of HPV in HNSCCs from young and older patients. HPV infection was most prevalent in oropharyngeal cancers (16/22, 73%), rarely found in oral cavity cancers (2/53, 4%), and other head and neck sites (1/17, 6%). HPV positive tumors were associated with patients that were >40 and <60 years old (p=0.02). The absence or shortened time of carcinogen exposure from common risk factors and the development of oral squamous cell carcinoma (OSCC) at an early age suggest aberrant genetic events that are different than those in OSSCs from older patients. We used Affymetrix SNP 6.0 arrays to genomically profile oral tumors from young and older patients. Tumors from young patients showed different regions/genes of copy number alterations than those from older patient tumors. An increase of regions of loss of heterozygosity (LOH) in tumors from older patients was observed, and there was a high prevalence of copy number neutral LOH on chromosome 9 in tumors from young and older patients. These data suggest different genetic mechanisms in these patient groups. We have previously shown that HNSCCs from younger patients exhibited a high incidence of microsatellite instability (MSI), a marker of defective mismatch repair (MMR). Deregulated mRNA levels of hPMS1, hPMS2 and hMLH1 were observed and absent/low expression of hPMS1, hPMS2 and hMLH1 protein levels were observed in >50% of OSCCs. No mutations were observed in hPMS1 and hPMS2 and no significant differences of MSI or LOH were observed across genomic loci between tumors of young and older patients. The role of these genetic mechanisms in oral cancer appears complex; studies such as ours should further improve our knowledge of the molecular mechanisms leading to early-onset oral carcinomas.

This dissertation focuses on the development of algorithms for analyzing and modeling of the signals from optical spectroscopy. This dissertation is motivated by the detection of oral cancer, but some of the methods developed can be generalized to epithelial cancers of other sites. Two main topics are covered in this dissertation: Analysis and Modeling. For analysis, the focus is on developing algorithms to make diagnostic predictions. The analysis methods are empirically tested using an oral cancer dataset. Statistical analyses show that polarized reflectance spectroscopy has the potential to aid screening and diagnosis of oral cancer. Also, a novel adaptive windowing technique is developed to extract spectral features with fewer windows that retain the diagnostic information. For modeling, a Monte Carlo model simulating light-tissue interactions is presented to aid in the design of diagnostic instrumentation. / text

Objectives: Intact cell peptidome profiling (ICPP) with MALDI-ToF Mass-Spectrometry holds promise as a non invasive method to detect head and neck squamous cell carcinoma (HNSCC) objectively, which may improve the early diagnosis of oral cancer tremendously. The present study was designed to discriminate between tumour samples and non-cancer controls (healthy mucosa and oral lesions) by analysing complete spectral patterns of intact cells using MALDI-ToF MS. Material and Methods: In the first step, a data base consisting of 26 patients suffering from HNSCC was established by taking brush biopsy samples of the diseased area and of the healthy buccal mucosa of the respective contralateral area. After performing MALDI-ToF MS on these samples, classification analysis was used as a basis for further classification of the blind study composed of additional 26 samples including HNSCC, oral lesions and healthy mucosa. Results: By analyzing spectral patterns of the blind study, all cancerous lesions were defined accurately. One incorrect evaluation (false positive) occurred in the lesion cohort, leading to a sensitivity of 100%, a specificity of 93% and an overall accuracy of 96.5%. Conclusion: ICPP using MALDI-ToF MS is able to distinguish between healthy and cancerous mucosa and between oral lesions and oral cancer with excellent sensitivity and specificity, which may lead to a more impartial early diagnosis of HNSCC.

Made available in DSpace on 2015-05-14T12:56:06Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 523465 bytes, checksum: 529315c7249a5c413789e7fee7cf1590 (MD5) Previous issue date: 2009-12-11 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this research was to investigate the level of information and preventive behavior of the users assisted in the Basic Heart Units (UBS) of Family Health Care Program (PSF) of Patos-PB, regarding oral cancer. The data were collected through the application of a route of individual interview in a sample of 383 users. Of these, 267 are women (69,7%) and 116 men (30,3%), the age varied from 18 to 78 years, with 33,36 year-old average, more of the half (55,9%) with complete or incomplete fundamental teaching and 67,4% lived regularly with family income of until a minimum wage. Starting from the obtained data a descriptive statistical analysis was accomplished, being taken in consideration a numeric scale established with punctuation variation for each question of the interview route. With base in the sum of the punctuations, in agreement with each answer supplied by the user, these were classified in levels: low, medium or high of information and of preventive behavior. The results presented in relation to the level of information they were that 56,4% of the users presented low level, 36,3% medium level and 7,3% were only classified as high level, however, none of the interviewees (0%) it reached the maximum punctuation. When the level of preventive behavior was evaluated, 16,6% demonstrated low level, 49,6% medium level and 23,7% high level, in that 52 users (13,6%) they obtained the maximum punctuation. Most of the users demonstrated appropriate knowledge with relationship to the risk factors for CB, however, it was also loud the percentile of inadequate answers with relationship to the factors that are not considered of risk. More of the half (53,5%) it considers contagious CB, 278 users (72,6%) they never heard to speak in the mouth self-exam. Appropriate answers were supplied on how to proceed to detect lesion in the own mouth and that would not delay to seek for to the professional's of health (PS) aid case noticed alterations in your mouth. According to the found results we can end that the users of PSF of the municipal district of Patos-PB they present the level of information so much, as the preventive behavior related CB unsatisfactory. / O objetivo desta pesquisa foi investigar o nível de informação e comportamento preventivo relacionados ao câncer bucal em usuários do Programa de Saúde da Família (PSF) do município de Patos-PB. Os dados foram coletados através da aplicação de um roteiro de entrevista individual em uma amostra de 383 usuários, destes, 267 são mulheres (69,7%) e 116 homens (30,3%), a idade variou de 18 a 78 anos, com média de 33,36 anos, mais da metade (55,9%) com ensino fundamental completo ou incompleto e 67,4% viviam regularmente com renda familiar de até um salário mínimo. A partir dos dados obtidos, foi realizada uma análise estatística descritiva, levando-se em consideração uma escala numérica estabelecida com variação de pontuação para cada questionamento do roteiro de entrevista. Com base na soma das pontuações, de acordo com cada resposta fornecida pelo usuário, estes foram classificados em níveis: baixo, médio ou alto de informação e de comportamento preventivo. Os resultados apresentados em relação ao nível de informação foram que, 56,4% dos usuários apresentaram nível baixo, 36,3% nível médio e apenas 7,3% foram classificados como nível alto, no entanto, nenhum dos entrevistados (0%) atingiu a pontuação máxima. Quando foi avaliado o nível de comportamento preventivo, 16,6% demonstraram nível baixo, 49,6% nível médio e 23,7% nível alto, em que 52 usuários (13,6%) atingiram a pontuação máxima. A maioria dos usuários demonstrou conhecimento adequado quanto aos fatores de risco para o CB, no entanto, também foi alto o percentual de respostas inadequadas quanto aos fatores que não são considerados de risco. Mais da metade (53,5%) considera o CB contagioso, 278 usuários (72,6%) nunca ouviram falar no auto-exame de boca. Respostas adequadas foram fornecidas sobre como proceder para detectar lesão na própria boca e que não demorariam a buscar o auxílio do profissional de saúde (PS) caso percebessem alterações na sua boca. Diante dos resultados encontrados podemos concluir que os usuários do PSF do município de Patos-PB apresentam nível de informação e comportamento preventivo relacionados ao CB insatisfatórios,

INTRODUÇÃO: O carcinoma espinocelular de origem bucal (CEC) apresenta uma alta taxa de mortalidade devido à invasividade das células tumorais. A migração celular, principal evento da invasão e metástase, pode ser regulada tanto por fatores intrínsecos, como adesão e contratilidade celular, quanto extrínsecos, como composição, densidade e remodelagem da matriz extracelular (MEC). OBJETIVO: Avaliar o papel de elementos intrínsecos e extrínsecos sobre o processo invasivo do carcinoma espinocelular de origem bucal. MÉTODOS: Foi realizada imuno-histoquímica para as proteínas: Miosina II (isoformas A, B e C), metaloproteinases de matriz (1, 2, 9 e 14); imunofluorescência as proteínas: e-caderina, n-caderina, FAK, paxilina, vinculina e fibronectina em amostras de CEC oral. Foi realizado ensaio de migração nas seguintes condições: 1 – matriz 2D com o substrato de fibronectina, ou laminina ou matrigel; 2 – matriz 3D com colágeno na presença ou não de fibronectina ou laminina; 3 – matriz 3D com diferentes concentrações de colágeno (0,6; 1,2 e 1,8 mg/ml) + fibronectina na presença ou não de um inibidor de MMP. Foi realizado análise de adesão celular utilizando-se o microscópio TIRF e o microscópio confocal, tanto em matrizes 2D quanto 3D. Foram realizados esferoides celulares para avaliar a contratilidade celular, através do plaqueamento das células em gel de agarose e a utilização de drogas que inibem ou que induzem a contratilidade, bem como a partir de células transfectadas com versões fosfomiméticas para a cadeia leve de miosina. Foi realizado ainda western blotting para proteínas: e-caderina, FAK, vinculina, paxilina, N-caderina, integrinas e as isoformas de miosina II, bem como foi avaliado os níveis de ativação das proteínas da família RhoGTPase, as quais estão envolvidas no controle da migração celular. RESULTADOS: A expressão das MMPs analisadas e das isoformas de miosinas foi maior nas zonas de invasão tumoral, sendo que o CEC oral também apresenta uma maior expressão de proteínas associadas à adesão com a MEC. A migração celular foi afetada pela densidade e a composição da MEC, bem como pela atividade das MMPs. Adicionalmente, a modulação das proteínas de adesão célula-matriz altera a velocidade de migração, a direcionalidade dessa migração e também a forma de migração, mudando de uma migração coletiva para uma migração individual. O aumento na contratilidade células resulta numa dispersão celular enquanto que a diminuição da contratilidade resulta numa melhor adesão célula – célula. CONCLUSÕES: O comportamento das células tumorais pode ser modulado através de fatores extrínsecos como, por exemplo, a alteração no microambiente tumoral, seja ela por mudança no substrato ou na densidade da matriz, e também dos fatores intrínsecos como a alteração nos níveis de miosina. / INTRODUCTION: Oral squamous cell carcinoma (OSCC) presents high mortality index due to the invasive phenotype of tumor cells. Cell migration is the main event in cell invasion and metastasis and it can be regulated by intrinsic factor, such as adhesion and cell contractility, and extrinsic factors, such as density and extracellular matrix (EMC) remodeling. OBJECTIVE: Analyze the role of intrinsic and extrinsic factor during the invasive process of oral squamous cell carcinoma. METHODS: We performed immunostaining in OSCC samples for the following proteins: myosin II (isoforms A, B and C), matrix metalloproteinase (1, 2, 9 and 14) e-cadherin, n-cadherin, FAK, paxillin, vinculin and fibronectin. We also performed migration assays with OSCC cell line in the following conditions 1 – 2D matrix with fibronectin or laminin or matrigel; 2 – 3D matrix with collagen in the presence or not of fibronectin or laminin; 3 – 3D matrix with different collagen concentration (0,6; 1,2 e 1,8 mg/ml) with fibronectin in the presence or not of the MMP inhibitor. In order to analyze cell adhesion, it was performed Total Internal Reflectance Fluorescence and Confocal microscopy, in 2D and 3D matrix. To analyze cell contractility, cells were plated in agarose gel in order to produce spheroids, which were treated with drugs that inhibit or induce cell contractility or cells were previously transfected with Myosin Light Chain phosphomimetics mutants. It was also performed western blotting to: e-cadherin, n-cadherin, FAK, paxillin, vinculin and myosin II isoforms, as well as it was analyze the levels in RhoGTPase family, which are involved in cell migration control. RESULTS: The expression to MMPs and myosin II isoforms were higher at invasion zone of the tumor, and the OSCC presented higher expression of proteins associated to adhesion to ECM. Cell migration was affected by the EMC composition and density and by MMP activity. Also, the modulation of cell-matrix adhesion proteins altered migration speed, cell directionality as well as influenced the switch between collective and single cell migration. The increase in cell contractility resulted in cell dispersion while the decrease in cell contractility resulted in a better cell-cell adhesion. CONCLUSIONS: The behavior of cell tumor can be modulate by extrinsic factors, for example, the change in tumor microenvironment, by the change in the EMC substrate or density and by intrinsic factors such as the alteration in myosin levels.

Reduction of oral health disparities is a worldwide goal because oral health has been shown to mimic individual and community health overall. At the end of the twentieth century, oral health made remarkable achievements; however, problems still remain in many communities around the world, especially within third world countries, such as those in South Asia. Member countries of the South-East Asia region of the World Health Organization (WHO) have stated that dental caries, tooth loss, periodontal disease, and oral cancer are some of the contending public health issues in their countries and action must be taken to reduce their numbers (WHO, 2008). The goals of this study are to determine what cultural aspects of the South Asian population aid in the increase of poor dental care in these communities. Our overall goal is to provide recommendations for a new oral health promotion program in South Asia that has been determined by understanding what cultural aspects are important in creating a successful dental care community program. As seen by the various studies, smokeless tobacco is a cultural norm in South Asia and is affecting the quality of life for many of the people there. Tobacco use is common but smokeless tobacco is becoming more prevalent in these countries. It is clear that with such statistics there is a need for governmental public programs to educate the population on the importance of proper oral care. This study analyzed the current literature to determine (i) what were the cultural aspects of South Asia that are detrimental to oral health, (ii) what is the oral health status of the individual countries found in South Asia, and lastly (iii) what aspects are necessary in creating an effective oral health program. The goal of this study is to determine what cultural aspects of the South Asian population contribute to poor dental care in these communities and to provide recommendations for a new oral health promotion program in South Asia that is strengthened by understanding what cultural aspects are important in creating a successful dental care community program. The conclusions presented here suggest an oral policy framework for the initiation of discussions aimed at designing and implementing an oral health program in their South-Asian country. Additionally, we suggest future directions once the guidelines are met. Overall, proper oral health should be enjoyed by all and this study aims to the aid the South Asian region’s governments towards moving forward in meeting those goals.

O câncer representa um importante problema de saúde pública no mundo, devido ao aumento da sua prevalência, além do grande impacto individual, institucional e social. Assim, merece uma abordagem ampliada, integral e interdisciplinar, a fim de minimizar as seqüelas decorrentes da doença ou do seu tratamento, visando à cura com manutenção da qualidade de vida (QV). Dessa forma, este trabalho teve como objetivos descrever o perfil sócio-demográfico e de saúde bucal de pacientes com câncer de cabeça e pescoço assistidos no HNSC, Porto Alegre – RS e, verificar o impacto na QV destes de um protocolo de cuidados odontológicos sistemático, antes, durante e depois da terapia oncológica. O estudo, delineado como um Ensaio Clínico Randomizado, teve a participação de 46 sujeitos com diagnóstico de neoplasia primária de cabeça e pescoço, captados por conveniência, consecutivamente e distribuídos aleatoriamente em dois grupos. No grupo controle, os pacientes foram examinados e orientados sobre os possíveis efeitos do tratamento oncológico e encaminhados aos serviços de atenção básica de referência para atendimento odontológico. No grupo intervenção, os pacientes foram examinados e orientados, sobre os possíveis efeitos do tratamento oncológico. Os sujeitos incluídos neste grupo receberam um protocolo de cuidados odontológicos na instituição, com acompanhamento profissional sistemático antes, durante e depois da terapia oncológica. Também foram fornecidas, aos cuidadores e pacientes, em ambos os grupos, orientações sobre os possíveis efeitos secundários da terapia oncológica e de ações para minimizar estes problemas. Os dados coletados referem-se a condições sócio-demográficas e de saúde bucal e também de avaliação da QV através de dois questionários - EORTC (específico para pacientes com câncer de cabeça e pescoço) e WHOQOL (avaliação geral da QV), aplicados em dois momentos distintos: antes e quinze dias depois da terapia oncológica concluída. Os resultados mostraram uma maior prevalência do câncer de cabeça e pescoço em homens, de baixo nível educacional e sócio-econômico, com pobre condição oral e média de idade de 54,2 anos. O diagnóstico histopatológico mais freqüente foi o carcinoma epidermóide, sendo as localizações preferenciais a língua e orofaringe. Mais de 60% dos diagnósticos foram realizados nas fases avançadas (III e IV – TMN) e os principais tratamentos realizados a cirurgia e a radioterapia. Apesar das características basais serem desfavoráveis, o grupo intervenção apresentou melhora na avaliação geral de QV e manutenção da específica após o tratamento oncológico, enquanto que o grupo controle mostrou piora em ambos, porém não houve diferença significativa entre os grupos. Entretanto, a variação das medidas (delta) no grupo intervenção, quando comparadas as características basais e finais, mostra uma projeção que tendencia uma melhoria significativa ao longo do tempo. Verifica-se também uma redução de candidíase (p<0,05) e mucosite no grupo intervenção. Conclui-se que os pacientes assistidos no Serviço de Oncologia do HNSC apresentaram o perfil típico dos tumores de localização de cabeça e pescoço no país, com maior prevalência de homens, tabagistas, de baixo nível sócio-econômico e educacional e pobre saúde oral. O protocolo de cuidados odontológicos desenvolvido foi capaz de reduzir danos decorrentes da terapia oncológica, além de poder contribuir para uma melhoria da QV ao longo do tempo aos pacientes com câncer de cabeça e pescoço. / Cancer represents a major public health problem all over the world due to the increase in its prevalence, besides its great individual institutional, and social impact. Thus, it deserves a wide, integral, and interdisciplinary approach in order to minimize the sequelae resulting from the disease or its treatment, and aiming to the healing with maintenance of the quality of life (QoL). This way, this study aimed to describe the social-demographic and oral health profile of head and neck cancer patients treated in Hospital Nossa Senhora da Conceição (HNSC), Porto Alegre, Brazil, and to check the impact of a systematic dental care guideline on the QoL before, during, and after the oncological therapy. The study, designed as a Randomized Clinical Trial, had the participation of 46 subjects with diagnosis of head and neck primary neoplasy, captured by convenience, consecutively, and randomly distributed in two groups. In the control group, patients were examined and advised about the possible effects of the oncological treatment and referred to the basic health care services for dental care. In the test group, patients were examined and advised about the possible effects of oncological treatment. The subjects included in this group received a dental care guideline in the institution, with a systematic professional follow-up before, during, and after the oncological therapy. Also, both caretakers and patients from each group received guidance about the possible secondary effects of the oncological therapy and the actions to minimize these problems. Collected data refer to the social-demographic and oral health status, as well as the evaluation of QoL by means of two questionnaires - EORTC (specific for head and neck cancer patients), and WHOQOL (general evaluation of QoL). These were administered in two distinct moments: before the onset and fifteen days after the conclusion of the oncological therapy. Results showed a higher prevalence of head and neck cancer in men, with low educational and social-economic level, with a poor oral condition, and an average age of 54.2 years. The most frequent histopathological diagnosis was epidermoidis carcinoma, being the preferential sites the tongue and the oropharynx. More than 60% of the diagnosis was done in the advanced phases (III e IV – TMN), and the main treatments performed were surgery and radiotherapy. In spite of the unfavorable baseline characteristics, the test group showed an improvement in the general evaluation of QoL, and maintenance of the specific QoL after the oncological treatment. The control group showed a worsening in both of them, although there was no significant difference between the groups. However, the range of the measures (delta) in the test group, when compared to the baseline and final characteristics, shows a projection tending to a significant improvement along time. A decrease in candidiasis (p<0,05) and muccositis was also shown in the test group. It is concluded that the patients treated in the Oncology Service of HNSC have shown a profile that is typical of the head and neck tumors in the country, with higher prevalence in men, smokers, low social-economic and educational level, and poor oral health. The dental care guideline that was developed was able to decrease harm resulting from the oncological therapy, as well as to contribute for an improvement of QoL along the time for the patients with head and neck cancer.

O carcinoma espinocelular de boca (CEB) é a neoplasia maligna mais comum da cavidade oral, correspondendo à aproximadamente 94% dos casos dessa região. Apesar dos diversos estudos moleculares e celulares do CEB, a taxa de sobrevida dos pacientes é de aproximadamente 50%, devido principalmente ao tamanho do tumor, metástase em linfonodos regionais, grau de diferenciação das células e sítio anatômico. O microambiente tumoral do CEB, é extremamente complexo e diversificado, tendo como característica principal um estado inflamatório crônico imunossupressivo. Este microambiente é sustentado pela liberação de diferentes citocinas inflamatórias, como IL-6, TNF- - atividades exercidas tanto pelas células tumorais quanto pelas estromais. Dentre essas atividades, tem sido relatado na literatura que as citocinas inflamatórias são capazes de aumentar a migração e a capacidade de invasão das células tumorais. Entre as células estromais, os macrófagos são as mais abundantes e participam da manutenção do microambiente tumoral. De acordo com o estímulo, podem ser polarizados M1, com papel pró-inflamatório e antitumoral, e M2, com papel anti-inflamatório e pró-tumoral. O objetivo desta tese foi compreender o papel dos macrófagos no prognóstico de CEB e das citocinas inflamatórias IL-6, TNF- - linhagens celulares de CEB. Para verificar o papel dos macrófagos no prognóstico, foi realizada uma revisão sistemática na qual foram incluídos apenas os estudos que utilizavam amostra de pacientes com CEB e avaliavam o prognóstico com marcadores para macrófagos. Foi observado que maiores concentrações de macrófagos CD68+ e CD163+ estavam relacionados com pior prognóstico de pacientes com CEB, embora não tenha sido possível concluir qual região tumoral a presença destas células seja mais importante 7 para o desfecho. Para analisar o papel das citocinas inflamatórias IL-6, TNFILensaios in vitro utilizando duas linhagens celulares, SCC25 e Cal27, em condições promotoras de migração sob a influência dessas citocinas. Foi observado que a citocina IL-6 foi capaz de aumentar a velocidade de migração e a direcionalidade tanto da SCC25 quanto da Cal 27 e que esta melhora na capacidade migratória ocorreu através de um crosstalk entre a via de sinalização relacionada a IL6 (STAT3) e a via reguladora de migração celular, Rho GTPase Rac1. Estes dados reforçam o papel do microambiente tumoral no processo de progressão tumoral e sugerem potenciais alvos terapêuticos como a modulação do perfil da população de macrófagos e o papel de interleucinas no controle de invasão tecidual e metástase. / Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, corresponding to approximately 94% of the cases in this region. Despite the diverse molecular and cellular studies of OSCC, the patient survival rate is approximately 50%, mainly due to tumor size, regional lymph node metastasis, cell differentiation and anatomic site. The OSCC tumor microenvironment is extremely complex and diverse, with the main characteristic being an immunosuppressive chronic inflammatory state. This microenvironment is supported by the release of different inflammatory cytokines, such as IL-6, TNF- - and enhance the activities of both tumor and stromal cells. Among these activities, it has been reported in the literature that inflammatory cytokines are capable of increasing migration and invasiveness of tumor cells. Among stromal cells, macrophages are the most abundant and participate in the maintenance of the tumor microenvironment. According to the stimulus, macrophages can be polarized in M1, with pro-inflammatory and anti-tumoral role, and M2, with antiinflammatory and pro-tumoral role. Thus, the aim of this thesis was to evaluate the role of macrophages in the prognosis of OSCC and the influence of inflammatory cytokines IL-6, TNF- - OSCC cell lines. To assess the role of macrophages in the prognosis, a systematic review was conducted in which only studies using a sample of OSCC patients were evaluated and the prognosis was evaluated with macrophage markers. It was observed that higher concentrations of CD68 + and CD163 + macrophages were related to worse prognosis in patients with OSCC, although it was not possible to conclude which tumor region the presence of these cells is more important for the outcome. In order to analyze the role of the inflammatory cytokines IL-6, TNF- - atory 9 behavior of OSCC cells, in vitro assays using two cell lines, SCC25 and Cal27, were performed in migration-promoting conditions under the influence of these cytokines. It was observed that IL-6 was able to increase the speed migration and directionality of both SCC25 and Cal 27 and that this improvement in migratory capacity occurred through a crosstalk between the IL6-related signaling pathway (STAT3) and cell migration-related pathway, RhoGTPase Rac1. These data reinforce the role of the tumor microenvironment in the tumor progression process and suggest potential therapeutic targets such as the modulation of the profile of the macrophages population and the role of interleukins in the control of tissue invasion and metastasis.

Proposição: Avaliar a associação entre as condições de saúde bucal, fatores comportamentais e sociodemográficos e o padrão citopatológico da mucosa bucal de homens adultos. Correlacionando o padrão citopatológico quantitativo e qualitativo com as variáveis bucais e sociodemográficas. Materiais e Métodos: A partir de dois esfregaços, um da borda da língua e outro do assoalho bucal de 117 homens com mais de 25 anos, foram quantificadas cem células de cada. As células foram coradas pelo método Papanicolaou modificado e classificadas em: Escamas, células superficiais com núcleo, células intermediárias e células parabasais. Variáveis sociodemográficas e comportamentais foram coletadas a partir de um questionário estruturado. Índice CPO-D e uso de próteses foram registradas a partir de um exame clínico intra-oral.As análises foram conduzidas utilizando o pacote estatístico Stata versão 10. O indivíduo foi considerado a unidade analítica. O nível de significância foi estabelecido em 5%. Resultados: No total das células na borda da língua, 75% eram intermediárias, 20% superficiais com núcleo e 5% escamas, sendo que células parabasais foram raramente observadas. Não foram observadas diferenças significativas para todas as variáveis em estudo em todos os tipos celulares, com exceção da ingestão de bebidas alcoólicas.Observou-se percentual significativamente maior de escamas e células superficiais com núcleo nos indivíduos que ingeriam de álcool comparados aos que não ingerem. Para as células intermediárias, o percentual foi significativamente menor nos indivíduos que bebem comparados aos que não bebem. Um padrão semelhante de distribuição celular foi observado no assoalho de boca. O consumo de álcool foi o único fator comportamental que influenciou significativamente no padrão citológico da mucosa bucal dos indivíduos analisados nos modelos multivariados. Conclusões: Foi encontrada associação entre um dos fatores comportamentais (o álcool) e o padrão citopatológico da mucosa bucal de homens adultos. As demais variáveis estudadas não apresentaram associação significativa com o padrão de descamação da mucosa bucal normal com a técnica utilizada. / Proposition: To evaluate the association between oral health status, socio- demographic and behavioral factors and standard cytology of the oral mucosa of adult men. Correlating the standard cytopathology quantitative and qualitative with oral and sociodemographic variables. Materials and Methods: From two smears, one edge of the tongue and other oral floor of 117 men over 25 years old, were quantified hundred cells each. Cells were stained with modified Papanicolaou method and classified into: Scales, superficial cells with nuclei, intermediate and parabasal cells. Sociodemographic and behavioral variables were collected from a structured questionnaire. DMFT index and use of prostheses were recorded from a clinical intra - oral.As analyzes were conducted using Stata version 10. The individual was considered the analytical unit. The level of significance was set at 5 %. Results: In total cells at the edge of the tongue 75% were intermediate, 20% core surface scales and 5%, and parabasal cells were rarely observed. No significant differences were observed for all study variables in all cell types, with the exception of beverage intake alcoólicas.Observou is significantly greater percentage of scales and superficial cells in the core subjects ingestores alcohol compared to those who do not drink. For intermediate cells, the percentage was significantly lower in individuals who drink compared to those who do not drink. A similar pattern of cell distribution was observed in the floor of mouth. Alcohol consumption was the only factor that significantly influenced the behavioral cytology of the oral mucosa of individuals analyzed in the multivariate models. Conclusions: An association between a behavioral factor (alcohol) and standard cytology of the oral mucosa of adult men. The other variables were not significantly associated with the default scaling of normal oral mucosa with the technique used.