Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-04-17T18:56:08Z No. of bitstreams: 1 Ribeiro, Mara Fernandes [Dissertação, 2014].pdf: 3051138 bytes, checksum: 7536143779553e35c3e2d8ad11a9b9bf (MD5) / Made available in DSpace on 2017-04-17T18:56:08Z (GMT). No. of bitstreams: 1 Ribeiro, Mara Fernandes [Dissertação, 2014].pdf: 3051138 bytes, checksum: 7536143779553e35c3e2d8ad11a9b9bf (MD5) / Os acidentes causados por aranhas do gênero Loxosceles representam importante problema de saúde pública no Brasil, sendo as principais espécies de importância médica L. intermedia, L. laeta e L. gaucho. O veneno dessas aranhas promove grave dermonecrose no local da picada, e menos comumente, doença sistêmica que pode ser fatal. O mecanismo de ação desse veneno não está completamente elucidado, trata-se de um processo multifatorial, que envolve a ação direta do veneno sobre os tecidos e a resposta do organismo a agressão causada pelo mesmo. Os camundongos constituem o modelo experimental menos susceptível ao desenvolvimento dos efeitos locais decorrentes do envenenamento por aranhas Loxosceles, dessa forma, sua utilização representa grande interesse clínico, cujo objetivo é desvendar tal mecanismo de proteção presente nestes animais. Este trabalho teve como objetivo caracterizar as atividades do veneno de Loxosceles intermedia, bem como avaliar as atividades in vivo deste veneno em camundongos. A manipulação e os procedimentos com os animais obedeceram aos princípios da CEUA/UFF (Comissão de Ética no Uso de Animais da Universidade Federal Fluminense). Foi demonstrado, in vitro, que o veneno de L. intermedia não apresenta atividade fosfolipásica A2, a atividade hialuronidásica e colágenásica foram dependente da concentração do veneno enquanto que a atividade proteolítica e esfingomielinásica foram observadas apenas em altas concentrações. Para descrever as ações do veneno de L. intermedia em camundongos, foi proposta a utilização de três diferentes linhagens: BALB/c, C57BL/6 e Suiço. A atividade edematogênica na pata dos camundongos inoculados com o veneno foi observada para as três linhagens testadas, sendo persistente por 24 horas, apenas para as linhagens BALB/c e C57BL/6. A análise histopatológica do local de inoculação intradérmica do veneno no abdomen apresentou diferenças relevantes, como, intensa congestão vascular em Suiços e presença de infiltrado inflamatório no local de inoculação na pele de BALB/c e C57BL/6. A partir destes achados, investigou-se a mobilização de células inflamatórias a partir da medula óssea, no baço e no sangue por citometria de fluxo, que demonstrou resposta imunológica inata típica, com aumento da cinética de células mieloides e linfócitos T citotóxicos para camundongos C57BL/6, e resposta tipicamente adquirida/humoral, com aumento preferencial de linfócitos B convencionais e T auxiliar para camundongos BALB/c. Desta forma, este trabalho demonstrou que modelos animais semelhantes podem apresentar diferentes respostas a inoculação deste veneno. A presença do infiltrado inflamatório no local de inoculação do veneno e a mobilização de células inflamatórias a partir da medula óssea, baço e sangue revelaram que diferentes linhagens de camundongos apresentam diferenças no tipo celular envolvido na resposta imunológica decorrente do envenenamento ou esta diferença pode estar relacionada ao tempo e velocidade da resposta em cada linhagem de camundongos. A partir destes resultados este trabalho sugere que camundongos da linhagem BALB/c podem ser utilizados como modelo para estudar a produção de IgM e IgG induzido pelo veneno, incluindo análise de citocinas, quimiocinas e mecanismos moleculares, por outro lado camundongos C57BL/6 podem ser utilizados para descrever a participação de células mielóides durante o envenenamento por aranhas do gênero Loxosceles / Accidents caused by spiders of the genus Loxosceles represent an important public health problem in Brazil, being the major species of medical importance L. intermedia, L. laeta and L. gaucho. The venom of these spiders induces an intense dermonecrosis at the bite site, and less commonly, systemic disease that can be fatal. The mechanism of action of this venom is not fully elucidated, it is a multifactorial process, which involves the direct action of the venom on the tissues and the body's response to aggression caused by it. The mice are an experimental model less susceptible to development the local effects of poisoning Loxosceles spiders. Thus, their use is great clinical interest, whose goal is to unravel the mechanism of this protection in these animals. This study aimed to characterize the activities of Loxosceles intermedia venom, as well as evaluating the in vivo activity of this venom in mice. Manipulation and procedures with animals obeyed the principles of CEUA / UFF (Ethics Committee on Animal Use Universidade Federal Fluminense). It has been shown in vitro that the venom of L. intermedia shows no phospholipase A2 activity and the hyaluronidase and collagenase were dependent on the concentration of the poison and while the proteolytic and sphingomyelinase activity were observed only at high concentrations. To describe the actions of the venom of L. intermedia in mice, it was proposed to use three different strains: BALB/c, C57BL/6 and Swiss. The activity in the paw edema of mice inoculated with the venom was observed for the three strains tested, being persistent for 24 hours, only for the strains BALB/c and C57BL/6. Histopathological analysis of the site of venom intradermal inoculation in the abdomen showed significant differences, as intense vascular congestion in Swiss and inflammatory infiltration at the site of inoculation in the skin of BALB/c and C57BL/6. From these findings, we investigated the mobilization of inflammatory cells from the bone marrow, spleen like effector organ, and migration into the blood by flow cytometry, which showed a typical innate immune response, with increased kinetics of myeloid cells and cytotoxic T lymphocytes to C57BL/6 mice, and response typically acquired / humoral, with a preferential increase of conventional B lymphocytes and T helper to BALB/c mice. Thus, this study demonstrated that similar animal models may have different responses to inoculation of this venom. The presence of the inflammatory infiltrate at the site of inoculation of the venom and the mobilization of inflammatory cells from the bone marrow, spleen and blood revealed that different strains of mice differ in cell type involved in the immune response resulting from poisoning and this difference can be related time and speed of response for each strain of mice. From these results, this study suggests that BALB/c mice can be used as a model to study the production of IgM and IgG induced by the venom, including analysis of cytokines, chemokines and molecular mechanisms, on the other hand C57BL/6 mice can be used to describe the involvement of myeloid cells during poisoning by spiders of the genus Loxosceles

Magister Chirurgiae Dentium (MChD) / Oral lichen planus (OLP) is a T-cell mediated chronic inflammatory disease with different clinical types that remains inscrutable in respect of its pathogenetic mechanisms and effective therapy. Increased apoptosis may influence the histopathological criteria of oral lichen planus (decrease in thickness of the epithelium and band of inflammatory infiltrate). Null hypothesis: The apoptotic rate does not correlate with a decrease in the epithelial thickness as well as the thickness of the band of inflammatory infiltrate in OLP. Aim: The present study aims to quantify apoptotic activity and to correlate the apoptotic rate with epithelial thickness as well as thickness of the inflammatory infiltrate of OLP cases diagnosed at Tygerberg Hospital from 2006 – 2015. Further, the epithelial thickness and thickness of the inflammatory infiltrate were also assessed for their association, if any. Materials and Methods: The study sample comprised 17 diagnostically verified cases of OLP. Sections stained with Haematoxylin and Eosin (H&E) were used to identify and count the number of apoptotic cells as well as measure the thickness of epithelium and the thickness of the lymphocytic inflammatory infiltrate by using software morphometric analysis (Zen Blue lite 2012). Statistical analysis was applied to analyse the correlation between apoptotic cells and histopathological features of OLP. Results: The present study's results showed no statistically significant association between the apoptotic rate, the epithelial thickness and the thickness of the lymphocytic inflammatory infiltrate.

Changes in the microenvironment have been implicated in the transition of pre-invasive ductal carcinoma in-situ (DCIS) to invasive breast cancer. Normal myoepithelial cells have a tumour suppressor phenotype but they are altered in DCIS and ultimately lost with transition to invasive cancer. A consistent change in DCIS is up-regulation of the integrin αvβ6 in myoepithelial cells. Preliminary observations identified a correlation between myopeithelial αvβ6 and an increased peri-ductal inflammatory infiltrate. The hypothesis of this study is that the altered myoepithelial phenotype influences the peri-ductal inflammatory environment, which in turn mediates a pro-apoptotic effect on myoepithelial cells contributing to their loss. To investigate this, the inflammatory infiltrate was characterised in a series of DCIS tissue in relation to αvβ6 status. This demonstrated significantly higher levels of CD4+ve and FOXP3+ve T cells around αvβ6+ve DCIS ducts compared to αvβ6-ve ducts (P=<0.01), suggesting an increase in Treg cells. In-vivo, Matrigel plugs containing injected into the flanks of female C57/Blk6 normal mice generated influx of higher levels of CD4+ve cells (p=0.005) and FOXP3+ T cells (p=0.007) in the presence of αvβ6+ve myoepithelial cells compared to αvβ6-ve cells, supporting the findings in human tissue samples. Since Treg cells produce TRAIL that can induce apoptosis, we investigated the influence of αvβ6 on myoepithelial cells on the levels of TRAIL in T cells and the hypothesis that αvβ6-positive myoepithelial ells may be more susceptible to TRAIL-induced apoptosis, leading to loss of the myoepithelial barrier. Firstly, levels of TRAIL in Jurkat and primary T cell populations co-cultured with β4 (ii) or β6 myoepithelial cells were measured. This demonstrated a higher level of TRAIL in primary T cells co-cultured β6 myoepithelial cells compared to those co-cultured with β4 myoepithelial cells. β6+ve and β6-ve myoepithelial cells were exposed to TRAIL, and this demonstrated that TRAIL enhanced apoptosis, measured by cleaved PARP, in β6+ve cells. Furthermore, these cells showed loss of the anti-apoptotic protein Galectin-7, and knockdown of Galectin-7 in normal β6-ve myoepithelial cells rendered them more susceptible to TRAIL-induced apoptosis. In DCIS tissues, an inverse relationship between αvβ6 and Galectin-7 in myoepithelial cells was demonstrated, and Cytokine Array analysis showed that αvβ6+ve myoepithelial cells express higher levels of IL-16, which has a role in Treg cell recruitment. Taken together these results suggest that expression of αvβ6 by myoepithelial cells in DCIS generates a tumour-promoter peri-ductal inflammatory infiltrate through altered cytokine release, is associated with reduced galectin-7 expression and enhances myoepithelial cell apoptosis in response to TRAIL. This provides a potential mechanism by which myoepithelial cells may be lost during evolution of DCIS and so contribute to progression to invasive disease.

Submitted by Adriana Martinez (amartinez@unoeste.br) on 2017-02-10T16:34:06Z No. of bitstreams: 1 Fabíola Azevedo.pdf: 1121993 bytes, checksum: 7e7e5309d63e8985debf7b6b2d17469c (MD5) / Made available in DSpace on 2017-02-10T16:34:06Z (GMT). No. of bitstreams: 1 Fabíola Azevedo.pdf: 1121993 bytes, checksum: 7e7e5309d63e8985debf7b6b2d17469c (MD5) Previous issue date: 2016-12-15 / Introduction: Increased sugarcane production among the rise in use of herbicides, such as the 2,4-dichlorophenoxyacetic acid (2,4-D), might causes several harm for health. Studies that evaluate the alterations due to the use of this herbicide in the hemogram and in the cells of the nasal mucosa are very important, since the information provided helps in understanding the interactions of substances as the 2,4-D with the human organism. Objective: To analyze blood count components and inflammatory infiltrate in experimental models submitted to nebulization with 2,4-D herbicide, in different time intervals and concentrations. Method: Eighty male Swiss mice were divided into four groups (n = 20): saline, low (3,71 x 10-3 grams of active ingredient per hectare), medium (6,19 x 10-3 grams of active ingredient per hectare) and high concentrations (9,28 x 10-3 grams of active ingredient per hectare). All animals were exposed to the nebulization predefined for each group for 15 minutes during different time intervals: 24, 48, 72 and 192 hours. Blood samples were taken by intracardiac puncture and after euthanasia, the muzzle of each animal was removed for mast cell quantification through toluidine blue staining and analysis of the inflammatory infiltrate by Hematoxylin-Eosin staining (HE). Analysis of normality was conduced using the statistical package Shapiro-Wilk, and for statistical analysis of data Two-way Anova test was performed, considering statistically significant results with p <0.05. Results: All animals in the low concentration group presented microcytosis and hypochromia within 72 hours; Eosinophilia and lymphocytosis within 48 hours. Neutrophilia was observed in the high concentration group over the 192 hour interval. The mast cell count showed significantly increased values in the high concentration group, in the time interval of 48 hours, when compared to the 24 hour period. Conclusion: In conclusion, we observed that in spite of changes in haematological values, the 2,4-dichlorophenoxyacetic acid herbicide can not be considered dose-dependent and time-dependent herbicide, but it might provoke allergic reactions. / Introdução: O aumento da produção de cana-de-açúcar em conjunto com a utilização de herbicidas, como o ácido 2,4-diclorofenoxiacético (2,4-D) traz diversos agravos à saúde humana. Estudos que avaliam as alterações decorrentes do uso desse herbicida no hemograma e nas células da mucosa nasal são de grande importância, pois as informações fornecidas podem ser utilizadas com o intuito de ajudar na compreensão da interação dessa substância com o organismo humano. Objetivo: Analisar os componentes do sangue e infiltrado inflamatório em modelos experimentais submetidos à nebulização ao herbicida 2,4-D, em diferentes intervalos de tempo e concentrações. Metodologia: Foram utilizados 80 camundongos Swiss machos, divididos em quatro grupos (n=20): salina, baixa (3,71 x 10-3 gramas de ingrediente ativo por hectare), média (6,19 x 10-3 gramas de ingrediente ativo por hectare) e alta concentração (9,28 x 10-3 gramas de ingrediente ativo por hectare). Todos os animais foram expostos às nebulizações preconizadas para cada grupo por 15 minutos, em diferentes intervalos de tempo: 24, 48, 72 e 192 horas. A coleta das amostras de sangue foi através de punção intracardíaca e após a eutanásia, o focinho de cada animal foi retirado para a quantificação de mastócitos, através da coloração de azul de toluidina e análise do infiltrado inflamatório, pela coloração de Hematoxilina-Eosina (HE). Para a análise de normalidade foi utilizado o pacote estatístico Shapiro-Wilk e para a análise estatítica dos dados, utilizamos o teste Two-way Anova, considerando estatisticamente diferentes os resultados que apresentaram p< 0,05. Resultados: Todos os animais do grupo baixa concentração apresentaram microcitose e hipocromia no intervalo de 72 horas; eosinofilia e linfocitose no intervalo de 48 horas. Foi verificada neutrofilia no grupo alta concentração no intervalo de 192 horas. A contagem de mastócitos apresentou valores significativamente aumentados no grupo alta concentração, no intervalo de tempo de 48 horas, quando comparado ao de 24 horas. Conclusão: Em conclusão observamos que, apesar das alterações nos valores hematológicos, o herbicida ácido 2,4-diclorofenoxiacético não pode ser considerado dose e tempo-dependentes, mas pode provocar reações alérgicas.

A história natural do câncer cervical invasivo começa com uma infecção produtiva pelo Papiloma vírus humana (HPV) na camada basal do epitélio. Infecções persistentes por vírus de HPVs de alto risco poderão provocar lesões que eventualmente darão origem ao carcinoma invasivo. Sabe-se que o infiltrado inflamatório pode ter um papel importante na evolução da doença. Neste trabalho, quantificamos e caracterizamos fenotipicamente linfócitos T, macrófagos e neutrófilos nas lesões precursoras assim como no carcinoma invasivo. Além disso, para determinar se existia alguma relação entre as populações foi realizada uma análise de correlação entres as populações descritas. Por outro lado, tentando determinar o efeito sistêmico do tumor avaliou-se a frequência de subtipos de monócitos circulantes e através de ensaios alogênicos foi avaliada a capacidade estimuladora das células dendríticas diferenciadas de monócitos circulantes. Os dados apresentados ajudarão a entender o papel que as células do sistema imune podem ter sobre a progressão da doença. / The natural history of cervical cancer begins with a human papilloma virus (HPV) infection of the cells of the basal layer of the epithelium. Persistent infection by high risk HPVs can originate precancerous lesions that may progress to invasive cancer. It has been established the role of the infiltrated inflammatory cells on the progression of the disease. In this work, the phenotype and the frequency of T lymphocytes, macrophages and neutrophils were characterized both in precursor lesions as in invasive carcinoma. In order to stablish a possible relation between the characterized cells, we made a correlation analysis. On the other hand, trying to determine the systemic effect of the tumor we evaluated the frequency of circulating monocyte subtypes and the capacity of dendritic cells to stimulate allogeneic T cells. The data presented will help to understand the role of the immune system cells on the progression of the disease.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-01-17T11:14:30Z No. of bitstreams: 2 Dissertação - Barbara Hess Rodrigues Gonçalves - 2016.pdf: 1742093 bytes, checksum: 80bd9955d0b421c59b1e6faf6d41f773 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-01-17T11:14:56Z (GMT) No. of bitstreams: 2 Dissertação - Barbara Hess Rodrigues Gonçalves - 2016.pdf: 1742093 bytes, checksum: 80bd9955d0b421c59b1e6faf6d41f773 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-01-17T11:14:56Z (GMT). No. of bitstreams: 2 Dissertação - Barbara Hess Rodrigues Gonçalves - 2016.pdf: 1742093 bytes, checksum: 80bd9955d0b421c59b1e6faf6d41f773 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-12-13 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Canine atopic dermatitis (CAD) is the second most frequent disease in dermatological clinical routine of dogs. It is defined as a pruritic allergic skin disease, with genetic predisposition and clinical features, being related to the response to environmental allergens. Interleukin 31 (IL) 31 is a cytokine that participates in inflammatory processes and it is associated with pruritic diseases, especially those involving chronic inflammation such as allergic dermatitis. Produced by mononuclear cells, IL-31 is described to play an important role in the pathogenesis of atopic dermatitis. Two studies were performed in order to correlate clinical features, histopathological changes and the presence of IL-31 in the skin of dogs with atopic dermatitis. 34 dogs were selected from clinical routine, which 31 animals were diagnosed with CAD and three were healthy. The animals were evaluated for pruritus level by the owners' report and by clinical examination according to the CAD extent and severity index (CADESI-4). The dogs were grouped in discreetly, moderately and markedly compromised by CAD following the sum of scores’ values assigned in the clinical examination. Cutaneous samples from the axillary and interdigital regions of each dog were collected and submitted to histopathological (HE and toluidine blue) and immunohistochemical analyzes (IL-31). There was a correlation between the clinical score and the microscopic changes. As well, there was correlation among all the microscopic changes, but not between the degree of pruritus and the clinical score of CAD. Also, the inflammatory infiltrate was more intense in the axillary region in relation to interdigital skin. An increased numbers of cells immunostained for IL-31 was observed in dogs severely compromised by CAD. There was a correlation between the clinical score and the amount of interdigital mast cells, with an amount of cells immunostained for IL-31 in the axilla. It was also verified correlation between the amount of mast cells and cells immunostained for IL-31 in the axilla, as well as between acanthosis and all other histopathological alterations of the skin in the axillary region. We concluded that there is a correlation between severity of dermathological lesions, IL-31 immunostaining, mast cell count and histopathological changes in dogs with atopic dermatitis, but there is no correlation between the degree of pruritus reported by owners and severity of cutaneous lesions in animals with CAD. Moreover, the intensity of the inflammatory process may vary depending on the anatomical site of the lesion. / A dermatite atópica canina (DAC) é a segunda doença mais incidente na rotina de atendimento clínico dermatológico de cães. É definida como doença cutânea alérgica pruriginosa, de predisposição genética e características clínicas definidas, estando relacionada a resposta a alérgenos ambientais. A interleucina 31 (IL) 31 é uma citocina que participa de processos inflamatórios e está associada a doenças pruriginosas, principalmente as que envolvem inflamação crônica como as dermatites alérgicas. Produzida por células mononucleares, a IL-31 é descrita por desempenhar papel importante na patogênese da dermatite atópica.Com o objetivo de correlacionar as alterações clínicas, histopatológicas e a presença da IL-31 na pele de cães com dermatite atópica foram realizados dois estudos. Para isso, foram selecionados 34 cães da rotina de atendimento clínico, sendo 31 com diagnóstico de DAC e três hígidos. Os animais foram avaliados quanto ao nível de prurido a partir do relato de seus proprietários e quanto ao índice de extensão e severidade da DAC (CADESI-4) a partir do exame clínico. Os cães foram agrupados em discretamente, moderadamente e acentuadamente comprometidos pela DAC após somatório dos valores de escores atribuídos no exame clínico. Amostras cutâneas da região axilar e interdigital de cada cão foram colhidas e submetidas às análises histopatológica (HE e azul de toluidina) e imunoistoquímica (IL-31). Houve correlação entre o escore clínico e as alterações microscópicas, assim como entre as alterações microscópicas, mas não entre o grau de prurido e o escore clínico da DAC. Também o infiltrado inflamatório foi mais intenso na região axilar em relação a interdigital. Maior número de células imunomarcadas para IL-31 foi observado nos cães acentuadamente comprometidos pela DAC. Houve correlação entre o escore clínico e a quantidade de mastócitos no interdígito, do mesmo modo com a quantidade de células imunomarcadas para IL31 na axila. Também foi verificada correlação entre a quantidade de mastócitos e células imunomarcadas para IL-31 na axila, assim como entre acantose e todas as demais alterações histopatológicas da pele na região axilar. Conclui-se que há correlação entre a gravidade das lesões, a imunomarcação de IL-31, a contagem de mastócitos e as alterações histopatológicas em cães com dermatite atópica, mas não há correlação entre o grau de prurido relatado pelos proprietários e a gravidade das lesões cutâneas em animais com DAC. Ainda, a intensidade do processo inflamatório pode variar em função do sítio anatômico da lesão.

A história natural do câncer cervical invasivo começa com uma infecção produtiva pelo Papiloma vírus humana (HPV) na camada basal do epitélio. Infecções persistentes por vírus de HPVs de alto risco poderão provocar lesões que eventualmente darão origem ao carcinoma invasivo. Sabe-se que o infiltrado inflamatório pode ter um papel importante na evolução da doença. Neste trabalho, quantificamos e caracterizamos fenotipicamente linfócitos T, macrófagos e neutrófilos nas lesões precursoras assim como no carcinoma invasivo. Além disso, para determinar se existia alguma relação entre as populações foi realizada uma análise de correlação entres as populações descritas. Por outro lado, tentando determinar o efeito sistêmico do tumor avaliou-se a frequência de subtipos de monócitos circulantes e através de ensaios alogênicos foi avaliada a capacidade estimuladora das células dendríticas diferenciadas de monócitos circulantes. Os dados apresentados ajudarão a entender o papel que as células do sistema imune podem ter sobre a progressão da doença. / The natural history of cervical cancer begins with a human papilloma virus (HPV) infection of the cells of the basal layer of the epithelium. Persistent infection by high risk HPVs can originate precancerous lesions that may progress to invasive cancer. It has been established the role of the infiltrated inflammatory cells on the progression of the disease. In this work, the phenotype and the frequency of T lymphocytes, macrophages and neutrophils were characterized both in precursor lesions as in invasive carcinoma. In order to stablish a possible relation between the characterized cells, we made a correlation analysis. On the other hand, trying to determine the systemic effect of the tumor we evaluated the frequency of circulating monocyte subtypes and the capacity of dendritic cells to stimulate allogeneic T cells. The data presented will help to understand the role of the immune system cells on the progression of the disease.

Made available in DSpace on 2014-12-17T15:32:28Z (GMT). No. of bitstreams: 1 MartaRP.pdf: 1904281 bytes, checksum: 2912c6b8ea9a773c553d0776245f93a5 (MD5) Previous issue date: 2009-02-27 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The Oral Epithelial Dysplasia (OED) is the lesion that precedes or co-exists with the Oral Squamous Cell Carcinoma (OSCC), presenting molecular and/or histological similar alterations. The divergences about the malignization potential of OEDs and the role of inflammation in this process make hard the early diagnosis and evaluation of OSCCs aggressiveness. Thus, it became the goal of this study to evaluate the role of inflammation in oral carcinogenesis and tumoral aggressiveness. For this purpose a morphological study was performed in 20 OED cases and 40 OSCC cases to detect the malignization potential of OEDs and the histologic malignancy grading (HMG) of OSCCs, analyzing superficial masses for dismorphism evaluation and the invasive front for evaluation of tumoral growing; and immunohistochemical, using anti-CD8, anti-FOXP3, anti-TGF?, anti-TNF? and anti-NF-?B antibodies, comparing their with the types lesion, histological degree and intensity of the inflammatory infiltrate. The results were statistically significant for the parameters: cell maturity (p=0,0001), masses presence (p=0,038) and dismorphism (p=0,037), when associated to HMG. To compare the expression of the markers with the types lesion, a significantly higher expression of CD8 (p=0,001) and NF-?B (p=0,002) in the OED, and also a smaller expression of the epithelial TGF? in the severe OEDs (p=0,011), without significant expression between OSCC degrees. By relating the expression of the studied markers with the inflammatory infiltrate intensity, a positive relation was observed with: inflammatory TNF?(p=0,003), epithelial TNF? and NF-?B (p=0,051 and p=0,004), in OEDs; and with CD8 (p=0,021) and TNF? (p=0,015) in conjunctive OSCCs; and a negative relation with epithelial TNF? (p=0,034) in OSCCs. No significant relation was found between FOXP3 with any of the studied variables. These findings lead to the conclusion that, the study of the invasive front is as important as the study of superficial masses for the evaluation of tumoral aggressiveness; the intensity of the inflammatory infiltrate has no use as a parameter for prognostic evaluation of OSCC in routine exams, but, the molecular events detected in this study may be necessary to give basis for determining the malignant potential in OEDs and aggressiveness in OSCCs / A Displasia Epitelial Oral (DEO) ? a les?o que precede ou co-existe com o Carcinoma Epiderm?ide Oral (CEO), apresentando altera??es moleculares e/ou histol?gicas semelhantes. As diverg?ncias sobre o potencial de maligniza??o das DEO e o papel da inflama??o nestes processos t?m dificultado o diagn?stico precoce e a avalia??o da agressividade dos CEO. Sendo assim, tornou-se objetivo deste estudo avaliar o papel da inflama??o na carcinog?nese oral e agressividade tumoral. Para isso foi realizado estudo morfol?gico em 20 casos de DEO e 40 casos de CEO para detectar o potencial de maligniza??o das DEO e o Grau Histol?gico de Malignidade (GHM) dos CEO, analisando as massas superficiais para avalia??o do dismorfismo e o front invasivo para avalia??o do crescimento tumoral; e imuno-histoqu?mico, utilizando os anticorpos anti-CD8, anti-FOXP3, anti-TGF?, anti-TNF-? e anti-NF-?B, para comparar a express?o dos mesmos com o tipo de les?o, grau histol?gico e intensidade do infiltrado inflamat?rio. Os resultados foram estatisticamente significantes para os par?metros, maturidade celular (p=0,0001), presen?a de massas (p=0,038) e dismorfismo (p=0,037), quando associados aos GHM. Ao comparar a express?o dos marcadores com o tipo de les?o, encontrou-se uma express?o significativamente maior do CD8 (p=0,001) e do NF-?B (p=0,002) nas DEO, assim como uma menor express?o do TGF? epitelial nas DEO severas (p=0,011), n?o tendo express?o significativa entre os graus dos CEO. Ao relacionar a express?o dos marcadores estudados com a intensidade do infiltrado inflamat?rio, observou-se uma rela??o positiva com o TNF? inflamat?rio (p=0,003), o TNF? e o NF-?B epiteliais (p=0,051 e p=0,004), nas DEO; com o CD8 (p=0,021) e o TNF? (p=0,015) no conjuntivo dos CEO; e uma rela??o negativa com o TNF? (p=0,034) epitelial dos CEO. N?o foi encontrada rela??o significativa da FOXP3 com nenhuma das vari?veis estudadas. Esses achados levaram a concluir que, o estudo do front invasivo ? t?o importante quanto o estudo das massas superficiais para avalia??o da agressividade tumoral; a intensidade do infiltrado inflamat?rio n?o pode ser utilizado como par?metro para avalia??o progn?stica do CEO no exame de rotina; mas os eventos moleculares detectados neste estudo podem ser necess?rios para embasar a determina??o do potencial de malignidade nas DEO e da agressividade nos CEO

Made available in DSpace on 2014-12-17T15:32:34Z (GMT). No. of bitstreams: 1 ErickaJDS_tese.pdf: 814077 bytes, checksum: c31b79040c7db1898443078febad2a0d (MD5) Previous issue date: 2007-03-09 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The progression of the oral squamous cells carcinomas (OSCCs) seems to suffer influence from related factors to the host, as local and systemic immunologic response, which are essential to the antineoplasic defenses. The purpose of this study was evaluate the local immunity in 30 tongue and 20 lower lip SCC by immunohistochemistry method, utilizing antibodies anti-CD3, CD4, -CD8, -CD25 e -&#950;(zeta), which immunoexpressions were compared considering the anatomical localization, the intensity of the inflammatory infiltrate into the front of invasion and metastases. The CD4/CD8+ ratio was calculated for each case and associate with the mentioned variable, being the intensity of the inflammatory infiltrated also compared with the anatomical localization and metastase and for this the cases had been grouped in two categories: (n = 10) absent/scarce inflammatory infiltrate; and (n = 40) moderate/intense infiltrate. Fisher?s exact test was performed (&#945;= 0.05) and it was not observed any significant correlation between these groups with anatomical sites and metastases. With regard to the immunoexpression, the CD3+, CD4+, CD8+ and CD25+ cells count was higher in the lower lip SCCs while the anti-&#950;immunomarcation was more evident in the non metastatic cases. Through the statistical analyses, it was verified that the CD3 exhibited positive-significant correlation with the inflammatory infiltrate (p = 0.023). Furthermore, antibodies against CD8 and CD25 cells were also significantly correlated with the inflammatory infiltrate (p = 0.002 and 0.030, respectively) and with the anatomical site (p = 0.004 and p = 0.004) mainly in the lower lip SCCs. CD4/CD8 ratio did not show significant association with metastase nor with anatomical localization. We conclude that the inflammatory infiltrated of the Bryne s (1998) system did not constitute an indicator of aggressiveness in the tongue and lower lip SCCs analyzed and that clinical behavior of the SCCs studied was related in part to the immunohistochemical profile of infiltrated the inflammatory present in tumoral invasion front / A progress?o dos carcinomas epiderm?ides orais (CEOs) parece sofrer influ?ncia de fatores relacionados ao hospedeiro, como a resposta imunol?gica local e sist?mica, as quais parecem ser essenciais para a defesa anti-neopl?sica. O presente estudo teve por objetivo analisar a imunidade local em 30 casos de CEs de l?ngua e 20 de l?bio inferior, atrav?s do m?todo da imuno-histoqu?mica, utilizando os anticorpos anti-CD3, -CD4, -CD8, -CD25 e -&#950;(zeta), comparando a imunomarca??o em ambas as localiza??es, com a intensidade de infiltrado inflamat?rio no front de invas?o e com presen?a ou n?o de met?stase. A raz?o de c?lulas CD4/CD8+ foi calculada para cada caso e associada com as vari?veis mencionadas, sendo a intensidade do infiltrado inflamat?rio comparada tamb?m com a localiza??o anat?mica e met?stase e para isso os casos foram agrupados em duas categorias (infiltrado escasso ou ausente E/A e infiltrado intenso ou moderado I/M), sendo encontrado 10 casos na categoria E/A e 40 na categoria I/M. Aplicado o teste exato de Fisher n?o verificamos associa??o significativa destes grupos com o s?tio anat?mico ou com met?stase. Em rela??o ? imunomarca??o, a contagem das c?lulas CD3+, CD4+, CD8+ e CD25+ foi maior nos CEs de l?bio inferior e sem met?stase, enquanto que o anti-&#950;foi mais expresso apenas nos casos sem met?stase. Atrav?s da an?lise estat?stica verificou-se que os anticorpos anti-CD3, anti-CD8 e anti-CD25 exibiram associa??o significativa positiva com o infiltrado inflamat?rio (p=0.023, p=0.002 e p=0.030, respectivamente); e os anticorpos anti-CD8 a anti-CD25 estiveram associados de forma positiva com a localiza??o anat?mica, ambos com valores de p=0.004, estando estes mais presentes nos CEs de l?bio inferior. A raz?o CD4/CD8 n?o exibiu associa??o significativa com met?stase nem com localiza??o anat?mica. Conclu?mos que o padr?o infiltrado inflamat?rio da grada??o histol?gica de malignidade de Bryne (1998) n?o constituiu um indicador de agressividade nos CEs de l?ngua e l?bio inferior analisados, e que o comportamento cl?nico dos CEs estudados esteve relacionado em parte ao perfil imuno-histoqu?mico do infiltrado inflamat?rio presente no front de invas?o tumoral