Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-11T17:13:30Z No. of bitstreams: 1 EduardoAlonsoCruzMonroy_DISSERT.pdf: 2026837 bytes, checksum: 07d08221eedeeea6100a427aaf6ca1d9 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-14T17:30:27Z (GMT) No. of bitstreams: 1 EduardoAlonsoCruzMonroy_DISSERT.pdf: 2026837 bytes, checksum: 07d08221eedeeea6100a427aaf6ca1d9 (MD5) / Made available in DSpace on 2016-07-14T17:30:27Z (GMT). No. of bitstreams: 1 EduardoAlonsoCruzMonroy_DISSERT.pdf: 2026837 bytes, checksum: 07d08221eedeeea6100a427aaf6ca1d9 (MD5) Previous issue date: 2016-02-26 / Les?es odontog?nicas epiteliais benignas s?o entidades de grande import?ncia cl?nica que se desenvolvem nos ossos maxilares a partir dos tecidos que formam os dentes. Tem sido demonstrado que em tumores benignos e malignos, est?o presentes um grande n?mero de c?lulas tronco tumorais, as quais tem grandes implica??es no desenvolvimento dos tumores. Oct-4 e CD44 t?m sido demostrados como importantes marcadores para c?lulas-tronco tumorais. O objetivo deste estudo foi identificar c?lulas epiteliais que expressam marcadores de c?lulas tronco atrav?s da express?o imuno-histoqu?mica de Oct-4 e CD44 em uma s?rie de casos de les?es odontog?nicas epiteliais ben?gnas. A amostra foi constitu?da por 20 casos de ceratocisto odontog?nico (CCO), 20 caos de Ameloblastoma s?lido/multic?stico e 20 casos de Tumor Odontog?nico Adenomatoide (TOA). A express?o de Oct-4 e CD44 foi avaliada no epit?lio das les?es atrav?s do percentual de c?lulas positivas(PP) e da intensidade da express?o ( IE ), sendo realizado o somat?rio destes escores, resultando na Pontua??o de Imunomarca??o Total (PIT) que variou de 0 a 7. Os resultados do presente estudo foram analisados pelo valor da pontua??o de PIT. Todos os casos apresentaram positividade para os dois marcadores e a maioria exibiu alta express?o para ambos os marcadores. A an?lise da express?o de Oct-4 n?o revelou diferen?as estatisticamente significativas (p = 0,406) entre as les?es estudadas. Com rela??o ? express?o do CD44, houve diferen?a estatisticamente significativa entre os casos de ameloblastoma e CCO, apresentando este ?ltimo maior n?mero de casos no score 7 (p = 0,034). Na analise da correla??o da imunoexpress?o de ambos os marcadores nas tr?s les?es estudadas, n?o houve correla??o estatisticamente significativa . Os resultados do presente estudo identificaram a presen?a de c?lulas com caracter?sticas troncais dispostas em locais variados do componente epitelial das les?es ora estudadas sugerindo a sua poss?vel participa??o na histog?nese e diferencia??o em les?es odontog?nicas epiteliais benignas contribuindo assim para o desenvolvimento destas les?es. / benign epithelial odontogenic lesions are great clinical importance entities that develop in the jaws from the tissues that form teeth. It has been shown that in benign and malignant tumors, are present in a large number of tumor stem cells, which has great implications in the development of these lesions. Oct-4 and CD44 have been demos as important markers for tumoral stem cells. The objective of this study was to identify epithelial cells expressing stem cell markers by immunohistochemical expression of Oct-4 and CD44 in a series of cases of benign epithelial odontogenic lesions. The sample was comprised of 20 cases of odontogenic keratocyst (OKC), 20 cases of solid/multicystic ameloblastoma and 20 cases of adenomatoid odontogenic tumor (AOT). The expression of Oct-4 and CD44 was evaluated in epithelial lesions using the percentage of positive cells (PP) and the intensity of expression (IE), being realized the sum of these scores, resulting in Total Immunostaining Score (TIS) ranging 0 to 7. The results were submitted to the appropriate statistical test (nonparametric Kruskal-Wallis and Spearman correlation coefficient). All cases were positive for both markers and most showed high expression of both markers. The analysis of Oct-4 expression revealed no statistically significant differences (p = 0.406) among the studied lesions. Regarding the CD44 expression, there was a statistically significant difference between the cases of ameloblastoma and TOA in relation to the CCO, with the latter show more cases in the score 7 (p = 0.034). In the correlation analysis of the immunoreactivity of both markers in the three lesions studied, there was no statistically significant correlation. The results of this study identified the presence of cells with stemness characteristics arranged at various sites in the epithelial component of the studied lesions suggesting their possible role in the histogenesis and differentiation in benign epithelial odontogenic lesions, thus contributing to the development of these lesions.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-29T22:55:50Z No. of bitstreams: 1 EmiliaBeatrizDasNevesSilvaMaiaPimentel_TESE.pdf: 2954281 bytes, checksum: 39a346f6b0d47bccce334327ee69b78b (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-02T19:34:04Z (GMT) No. of bitstreams: 1 EmiliaBeatrizDasNevesSilvaMaiaPimentel_TESE.pdf: 2954281 bytes, checksum: 39a346f6b0d47bccce334327ee69b78b (MD5) / Made available in DSpace on 2016-03-02T19:34:04Z (GMT). No. of bitstreams: 1 EmiliaBeatrizDasNevesSilvaMaiaPimentel_TESE.pdf: 2954281 bytes, checksum: 39a346f6b0d47bccce334327ee69b78b (MD5) Previous issue date: 2015-02-27 / Tumores odontog?nicos prov?m de tecidos dent?rios por prolifera??o de tecido epitelial e/ou mesenquimal. Biologicamente, estas les?es poder ter naturezas distintas, sendo caracterizadas como altera??es no desenvolvimento tecidual (hamartomas), tumores benignos n?o agressivos ou agressivo e tumores malignos. No desenvolvimento e na progress?o desses tumores odontog?nicos, diferentes rela??es de intera??es epit?lio/mesenquimais ocorrem originando os diferentes tipos dessas les?es. Numerosas mol?culas sinalizadoras participam dessas rela??es, dentre estas o fator de crescimento fibrobl?stico (FGF), e a prote?na (?ssea Morfog?nica (BMP) e proteoglicanos de sulfato de heparan (sindecan), as mol?culas envolvidas nos processos de transcri??o e os produtos transcritos. Diante, objetivo dessa pesquisa foi investigar a imunolocaliza??o de fatores de crescimento (BMP-4 e FGF-8) e de prote?na mesenquimal (Sindecan-1) em uma s?rie de tumores odontog?nicos apresentando comportamento biol?gicos distintos, visando contribuir para um melhor entendimento da participa??o dessas proteinas no desenvolvimento tumoral. A amostra foi constitu?da por 21 ameloblastomas do tipo s?lido, 19 cerataocistos odontog?nicos e 14 tumores odontog?nicos adenomat?ides. As c?lulas imunomarcadas por BMP-4 e FGF-8 foram quantificadas, enquanto a contagem de sindecan-1 foi semi-quantitativa, e cada caso tumoral catergorizado em escores: 0 - ausente; 1 - 1 a 10% de c?lulas positivas, 2 - 11 a 50% de c?lulas positivas; e 3 - > < 50% de c?lulas positivas. Maior imunoexpress?o da sindecan-e foi observada no epit?lio das les?es quando comparada com o mesenquima. No ameloblastoma e o ceratocisto odontog?nico essa express?o foi maior que no TOA, o que pode caracterizar um comportamento biol?gico mais agressivo dessas duas primeiras les?es. A maior express?o de BMP-4 no mesenquima de ameloblastoma comparado ao ceratocisto ( p=0,009), pode indicar uma intera??o e participa??o ativa nas c?lulas parenquimais na patogenese desses tumores, enquanto que no tecido epitelial, nenhuma diferen?a signigicativa foi observada quando comparadas as tr?s les?es. Sendo que no ameloblastoma sua express?o foi predominantemente mesenquimal (p=0,008), enquanto no ceratocisto maior express?o foi observada no epit?lio (p = 0,0046). Em todas as les?es, correla??o forte ou moderada foi observada na imunoexpress?o de BMP-4 no epit?lio e mesenquima. Para FGF-8, em nenhuma les?o foi observaa diferen?a entre a imunoexprss?o no epit?lio ou mesenquima, contudo no ameloblastoma correla??o positiva foi encontrada (Correla??o Spearman, rho=0,857,p<0,001), indicando que a imunoexpress?o de FGF-8 concomitante foi indicar um pior progn?stico para ameloblastomas e tamb?m, estar a uma associado a uma maior atividade osteol?tica obsrervada nesses tumores. Concluiu-se ent?o que os tr?s biomarcadores avaliados nesse estudo (BMP-4, FGF-8 e Sindecan) participam ativamente da patogenese das les?es, sendo que maior imunoexpress?o de FGF-8 e sindecan pode estar associada a um comportamento biol?gico mais agressivo, enquanto BMP-4 apresentou padr?o de imunoexpress?o semelhante nas tr?s les?es, podendo estar associado ? diferencia??o celular e manuten??o do padr?o de crescimento da les?es. / The development and progression of odontogenic tumors have been associated with an imbalance in the activity of growth factors, adhesion molecules, extracellular matrix proteins and their degradation enzymes, angiogenic factors and osteolytic. Some studies have shown that interaction relationships inductive epithelial / mesenchymal determinants of Odontogenesis are mimicked by these tumors. The objective of this research was to investigate the immunolocalization of growth factors (BMP-4 and FGF-8) and Sindecan-1 structural protein in a series of odontogenic tumors presenting different biological behaviors, to contribute to a better understanding of the role of these proteins in tumor development. The sample consisted of 21 of the solid ameloblastoma, odontogenic keratocysts 19 and 14 odontogenic adenomatoid tumors. Increased Sindecan-1 immunostaining was seen in the epithelium of the lesions when compared with mesenchyme. In ameloblastoma and odontogenic keratocysts, this expression was higher than in AOT. Epithelial expression of BMP4 showed quantitatively similar in the three studied lesions; however, when anlisada mesenchymal immunoreactivity, was detected significant higher expression when compared to the ameloblastoma keratocysts. In ameloblastoma, mesenchymal expression was predominantly (p = 0.008), while in keratocyst higher expression in the epithelium was observed (p = 0.046). In all injuries, strong or moderate correlation was observed in the BMP-4 immunoreactivity in the epithelium and mesenchyme. FGF-8, no injury was observed difference between the immunoreactivity in the epithelium or mesenchyme, however in ameloblastoma positive correlation was found (Spearman correlation, rho = 0.857, p <0.001). The results of this study suggest that the three evaluated biomarkers actively involved in the pathogenesis of lesions, especially the expression of ameloblastomas indicating a strong interaction between parenchymal and stromal cells which may contribute to its marked aggressiveness.

Made available in DSpace on 2014-12-17T15:32:24Z (GMT). No. of bitstreams: 1 LuizERJ_DISSERT.pdf: 1737074 bytes, checksum: 8941b0b8844e6080e5a540ee05d65531 (MD5) Previous issue date: 2014-02-28 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Ameloblastomas and keratocystic odontogenic tumors (KOT) represent odontogenic lesions that, despite their benign nature, are distinguished by a distinct biological behavior, characterized by locally aggressive growth and recurrent episodes. The gnathic bone resorption caused by the growth of these lesions is a key to the expansion of the same, both being mediated by osteoclastic cells like enzymatic activity of various matrix metalloproteinases (MMPs) factor. The expression of stimulatory factors and inhibitors of bone resorption has been correlated with the development of these lesions, with emphasis to some MMPs such as collagenases and gelatinases and tissue inhibitors of metalloproteinases (TIMPs), among others. Based on the premise that stimulatory and inhibitory factors of osteolytic processes can be decisive for the growth rate of intraosseous odontogenic lesions, this experiment evaluated the immunoreactivity of MMP-9, -13 and TIMP-1 protein in the epithelium and mesenchyme of ameloblastoma and the KOT specimens, by a quantitative analysis of the immunoreactivity cells. Statistical analysis was performed using the Mann-Whitney and Wilcoxon tests with a significance level set at 5 %. Immunohistochemical expression of MMP-9, -13 and TIMP-1 was observed in 100% of cases both in the epithelium and in mesenchyme. The immunoreactivity in the epithelium of KOT and ameloblastomas revealed a predominance of score 3 for MMP-9 (p=0.382) and MMP-13 (p=0.069) and no statistically significance for TIMP-1, the latter being significantly higher immunoreactivity in ameloblastomas. In the mesenchyme, there was a higher score immunoreactivity of MMP-13 (p=0.031) in ameloblastomas in relation to KOT, whereas for MMP-9 and TIMP-1 no statistically significant difference (p=0.403 was observed, p=1.000). The calculation of the ratio of scores revealed expression of proteins in general, similarity of the lesions, a significant predominance of equal expression of TIMP-1 and MMP-9 was observed only in the epithelium of ameloblastoma. The marked immunostaining of MMP-9 , MMP-13 and TIMP-1 in epithelium and mesenchyme of the lesion indicate that these proteins involved in ECM remodeling required for tumor progression, however, specific differences in the expression of some of these proteins, are not sufficient to suggest differences in the biological behavior of ameloblastomas and KOTs / Os ameloblastomas e tumores odontog?nicos ceratoc?sticos (TOC) representam les?es odontog?nicas que, apesar de sua natureza benigna, se destacam por um comportamento biol?gico distinto, caracterizado pelo crescimento localmente agressivo e epis?dios recidivantes. A reabsor??o dos ossos gn?ticos provocada pelo crescimento dessas les?es constitui um fator determinante ? expans?o das mesmas, sendo mediada tanto por c?lulas osteocl?sticas como pela a??o enzim?tica de diversas metaloproteinases de matriz (MMPs). A express?o de fatores estimuladores e inibidores da reabsor??o ?ssea vem sendo correlacionada com o desenvolvimento destas les?es, merecendo destaque algumas MMPs como as colagenases e as gelatinases e os inibidores teciduais de metaloproteinases (TIMPs), dentre outros. Baseados na premissa de que fatores estimuladores e inibidores de processos osteol?ticos podem ser determinantes para o ritmo de crescimento de les?es odontog?nicas intra?sseas, o objetivo de estudo foi avaliar a imunoexpress?o das prote?nas MMP-9, -13 e TIMP-1 no epit?lio e mes?nquima de esp?cimes de ameloblastomas e TOC. A an?lise estat?stica foi realizada atrav?s dos testes de Mann-Whitney e Wilcoxon com n?vel de signific?ncia estabelecido em 5%. Atrav?s de uma an?lise quantitativa das c?lulas imunomarcadas, foi observada a express?o imuno-histoqu?mica das MMP-9, -13 e TIMP-1 em 100% dos casos, tanto no epit?lio quanto no mes?nquima tumoral. Mais de 76% das c?lulas epiteliais (escore 3) dos TOC e ameloblastomas apresentaram imunomarca??o para MMP-9 (p=0,382) e MMP-13 (p=0,069), sendo estatisticamente significativa para o TIMP-1 (p=0,003) nos ameloblastomas. No mes?nquima, observou-se maior escore de imunomarca??o da MMP-13 (p=0,031) nos ameloblastomas em rela??o aos TOC, enquanto para a MMP-9 e TIMP-1 n?o se observou diferen?a estatisticamente significativa (p=0,403; p=1,000). O c?lculo da raz?o entre os escores de express?o das prote?nas revelou, de uma maneira geral, similaridade entre as les?es, sendo observado predom?nio significante de igualdade de express?o do TIMP-1 e da MMP-9 apenas no epit?lio dos ameloblastomas. A imunoexpress?o marcante das MMP-9, MMP-13 e TIMP-1 no epit?lio e mes?nquima das les?es estudadas indica que estas prote?nas participam na remodela??o da MEC necess?ria ? progress?o tumoral, no entanto, as diferen?as pontuais observadas na express?o de algumas destas prote?nas, n?o s?o suficientes para sugerir diferen?as no comportamento biol?gico dos ameloblastomas e dos TOCs