Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-11T17:13:31Z No. of bitstreams: 1 PatriciaGuerraPeixeGoncalves_DISSERT.pdf: 943209 bytes, checksum: 858cf53a3d375685e3e69be1d38caba2 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-15T20:21:04Z (GMT) No. of bitstreams: 1 PatriciaGuerraPeixeGoncalves_DISSERT.pdf: 943209 bytes, checksum: 858cf53a3d375685e3e69be1d38caba2 (MD5) / Made available in DSpace on 2016-07-15T20:21:04Z (GMT). No. of bitstreams: 1 PatriciaGuerraPeixeGoncalves_DISSERT.pdf: 943209 bytes, checksum: 858cf53a3d375685e3e69be1d38caba2 (MD5) Previous issue date: 2016-02-22 / A angiog?nese e a linfangiog?nese s?o altera??es tamb?m decorrentes da inflama??o gengival provocada por microrganismos presentes no biofilme dental, bem como pela a migra??o de c?lulas de defesa e secre??o de mediadores inflamat?rios no local da agress?o. Este estudo teve por objetivo avaliar a angiog?nese e linfangiog?nese em 90 esp?cimes de bi?psias de tecido gengival clinicamente saud?vel, com gengivite e com periodontite cr?nicas. Os cortes histol?gicos foram avaliados pela colora??o de hematoxilina e eosina e pela t?cnica de imunoistoqu?mica atrav?s da imunomarca??o de CD34 e podoplanina, para avaliar, respectivamente, o ?ndice angiog?nico e linfangiog?nico, por meio da t?cnica de contagem microvascular. Os resultados mostraram que h? correla??o entre os ?ndices (p=0,030), por?m, mostrou que na periodontite h? menos n?meros de vasos linf?ticos do que no tecido gengival clinicamente saud?vel (p=0,016). A podoplanina mostrou marca??o no epit?lio e que h? rela??o da intensidade de marca??o com a intensidade do infiltrado inflamat?rio, sendo mais intensa a marca??o na presen?a de infiltrado inflamat?rio severo (p=0,033). Concluiu-se neste estudo que h? menor n?mero de vasos sangu?neos na periodontite em compara??o com a gengiva clinicamente saud?vel. As sinaliza??es presentes no processo inflamat?rio, bem como o real papel da vasculatura sangu?nea e linf?tica gengival ainda n?o est?o totalmente elucidadas / Angiogenesis and lymphangiogenesis are changes that occur due to gingival inflammation caused by microorganisms present in the biofilm, as well as the migration of immune cells and secretion of mediators in the aggressed site. This study aimed to research angiogenesis and lymphangiogenesis in 90 specimens of clinically healthy, with gingivitis and chronic periodontitis gingival tissue biopsies. The histological sections were evaluated by hematoxylin and eosin and the immunohistochemical technique through immunostaining for CD34 and podoplanin. To evaluate the angiogenic and lymphangiogenic indexes we performed a microvessel counting technique. The results showed that there is a correlation between the indexes (p = 0.030), however, we observed that periodontitis showed less lymphatic vessels than clinically healthy gingival tissue (p = 0.016). Podoplanin showed positive staining in the basal layers of the epithelium, and we observed a relationship between immunostaining intensity and the intensity of inflammatory infiltrate, with more intense staining in the presence of severe inflammatory infiltrate (p = 0.033). For this study, we concluded that there are fewer blood vessels in periodontitis compared with clinically healthy gingiva. The signaling present in the inflammatory process and the actual role of gingival blood and lymphatic vasculature are not fully understood, with further studies on angiogenesis and lymphangiogenesis being suggested.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-11T17:13:29Z No. of bitstreams: 1 RodrigoPorpinoMafra_DISSERT.pdf: 2938922 bytes, checksum: c44070e8d06f2305cff5199e620a1c1c (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-15T20:45:06Z (GMT) No. of bitstreams: 1 RodrigoPorpinoMafra_DISSERT.pdf: 2938922 bytes, checksum: c44070e8d06f2305cff5199e620a1c1c (MD5) / Made available in DSpace on 2016-07-15T20:45:06Z (GMT). No. of bitstreams: 1 RodrigoPorpinoMafra_DISSERT.pdf: 2938922 bytes, checksum: c44070e8d06f2305cff5199e620a1c1c (MD5) Previous issue date: 2016-02-16 / O carcinoma epiderm?ide de l?ngua oral (CELO) apresenta um comportamento biol?gico agressivo, com elevada propens?o ao desenvolvimento de met?stases nodais. Nesse contexto, a linfangiog?nese ? considerada um fen?meno importante para a dissemina??o das c?lulas tumorais e pode sofrer influ?ncia de est?mulos do microambiente. Os mast?citos t?m sido relacionados ? progress?o de neoplasias malignas, no entanto o seu papel na forma??o de vasos linf?ticos ainda n?o est? bem estabelecido. O prop?sito desta pesquisa foi avaliar poss?veis correla??es entre a densidade linf?tica, a contagem de mast?citos e o perfil clinicopatol?gico em casos de CELO, incluindo o estadiamento cl?nico TNM, a grada??o histol?gica de malignidade (Bryne, 1998) e a presen?a/aus?ncia de met?stases nodais. A amostra foi constitu?da por 50 casos de CELO, dos quais 26 apresentavam met?stase nodal, e os 24 restantes eram isentos de met?stases. A densidade linf?tica foi estabelecida como a m?dia de vasos linf?ticos imunomarcados pelo anticorpo anti-podoplanina (D2-40), identificados em cinco campos microsc?picos (200x). Para a an?lise dos mast?citos, foram quantificadas as c?lulas imunorreativas ao anticorpo anti-triptase, em cinco campos (400x). Destaca-se que ambas as imunomarca??es foram analisadas no centro tumoral e no front de invas?o. A densidade linf?tica intratumoral (DLI) foi superior nos casos em est?gios cl?nicos avan?ados (III-IV), quando comparados ?queles em est?gios iniciais (I-II), assim como nos casos metast?ticos em rela??o aos n?o-metast?ticos (p<0,05). N?o houve diferen?as estatisticamente significativas entre os casos de baixo grau e alto grau de malignidade no tocante ? DLI (p>0,05). De outro modo, a densidade linf?tica peritumoral (DLP) e as contagens de mast?citos n?o demonstraram rela??es significativas com nenhum dos par?metros clinicopatol?gicos avaliados (p>0,05). Tamb?m n?o foram encontradas correla??es significativas entre as densidades linf?ticas e as contagens de mast?citos, seja na regi?o intratumoral (r = -0,004; p=0,977) ou na peritumoral (r = -0,154; p=0,285). Os resultados do presente estudo sugerem que os vasos linf?ticos intratumorais contribuem na progress?o do CELO. Por sua vez, a DLP pode n?o ser suficiente para justificar diferen?as no comportamento biol?gico do CELO, o que sustenta a hip?tese de envolvimento de outros mecanismos na dissemina??o metast?tica das c?lulas malignas, que complementariam os efeitos da linfangiog?nese. Os mast?citos, ainda que realizem diversas fun??es pr?- e antitumorais, parecem n?o influenciar diretamente o potencial de agressividade do CELO. Adicionalmente, ? poss?vel que a quantidade destas c?lulas n?o seja um fator determinante para a forma??o de vasos linf?ticos. / Oral tongue squamous cell carcinoma (OTSCC) has an aggressive biological behavior, with a high propensity for the development of lymph node metastases. In this context, lymphangiogenesis is considered an important phenomenon for the spread of tumor cells and may be influenced by microenvironmental stimuli. Mast cells have been implicated in tumor progression, although their influence in the formation of lymphatic vessels is not well established. The aim of this study was to analyze, in a case series of OTSCC (n=50), possible correlations between lymphatic vessel density (LVD), mast cell count and clinicopathological features, including tumor-node-metastasis (TNM) stage, histological grade of malignancy (Bryne, 1998), and nodal metastasis. LVD was established as the mean number of lymphatic vessels immunostained by anti-podoplanin (D2-40) antibody, identified in five microscopic fields (200x). For the analysis of mast cells, tryptase-immunoreactive cells were quantified in five fields (400x). Both immunostainings were analyzed in the tumor center and invasion front. Intratumoral lymphatic density (ILD) was higher in cases in advanced clinical stages (III-IV), compared to those in initial stages (I-II), as well as in metastatic cases in respect of non-metastatic (p<0,05). There were no statistically significant differences between low-grade and high-grade malignancy cases with respect to ILD (p>0,05). Peritumoral lymphatic density (PLD) and mast cell counts showed no significant relations with any of the clinicopathological parameters evaluated (p>0,05). Also there were no significant correlations between LVD and mast cell counts, whether in intratumoral (r = -0,004; p=0,977) or peritumoral region (r = -0,154; p=0,285). The results of the present study suggest that intratumoral lymphatic vessels may contribute in part to the progression of OTSCC, although PLD may be insufficient to justify differences in biological behavior. This supports the hypothesis of involvement of other mechanisms in metastatic spread of malignant cells, which could complement the effects of lymphangiogenesis. Although mast cells perform several pro- and antitumoral functions, they do not appear to directly influence aggressiveness of OTSCC. In addition, the quantity of these cells may not be essential for lymphatic vessel formation.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-01-20T21:18:47Z No. of bitstreams: 1 KeilaMarthaAmorimBarroso_TESE.pdf: 21818921 bytes, checksum: 6e052052d865c5daec54b63d43d919f5 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-01-22T20:15:18Z (GMT) No. of bitstreams: 1 KeilaMarthaAmorimBarroso_TESE.pdf: 21818921 bytes, checksum: 6e052052d865c5daec54b63d43d919f5 (MD5) / Made available in DSpace on 2016-01-22T20:15:18Z (GMT). No. of bitstreams: 1 KeilaMarthaAmorimBarroso_TESE.pdf: 21818921 bytes, checksum: 6e052052d865c5daec54b63d43d919f5 (MD5) Previous issue date: 2014-02-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / As neoplasias de gl?ndulas salivares exibem uma grande diversidade morfol?gica e comportamentos biol?gicos variados o que suscita o interesse na pesquisa destas les?es. A dissemina??o das c?lulas tumorais ? um passo inicial para a progress?o de neoplasias malignas e, dentro deste contexto, os vasos linf?ticos neoformados s?o considerados essenciais para que ocorra essa dissemina??o. O papel do VEGF (fator de crescimento endotelial vascular) na forma??o dos vasos ? fato conhecido mas, pouco se sabe a respeito de sua participa??o em tumores de gl?ndula salivar. Desta forma, o objetivo deste estudo foi avaliar a express?o do VEGF-C e VEGF-D, a densidade linf?tica tumoral (D2-40) e a prolifera??o endotelial linf?tica (dupla marca??o D2-40/Ki-67) em uma s?rie de neoplasias de gl?ndulas salivares. A amostra foi composta por 20 adenomas pleom?rficos, 20 carcinomas aden?ides c?sticos, 20 carcinomas mucoepiderm?ides e 10 casos de tecido glandular salivar com caracter?sticas de normalidade para efeito comparativo. Todos os casos estudados exibiram express?o positiva para VEGF-C em regi?o peritumoral e intratumoral, n?o sendo encontrada diferen?as de imunoexpress?o entre os grupos. No entanto, o grupo dos carcinomas aden?ides c?sticos demonstrou diferen?a significativa da imunoexpress?o do VEGF-C segundo o padr?o cribriforme e s?lido (p = 0,004). A maioria dos casos constantes do presente estudo, apresentou fraca marca??o para VEGF-D em regi?o peritumoral e intratumoral. Na avalia??o da densidade endotelial linf?tica peritumoral, intratumoral e total, os grupos estudados revelaram um gradiente crescente, com valores menores para o grupo dos adenomas pleom?rficos, seguido dos carcinomas mucoepiderm?ides e carcinomas aden?ides c?sticos. A densidade endotelial linf?tica foi maior entre os tumores malignos do que nos tumores benignos. N?o foi observada correla??o entre a imunoexpress?o de VEGF-C e VEGF-D em rela??o a densidade linf?tica tumoral e a prolifera??o endotelial linf?tica / Salivary gland neoplasms exhibit a great morphological diversity and varied biological behavior which raises the interest in the study of these lesions. The spread of tumor cells is an early step in the progression of malignancies and the neoformed lymphatic vessels are considered essential in tumor dissemination. Vascular endotelial growth fator (VEGF) is a family of proteins involved in angiogenesis e lymphangiogenesis. However, in salivar tumors we have limited information on the expression. The aim of this study was to assess the expression of VEGF-C and VEGF-D, lymphatic vessel density (single-staining D2-40) and lymphatic endothelial proliferation (double labeling D2-40/Ki-67) in a series of salivary glands neoplasms. We selected 20 cases of pleomorphic adenoma, 20 of mucoepidermoide carcinoma, 20 of adenoid cystic carcinoma and 10 tissue sample of normal salivary gland. All cases studied showed positive expression of VEGF-C in intratumoral and peritumoral region, no differences in immunoreactivity was found between the groups. However, the group of adenoid cystic carcinoma showed a significant difference in immunoreactivity of VEGF-C by the cribriform and solid pattern (p = 0.004). Most of the cases included in this study showed weak immunoreactivity for VEGF-D in intratumoral and peritumoral region. In the assessment of lymphatic endotelial density peritumoral, intratumoral and total, the groups showed an increasing gradient, with lower values for the group of pleomorphic adenomas followed by mucoepidermoid carcinoma and adenoid cystic carcinoma. Lymphatic endothelial cell density was higher in malignant than benign tumors. No correlation was observed between the immunoreactivity of VEGF-C and VEGF-D in relation to tumor lymphatic density and lymphatic endothelial proliferation

Made available in DSpace on 2014-12-17T15:32:31Z (GMT). No. of bitstreams: 1 AnaRLAM_TESE.pdf: 3774507 bytes, checksum: 2b9028dcadafe1a4c66e01ba9daab791 (MD5) Previous issue date: 2012-07-19 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Squamous cell carcinoma of the lower lip is among the most common malignant tumors of the oral and maxillofacial region, with good prognosis in more than 90% of patients with 5-year survival. In these carcinomas, the development of lymph node metastasis decreases the prognosis and it has been associated with the formation of new lymphatic vessels. It has been suggested the important role of vascular endothelial growth factor-C (VEGF-C), the receptor type 3 VEGF (VEGFR-3) and hypoxia-induced factor 1 (HIF-1) in this process. The aim of this study was to evaluate the immunoexpression of VEGF-C, VEGFR-3 and HIF-1? and correlate with intra and peritumoral lymphatic density in squamous cell carcinomas of the lower lip metastatic and non-metastatic. The sample consisted of 50 cases of squamous cell carcinoma of lower lip, of which 25 had regional lymph node metastasis and 25, absence of metastasis. The percentages of cells immunostained for VEGF-C, VEGFR-3 and HIF-1? in front of tumor invasion and in the center of tumor were evaluated. Microvessel density lymphatic (MDL) was determined by the counting of lymph microvessels immunostained by the anti-D2-40 in five fields (200?), in an area of evaluation with 0.7386 mm2. The invasion of the lymph vessels by malignant cells was also evaluated. Immunostaining was correlated with the presence and absence of metastasis, TNM clinical stage, local recurrence, disease outcome (remission of injury or patient death) and histological grading. The analysis of intra and peritumoral lymphatic density showed no significant association with clinicopathological parameters and immunoexpressions of VEGF-C, VEGFR-3 and HIF-1? (p > 0,05). There was a weak positive correlation, significant, between intra and peritumoral lymphatic density (r = 0,405; p = 0,004). VEGF-C showed no significant association with clinicopathological and prognosis parameters (p > 0,05). For VEGFR-3, there was scarce membrane staining and intense and homogenous cytoplasmic staining in neoplastic cells. Percentage of positive cytoplasmic VEGFR-3 in center of tumor, exhibited a statistically significant association with metastasis (p = 0,009), patient death (p = 0,008) and histological grades of malignancy proposed by Bryne et al. (1992) (p = 0,002) and World Health Organization (p = 0,003). A low positive correlation was statistically significant between the immunoreactivity of VEGFC and VEGFR-3 cytoplasmic (r = 0,358; p = 0,011) and between the percentage of positive cytoplasmic VEGFR-3 in front of tumor invasion and in the center of the tumor (r = 0,387; p = 0,005) was also demonstrated. There was no association between HIF-1?, clinicopathological and prognosis parameters, and VEGF-C and VEGFR-3. The percentage of nuclear positivity for HIF-1? was significantly higher in cases without invasion of peritumoral lymphatic (p = 0,040). Based on the results we can conclude that most cytoplasmic expression of VEGFR-3 in center of tumor in metastatic cases, high degree of malignancy and poorly differentiated, contributes to poor outcome of squamous cell carcinoma of the lower lip, including patient death. Intra and peritumoral lymphatic density seems to be not associated with lymph node metastasis in these carcinomas / O carcinoma epiderm?ide de l?bio inferior est? entre as les?es malignas mais comuns da regi?o oral e maxilofacial, com progn?stico bom, em mais de 90% dos pacientes com sobrevida de 5 anos. Nestas les?es, o desenvolvimento de met?stase linfonodal diminui sobremaneira o progn?stico e tem sido associado ? forma??o de novos vasos linf?ticos. Tem sido sugerido o importante papel do fator de crescimento endotelial vascular-C (VEGF-C), do receptor tipo 3 do VEGF (VEGFR-3) e do fator 1 induzido por hip?xia (HIF-1) neste processo. O objetivo desta pesquisa foi avaliar as imunoexpress?es de VEGF-C, VEGFR-3, HIF-1? e a densidade linf?tica intra e peritumoral em carcinomas epiderm?ides de l?bio inferior metast?ticos e n?o-metast?ticos, correlacionando-as com par?metros clinicopatol?gicos e progn?sticos. A amostra foi constitu?da por 50 casos de carcinoma epiderm?ide de l?bio inferior, 25 com met?stase linfonodal regional e 25 sem met?stase. Foram avaliados os percentuais de c?lulas imunomarcadas para os anticorpos anti-VEGF-C, anti-VEGFR-3 e anti-HIF-1?, no front de invas?o e no centro tumoral. A densidade microvascular linf?tica (LMVD) foi estabelecida por meio da soma da contagem de microvasos linf?ticos imunomarcados pelo anticorpo anti-D2-40, em cinco campos (200?), em uma ?rea de avalia??o com 0,7386 mm2. A invas?o dos vasos linf?ticos por c?lulas neopl?sicas tamb?m foi avaliada. A imunomarca??o foi relacionada com a presen?a e aus?ncia de met?stase, estadiamento cl?nico TNM, recidiva local, desfecho da doen?a (remiss?o da les?o ou ?bito dos pacientes) e grada??o histol?gica. A an?lise das densidades linf?ticas intra e peritumorais n?o demonstrou associa??o significativa com os par?metros clinicopatol?gicos, progn?sticos e imunoexpress?es de VEGF-C, VEGFR-3 e HIF-1? (p > 0,05). Houve fraca correla??o positiva, significativa, entre as densidades linf?ticas intra e peritumorais (r = 0,405; p = 0,004). O VEGF-C n?o exibiu associa??o significativa entre os par?metros clinicopatol?gicos e progn?sticos avaliados (p > 0,05). Para o VEGFR-3, houve escassa marca??o membranar e intensa e homog?nea marca??o citoplasm?tica nas c?lulas neopl?sicas. O percentual de positividade citoplasm?tica do VEGFR-3, no centro tumoral, exibiu associa??o estatisticamente significativa com a presen?a de met?stase (p = 0,009), ?bito dos pacientes (p = 0,008) e grada??es histol?gicas de malignidade proposta por Bryne et al. (1992) (p = 0,002) e pela Organiza??o Mundial de Sa?de (p = 0,003). Uma fraca correla??o, estatisticamente significativa, entre a imunoexpress?o de VEGF-C e VEGFR-3 citoplasm?tica (r = 0,358; p = 0,011) e entre os percentuais de positividade citoplasm?tica de VEGFR-3 no front de invas?o e no centro tumoral (r = 0,387; p = 0,005) tamb?m foi demonstrada. N?o foi observada associa??o entre o HIF-1? os par?metros clinicopatol?gicos, progn?sticos e o VEGF-C e VEGFR-3. O percentual de positividade nuclear para HIF-1? foi significativamente maior nos casos sem invas?o dos linf?ticos peritumorais (p = 0,040). Com base nos resultados pode-se concluir que a maior express?o citoplasm?tica de VEGFR-3, no centro tumoral, nos casos metast?ticos, de alto grau de malignidade e pobremente diferenciados, contribui para pior evolu??o dos carcinomas epiderm?ides de l?bio inferior, incluindo o ?bito dos pacientes. As densidades linf?ticas intra e peritumorais parecem n?o estar associadas ao densenvolvimento de met?stase linfonodal nestes carcinomas