Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-05-03T22:56:48Z No. of bitstreams: 1 HeltonMaiaPeixoto_TESE.pdf: 4738937 bytes, checksum: ea09c631840db43949ce6fbc2d32045c (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-05-05T20:05:06Z (GMT) No. of bitstreams: 1 HeltonMaiaPeixoto_TESE.pdf: 4738937 bytes, checksum: ea09c631840db43949ce6fbc2d32045c (MD5) / Made available in DSpace on 2016-05-05T20:05:06Z (GMT). No. of bitstreams: 1 HeltonMaiaPeixoto_TESE.pdf: 4738937 bytes, checksum: ea09c631840db43949ce6fbc2d32045c (MD5) Previous issue date: 2015-07-31 / As prote?nas fluorescentes constituem uma ferramenta fundamental em v?rios campos da biologia, pois permitem enxergar o desenvolvimento de estruturas e processos din?micos de c?lulas em tecido vivo, com o aux?lio da microscopia de fluoresc?ncia. A Optogen?tica ? outra t?cnica que atualmente ganha destaque na Neuroci?ncias e que, de forma geral, permite ativar/desativar neur?nios a partir da irradia??o luminosa de certos comprimentos de onda sobre as c?lulas que possuem canais i?nicos sens?veis ? luz, e ainda pode ser utilizada concomitantemente com as prote?nas fluorescentes. Esta tese possui dois objetivos principais. Inicialmente, s?o estudados os efeitos da intera??o da luz e o c?rebro de camundongos para aplica??es em experimentos de Optogen?tica. Nesta etapa, s?o modelados, a partir de caracter?sticas do c?rebro de camundongos e utilizando a teoria de Kulbelka-Munk, os efeitos de absor??o e espalhamento da luz, em comprimentos de onda espec?ficos, em fun??o da dist?ncia de penetra??o no tecido cerebral. Al?m disso, s?o modeladas as varia??es de temperatura utilizando o m?todo dos elementos finitos na resolu??o da equa??o de bioaquecimento de Pennes, com o aux?lio do COMSOL Multiphysics Modeling Software 4.4, onde s?o simulados protocolos de estimula??o luminosa, tipicamente utilizados em Optogen?tica. Posteriormente, s?o desenvolvidos algoritmos computacionais capazes de reduzir a exposi??o das c?lulas nervosas ? irradia??o luminosa necess?ria ? visualiza??o da fluoresc?ncia emitida por elas. Nesta etapa, s?o descritas as t?cnicas de processamento digital de imagens desenvolvidas para uso em microscopia de fluoresc?ncia, com o intuito de reduzir a exposi??o das amostras de c?rebro ? luz cont?nua, respons?vel pela excita??o dos fluorocromos. As t?cnicas de processamento de imagens desenvolvidas e utilizadas s?o capazes de rastrear, em tempo real, uma regi?o de interesse (ROI) e substituir a fluoresc?ncia emitida pelas c?lulas por uma m?scara virtual, como resultado da sobreposi??o da ROI que est? sendo rastreada e a informa??o de fluoresc?ncia previamente armazenada, mantendo a localiza??o das c?lulas independentemente do tempo de exposi??o ? luz fluorescente. Em resumo, esta tese pretende entender os efeitos da irradia??o luminosa no c?rebro, no contexto da Optogen?tica, al?m de fornecer uma ferramenta computacional que possa auxiliar certos experimentos em microscopia de fluoresc?ncia na redu??o do desvanecimento (bleaching) das amostras e dos danos (photodamage) causados ao tecido devido ? intensa exposi??o das estruturas fluorescentes ? luz. / The fluorescent proteins are an essential tool in many fields of biology, since they allow us to watch the development of structures and dynamic processes of cells in living tissue, with the aid of fluorescence microscopy. Optogenectics is another technique that is currently widely used in Neuroscience. In general, this technique allows to activate/deactivate neurons with the radiation of certain wavelengths on the cells that have ion channels sensitive to light, at the same time that can be used with fluorescent proteins. This dissertation has two main objectives. Initially, we study the interaction of light radiation and mice brain tissue to be applied in optogenetic experiments. In this step, we model absorption and scattering effects using mice brain tissue characteristics and Kubelka-Munk theory, for specific wavelengths, as a function of light penetration depth (distance) within the tissue. Furthermore, we model temperature variations using the finite element method to solve Pennes? bioheat equation, with the aid of COMSOL Multiphysics Modeling Software 4.4, where we simulate protocols of light stimulation tipically used in optogenetics. Subsequently, we develop some computational algorithms to reduce the exposure of neuron cells to the light radiation necessary for the visualization of their emitted fluorescence. At this stage, we describe the image processing techniques developed to be used in fluorescence microscopy to reduce the exposure of the brain samples to continuous light, which is responsible for fluorochrome excitation. The developed techniques are able to track, in real time, a region of interest (ROI) and replace the fluorescence emitted by the cells by a virtual mask, as a result of the overlay of the tracked ROI and the fluorescence information previously stored, preserving cell location, independently of the time exposure to fluorescent light. In summary, this dissertation intends to investigate and describe the effects of light radiation in brain tissue, within the context of Optogenetics, in addition to providing a computational tool to be used in fluorescence microscopy experiments to reduce image bleaching and photodamage due to the intense exposure of fluorescent cells to light radiation.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-11T17:13:30Z No. of bitstreams: 1 LuizArthurBarbosaDaSilva_DISSERT.pdf: 4460566 bytes, checksum: 2c38f38ad7f85e1ed2fa49de5dcf3fe9 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-15T17:09:15Z (GMT) No. of bitstreams: 1 LuizArthurBarbosaDaSilva_DISSERT.pdf: 4460566 bytes, checksum: 2c38f38ad7f85e1ed2fa49de5dcf3fe9 (MD5) / Made available in DSpace on 2016-07-15T17:09:16Z (GMT). No. of bitstreams: 1 LuizArthurBarbosaDaSilva_DISSERT.pdf: 4460566 bytes, checksum: 2c38f38ad7f85e1ed2fa49de5dcf3fe9 (MD5) Previous issue date: 2016-02-26 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / O carcinoma de c?lulas escamosas oral apresenta altas taxas de morbidade e mortalidade na popula??o, com isso, enormes esfor?os est?o sendo feitos para categorizar altera??es morfol?gicas e identificar biomarcadores que tenham valor progn?stico, bem como que estratifiquem os pacientes em op??es terap?uticas individualizadas. Nessa perspectiva, destaca-se o fator do choque t?rmico 1 (HSF1), o qual ? um fator de transcri??o de prote?nas do choque t?rmico (HSPs) que permite ao c?ncer lidar com estressores associados ? malignidade, atuando de diferentes formas na progress?o tumoral. Esta pesquisa objetivou realizar a an?lise clinicopatol?gica de 70 casos de carcinoma de c?lulas escamosas de l?ngua oral (CCELO) e o estudo imunoistoqu?mico dos n?veis de express?o da prote?na HSF1 em CCELO em compara??o com 30 esp?cimes de mucosa oral normal (MON), correlacionando-se, ainda, esta imunoexpress?o com aspectos clinicopatol?gicos do CCELO. Quanto aos casos de CCELO, 57,1% exibiram estadiamento cl?nico III ou IV, 82,9% foram gradados como de alto grau segundo Bryne (1998) e 47,1% como de alto risco de malignidade segundo Brandwein-Gensler et al., (2005). Foi observada uma taxa de sobrevida livre de doen?a de 47,84% e taxa de sobrevida global de 68,20% nos casos analisados e que o alto grau de malignidade segundo a Grada??o de Bryne (1998) (p= 0,05) e tamanho do tumor T3 ou T4 (p= 0,04), recidiva local (p= 0,02) e invas?o perineural (p= 0,02) determinaram impactos negativos nesses tempos de sobrevida. Estes resultados corroboram as informa??es consolidadas na literatura quanto ? influ?ncia negativa de alguns indicadores clinicopatol?gicos na sobrevida dos pacientes com CCELO. Encontrou-se resultado estatisticamente significativo (p<0,01) quando comparou-se a imunoexpress?o de HSF1 entre a MON e o CCELO. Esta significativa maior express?o de HSF1 nos casos de CCELO sugere que esta prote?na atue, de fato, no processo de patog?nese desta les?o. Entretanto, n?o foram encontradas associa??es estatisticamente significativas entre esta superexpress?o com os par?metros cl?nicopatol?gicos analisados. Esse achado pode refletir a influ?ncia de eventos epigen?ticos sobre o gene HSF1 ou uma poss?vel estabilidade da express?o desta prote?na ao longo da progress?o da doen?a. / Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score. Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne?s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-11T17:13:30Z No. of bitstreams: 1 MariannaSampaioSerpa_DISSERT.pdf: 1809045 bytes, checksum: 8e36684515735c29c16965b8e9759877 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-15T19:53:50Z (GMT) No. of bitstreams: 1 MariannaSampaioSerpa_DISSERT.pdf: 1809045 bytes, checksum: 8e36684515735c29c16965b8e9759877 (MD5) / Made available in DSpace on 2016-07-15T19:53:50Z (GMT). No. of bitstreams: 1 MariannaSampaioSerpa_DISSERT.pdf: 1809045 bytes, checksum: 8e36684515735c29c16965b8e9759877 (MD5) Previous issue date: 2016-02-12 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O carcinoma epidermoide oral (CEO) ? a neoplasia maligna mais comum da cavidade oral, apresentando uma alta taxa de mortalidade. Devido a isto, a descoberta de biomarcadores que facilitem a compreens?o do comportamento biol?gico desse tumor e aprimorem o tratamento ? necess?rio. O ativador de plasminog?nio do tipo uroquinase (uPA) e o seu receptor, uPAR, t?m se destacado por atuarem na prote?lise de estruturas da membrana basal e matriz extracelular, facilitando a invas?o tumoral. O presente estudo se prop?s a avaliar a imunoexpress?o dessas prote?nas em 46 casos de carcinoma epidermoide de l?ngua oral (CELO). Esses resultados foram relacionados com a presen?a de met?stase, estadiamento cl?nico TNM, recidiva locoregional, desfecho da les?o e grada??o histol?gica de malignidade. A imunomarca??o de cada caso foi avaliada semiquantitativamente, tanto no front de invas?o como no centro do tumor, na qual foram atribu?dos os escores: 0 (0% de c?lulas positivas), 1(1-10% de c?lulas positivas), 2 (11-50% de c?lulas positivas), 3 (mais de 50% de c?lulas positivas). A express?o do uPA foi observada em 93,5% dos casos no front de invas?o, com predom?nio do escore 2 (34,8%), e em 67,9% dos casos no centro do tumor, com predom?nio do escore 1 (32,6%). De modo geral, os par?metros cl?nicos n?o exerceram influ?ncia na imunoexpress?o do uPA. Em rela??o ? grada??o histol?gica, foi observada uma maior express?o de uPA nos casos de alto grau de malignidade em rela??o aos de baixo grau de malignidade (p=0,05). Quando analisado em rela??o aos par?metros morfol?gicos, foi identificado uma maior express?o do uPA nos casos de pior padr?o de invas?o (p=0,03). A express?o do uPAR foi observada em 73,9% dos casos no front de invas?o, com predom?nio do escore 1 (45,65%), e em 47,5% dos casos no centro do tumor, com predom?nio do escore 0 (54,35%). Embora n?o tenham sido observadas signific?ncias estat?sticas em rela??o ? met?stase linfonodal, estadiamento cl?nico TNM, desfecho e grada??o histol?gica, houve uma maior express?o do uPAR nos casos com recidiva locoregional em rela??o aos sem recidiva (p=0,04). Em rela??o ? an?lise da localiza??o tumoral, foi observada uma maior express?o de uPA e uPAR no front de invas?o em rela??o ao centro do tumor (p<0,001). Na correla??o entre uPA e uPAR, n?o foi observada signific?ncia estat?stica. Com base nestes resultados, sugere-se que o uPA e uPAR estejam envolvidos na progress?o do CELO, atuando principalmente na regi?o mais profunda do tumor. / Squamous cell carcinoma (SCC ) is the most common malignancy of the oral cavity (OSCC), with a high mortality rate. Due to this, the discovery of biomarkers that facilitate the understanding of the biological behavior of the tumor and improve treatment is necessary. Urokinase type plasminogen activator (uPA) and its receptor, uPAR, are responsible for the proteolysis of structures of the basement membrana and extracellular matrix, facilitating tumor invasion. This study aims to assess the immuno expression of these proteins in 46 cases of squamous cell carcinoma of the oral tongue (OTSCC). These results were related to the presence of metastasis, clinical TNM staging, locoregional recurrence, outcome of the lesion and histological grading. Immunostaining of each case was evaluated semiquantitatively, in the front of invasion and center of the tumor, in which scores were assigned: 0 (0% of positive cells), 1 (1-10% of positive cells), 2 (11 -50% positive cells) and 3 (more than 50% positive cells). The expression of uPA was observed in 93.5% (n=43) of the cases in the front of invasion, with predominance of score 2 (n=16; 34.8%) and in 67.9% (n=31) of the cases in the center of the tumor, with predominance of score 1 (n=15; 32.6%). Overall, the immunoexpression of uPA was not associated with clinical parameters. Regarding the malignant histological grading, a higher expression of uPA was observed in cases of high-grade malignancy comp ared to low-grade malignancy (p=0.05). Regarding the morphological parameters, increased expression of uPA was observed in the worst mode of invasion (p=0.03 ). The expression of uPAR was observed in 73.9% of cases in the front of invasion, with a predominance of score 1 (n=21; 45.6 %), and in 47.5% (n=21) of the cases in the center of the tumor, with a predominance of score 0 (n=25; 54.4%). Although no statistical differences were observed in relation to lymph node metastasis, clinical TNM staging, outcome, and histological grading, there was a higher expression of uPAR in cases with locoregional recurrence (p=0.04). Regarding the tumor intra -localization, it was observed an increased expression of uPA and uPAR at the front of invasion in relation to the center of the tumor (p<0.001). Regarding the correlation between uPA and uPAR, there was no statistical sign ificance. Based on these results, it is suggested that uPA and uPAR are involved in the progression of CELO, mainly in the deeper region of the tumor.

Made available in DSpace on 2014-12-17T15:01:23Z (GMT). No. of bitstreams: 1 GracianaCD_DISSERT.pdf: 963468 bytes, checksum: 406e6de21c3be72fd5a9ff01dcdda958 (MD5) Previous issue date: 2010-08-02 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Among the pests that attack corn crop in Brazil, there is Spodoptera frugiperda (JE Smith, 1797) (Lepidoptera: Noctuidae), known as fall armyworm, which is the major corn pest. Due to genetic instability during serial passage of baculoviruses in insect cell culture, the viral bioinseticides in vitro production development is the greatest challenge for mass production of this bioproduct. Successive passages of virus using extracellular viruses (BVs), necessary during viral bioinseticides production scaling up, leads to the appearance of aberrant forms of virus, a process so called as "passage effect ". The main consequence of passage effect is the production of occlusion bodies (OB) decrease, preventing its production using in vitro process. In this study, it was carried out a serial passage of baculovirus Spodoptera frugiperda multiple nucleopolyhedrovirus, isolate 18, using Sf21 cells. A decrease in the production of occlusion bodies from 170 to 92 in the third to fourth passage was observed. A factorial experimental design (22) was employed to verify the influence of two input variables, concentration of the hormone 20 - hydroxyecdysone (CH) and cholesterol (CC) on the values of response variables (volumetric and the specific OB production) of the process, seeking to define the optimum operating ranges trying to reverse or minimize the passage effect. The result indicated a negative influence of the cholesterol addition and positive effect in the hormone supplementation which the optimum range found for the concentrations studied were 8 to 10&#956;g/mL and 5 to 6.5 mg / mL, for cholesterol and hormone concentrations respectively. New experiments were performed with addition of hormone and cholesterol in order to check the influence of these additives on the OB production independently. While the best result obtained from the factorial experiment was 9.4 x 107 OB/mL and 128.4 specific OB/cell, with the addition of only 6&#956;g/mL 20-hydroxyecdysone these concentrations increased to 1.9 x 108 OB/mL and 182.9 OB/cell for volumetric and specific OB production, respectively. This result confirms that the addition of the hormone 20-hydroxyecdysone enhances the SfMNPV in vitro production process performance using Sf21 cells / Dentre as pragas que atacam a cultura do milho no Brasil, destaca-se a Spodoptera frugiperda (J. E. Smith, 1797) (Lepidoptera: Noctuidae), conhecida no est?dio larval como lagarta-do-cartucho, considerada a praga chave da cultura, alimentando-se da planta em todas as suas fases de crescimento, principalmente dos cartuchos de plantas jovens. Para seu controle, tem-se empregado inseticidas qu?micos de amplo espectro, o que tem causado efeitos adversos ao homem e ao meio ambiente. Por essa raz?o, torna-se necess?ria a busca de alternativas mais eficientes, de baixo custo e de f?cil utiliza??o, como o uso de bioinseticidas, especialmente os baculov?rus. Devido ? instabilidade gen?tica durante a passagem seriada de baculov?rus em cultivo de c?lulas de inseto, o desenvolvimento da produ??o in vitro de bioinseticidas virais ? o maior desafio para a sua produ??o massal. Passagens sucessivas de v?rus usando v?rus extracelulares (BVs), necess?rias para o aumento de escala durante a produ??o de bioinseticida viral, leva ao aparecimento de formas aberrantes de v?rus, processo conhecido como efeito de passagem . A principal consequ?ncia do efeito passagem ? a diminui??o da produ??o de corpos de oclus?o (OB), inviabilizando economicamente sua produ??o pelo processo in vitro. Neste trabalho, foi realizada a passagem seriada do isolado 18 do baculov?rus Spodoptera frugiperda multiple nucleopolyhedrovirus em c?lulas Sf21. Foi observada uma queda na produ??o de OB de 170 para 92 da terceira para quarta passagem. Um planejamento experimental fatorial (22) foi empregado para verificar a influ?ncia de duas vari?veis de entrada, concentra??o de horm?nio 20- Hidroxiecdisona (CH) e concentra??o de colesterol (CC), sobre os valores das vari?veis de resposta do processo (produ??o volum?trica e produ??o espec?fica de OB), procurando definir as faixas ?timas de opera??o para reverter ou minimizar o efeito passagem. O resultado deste planejamento indicou influ?ncia negativa da adi??o do colesterol e positiva na adi??o de horm?nio, onde as faixas ?timas encontradas para as concentra??es estudadas foram: 8 a 10&#956;g/mL e 5 a 6,5&#956;g/mL, para as concentra??es de colesterol e horm?nio, respectivamente. Novos experimentos foram realizados com a adi??o individual de horm?nio e colesterol com a finalidade de verificar a influ?ncia destes adjuvantes na produ??o de OB de forma independente. No planejamento experimental obteve-se produ??o volum?trica de 9,4 x 107 OB/mL e espec?fica de 128,4 OB/c?lula. Quando se adicionou 6 &#956;g/mL de 20-Hidroxiecdisona, as concentra??es elevaram-se para 1,9 x 108 OB/mL e 182,9 OB/c?lula, indicando que a adi??o do horm?nio melhorou a efici?ncia da produ??o in vitro de produ??o de SfMNPV em cultivos de c?lulas Sf21

Made available in DSpace on 2014-12-17T15:32:16Z (GMT). No. of bitstreams: 1 PedroPAS.pdf: 6126862 bytes, checksum: 3ae3ec2483d9e09d3a05fcd73782e862 (MD5) Previous issue date: 2008-02-27 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The giant cell fibroma is a benign neoplasm characterized by the presence of mono, bi or multinucleate cells, which can have a connection to the presence of mast cells. This research aims to analyze, descriptively and comparatively, the immunohystochemistry expression of the tryptase in mast cells of the giant cell f ibroma, f ibrous hyperplasia and samples of the normal oral mucosa. Thirty cases of giant cell fibroma, ten cases of fibrous hyperplasia and ten cases of normal oral mucosa were selected for the analysis of the immunohistochemistry expression, determination of the number of present mast cells, as well as their location and shape. It could be stated that there was a statistically signif icant difference (p<0,001) in relation to the quantity of mast cells among other samples analyzed where the giant cell f ibroma presented lesser quantity of mast cell and the hyperplasia showed higher concentration of this cellular type. Although the oral mucosa has presented a higher quantity of mast cells when compared to the giant cells fibroma, these were found in usual locations in the connective tissue in normal tissues. There could be noticed a statistically significant difference in relation to the number of non-granulated mast cells (p<0,001). On the areas of fibrosis, we could observe a statistically signif icant difference (p<0,006) among the samples. In relation to the present mast cells in perivascular location, no statistically signif icant difference was found. On the morphological analysis there was a predominance of oval mast cells. It was concluded that despite of the fact there was a lesser quantity of mast cells present in cases of giant cell f ibroma, they appeared to have a stronger relation to the present giant fibroblasts in this lesions, around 59,62%, being also evidenced a strong relation between these cells and the fibrosis areas in both cases of giant cell f ibroma and f ibrous hyperplasias and samples of normal oral mucosa, used as control group in our study, confirming, this way, the role of the mast cells as fibrinogenous inductor / O fibroma de c?lulas gigantes constitui-se de uma neoplasia benigna, caracterizada pela presen?a de c?lulas gigantes, mono, bi ou multinucleadas, c?lulas estas que podem guardar rela??o com a presen?a de mast?citos. O prop?sito desta pesquisa consistiu em analisar descritiva e comparativamente a express?o imuno-histoqu?mica da triptase em mast?citos de fibroma de c?lulas gigantes, hiperplasia fibrosa e esp?cimes de mucosa oral normal. Foram selecionados 30 casos de fibroma de c?lulas gigantes, 10 casos de hiperplasia fibrosa e 10 casos de mucosa oral normal, para a an?lise da express?o imuno-histoqu?mica, determina??o do n?mero de mast?citos presentes, bem como a sua forma e localiza??o. Constatou-se diferen?a estatisticamente significativa (p<0,001) em rela??o a quantidade de mast?citos entre os esp?cimes analisados, onde o fibroma de c?lulas gigantes apresentou a menor quantidade de mast?citos e a hiperplasia exibiu a maior concentra??o deste tipo celular. Embora a mucosa oral tenha apresentado uma maior quantidade de mast?citos quando comparado com os casos de f ibroma de c?lulas gigantes, estes se encontravam em localiza??es usuais no tecido conjuntivo em tecidos normais. Verif icou-se, diferen?a estatisticamente significativa, no que diz respeito ao n?mero de mast?citos n?o degranulados (p<0,001). Nas ?reas de fibrose, observamos diferen?a estatisticamente signif icativa (p<0,006) entre os esp?cimes. Com rela??o aos mast?citos presentes em localiza??o perivascular n?o se observou diferen?a estatisticamente significativa. Na an?lise morfol?gica verif icou-se uma predomin?ncia de mast?citos ovais. Concluiu-se que embora uma menor quantidade de mast?citos estivesse presente nos casos de fibroma de c?lulas gigantes, estes exibiam maior rela??o com os fibroblastos gigantes presentes nestas les?es em torno de 59,62%, sendo evidenciada tamb?m uma forte rela??o entre estas c?lulas e ?reas de fibrose tanto nos casos de fibroma de c?lulas gigantes como de hiperplasias fibrosas e esp?cimes de mucosa oral normal, utilizados como controle em nosso estudo, confirmando desta forma, o papel dos mast?citos como indutor fibrinog?nico

Made available in DSpace on 2014-12-17T15:32:19Z (GMT). No. of bitstreams: 1 DmitryJSS_DISSERT.pdf: 3987707 bytes, checksum: acff9df3451c8d6fc62a6e590d027fca (MD5) Previous issue date: 2011-12-09 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Lip squamous cell carcinoma (SCC) may develop from a premalignant condition, actinic cheilitis (AC) in 95% of the cases. Both premalignant and neoplastic lip diseases are caused mainly by chronic exposure to the ultraviolet component of solar radiation, especially UVB. This exposure causes disruption of the cell cycle and damage to DNA repair systems, like mismatch repair, altering proteins repair as hMLH1 and hMSH2. This research aimed to investigate the immunohistochemical expression of hMLH1 and hMSH2 proteins in lower lip SCCs and ACs, providing additional information about carcinogenesis of the lower lip. The sample consisted 40 cases of ACs and 40 cases of lower lip SCCs. Histological sections of 3 &#956;m were submitted to immunoperoxidase method, for immunohistochemical analysis of lesions were counted in 1000 cells (positive and negative), data were evaluated both in absolute numbers and percentage of immunostained cells, the latter by assigning scores. Associations of the variables and comparative analysis of biomarker expression were performed by Fisher s exact and Pearson s chi-square, "t" student, one-way ANOVA, Mann- Whitney e Kruskal-Wallis tests. The level of significance was 5%. It was found that, in lower lip SCC, the mean of the proteins was higher in female patients (hMLH1= 369,80 + 223,98; hMHS2 = 534,80 + 343,62), less than 50 years old (hMLH1 = 285,50 + 190,65; hMHS2 = 540,00 + 274,79) and classified as low-grade malignancy (hMLH1 = 264,59 + 179,21; hMHS2 = 519,32 + 302,58), in these data only to sex, for hMLH1 protein, was statistically significant (p=0.034). Comparing the different lesions, we observed that for both hMLH1 and hMSH2 protein, the average of positive epithelial cells decreased as the lesion was graded at later stages. The ACs classified without dysplasia or mild dysplasia had the highest average of immunostained cells (hMLH1 = 721.23 + 88.116; hMHS2 = 781.50 + 156.93). The ACs classified as moderate or severe dysplasia had intermediate values (hMLH1 = 532,86 + 197,72; hMHS2 = 611,14 + 172,48) and SSCs of the lower lip had the lowest averages (hMLH1 = 255,03 + 199,47; hMHS2 = 518,38 + 265,68). There was a statistically significant difference between groups (p<0.001). In conclusion, our data support the hypothesis that changes in immunoexpression of these proteins is related to the process of carcinogenesis of the lower lip / O carcinoma epiderm?ide (CE) de l?bio inferior evolui, em 95% dos casos, de uma condi??o potencialmente maligna denominada queilite act?nica (QA). Ambas les?es s?o causadas principalmente pela exposi??o cr?nica ao componente ultravioleta da radia??o solar, especialmente o subtipo UVB. Esta exposi??o pode causar altera??es no ciclo celular e danos aos sistemas de reparo do DNA, como o mismatch repair, conduzindo a altera??es em prote?nas de reparo, como hMLH1 e hMSH2. Esta pesquisa objetivou investigar a express?o imunoistoqu?mica das prote?nas hMLH1 e hMSH2 em CEs de l?bio inferior e QAs com graus variados de displasia epitelial e desse modo tentar fornecer informa??es adicionais sobre a carcinog?nese de l?bio inferior. A amostra foi composta por 40 casos de QAs e 40 casos de CEs de l?bio inferior. Cortes histol?gicos de 3 &#956;m foram submetidos ao m?todo da imunoperoxidase, para a an?lise imunoistoqu?mica das les?es foram contadas 1000 c?lulas (positivas e negativas), os dados foram avaliados tanto em n?meros absolutos quanto em percentual de c?lulas imunomarcadas, este ?ltimo atrav?s da atribui??o de escores. Para as associa??es e compara??es das m?dias e escores da imunoexpress?o das prote?nas foram utilizados os testes estat?sticos Qui-quadrado de Pearson, Exato de Fisher, t student, ANOVA one-way, Mann-Whitney e Kruskal-Wallis. O n?vel de signific?ncia adotado foi de 5%. Verificou-se que, em CEs de l?bio inferior, as m?dias das prote?nas foram maiores em pacientes do sexo feminino (hMLH1 369,80 + 223,98 =; hMHS2 = 534,80+343,62), com menos de 50 anos (hMLH1 = 285,50 + 190,65; hMHS2 = 540,00 + 274,79) e que foram classificados como de baixo grau de malignidade (hMLH1 = 264,59 + 179,21; hMHS2 = 519,32 + 302,58), apenas a vari?vel sexo (prote?na hMLH1) apresentou signific?ncia estat?stica (p=0,034). Ao comparar as diferentes les?es, observou-se que em ambas prote?nas, a m?dia das c?lulas epiteliais positivas diminuiu conforme a les?o era gradada em est?gios mais avan?ados. As QAs classificadas sem displasia ou com displasia epitelial leve apresentaram a maior m?dia de c?lulas imunomarcadas (hMLH1 = 721,23 + 88,116; hMHS2 = 781,50 + 156,93). As QAs gradadas como displasia epitelial moderada ou severa apresentaram valores intermedi?rios (hMLH1 = 532,86 + 197,72; hMHS2 = 611,14 + 172,48) e os CEs de l?bio inferior apresentaram as menores m?dias (hMLH1 = 255,03 + 199,47; hMHS2 = 518,38 + 265,68), observou-se diferen?a estat?stica significante entre os grupos (p<0.001). Em conclus?o, os dados deste estudo sustentam a hip?tese de que altera??es na imunoexpress?o destas prote?nas est?o relacionadas ao processo de carcinog?nese de l?bio inferior

Made available in DSpace on 2014-12-17T15:32:20Z (GMT). No. of bitstreams: 1 AnaLDLA_DISSERT.pdf: 3287914 bytes, checksum: 244a318f2c60d05b41aef3b1d3d6d2a0 (MD5) Previous issue date: 2012-02-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Periapical lesions are chronic inflammatory conditions of periradicular tissues considered direct consequences of infectious diseases resulting from pulp necrosis and subsequent progression to periapical region. The participation of the immune response and bone resorption in the formation of these lesions has been investigated, so that different cell types and cytokines have been identified as contributors to this process. In this perspective, this study aimed to evaluate the immunohistochemical expression of IL-17, TGF-?1 and FoxP3 in periapical granulomas (PGs), radicular cysts (RCs) and residual radicular cysts (RRCs), seeking a better understanding of the etiopathogenesis these periapicopatias. To this end, we selected 20 cases of GPs, 20 CRs and 10 RRCs to undergo morphological analysis and immunohistochemistry for biomarkers above, the latter being performed quantitatively using scores and average percentages of immunostaining for the analysis of IL-17 and TGF- ?1, while for the FoxP3 were counted only the positive lymphocytes. The results showed statistically significant differences between TGF-?1 and FoxP3 imunoexpressions, in relation to the periapical lesions studied (p = 0.002, p <0.001, respectively) but not between IL-17 and these (p = 0.355). Furthermore, the analysis of lymphocytes FoxP3-positive revealed significant statistical differences in that refers to the intensity of inflammatory infiltrate (p = 0.003) and also regarding thickness of the epithelial lining (p = 0.009). Finally, it was observed in the case of PGs, strong positive correlation between the amount of FoxP3- positive lymphocytes and the immunohistochemical expression of TGF-?1 (r = 0.755, p<0.001), as well as moderate positive correlation between IL-17 and TGF-?1 imunoexpressions (r = 0.503, p = 0.024). Thus, we can conclude that interactions between Th17 and Treg cells seem to be established at the site of injury, suggesting the involvement of both pro-inflammatory and immunoregulatory cytokines in the pathogenesis of periapical lesions / Les?es periapicais cr?nicas s?o condi??es inflamat?rias dos tecidos perirradiculares consideradas sequelas diretas de processos infecciosos resultantes da necrose pulpar e consequente progress?o para a regi?o periapical. A participa??o da resposta imunol?gica e da reabsor??o ?ssea na forma??o destas les?es tem sido bastante investigada, de modo que diversos tipos celulares e citocinas foram apontados como colaboradores deste processo. Nesta perspectiva, o presente estudo objetivou avaliar a express?o imuno-histoqu?mica da IL- 17, TGF-?1 e FoxP3 em granulomas periapicais (GPs), cistos radiculares (CRs) e cistos radiculares residuais (CRRs), buscando um melhor entendimento sobre a etiopatog?nese destas periapicopatias. Para tanto, foram selecionados 20 casos de GPs, 20 de CRs e 10 de CRRs para serem submetidos ? an?lise morfol?gica e imuno-histoqu?mica para os biomarcadores supracitados, sendo esta ?ltima realizada quantitativamente atrav?s de escores e percentuais m?dios de imunomarca??o para a an?lise da IL-17 e do TGF-?1, enquanto que para o FoxP3 foram contados apenas os linf?citos positivos. Os resultados demonstraram diferen?as estatisticamente significativas entre as imunoexpress?es do TGF-?1 e do FoxP3 em rela??o as les?es periapicais pesquisadas (p = 0,002; p < 0,001, respectivamente), mas n?o entre a IL-17 e estas (p = 0,355). Al?m disso, a an?lise dos linf?citos FoxP3-positivos revelou diferen?as estat?sticas significativas no que se refere ? intensidade do infiltrado inflamat?rio (p = 0,003) e tamb?m quanto ? espessura do revestimento epitelial (p = 0,009). Por fim, observou-se nos casos de GPs, forte correla??o positiva entre a quantidade de linf?citos FoxP3-positivos e a imunoexpress?o do TGF-?1 (r = 0,755; p < 0,001), assim como moderada correla??o positiva entre as imunoexpress?es da IL-17 e do TGF-?1 (r = 0,503; p = 0,024). Destarte, pode-se concluir que intera??es entre c?lulas Th17 e Treg parecem ser estabelecidas no local da agress?o, sugerindo a participa??o de citocinas tanto pr?inflamat?rias como imunorregulat?rias na patogenia das les?es periapicais

Made available in DSpace on 2014-12-17T15:32:21Z (GMT). No. of bitstreams: 1 BarbaraVBM_DISSERT.pdf: 1563576 bytes, checksum: c536e73cdfce0251b3446e74e0f9cc69 (MD5) Previous issue date: 2012-02-24 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Th17 cells have been strongly associated with the pathogenesis of several autoimmune and inflammatory diseases. IL-17 and IL-23 are important cytokines associated with this lineage. The aim of this study was to analyze, through immunohistochemical methods, the immunoexpression of IL-17 and IL-23 in the inflammatory infiltrate of oral lichen planus (OLP) lesion compared to that of inflammatory fibrous hyperplasia (IFH) and between clinical forms reticular and erosive of OLP. The sample included 41 cases of OLP, of which 23 were reticular and 18 erosive and 10 cases of IFH. The results were subjected to nonparametric statistical tests with a 5% significance level. In OLP lesions histomorphological analysis, the most common findings were: hyperparakeratinization, specimens with atrophic epithelium in erosive clinical form (p = 0.011), epithelial projections in most of reticular type of lesions, in addition Civatte bodies were identified in most samples of both clinical forms. For immunohistochemistry analysis, five fields with strong immunoreactivity for IL-17 and IL-23 were photomicrographed at 400x magnification, images were transferred to a computer where with ImageJ software?, lymphocytes that exhibited cytoplasmic immunostaining for these cytokines were counted. A mean was established after for each case. There was no statistically significant difference in the number of imunopositive lymphocytes for IL-17 and IL-23 among the group of OLP and IFH group, however a larger amount of lymphocytes imunopositive for IL-17 was found in the LPO group (p = 0.079) and significantly higher amounts of those lymphocytes were found in the erosive OLP when compared to the group of reticular OLP and IFH (p = 0.019). Furthermore, a marker epithelial immunopositivity for IL-17 was observed in OLP group. Although the results of this study do not permit the forceful assertion about the participation of Th17 lineage in OLP lesions, the findings of immunopositive lymphocytes counting for IL-17 and IL-23, which are potent proinflammatory cytokines, together with the the marked epithelial immunopositivity found for IL-17 in this study, suggest a possible role of this lineage in the pathogenesis of this disorder / As c?lulas Th17 t?m sido fortemente associadas com a patogenia de diversas doen?as autoimunes e inflamat?rias. A IL-17 e a IL-23 s?o importantes citocinas associadas com esta linhagem. O objetivo do presente trabalho foi analisar, atrav?s de m?todos imunohistoqu?micos, a imunoexpress?o da IL-17 e da IL-23 no infiltrado inflamat?rio das les?es de l?quen plano oral (LPO) comparando ao da hiperplasia fibrosa inflamat?ria (HFI) e entre as formas cl?nicas reticular e erosiva do LPO com o intuito de esclarecer se a linhagem Th17 participa da patog?nese do LPO. Na amostra foram inclu?dos 41 casos de LPO, dos quais 23 eram reticulares e 18 erosivos, al?m de 10 casos de HFI. Os resultados foram submetidos a testes estat?sticos n?o param?tricos com n?vel de signific?ncia de 5%. Na an?lise histomorfol?gica das les?es de LPO, observou-se predom?nio de: les?es hiperparaceratinizadas, esp?cimes com epit?lio atr?fico na forma cl?nica erosiva (p=0,011), proje??es epiteliais nas les?es do tipo reticular, al?m de corpos de Civatte identificados na maior parte da amostra de ambas as formas cl?nicas. Para o estudo imuno-histoqu?mico, cinco campos com forte imunorreatividade para a IL-17 e para a IL-23 foram fotomicrografados sob o aumento de 400x, as fotos foram transferidas para um computador onde com o aux?lio do software ImageJ?, realizou-se a contagem dos linf?citos que exibiram imunomarca??o citoplasm?tica para estas citocinas. Posteriormente, foi estabelecida uma m?dia para cada caso. N?o foram observadas diferen?as estatisticamente significativas na quantidade de linf?citos imunopositivos para a IL-17 e para a IL-23 entre o grupo do LPO e da HFI, no entanto uma maior quantidade desses linf?citos para a IL-17 foi encontrada no grupo do LPO (p=0,079) e uma quantidade significativamente maior de linf?citos imunopositivos para a IL- 23 foi encontrada entre o grupo do LPO erosivo e da HFI (p=0,019). Al?m disto, foi observada uma marcante imunopositividade epitelial para a IL-17 no grupo do LPO. Ainda que os resultados do presente estudo n?o permitam a afirma??o contundente da participa??o da linhagem Th17 nas les?es de LPO, os achados da contagem dos linf?citos imunopositivos para a IL-17 e para a IL-23, que s?o potentes citocinas pr?-inflamat?rias, somados ? marcante imunopositividade epitelial encontrada para a IL-17 neste estudo, sugerem uma poss?vel participa??o desta linhagem na patog?nese desta desordem

Made available in DSpace on 2014-12-17T15:32:24Z (GMT). No. of bitstreams: 1 ThamaraMMB_DISSERT.pdf: 1856423 bytes, checksum: d77238963a3bf6663f56d36a18db57b6 (MD5) Previous issue date: 2014-02-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Th17 cells have been strongly associated to the pathogenesis of inflammatory and autoimmune diseases, although their influence on the carcinogenesis is still little known, there are reports of anti-tumor and protumoral actions. The objective of this study is to research the presence of Th17 lineage in lip and tongue SCC, using the analysis of the immunoexpression of IL-17 and ROR?t, relating this immunoexpression with clinical and morphological findings in the attempt to better comprehend the role of these cells on the tumoral immunity of OSCCs. The results were submitted to non-parametric statistical tests with significance level of 5%. On the histomorphological analysis, it was observed the predominance of low level lesions on lip and high level lesions on tongue (p=0,024). It was not observed statistical significance between clinical stage and histological gradation of malignancy (p=0,644). For the immunohistochemical study, 5 random fields with greater immunoreactivity of the peritumoral inflammatory infiltrate were photomicrographed on the 400x magnification. It was done the count of lymphocytes which showed cytoplasmic and pericytoplasmic staining for the IL-17 cytokine as well as nuclear and cytoplasmic staining for ROR?t. It was observed statistical significance difference on the quantity of immunopositive lymphocytes to IL-17 between the groups of SCC of lip and tongue (p=0,028). For the ROR?t it was not observed statistical significance difference between the groups of SCC of lip and tongue (p=0,915). It was not observed statistical difference between the immunostaining of IL-17 and ROR?t with histological gradation of malignancy and clinical staging. The findings of this research suggest a possible anti-tumor role of IL-17 for cases of lip. The results of the analysis of the ROR?t are possibly due to the wide duality of the anti-tumor and protumoral role of the Th17 cells and their plasticity which, in the presence of different cytokines expressed on the tumor microenvironment, can alter its phenotype. / As c?lulas Th17 t?m sido fortemente associadas ? patogenia de doen?as autoimunes e inflamat?rias, por?m sua influ?ncia na carcinog?nese ainda ? pouco conhecida, havendo relatos de suas a??es tanto antitumorais quanto pr?-tumorais. O objetivo do presente trabalho foi pesquisar a presen?a da linhagem Th17 intratumoral em CCE de l?bio e l?ngua, atrav?s da an?lise da imunoexpress?o da IL-17 e do ROR?t, relacionando estes achados com dados cl?nicos e morfol?gicos na tentativa de melhor compreender o papel dessas c?lulas na imunidade tumoral dos CCEOs. Na an?lise histomorfol?gica, observou-se predom?nio de les?es de baixo grau em l?bio e de alto grau em l?ngua (p = 0,024). N?o foi observada signific?ncia estat?stica entre estadiamento cl?nico e grada??o histol?gica de malignidade (p = 0,644). Para o estudo imunoistoqu?mico, 5 campos aleat?rios com maior imunorreatividade do infiltrado inflamat?rio peritumoral foram fotomicrografados no aumento de 400x. Realizou-se a contagem de linf?citos que exibiram marca??o citoplasm?tica e pericitoplasm?tica para a citocina IL-17 bem como nuclear e citoplasm?tica para o ROR?t. Foi observada diferen?a estatisticamente significativa na quantidade de linf?citos imunopositivos para IL-17 entre os grupos de CCE de l?bio e l?ngua (p = 0,028). Para o ROR?t n?o foi observada diferen?a estatisticamente significativa entre os grupos de CCE de l?bio e l?ngua (p = 0,915). N?o foi observada diferen?a estat?stica entre a imunomarca??o da IL-17 e ROR?t com grada??o histol?gica de malignidade e com estadiamento cl?nico. Os achados dessa pesquisa sugerem um poss?vel papel antitumoral da IL-17 para os casos de l?bio. Os resultados da an?lise do ROR?t, possivelmente se devem ? ampla dualidade do papel pr?-tumoral e antitumoral das c?lulas Th17 e ? sua plasticidade que, na presen?a de diferentes citocinas expressas no microambiente tumoral, podem alterar seu fen?tipo

Made available in DSpace on 2014-12-17T15:32:30Z (GMT). No. of bitstreams: 1 MarceloGV_TESE.pdf: 4128129 bytes, checksum: ebce1d2816c557119bfc6ec3a006f620 (MD5) Previous issue date: 2011-11-18 / The tumor hypoxia modulates a series of genetic changes related to adaptive development, invasion and metastasis of various human cancers, among which squamous cell carcinoma of the tongue (SCCT). The objective of this study was to analyze clinical, morphological and immunohistochemical expression by HIF-1&#945;, GLUT-1 and CA-IX in 57 cases of CEL and correlated this expression to clinical parameters and morphological. After a descriptive analysis of data on gender, age, race, and habits of patients, it was found that the results were consistent with the literature. The clinical and morphological parameters analyzed and the expression of these markers of hypoxia were subjected to statistical analysis (Qui2 test), verifying that they can be used as indicators of the biological behavior of CEL. Among the results of this study, we observed that the intensity of expression for HIF-1&#945;, in most cases located in the cytoplasm and nucleus, statistically correlated with clinical staging (p = 0.011) and histological grading (p = 0.002). As for the relationship between the distribution of labeling for HIF-1&#945; and metastasis, the chi-square (Qui2) showed that there was statistically significant differences between the groups (p = 0.040). 75.8% of the sample who had metastases, there was the predominance of diffuse marking. The immunoexpression cytoplasmic/membrane GLUT-1 showed a statistically significant correlation with the clinical stage (p = 0.002) and histological grading (p = 0.000). Concerning the location of markings for GLUT-1 tumor on the island, there was a predominance of peripheral marking specimens in most low-grade (78.6%). In the sample of high-grade, prevailed the location center/periphery (55.8%). According to the chi-square (Qui2), the location on the island of the tumor (p = 0.025) showed statistically significant difference in histological grading. The immunoreactivity of CA-IX, in most cases located in the membrane and cytoplasm, exhibited a statistically significant correlation with histological grading (p = 0.005). Based on these results, we can conclude a broad participation of these markers of hypoxia in oral carcinogenesis and its possible use as markers of biological behavior and tumor progression in CEL / A hip?xia tumoral modula uma s?rie de mudan?as gen?ticas adaptativas relacionadas ao desenvolvimento, invas?o e met?stase de diversos c?nceres humanos, dentre os quais o carcinoma epiderm?ide de l?ngua (CEL). O objetivo do presente trabalho foi realizar uma an?lise cl?nica, morfol?gica e imuno-histoqu?mica atrav?s da express?o do HIF-1&#945;, GLUT-1 e da CA-IX em 57 casos de CEL, correlacionando essa express?o ? par?metros cl?nicos e morfol?gicos. Ap?s uma an?lise descritiva dos dados referentes ao sexo, faixa et?ria, ra?a e h?bitos dos pacientes, constatou-se que os resultados encontrados foram condizentes com a literatura. Os par?metros cl?nicos e morfol?gicos analisados e a express?o desses marcadores de hip?xia foram submetidos ? an?lise estat?stica (teste do Qui2), verificando-se que os mesmos podem ser utilizados como indicadores do comportamento biol?gico do CEL. Dentre os resultados da presente pesquisa, observou-se que a intensidade de express?o para o HIF-1&#945;, localizada na maioria dos casos no citoplasma e n?cleo, correlacionou-se estatisticamente com o estadiamento cl?nico (p = 0,011) e grada??o histol?gica (p = 0,002). Quanto ? rela??o entre a distribui??o de marca??o para o HIF-1&#945; e met?stase, o teste qui-quadrado (Qui2) demonstrou haver diferen?as estatisticamente significativas entre os grupos analisados (p = 0,040). Dos 75,8% da amostra que tinham met?stase, constatou-se a o predom?nio da marca??o difusa. A imunoexpress?o citoplasm?tica/membranar do GLUT-1 exibiu uma correla??o estatisticamente significativa com o estadiamento cl?nico (p = 0,002) e grada??o histol?gica (p = 0,000). Em rela??o ? localiza??o de marca??o para o GLUT-1 na ilha tumoral, evidenciou-se predom?nio da marca??o perif?rica na maioria dos esp?cimes de baixo grau (78,6%). Na amostra de alto grau, prevaleceu a localiza??o centro/periferia (55,8%). De acordo com o teste qui-quadrado (Qui2), a localiza??o na ilha tumoral (p = 0,025) demonstrou haver diferen?as estatisticamente significativas com a grada??o histol?gica. A imunoexpress?o da CA-IX, localizada na maioria dos casos na membrana e citoplasma, exibiu uma correla??o estatisticamente significativa com a grada??o histol?gica (p = 0,005). Com base nestes resultados, pode-se concluir uma ampla participa??o desses marcadores de hip?xia na carcinog?nese oral, bem como a sua poss?vel utiliza??o como marcadores do comportamento biol?gico e da progress?o tumoral em CEL