Made available in DSpace on 2015-04-14T13:30:25Z (GMT). No. of bitstreams: 1 448387.pdf: 2406290 bytes, checksum: b9c686175b2c7a33644bea96bc032d9a (MD5) Previous issue date: 2013-03-22 / The present study aimed at analyzing the expression of toll-like receptors (TLR) 5 and 9 and forkhead box p3 regulatory T cells transcription factor (Foxp3) in oral lesions of lichen planus and lupus erythematosus. Twenty-one biopsy specimens of lichen planus, 21 of lupus erythematosus and 21 of inflammatory fibrous hyperplasia (control group) were subjected to immunohistochemical staining with anti-TLR5, anti-TLR-9 and anti-Foxp3, whose expressions were quantified using Image Pro Plus 4.5.1 software (Media Cybernetics). Immunostaining for Foxp3 differed significantly between the three groups, where the highest levels were shown by lichen planus and the lowest ones by controls. TLR5 expression did not differ significantly between lupus erythematosus and control group, but it was significantly greater in these two groups than in lichen planus. When we considered the two types of lupus separately, there was no significant difference of TLR5 between lichen planus and systemic lupus erythematosus, but discoid lupus erythematosus as well as the control group showed significantly greater values than lichen planus. TLR9 immunostaining did not differ significantly between the groups analyzed. A weak negative correlation was observed between Foxp3 and TLR5 (r= -0.279), while there was no other correlation. When this analysis was performed within each group, no correlation was observed between the variables. In conclusion, Foxp3 expression is increased in oral lesions of lichen planus and lupus erythematosus, whereas TLR5 and TLR9 do not show increased expression in these lesions. Foxp3 and TLR5 are inversely correlated. Further investigations analyzing Treg cells and proinflammatory cytokines in these diseases are warranted. / O presente estudo teve por objetivo avaliar o padr?o de express?o dos receptores toll-like (TLR) 5 e 9 e do fator de transcri??o forkhead box p3 (Foxp3) de c?lulas T regulat?rias em les?es orais de l?quen plano e l?pus eritematoso. Vinte e um esp?cimes de bi?psias de l?quen plano, 21 de l?pus eritematoso e 21 de hiperplasia fibrosa inflamat?ria (grupo-controle) foram submetidos a processamento imunoistoqu?mico com os marcadores anti-TLR5, anti-TLR9 e anti-Foxp3, e a quantifica??o da express?o desses marcadores foi realizada por meio do software Image Pro Plus 4.5.1 (Media Cybernetics). O padr?o de express?o do Foxp3 diferiu significativamente entre os tr?s grupos, sendo os maiores n?veis observados no grupo l?quen plano, e os menores, no grupo-controle. A express?o do TLR5 n?o diferiu significativamente entre os grupos l?pus eritematoso e controle, mas foi maior nesses grupos quando comparados ao grupo l?quen plano. Ao discriminarem-se os subtipos de l?pus eritematoso sist?mico e discoide, n?o foi verificada diferen?a significativa na express?o do TLR5 entre l?quen plano e l?pus sist?mico, mas foram verificados maiores n?veis desse marcador no l?pus discoide e no grupo-controle quando comparados ao grupo l?quen plano. O padr?o de express?o do TLR9 n?o diferiu significativamente entre os grupos. Foxp3 e TLR5 apresentaram correla??o negativa fraca (r= -0.279). As demais vari?veis n?o apresentaram correla??o, mesmo quando analisadas intragrupo. Os resultados do presente estudo permitem concluir que a express?o de Foxp3 est? aumentada em les?es orais de l?quen plano e l?pus eritematoso, enquanto TLR5 e TLR9 n?o exibem maior express?o nessas les?es; Foxp3 e TLR5 est?o inversamente correlacionados. Novas investiga??es sobre c?lulas T regulat?rias, receptores toll-like e citocinas pr?-inflamat?rias fazem-se necess?rias para o melhor entendimento de doen?as como l?quen plano e l?pus eritematoso.

Made available in DSpace on 2015-04-14T13:34:58Z (GMT). No. of bitstreams: 1 424761.pdf: 969784 bytes, checksum: 096741a9b7c46edcefe360a98fe1cf59 (MD5) Previous issue date: 2010-03-29 / Introdu??o: A decis?o terap?utica em c?ncer de mama atualmente ? o produto da avalia??o de diversas vari?veis, o que corrobora a heterogeneidade da doen?a e a tend?ncia cada vez maior da individualiza??o do tratamento. A quimioterapia neoadjuvante ? uma modalidade de tratamento bastante eficiente em diferentes situa??es, incluindo os tumores inflamat?rios e localmente avan?ados. A quimioterapia neoadjuvante, al?m de permitir a ressec??o completa do tumor em muitas situa??es em que seriam necess?rios procedimentos muito extensos, tamb?m possibilita observar a sensibilidade tumoral ao tratamento quimioter?pico. Desta forma, esta modalidade terap?utica tamb?m pode ser compreendida como um importante modelo de resposta podendo ser utilizada como marcador de intervalo livre de doen?a e sobrevida global. A descoberta de novos marcadores biol?gicos que permitam a predi??o de resposta a certas drogas, da mesma forma que a express?o de receptores hormonais ou de Her-2 o fazem atualmente, ? detrimental para a melhora da individualiza??o do tratamento do c?ncer de mama. O contexto da neoadjuv?ncia ? o mais adequado para se testar estes biomarcadores, dada a rapidez de resposta que esta modalidade terap?utica confere. Entre os in?meros candidatos a preditores de resposta, encontram-se prote?nas respons?veis pela sobreviv?ncia celular, pela apoptose e fatores de transcri??o que ativam o ciclo celular. No presente trabalho avaliamos a express?o de Survivina, Ciclina D1, Bcl-2, PDEF e ETS1 em pacientes com c?ncer de mama submetidas a neoadjuv?ncia com um esquema quimioter?pico padr?o. M?todos: Pacientes com c?ncer de mama Est?gios Cl?nicos II e III receberam quimioterapia pr?-operat?ria com protocolo AC-T (doxorrubicina 60mg/m2 D1 e Ciclofosfamida 600 mg/m2 D1 por 4 ciclos de 21 dias, seguidos de Docetaxel 75 mg/m2 D1 por 4 ciclos de 21 dias). A cirurgia da mama foi realizada, aproximadamente, 30 dias ap?s. N?veis de express?o de Survivina, Ciclina D1, Bcl-2, PDEF e ETS1 foram avaliados pela t?cnica de imunoistoqu?mica por visualiza??o direta em amostras de tumor obtidas na bi?psia do diagn?stico. Foram associados 8 os n?veis de cada marcador molecular com a resposta patol?gica completa, para tal utilizamos: Teste Exato de Fisher, Regress?o de Cox e Teste de Mann Witney. Resultados: Foram estudadas 45 pacientes. Duas pacientes (4,44%) apresentaram doen?a irressec?vel. A idade m?dia foi de 47,24 (25 ? 70). O estagiamento conforme TNM apresentou a seguinte distribui??o: IIA n=13 (29%), IIB n=10 (22%), IIIA n=13 (29%), IIIB n=4 (9%) e IIIC n=4 (9%). Tr?s pacientes (7,14%) obtiveram resposta patol?gica completa. A m?dia da express?o de Survivina foi de 3,99 (0 ? 11). A m?dia da express?o dos demais marcadores foi de 7,67 (0 ? 15) para ETS1, de 8,72 (2,33 ? 15) para Bcl2, de 2,24 (0 ? 15) para PDEF e de 2,35 (0 ? 9) para Ciclina D1. O n?vel m?dio de Survivina foi significativamente maior (P=0,01) naquelas pacientes com resposta completa (9,33) do que naquelas sem resposta completa (3,42). Os demais marcadores n?o tiveram signific?ncia. Conclus?es: A Survivina ? potencial marcador de resposta ? terap?utica neoadjuvante em c?ncer de mama e consequentemente de sobrevida global e intervalo livre de doen?a.

Submitted by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2015-01-23T16:14:44Z No. of bitstreams: 5 saulo.pdf: 2174121 bytes, checksum: 837d6359c95ce3c616f0b0f600ff2489 (MD5) license_url: 52 bytes, checksum: 3d480ae6c91e310daba2020f8787d6f9 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) license.txt: 2109 bytes, checksum: aa477231e840f304454a16eb85a9235f (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2015-02-10T10:50:10Z (GMT) No. of bitstreams: 5 saulo.pdf: 2174121 bytes, checksum: 837d6359c95ce3c616f0b0f600ff2489 (MD5) license_url: 52 bytes, checksum: 3d480ae6c91e310daba2020f8787d6f9 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) license.txt: 2109 bytes, checksum: aa477231e840f304454a16eb85a9235f (MD5) / Made available in DSpace on 2015-02-10T10:50:10Z (GMT). No. of bitstreams: 5 saulo.pdf: 2174121 bytes, checksum: 837d6359c95ce3c616f0b0f600ff2489 (MD5) license_url: 52 bytes, checksum: 3d480ae6c91e310daba2020f8787d6f9 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) license.txt: 2109 bytes, checksum: aa477231e840f304454a16eb85a9235f (MD5) Previous issue date: 2013 / Muito ainda se discute com rela??o ? fisiopatologia das les?es perif?ricas de c?lulas gigantes (LPCG) e les?es centrais de c?lulas gigantes (LCCG). Ambas as les?es apresentam caracter?sticas cl?nicas distintas, apesar de possu?rem caracter?sticas histol?gicas semelhantes. Assim, estudos imunoistoqu?micos em LPCG e LCCG est?o sendo realizados, para permitir um melhor entendimento dessas les?es. Tem sido relatado que a express?o aumentada de FASN e a angiog?nese est?o diretamente ligadas com desenvolvimento dos tumores. No entanto, ainda n?o se sabe se estes eventos est?o envolvidos na patog?nese das LPCG e LCCG. O objetivo deste trabalho foi avaliar a express?o de FASN e o grau de angiog?nese entre LPCG e LCCG, al?m de verificar a correla??o entre essas vari?veis. Assim, 13 casos de LCCG e 14 casos de LPCG foram selecionados para an?lise da express?o imunoistoqu?mica de FASN, CD34, CD105 e D2-40. A express?o de FASN foi avaliada nos componentes celulares da les?o, seguida da mensura??o da densidade microvascular (DMV) e ?rea microvascular (AMV) para cada uma das amostras selecionadas. Os dados coletados foram submetidos ? an?lise descritiva e sequencialmente aos testes de Mann Whitney, teste t para amostras independentes e testes de correla??o de Pearson e Spearman. Os resultados do nosso estudo indicam que: (1) n?o h? diferen?as na imunoexpress?o de FASN entre os grupos de les?es (CM ? 8% FASN+ / CGM ? 38% FASN+); (2) LPCG possuem maior DMV em CD34; n?o houve diferen?as na DMV em CD105 e D2-40 entre as les?es. A AMV em LPCG foi maior que em LCCG para CD34, CD105 e D2-40; (3) em LPCG houve correla??o positiva entre (CM ? FASN+ com DMV/CD105); (4) nas LCCG houve correla??o positiva entre (CM ? FASN+ com DMV/CD105), (CM ? FASN+ com AMV/CD105 e CD34), (CGM ? FASN+ com AMV/CD105). A partir dos resultados obtidos concluiu-se que os n?veis similares da express?o imunoistoqu?mica de FASN indicam processos constitutivos da manuten??o tissular de ambas as les?es. No entanto, as diferen?as na vasculariza??o, entre os grupos de les?es, parecem ser influenciadas por CM positivas para FASN. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Odontologia, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2012. / ABSTRACT There is still a lot of discussion about the pathophysiology of Peripheral Giant Cell Lesion (PGCL) and Central Giant Cell Lesion (CGCL). These lesions show distinct clinical features, although they have similar histological characteristics. Thus, immunohistochemical studies in PGCL and CGCL are being done to improve understanding these diseases. It has been reported that high level of FASN and angiogenesis are linked with tumors development. However, remains unknown whether these events are involved in the pathogenesis of LPCG and LCCG. The aim of this research was to study FASN expression and angiogenesis degree between PGCL and CGCL, in addition, verify the correlation between this variables. Thus, 13 cases of CGCL and 14 cases of PGCL were selected and examined by immunoexpression of FASN, CD34, CD105 and D2-40. The immunoexpression of FASN was assessed in components cells of lesions, followed by measurement of Microvassel Density (MVD) and Microvassel Area (MVA) for each selected sample. Data collected was submitted to descriptive analysis and followed by Mann Whitney test, ?t? test to independent samples and Person?s and Spearman?s correlation. The results of this study indicate that: (1) there are no differences in FASN immunoexpression between group lesions (MC ? 8% FASN+ / MGC ? 38% FASN+); (2) PGCL have greater MVD in CD34 than CGCL; there are no MDV differences in CD105 and D2-40 between lesions. PGCL have greater MVA in CD34, CD105 and D2-40 than CGCL; (3) in PCGL there was a positive correlation between (MC ? FASN+ and MVD/CD105); (4) in CGCL there was a positive correlation between (MC ? FASN+ and MVD/CD105), (MC ? FASN+ and MVA/CD105 and CD34), (MGC ? FASN+ and MVA/CD105). With base on these results it is concluded that similar expression of FANS levels indicate constituent process of tissue maintenance in both lesions. On the other hand, differences on angiogenesis between lesions seem be influenced by FASN+ mononuclear cells.

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.

Made available in DSpace on 2014-12-17T15:32:18Z (GMT). No. of bitstreams: 1 JoabeSP.pdf: 1318134 bytes, checksum: 051d3ab3425024319d41e93c3e0af738 (MD5) Previous issue date: 2010-03-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / T regulatory cells have the function of controlling immune responses and maintaining self-tolerance. The FoxP3 has been considered the most specific marker for Treg cells. The aiming of this paper was to evaluate the immunoexpression of FoxP3 in the inflammatory infiltrate from oral lichen planus (OLP) and to compare it with the infiltrate in fibrous inflammatory hyperplasia (FIH) and then, between reticular and erosive forms of OLP. The samples were composed by 32 cases of OLP (17 reticular and 15 erosive) beyond 10 cases of FIH that were submitted to immunohistochemistry staining for FoxP3. Localization of the staining was classified in underepithelial and intraepithelial and the amount of FoxP3+ cells was evaluated through cells counting in 10 consecutive fields, at 400x power magnification. The values were expressed in mean ? standart deviation, and submitted to statistical tests with 5% of significance level. It was observed a statistical significant difference in the amount of FoxP3+ Treg cells between the two combined forms of OLP (1,6 ? 2,2) and the FIH (0,5 ?0,4) (P<0,05). This maybe could be explained by immunological mechanism of OLP, which involves a permanent antigenic induction likely with consequent perpetuation of lesion, eliciting the proliferation and constant recruitment of Treg cells. Otherwise, FIH presents a different etiopathogenesis, in which there is also generation of a variable inflammatory infiltrate, however qualitatively distinct from that seen in OLP. The erosive form of OLP exhibited a greater number (1,7 ? 2,4) of FoxP3+ Treg cells than reticular form (1,5 ? 2,1). These alterations could have relation with the great disease activity verified in erosive OLP, or also, with abnormalities in the regulatory function of Treg cells that could cause the increase observed. Considering the capacity already well established in the literature, both about Treg cells in modulating immune responses, as in the oral mucosa in showing great potential for regeneration, it is suggested that the possibility of development and implantation of immunotherapeutic strategies that regulate the frequency and function of these cells, may help in future treatment of immune-mediated inflammatory diseases such as OLP / As c?lulas T regulat?rias (Treg) possuem a fun??o de controlar respostas imunes e manter a autotoler?ncia. O FoxP3 tem sido considerado o marcador mais espec?fico para c?lulas Treg. O objetivo deste estudo foi avaliar a imunoexpress?o do FoxP3 no infiltrado inflamat?rio do l?quen plano oral (LPO) comparado ao da hiperplasia fibrosa inflamat?ria (HFI) e posteriormente entre as formas reticular e erosiva do LPO. A amostra foi composta por 32 casos de LPO (17 reticulares e 15 erosivos) al?m de 10 casos de HFI que foram submetidos ? marca??o imunoistoqu?mica para o FoxP3. A localiza??o da marca??o foi classificada em justaepitelial ou intraepitelial e a quantidade das c?lulas FoxP3+ foi avaliada atrav?s da contagem destas em 10 campos consecutivos, com aumento de 400x. Os valores foram expressos em m?dia ? desvio-padr?o, e submetidos aos testes estat?sticos com n?vel de signific?ncia de 5%. Observou-se uma diferen?a estatisticamente significativa na quantidade de c?lulas Treg FoxP3+ entre os dois tipos de LPO reunidos (1,6 ? 2,2) e a HFI (0,5 ? 0,4) (P<0,05). Isto talvez possa ser explicado pelo mecanismo imunol?gico do LPO, que envolve uma prov?vel indu??o antig?nica permanente com conseq?ente perpetua??o da les?o, suscitando a prolifera??o e recrutamento constante das c?lulas Treg. Em contrapartida, a HFI apresenta uma etiopatogenia diferente, na qual tamb?m h? gera??o de um infiltrado inflamat?rio vari?vel, por?m qualitativamente distinto do verificado no LPO. A forma erosiva do LPO exibiu um maior n?mero (1,7 ? 2,4) de c?lulas Treg FoxP3+ que a forma reticular (1,5 ? 2,1). Estas altera??es podem ter rela??o com a maior atividade da doen?a verificada no LPO erosivo, ou ainda, com anormalidades na fun??o reguladora das c?lulas Treg que ocasionariam o aumento observado. Considerando-se a capacidade j? bem estabelecida na literatura, tanto das c?lulas Treg modularem as respostas imunol?gicas, quanto da mucosa oral em exibir um grande potencial de regenera??o, sugere-se que a possibilidade de desenvolvimento e implanta??o de estrat?gias imunoterap?uticas que regulem a freq??ncia e a fun??o destas c?lulas, possa futuramente auxiliar no tratamento de doen?as inflamat?rias mediadas imunologicamente, como o LPO

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 2014-12-17T15:32:20Z (GMT). No. of bitstreams: 1 RoseaneCV_DISSERT.pdf: 1364911 bytes, checksum: 1503d99f23893ef62ce15add6f41141c (MD5) Previous issue date: 2012-02-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Periodontal disease is a complex inflammatory and infectious condition that immune host, front of the microbial aggressions, can lead to disease progression, resulting in tissue destruction. The tissue damage induces the release of regulatory molecules, which protective roles and / or destructive, including proteins VEGF (vascular endothelial growth factor vascular) and HIF-1 ? (hypoxia-induced factor ? -1). Thus, this study investigated, quantitatively and comparatively, the immunohistochemical expression of VEGF (vascular endothelial growth factor) and HIF-1 ? (hypoxia induced factor 1-?), proteins involved in inflammation, angiogenesis and hypoxia, in human gingival tissues. Therefore, 75 samples of gingival tissues were examined. Thirty samples were chronic periodontitis, 30 with chronic gingivitis and 15 healthy gingival. After sections analysis, positives and negatives inflammatory and endothelial cells in the connective tissue were counted and converted into percentage. Data were statistically analyzed using Kruskal-Wallis test and Spearman correlation. The results showed that both proteins marked. It was observed higher immunoreactivity for HIF-1 ? at chronic gingivitis and periodontitis specimens compared to healthy sites, however, no statistically significant differences were observed among them (p>0.05). The VEGF immunostaining showed similarity among the cases of periodontitis, gingivitis and healthy gingiva. Moderate and positive correlation statistically significant differences were verified for the expressions of VEGF and HIF-1? in gingival health (r = 0,529, p = 0.04). Thus, it can be conclude that possibly the route of HIF-1 ?, is activated in periodontal disease may have involvement of the protein in pathogenesis and progression of disease, and that activation of VEGF, can be in addition to being triggered transcription by HIF-1 ? may be also influenced by other additional factors such as the action of periodontal microorganisms endotoxins / A doen?a periodontal ? uma condi??o infecciosa e inflamat?ria complexa em que a resposta imune do hospedeiro, frente aos produtos microbianos, pode conduzir ? progress?o da doen?a. A agress?o tecidual induz a libera??o de mol?culas reguladoras, que desempenham pap?is protetores e/ou destrutivos, incluindo as prote?nas VEGF (Fator de crescimento endotelial vascular) e o HIF-1 ? (Fator induzido por hip?xia -1 ?). Diante disso, este estudo buscou analisar, de forma quantitativa e comparativa, a express?o imuno-histoqu?mica destas prote?nas, envolvidas nos processos de angiog?nese e hip?xia, observadas em condi??es inflamat?rias. Para tanto, 75 amostras de tecidos gengivais foram examinadas. Destas, 30 foram de periodontite cr?nica, 30 de gengivite cr?nica e 15 de gengivais saud?veis. Foram contadas, as c?lulas inflamat?rias e endoteliais, positivas e negativas, no tecido conjuntivo fibroso, e posteriormente, convertidas em porcentagem. Os dados foram analisados estatisticamente por meio do teste de Kruskal-Wallis e Correla??o de Spearman. Os resultados mostraram imunoexpress?o para ambas as prote?nas. Foi observada, uma elevada imunoexpress?o para HIF-1 ?, nos esp?cimes de periodontite e gengivites cr?nicas, em rela??o aos s?tios saud?veis, por?m, sem diferen?as estat?sticas entre elas (p>0,05). A imunoexpress?o do VEGF demonstrou similaridade, entre os casos de periodontite, gengivite e gengiva saud?vel. Correla??o positiva moderada e diferen?a estatisticamente significativa foram verificadas para as express?es do VEGF e HIF-1?, em gengivais saud?veis (r=0.529; p= 0.04). Desta forma, pode-se concluir que, possivelmente a via de ativa??o do HIF-1 ?, est? ativada na doen?a periodontal, podendo haver participa??o desta prote?na, na patog?nese e progress?o da doen?a periodontal e que a ativa??o do VEGF, al?m de ser desencadeada via transcri??o do HIF-1 ?, pode ser tamb?m, influenciada por outros fatores adicionais, como, por exemplo, a??o das endotoxinas bacterianas periodontopatog?nicas

Made available in DSpace on 2014-12-17T15:32:21Z (GMT). No. of bitstreams: 1 ClarissaFD_DISSERT.pdf: 1047575 bytes, checksum: 1162ac27915144b24bb631aefd3e421b (MD5) Previous issue date: 2012-02-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The Epidermoid Carcinoma (EC) is the most common lesions located in the region of the head and neck and, despite advances in treatment modalities, the prognosis is still poor. The malignant cells show an increase in glucose uptake, process mediated by glucose transporters (GLUTs). Increased expression of GLUT 1 and GLUT 3 is related to the aggressive behavior of this lesion. The aim of this study was to evaluate, through immunohistochemistry, the expression of GLUTs 1 and 3 in EC of the lower lip. The sample consisted of 40 cases of EC of the lower lip, of which 20 had regional lymph node metastasis and the remaining 20 with absence of metastasis. The percentages of immunostained cells in front of tumor invasion and in the center of tumor were evaluated. These results were related to the presence and absence of lymph node metastasis, TNM classification and histological grading. The percentage of cytoplasmic/membranous expression of GLUT 1 ranged from 77.35% to 100%, while for GLUT 3 this value ranged from 0.79% to 100%. As for nuclear staining for GLUT 1, this percentage ranged from 0 to 0.42%, however. GLUT 3 showed only one case with nuclear staining. Despite the significant expression of tumor cells related to the proteins studied, we observed no statistically significant relationship between the variables and the antibodies analyzed, regardless of the region evaluated. However, there was a moderate positive correlation between cytoplasmic/membranous immunoexpressions of GLUT 1 in invasion front and in the tumor center (r = 0.679, p <0.001). Similarly, moderate positive correlation was found between the nuclear immunoexpressions of GLUT 1 in the invasion front and in the tumor center (r = 0.547, p <0.001). For GLUT 3, was also observed a moderate statistically significant positive correlation between cytoplasmic/membranous expression in tumor invasion front and in tumor center (r = 0.589, p <0.001). We also observed that the immunoreactivity for GLUT 1 was higher than GLUT 3 expression in invasion front (p <0.001) and tumor center (p <0.001). From these results, this study suggests that tumor hypoxia is a remarkable characteristic of the EC of the lower lip and GLUT 1 may be primarily responsible for glucose uptake into the interior of the malignant cells / O Carcinoma epiderm?ide (CE) est? entre as les?es mais comuns localizadas na regi?o de cabe?a e pesco?o e apesar dos avan?os nas modalidades de tratamento, o progn?stico ainda ? pobre. As c?lulas malignas apresentam um aumento na absor??o de glicose, processo esse mediado pelos transportadores de glicose (GLUTs). O aumento da express?o de GLUT 1 e GLUT 3 encontra-se relacionado com o comportamento agressivo dessa les?o. O objetivo desse estudo consistiu em avaliar, atrav?s de estudo imuno-histoqu?mico, a express?o dos GLUTs 1 e 3 em CE de l?bio inferior. A amostra foi composta por 40 casos de CE de l?bio inferior, dos quais 20 apresentavam met?stase linfonodal regional e os 20 restantes com aus?ncia de met?stase. Foram avaliados os percentuais de c?lulas imunomarcadas no front de invas?o e no centro do tumor, esses resultados foram relacionados com a presen?a e aus?ncia de met?stase linfonodal, estadiamento cl?nico TNM e grada??o histol?gica. O percentual de marca??o citoplasm?tica/membranar para GLUT 1 variou de 77,35% a 100%, j? para GLUT 3 esse valor variou de 0,79% a 100%. Quanto ? marca??o nuclear para GLUT 1, este percentual variou de 0 a 0,42%, no entanto, GLUT 3 apresentou apenas um caso com marca??o nuclear. Apesar da expressiva marca??o das c?lulas tumorais frente aos marcadores estudados, n?o foi poss?vel observar rela??o estatisticamente significativa entre as vari?veis estudadas e os marcadores analisados, independente da regi?o avaliada. Contudo, foi observada moderada correla??o positiva estatisticamente significativa entre as imunoexpress?es citoplasm?tica/membranar de GLUT 1 no front de invas?o e no centro do tumor (r=0,679; p<0,001). De forma similar, foi constatada moderada correla??o positiva entre as imunoexpress?es nucleares de GLUT 1 no front de invas?o e no centro tumoral(r=0,547; p<0,001). Para GLUT 3, tamb?m foi observada moderada correla??o positiva entre as imunoexpress?es membranar/ citoplasm?tica dessa prote?na no front de invas?o e no centro tumoral (r=0,589; p<0,001). Foi observado, ainda, que a imunoexpress?o de GLUT 1 em rela??o a GLUT 3 foi maior tanto no front de invas?o (p < 0,001) como no centro do tumor (p<0,001). A partir desses resultados, conclui-se que a hip?xia tumoral ? uma caracter?stica marcante no CE de l?bio inferior e GLUT 1 pode ser o principal respons?vel pela capta??o de glicose para o interior das c?lulas malignas

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