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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Avaliação dos parâmetros clínico, histopatológico e imunoistoquímico dos tumores odontogênicos queratocísticos associados ou não à Síndrome do Carcinoma basocelular nevóide / Evaluation of clinical, histopathological and immunohistochemistry parameters of Keratocystic Odontogenic Tumor associated or not with Nevoid Basal Cell Carcinoma Syndrome

Luana Eschholz Bomfin 05 October 2011 (has links)
Introdução. O Tumor Odontogênico Queratocístico (TOQC) é uma lesão de origem odontogênica que se apresenta exclusivamente nos ossos gnáticos e possui alto potencial de agressividade local. Pode estar associado à Síndrome do Carcinoma Nevóide Basocelular (SCNBC), que se caracteriza por apresentar inúmeras alterações de desenvolvimento, múltiplos carcinomas basocelulares (CBCs) além de anormalidades esqueléticas. Cerca de 65 a 100% dos pacientes com a síndrome podem apresentar múltiplos TOQCs. Objetivo. Avaliar e correlacionar os achados clínicos, histopatológico e expressão imunoistoquímica (IQ) dos marcadores de prognóstico (p53 e ki-67) e de histogênese tumoral (Citoqueratinas 14, 17 e 19) em TOQCs associados ou não à SCNBC diagnosticados entre 1970 e 2009 no Hospital AC Camargo, São Paulo. Pacientes e Métodos. Estudo retrospectivo em que foram avaliados 74 pacientes, 60 não portadores da SCNBC (Grupo 1) e 14 portadores da SCNBC (Grupo 2). Os dados clínicos dos pacientes foram obtidos a partir dos prontuários médicos e sumarizados em fichas clínicas padronizadas para o estudo. Os pacientes do Grupo 1 apresentaram 61 TOQCs primários e 15 TOQCs recorrentes. O Grupo 2 apresentou 31 TOQCs primários e 8 recorrentes. Resultados. No Grupo 1, houve predomínio de pacientes nas 3ª e 4ª décadas de vida e no Grupo 2, na 2ª década (p = 0.02). De acordo com o sexo, houve predileção pelas mulheres em ambos os Grupos (53,33% no Grupo 1 e 64,29% no Grupo 2). A mandíbula foi mais frequentemente acometida nos dois Grupos (81,96% no Grupo 1 e 58,06% no Grupo 2). Contudo, a discrepância em relação à distribuição entre mandíbula e maxila foi menor no Grupo 2 (p = 0.009). O padrão radiográfico multilocular foi mais frequente no Grupo 1 (39,34%) e unilocular no Grupo 2 (48,39%) (p = 0.008). A associação de enucleação e curetagem foi frequentemente realizada em ambos os Grupos (55,74% no Grupo 1 e 96,78 no Grupo 2). A taxa de recorrência foi de 21,31% no Grupo 1 e 22,58% no Grupo 2. As manifestações clínicas mais comuns dos pacientes com SCNBC foram CBCs, calcificação da foice cerebral e pits palmares. De acordo com a análise imunoistoquímica dos marcadores CQ 14, CQ 17, CQ 19, p53 e ki-67, não foram observadas diferenças no padrão de expressão entre os Grupos de TOQCs avaliados. Conclusões. Os TOQCs associados à SCNBC acometem mais frequentemente indivíduos do sexo feminino e em idade mais precoce do que os TOQCs esporádicos. Múltiplos TOQCs foram frequentemente observados em pacientes sindrômicos e consequentemente houve menor discrepância em relação à distribuição entre mandíbula e maxila. O aspecto radiográfico unilocular é mais frequente em TOQCs associados à SCNBC e multilocular em TOQCs esporádicos. As taxas de recorrências foram similares em TOQCs associados e não associados à SCNBC. / Introduction. Keratocystic odontogenic tumor (KCOT) is a lesion of odontogenic origin which arise exclusively in gnatic bones and demonstrates high potential of local aggressiveness. KCOT may be associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) which is characterized by development defects, multiple basal cell carcinoma (BCC) and skeletal anomalies. Around 65 to 100% of patients with NBCCS present multiple KCOT affecting jaws. Objective. Evaluate clinical, histopathological and immunohistochemical (IHC) expression of prognostic markers (p53 and ki-67) and tumor histogenesis (citokeratin 14, 17 and 19) in KCOT associated or not to NBCCS diagnosed between 1970 and 2009 at AC Camargo Hospital (São Paulo). Patients and methods. Retrospective study which has evaluated 74 patients, being 60 not associated with NBCCS (Group 1) and 14 associated with NBCCS (Group 2). Clinical data of patients was obtained from medical charts and summarized into standardized records for this study. The patients of Group 1 presented 61 primary KCOT and 15 recurrent KCOT. Group 2 presented 31 primary KCOT and 8 recurrent KCOT. Results. In Group 1, patients was frequently affected in 3rd and 4th decades and Group 2, in 2nd decade (p = 0.02). According to gender, a predilection for females was observed in both groups (53.33% in Group 1 and 64.29% in Group 2). The mandible was more affected in both Groups (81.96% in Group 1 e 58.06% in Group 2). However, the discrepancy regarding the distribution between mandible and maxilla was shorter in Group 2 (p = 0.009). Radiographic pattern more observed was multilocular in Group 1 (39.34%) and unilocular in Group 2 (48.39%) (p = 0.008). The treatment mostly performed was association of enucleation and curettage in both Groups (55.74% in Group 1 and 96.78 and Group 2). Recurrent rates were 21.31% in Group 1 and 22.58% in Group 2. Most clinical manifestations of NBCCS patient´s beyond KCOT were BCC, falx cerebri calcification and palmar pits. According to IHC analyses of Ck14, Ck 17, Ck19, p53 and ki-67, there were no differences of expression in all groups of KCOT evaluated. Conclusions. KCOT associated with NBCCS affects more commonly female individuals and in earlier age than in KCOT not related to NBCCS. Multiple KCOT were frequently observed in patients with NBCCS and consequently there was less discrepancy in relation to the distribution between maxilla and mandible. Multilocular pattern is more frequent in sporadic KCOT and unilocular in syndromic KCOT. Recurrence rates were similar in KCOT associated and not associated to NBCCS.
2

Avaliação dos parâmetros clínico, histopatológico e imunoistoquímico dos tumores odontogênicos queratocísticos associados ou não à Síndrome do Carcinoma basocelular nevóide / Evaluation of clinical, histopathological and immunohistochemistry parameters of Keratocystic Odontogenic Tumor associated or not with Nevoid Basal Cell Carcinoma Syndrome

Bomfin, Luana Eschholz 05 October 2011 (has links)
Introdução. O Tumor Odontogênico Queratocístico (TOQC) é uma lesão de origem odontogênica que se apresenta exclusivamente nos ossos gnáticos e possui alto potencial de agressividade local. Pode estar associado à Síndrome do Carcinoma Nevóide Basocelular (SCNBC), que se caracteriza por apresentar inúmeras alterações de desenvolvimento, múltiplos carcinomas basocelulares (CBCs) além de anormalidades esqueléticas. Cerca de 65 a 100% dos pacientes com a síndrome podem apresentar múltiplos TOQCs. Objetivo. Avaliar e correlacionar os achados clínicos, histopatológico e expressão imunoistoquímica (IQ) dos marcadores de prognóstico (p53 e ki-67) e de histogênese tumoral (Citoqueratinas 14, 17 e 19) em TOQCs associados ou não à SCNBC diagnosticados entre 1970 e 2009 no Hospital AC Camargo, São Paulo. Pacientes e Métodos. Estudo retrospectivo em que foram avaliados 74 pacientes, 60 não portadores da SCNBC (Grupo 1) e 14 portadores da SCNBC (Grupo 2). Os dados clínicos dos pacientes foram obtidos a partir dos prontuários médicos e sumarizados em fichas clínicas padronizadas para o estudo. Os pacientes do Grupo 1 apresentaram 61 TOQCs primários e 15 TOQCs recorrentes. O Grupo 2 apresentou 31 TOQCs primários e 8 recorrentes. Resultados. No Grupo 1, houve predomínio de pacientes nas 3ª e 4ª décadas de vida e no Grupo 2, na 2ª década (p = 0.02). De acordo com o sexo, houve predileção pelas mulheres em ambos os Grupos (53,33% no Grupo 1 e 64,29% no Grupo 2). A mandíbula foi mais frequentemente acometida nos dois Grupos (81,96% no Grupo 1 e 58,06% no Grupo 2). Contudo, a discrepância em relação à distribuição entre mandíbula e maxila foi menor no Grupo 2 (p = 0.009). O padrão radiográfico multilocular foi mais frequente no Grupo 1 (39,34%) e unilocular no Grupo 2 (48,39%) (p = 0.008). A associação de enucleação e curetagem foi frequentemente realizada em ambos os Grupos (55,74% no Grupo 1 e 96,78 no Grupo 2). A taxa de recorrência foi de 21,31% no Grupo 1 e 22,58% no Grupo 2. As manifestações clínicas mais comuns dos pacientes com SCNBC foram CBCs, calcificação da foice cerebral e pits palmares. De acordo com a análise imunoistoquímica dos marcadores CQ 14, CQ 17, CQ 19, p53 e ki-67, não foram observadas diferenças no padrão de expressão entre os Grupos de TOQCs avaliados. Conclusões. Os TOQCs associados à SCNBC acometem mais frequentemente indivíduos do sexo feminino e em idade mais precoce do que os TOQCs esporádicos. Múltiplos TOQCs foram frequentemente observados em pacientes sindrômicos e consequentemente houve menor discrepância em relação à distribuição entre mandíbula e maxila. O aspecto radiográfico unilocular é mais frequente em TOQCs associados à SCNBC e multilocular em TOQCs esporádicos. As taxas de recorrências foram similares em TOQCs associados e não associados à SCNBC. / Introduction. Keratocystic odontogenic tumor (KCOT) is a lesion of odontogenic origin which arise exclusively in gnatic bones and demonstrates high potential of local aggressiveness. KCOT may be associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) which is characterized by development defects, multiple basal cell carcinoma (BCC) and skeletal anomalies. Around 65 to 100% of patients with NBCCS present multiple KCOT affecting jaws. Objective. Evaluate clinical, histopathological and immunohistochemical (IHC) expression of prognostic markers (p53 and ki-67) and tumor histogenesis (citokeratin 14, 17 and 19) in KCOT associated or not to NBCCS diagnosed between 1970 and 2009 at AC Camargo Hospital (São Paulo). Patients and methods. Retrospective study which has evaluated 74 patients, being 60 not associated with NBCCS (Group 1) and 14 associated with NBCCS (Group 2). Clinical data of patients was obtained from medical charts and summarized into standardized records for this study. The patients of Group 1 presented 61 primary KCOT and 15 recurrent KCOT. Group 2 presented 31 primary KCOT and 8 recurrent KCOT. Results. In Group 1, patients was frequently affected in 3rd and 4th decades and Group 2, in 2nd decade (p = 0.02). According to gender, a predilection for females was observed in both groups (53.33% in Group 1 and 64.29% in Group 2). The mandible was more affected in both Groups (81.96% in Group 1 e 58.06% in Group 2). However, the discrepancy regarding the distribution between mandible and maxilla was shorter in Group 2 (p = 0.009). Radiographic pattern more observed was multilocular in Group 1 (39.34%) and unilocular in Group 2 (48.39%) (p = 0.008). The treatment mostly performed was association of enucleation and curettage in both Groups (55.74% in Group 1 and 96.78 and Group 2). Recurrent rates were 21.31% in Group 1 and 22.58% in Group 2. Most clinical manifestations of NBCCS patient´s beyond KCOT were BCC, falx cerebri calcification and palmar pits. According to IHC analyses of Ck14, Ck 17, Ck19, p53 and ki-67, there were no differences of expression in all groups of KCOT evaluated. Conclusions. KCOT associated with NBCCS affects more commonly female individuals and in earlier age than in KCOT not related to NBCCS. Multiple KCOT were frequently observed in patients with NBCCS and consequently there was less discrepancy in relation to the distribution between maxilla and mandible. Multilocular pattern is more frequent in sporadic KCOT and unilocular in syndromic KCOT. Recurrence rates were similar in KCOT associated and not associated to NBCCS.
3

Mécanismes moléculaires sous-jacents au développement du médulloblastome

Racicot, Frédéric 11 1900 (has links)
Le médulloblastome est une des tumeurs les plus fréquentes du système nerveux central chez l’enfant. Son impact clinique, ainsi que les effets secondaires engendrés par les traitements actuels, sont significatifs en matière de morbidité et de mortalité. La caractérisation moléculaire des tumeurs du système nerveux central a grandement évolué, et ce, particulièrement en ce qui concerne le médulloblastome. Des travaux antérieurs ont permis d’établir qu’un des sous-groupes de médulloblastome est caractérisé par l’activation de la voie sonic hedgehog. La mutation la plus fréquente menant à ce sous-type de médulloblastome est la mutation du gène suppresseur de tumeur PTCH1. Grâce au modèle de souris Ptch1+/-, des données issues de notre laboratoire ont permis de caractériser le développement de cette tumeur comme étant en deux étapes. Ce travail porte sur la caractérisation du mécanisme par lequel cette première étape, soit la perte d’hétérozygotie de Ptch1, survient. Tout d’abord, nous revisitons le rôle in vivo du corécepteur Boc dans la tumorigenèse. Selon nos résultats, la modulation de Boc ne semble pas avoir un impact significatif sur le développement tumoral dans des expériences de transplantation orthotopiques. Ensuite, nous démontrons que le ligand Shh augmente le dommage à l’ADN, ce qui mène à une hausse des évènements de recombinaisons qui peuvent causer une perte d’hétérozygotie. Nous tentons de moduler l’activité de Rad51 en observant une tendance non statistiquement significative des évènements de recombinaison avec des inhibiteurs de Rad51. Nous démontrons ensuite qu’un inhibiteur de Cdc7 permet la diminution des évènements de recombinaisons ainsi qu’une diminution du stress réplicatif de l’ADN. En intervenant sur le gène Mcm2 grâce à un modèle de souris transgénique, nous parvenons à prouver qu’une diminution de l’action de Mcm2 permet une diminution du stress réplicatif de l’ADN. En somme, la première étape du développement du médulloblastome sonic hedgehog-activé est la perte d’hétérozygotie de Ptch1. Celle-ci est caractérisée par une augmentation du dommage à l’ADN engendrant une hausse des évènements de recombinaison. Plusieurs cibles potentielles de modulation s’avèrent prometteuses pour un éventuel traitement ciblé. / Medulloblastoma is one of the most common central nervous system tumors of the child. Its clinical impact, as well as the adverse effects caused by current treatments, are significant in terms of morbidity and mortality. The molecular characterization of tumors of the central nervous system has greatly evolved, particularly in the case of medulloblastoma. Previous work has established that one of the medulloblastoma sub-groups is characterized by the activation of the sonic hedgehog (Shh) pathway. The most common mutation leading to this medulloblastoma subtype is the PTCH1 tumor suppressor gene mutation. Working with the Ptch1+/- mouse model, data from our la-boratory characterized the medulloblastoma tumorigenesis as a two-step process. This work focuses on the characterization of the mechanism by which this first step, the loss of heterozygosity of Ptch1, occurs. First, we revisit the in vivo role of the Boc coreceptor in the medulloblastoma tumor-igenesis. According to our results, Boc modulation does not seem to have a significant impact on tumor development. Next, we show that the Shh ligand increases DNA dam-age. This leads to an increase in recombination events which predispose to loss of het-erozygosity. We attempt to modulate Rad51 activity and observe a non-statistically sig-nificant trend to decrease recombination events with Rad51 inhibitors. We then demonstrate that Cdc7 inhibition reduces recombination events as well as DNA replica-tive stress. Using an Mcm2 transgenic mouse model, we demonstrate that a reduction in the action of Mcm2 reduces DNA replicative stress. To conclude, the first step in the development of Shh-activated medulloblastoma is the loss of heterozygosity of Ptch1. This is characterized by an increase in DNA damage leading to an increase in recombination events. Several potential modulation targets hold promise for possible targeted therapy.
4

Estudo da imunoexpress?o de RANKL e OPG, do ?ndice angiog?nico (CD34) e da presen?a de miofibroblastos (?-SMA) em ceratocistos odontog?nicos isolados e associados ? s?ndrome de Gorlin

Nonaka, Cassiano Francisco Weege 23 September 2010 (has links)
Made available in DSpace on 2014-12-17T15:32:29Z (GMT). No. of bitstreams: 1 CassianoFWN_TESE.pdf: 3914655 bytes, checksum: c6fb9bd86bba433eb6a5a047a9337861 (MD5) Previous issue date: 2010-09-23 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The odontogenic keratocysts are distinguished from other odontogenic cystic lesions by their potentially aggressive clinical behavior and association, in some cases, with Gorlin syndrome. Studies have suggested that syndrome keratocysts, in comparison with sporadic lesions, have higher growth and infiltration capacity and higher recurrence tendency. The aim of this study was to analyze, by means of immunohistochemistry, the expressions of receptor activator of nuclear factor ?B ligand (RANKL) and osteoprotegerin (OPG), the angiogenic index (CD34) and the presence of myofibroblasts (?-SMA) in primary and recurrent sporadic keratocysts and in keratocysts associated with Gorlin syndrome. The sample was composed by 30 sporadic keratocysts (22 primary and 8 recurrent) and 22 syndrome keratocysts. In the epithelium and in the fibrous capsule of the lesions, the immunoexpression of RANKL and OPG was evaluated by determination of the percentage of positive cells, according to the following scores: 0 (less than 10% of positive cells), 1 (11% - 50% of positive cells), 2 (51% - 75% of positive cells) and 3 (more than 76% of positive cells). In addition, cases were classified according to the RANKL score/ OPG score ratio, as follows: RANKL > OPG, RANKL < OPG, and RANKL = OPG. The angiogenic index was analyzed by counting the microvessels immunoreactive to anti-CD34 antibody in 5 fields (200?). The analysis of myofibroblasts was performed by counting the cells immunoreactive to anti-?-SMA antibody in 10 fields (400?). The analysis of the expressions of RANKL and OPG in the epithelial lining and in the fibrous capsule did not reveal significant differences between groups (p > 0.05). Regarding the RANKL/ OPG ratio in the epithelial lining, most sporadic primary (54.5%) and syndrome lesions (59.1%) showed RANKL < OPG ratio and RANKL = OPG ratio, respectively (p > 0.05). With respect to the RANKL/ OPG ratio in the fibrous capsule, the majority of sporadic primary (81.8%) and sporadic recurrent lesions (75.0%) and most syndrome lesions (45.5%) showed RANKL = OPG ratio (p > 0.05). The mean number of microvessels was 69.2 in sporadic primary lesions, 67.6 in recurrent lesions, and 71.6 in syndrome lesions, with no significant differences between groups (p > 0.05). The mean number of myofibroblasts was 34.4 in sporadic primary lesions, 29.3 in recurrent lesions, and 33.7 in syndrome lesions, with no significant differences between groups (p > 0.05). In conclusion, the results of the present study suggest that the differences in the biological behavior between sporadic keratocysts and keratocysts associated with Gorlin syndrome may not be related to the expressions of RANKL and OPG, the RANKL/ OPG ratio, the angiogenic index or the number of myofibroblasts in these lesions / Os ceratocistos odontog?nicos se destacam em rela??o a outras les?es c?sticas odontog?nicas pelo comportamento cl?nico potencialmente agressivo e por se apresentarem associados, em alguns casos, ? s?ndrome de Gorlin. Estudos t?m sugerido que os ceratocistos sindr?micos, em compara??o ?s les?es isoladas, possuem maior capacidade de crescimento e infiltra??o e maior tend?ncia ? recorr?ncia. O objetivo do presente trabalho consistiu em analisar, por meio de imuno-histoqu?mica, as express?es do ligante do receptor ativador do fator nuclear ?B (RANKL) e da osteoprotegerina (OPG), o ?ndice angiog?nico (CD34) e a presen?a de miofibroblastos (?-SMA), em ceratocistos isolados prim?rios e recorrentes e ceratocistos associados ? s?ndrome de Gorlin. A amostra foi composta por 30 ceratocistos isolados (22 prim?rios e 8 recorrentes) e 22 ceratocistos sindr?micos. A express?o de RANKL e OPG foi avaliada no epit?lio e na c?psula fibrosa das les?es, estabelecendo-se o percentual de c?lulas imunopositivas, de acordo com os escores: 0 (? 10% das c?lulas positivas), 1 (11% - 50% das c?lulas positivas), 2 (51% - 75% das c?lulas positivas) e 3 (? 76% das c?lulas positivas). Al?m disso, os casos foram categorizados, segundo a propor??o RANKL/ OPG, em: RANKL > OPG, RANKL < OPG e RANKL = OPG. O ?ndice angiog?nico foi analisado por meio da contagem dos microvasos imunomarcados pelo anticorpo anti-CD34, em 5 campos (200?). Para a avalia??o dos miofibroblastos, foram quantificadas as c?lulas imunorreativas ao anticorpo anti-?-SMA, em 10 campos (400?). A an?lise das express?es de RANKL e OPG, no revestimento epitelial e na c?psula fibrosa, n?o revelou diferen?as significativas entre os grupos (p > 0,05). Em rela??o ? propor??o RANKL/ OPG no revestimento epitelial, grande parte das les?es isoladas prim?rias (54,5%) e sindr?micas (59,1%) exibiu propor??o RANKL < OPG e propor??o RANKL = OPG, respectivamente (p > 0,05). Em rela??o ? propor??o RANKL/ OPG na c?psula fibrosa, a maioria das les?es isoladas prim?rias (81,8%) e isoladas recorrentes (75,0%) e grande parte das les?es associadas ? s?ndrome de Gorlin (45,5%) revelaram propor??o RANKL = OPG (p > 0,05). O n?mero m?dio de microvasos foi de 69,2 nas les?es isoladas prim?rias, 67,6 nas les?es recorrentes e 71,6 nas les?es sindr?micas, sem diferen?as significativas entre os grupos (p > 0,05). A an?lise dos miofibroblastos revelou valores m?dios de 34,4 nas les?es isoladas prim?rias, 29,3 nas les?es recorrentes e 33,7 nas les?es sindr?micas, sem diferen?as significativas entre os grupos (p > 0,05). Em conclus?o, os resultados do presente estudo sugerem que as diferen?as no comportamento biol?gico entre ceratocistos isolados e associados ? s?ndrome de Gorlin podem n?o estar relacionadas ?s express?es de RANKL e OPG, ? propor??o RANKL/ OPG, ao ?ndice angiog?nico ou ? quantidade de miofibroblastos presentes nas les?es

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