No description available.

Made available in DSpace on 2014-06-11T19:33:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Bitstream added on 2014-06-13T18:45:07Z : No. of bitstreams: 1 oliveira_de_dr_botfm_prot.pdf: 3094399 bytes, checksum: 07e9c12ea2e876537a71bd24e6211cdd (MD5) / Clicar acesso eletrônico abaixo. / Click electronic access below.

Orientador: Maura Moscardi Bacchi / Resumo: Clicar acesso eletrônico abaixo. / Abstract: Click electronic access below. / Doutor

No description available.

Introdução: O câncer das Vias Aéreas e Digestivas Superiores compreendem um grupo de tumores que se distribuem por diversas regiões anatômicas. Para a maioria das localizações os principais fatores de risco são o tabaco e o álcool. Como os fatores de risco são conhecidos espera-se que as diversas campanhas de prevenção e detecção precoce estivessem propiciando à diminuição da incidência. Objetivos Estimar em algumas localidades do mundo as tendências da incidência dos tumores de lábio, língua, boca, glândulas salivares, orofaringe, nasofaringe e hipofaringe de 1969 a 1999. Métodos Analisou-se os coeficientes de incidência de 18 Registros de Câncer de Base Populacional que possuíam toda a série histórica publicada no “Cancer Incidence in Five Continents".utilizando-se modelos de regressão polinomial.Resultados Houve tendência de aumento, estatisticamente significativo, para o câncer de língua e boca em São Paulo em mulheres e em homens de diversos países europeus e localidades dos EUA. Em contrapartida houve queda em Porto Rico, Mumbai e Cingapura. O câncer de lábio decresceu na maioria das localidades em homens. Entretanto em países do norte da Europa e em Iowa houve aumento em mulheres. O câncer de orofaringe aumentou em homens na Europa e em Iowa e decresceu em Cali, Quebec, e localidades da Ásia. O câncer de hipofaringe apresentou tendência crescente em várias localidades da Europa em homens e queda na Suécia, Inglaterra, Cingapura e Porto Rico. Conclusão os tumores de língua, boca e orofaringe continuam apresentando tendências de crescimento para diversas localidades. Por isso há a necessidade de campanhas propiciando a prevenção e a detecção precoce. / Introduction: Upper Aerodigestive Tract Cancer comprises a group of neoplasms which spread over many anatomic regions. Considering most of the locations, the worst risk coefficients are tobacco and alcohol. Taken the coefficients are known, prevention and precocious detection campaigns are expected to lessen the incidence statistics. Objectives. To estimate the trends on lip, oral cavity (tongue and mouth), salivary gland, oropharyngeal, nasopharyngeal and hypopharyngeal cancer incidences in some locations worldwide between 1969 - 1999. Methods Incidence coefficient data of eighteen records from the Population Database Cancer Registry which had its history published in “Cancer Incidence in Five Continents" has been analysed applying polynomial regression models. Results There has been a statistically significant increase to the number of oral cavity cancer in Sao Paulo among women; in European countries as well as in some North American cities, the increase was detected among both men and women. On the other hand, there has been a decrease in Puerto Rico, Mumbai and Singapore. The incidence of lip cancer decreased in most locations (among men). However, an increase has been detected in North Europe and in Iowa, USA (among women). Oropharyngeal cancer has increased in number among men in Europe and Iowa, USA; it decreased in number in Cali, Quebec, and other areas in Ásia. Hypopharyngeal cancer has shown to be an increasing trend in many Europeans countries among men, but a decreasing one in Sweden, England, Singapore and Puerto Rico. Conclusion Oral cavity and oropharyngeal neoplasms trends proceed grow in many locations. Finally, the need for prevention and precocious detection campaigns is urgent.

Introdução: O câncer das Vias Aéreas e Digestivas Superiores compreendem um grupo de tumores que se distribuem por diversas regiões anatômicas. Para a maioria das localizações os principais fatores de risco são o tabaco e o álcool. Como os fatores de risco são conhecidos espera-se que as diversas campanhas de prevenção e detecção precoce estivessem propiciando à diminuição da incidência. Objetivos Estimar em algumas localidades do mundo as tendências da incidência dos tumores de lábio, língua, boca, glândulas salivares, orofaringe, nasofaringe e hipofaringe de 1969 a 1999. Métodos Analisou-se os coeficientes de incidência de 18 Registros de Câncer de Base Populacional que possuíam toda a série histórica publicada no “Cancer Incidence in Five Continents”.utilizando-se modelos de regressão polinomial.Resultados Houve tendência de aumento, estatisticamente significativo, para o câncer de língua e boca em São Paulo em mulheres e em homens de diversos países europeus e localidades dos EUA. Em contrapartida houve queda em Porto Rico, Mumbai e Cingapura. O câncer de lábio decresceu na maioria das localidades em homens. Entretanto em países do norte da Europa e em Iowa houve aumento em mulheres. O câncer de orofaringe aumentou em homens na Europa e em Iowa e decresceu em Cali, Quebec, e localidades da Ásia. O câncer de hipofaringe apresentou tendência crescente em várias localidades da Europa em homens e queda na Suécia, Inglaterra, Cingapura e Porto Rico. Conclusão os tumores de língua, boca e orofaringe continuam apresentando tendências de crescimento para diversas localidades. Por isso há a necessidade de campanhas propiciando a prevenção e a detecção precoce. / Introduction: Upper Aerodigestive Tract Cancer comprises a group of neoplasms which spread over many anatomic regions. Considering most of the locations, the worst risk coefficients are tobacco and alcohol. Taken the coefficients are known, prevention and precocious detection campaigns are expected to lessen the incidence statistics. Objectives. To estimate the trends on lip, oral cavity (tongue and mouth), salivary gland, oropharyngeal, nasopharyngeal and hypopharyngeal cancer incidences in some locations worldwide between 1969 - 1999. Methods Incidence coefficient data of eighteen records from the Population Database Cancer Registry which had its history published in “Cancer Incidence in Five Continents” has been analysed applying polynomial regression models. Results There has been a statistically significant increase to the number of oral cavity cancer in Sao Paulo among women; in European countries as well as in some North American cities, the increase was detected among both men and women. On the other hand, there has been a decrease in Puerto Rico, Mumbai and Singapore. The incidence of lip cancer decreased in most locations (among men). However, an increase has been detected in North Europe and in Iowa, USA (among women). Oropharyngeal cancer has increased in number among men in Europe and Iowa, USA; it decreased in number in Cali, Quebec, and other areas in Ásia. Hypopharyngeal cancer has shown to be an increasing trend in many Europeans countries among men, but a decreasing one in Sweden, England, Singapore and Puerto Rico. Conclusion Oral cavity and oropharyngeal neoplasms trends proceed grow in many locations. Finally, the need for prevention and precocious detection campaigns is urgent.

Contexte : L’amiante est maintenant une cause avérée de cancer du larynx, mais le rôle des expositions professionnelles dans la survenue des cancers des voies aéro-digestives supérieures (VADS) reste largement méconnu. Bien que plusieurs études aient rapporté des associations entre les expositions professionnelles et ces cancers, il est difficile de synthétiser les résultats et d’en tirer des conclusions définitives. Objectifs : (1) Le premier objectif est de synthétiser les données épidémiologiques disponibles sur les associations entre les cancers de la cavité buccale, du pharynx et du larynx (les cancers des VADS les plus fréquents) et les expositions professionnelles ; (2) le second objectif est, à partir des données d’une large étude cas-témoins, l'étude Icare, d'identifier les professions ou industries présentant des risques élevés de cancer des VADS, puis d'étudier le rôle de certaines expositions professionnelles suspectées (amiante, laines minérales (LM), poussières de ciment, silice). Matériel et méthodes : (1) Une recherche bibliographique et des séries de méta-analyses ont été réalisées pour certaines expositions professionnelles suspectées. (2) L'étude Icare est une étude cas-témoins en population générale française incluant 2415 cas de cancer des VADS et 3555 témoins. L'historique professionnel complet des sujets a été recueilli, avec une description détaillée de chaque emploi exercé. L'évaluation des expositions à l'amiante, aux LM, aux poussières de ciment et à la silice sur l’ensemble de la vie professionnelle a été réalisée à l'aide des matrices emplois-expositions développées dans le cadre du programme Matgéné (Institut de Veille Sanitaire). Résultats : Des méta-risques relatifs (méta-RR) significativement augmentés ont été observés pour le cancer du larynx et les expositions aux hydrocarbures aromatiques polycycliques (HAP), aux gaz d'échappement de moteurs, au travail dans l'industrie textile et dans l'industrie du caoutchouc, et pour le cancer de la cavité buccale et du pharynx et les expositions à l'amiante, aux HAP et aux gaz d'échappement de moteurs. Des augmentations de risque significatives ont été observées pour plusieurs professions et secteurs d'activité exposant notamment aux nuisances présentant des méta-RR augmentés. Les résultats des analyses par nuisance confirment l'association entre l'amiante et le cancer du larynx et suggèrent également une association avec les cancers de la cavité buccale et du pharynx. Une association avec les poussières de ciment est également suggérée. Les résultats ne sont pas en faveur d’un rôle de l’exposition aux LM et à la silice.Conclusion : Ce travail renforce l’hypothèse d’un rôle des expositions professionnelles dans la survenue des cancers des VADS. Dans l’ensemble, nos résultats suggèrent des associations entre le risque de cancer des VADS et les expositions à l'amiante, aux HAP, aux poussières de ciment, et le travail dans l'industrie du caoutchouc. / Background: There is sufficient evidence that asbestos causes laryngeal cancer, but overall the role of occupational exposures in the etiology of head and neck cancer (HNC) remains largely unknown. Although several studies have reported associations between occupational exposures and HNC, it is difficult to draw firm conclusions. Objectives: (1) To summarize available epidemiologic data on occupational exposures and cancers of the oral cavity (OC), pharynx and larynx (the most frequent HNC); (2) using data from a large case-control study, to identify occupations and industries with an increased risk of HNC, then to investigate the role of some suspected occupational exposures (asbestos, mineral wools (MW), cement dust, silica). Methods: (1) A literature research and a series of meta-analyses were performed. (2) The Icare study is a French population-based case-control study including 2415 HNC cases and 3555 controls. Complete and detailed occupational histories were collected. Analyses by job title were conducted. Job exposure matrices, developed by the Occupational Health Department of the French Institute for Public Health Surveillance (InVS), were used to assess lifetime occupational exposure to asbestos, MW, cement dust and silica. Results: Significantly increased meta-relative risks (meta-RR) were obtained considering laryngeal cancer and exposures to polycyclic aromatic hydrocarbons (PAH), engine exhausts, working in the textile industry and the rubber industry, and for cancer of the OC and pharynx and exposures to asbestos, PAH and engine exhausts. Significantly increased risks were found for several jobs and industries, some of them entailing exposures to agents for which meta-RR were increased. Analyses for specific occupational exposures confirmed the association between asbestos and laryngeal cancer and showed an association with the risk of oral cavity and pharyngeal cancer. An association with exposure to cement dust was also suggested. The results did not support an association between HNC risk and exposure to MW or silica. Conclusion: This work emphasizes the role of occupational exposures in HNC. Overall, our results suggest associations between HNC and exposure to asbestos, PAH, cement dust, and work in the rubber industry.

No description available.

Les carcinomes épidermoïdes de la tête et du cou sont souvent de mauvais pronostic, en raison de leur résistance aux traitements suivie de récidives loco-régionales, voire de métastases. Ce travail s'est focalisé sur le rôle des cellules souches cancéreuses (CSC) dans la radiorésistance d'un modèle cellulaire de cancer du larynx, SQ20B, ainsi que sur leur ciblage thérapeutique en association avec la radiothérapie photonique ou par ions carbone. Une sous-population a été isolée à partir de la lignée SQ20B par tris cellulaires successifs selon 3 critères spécifiques des CSC de tumeurs ORL : exclusion du Hoechst 33342, expression de CD44 et activité élevée de l'aldéhyde déshydrogénase (ALDH). Les cellules SQ20B/SP/CD44 high/ALDHhigh présentent bien les caractéristiques de CSC (tumorisphères, tumorigénèse, radiorésistance). La résistance des CSC aux 2 types d'irradiation, par rapport aux cellules « non souche » SQ20B/SP/CD44low/ALDHlow, implique une diminution de la mort par apoptose, une augmentation des capacités prolifératives ainsi qu'une surexpression de la voie de l'autorenouvellement Bmi1. L'effet radiosensibilisant de 3 molécules ciblant les CSC a été démontré : la mort apoptotique induite par l'UCN-01 en inhibant l'arrêt en phase G2/M ; les capacités prolifératives ciblées par l'acide trans-rétinoïque (ATRA) induisant la différenciation ; et la voie de l'autorenouvellement Bmi-1 inhibée par l'artésunate. Seule ou associées (UCN-01 + ATRA), elles agissent en synergie avec une irradiation par photons ou ions carbone. Des études pré-clinique, puis clinique, devraient confirmer l'intérêt du ciblage des CSC dans le contrôle de l'échappement de ces cancers radiorésistants / Head and neck squamous cell carcinomas (HNSCC) have a poor prognosis, due to their resistance to standard treatments. In most cases, locoregional recurrence or metastases occur. This study has focused on the role of cancer stem cells (CSC) in the radioresistance of the SQ20B HNSCC cell line and their therapeutic targeting in association with photon or carbon ions irradiation. A subpopulation of SQ20B-CSC has been isolated by cell sorting based on 3 specific characteristics of HNSCC-CSC : Hoechst 33342 exclusion, CD44 expression and high aldehyde dehydrogenase activity (ALDH). SQ20B/SP/CD44high/ALDHhigh cells show the CSC characteristics (in vitro and in vivo tumorigenesis, high radioresistance). The response of CSC to both types of irradiation was compared to the non-“stem cells” SQ20B/SP/CD44low sub-population. The observed radioresistance involves a decrease in apoptotic cell death, an increase in proliferative capacities and an overexpression of the Bmi1 self-renewing signaling pathway. The radiosensitizing effects of 3 molecules targeting the CSC has been demonstrated : an induction of apoptotic cell death by the inhibition of the G2/M phase arrest after a treatment with UCN01 ; an inhibition of proliferative capacities using the all-trans-retinoic acid (ATRA) which induce their differentiation ; and an inhibition of Bmi1 by artesunate. These treatments, alone or in combination (UCN01+ATRA) have a synergistic effect with photon or carbon ion irradiation to overcome CSC radioresistance. Preclinical and clinical studies should confirm the benefit of targeting CSC and improve the control of tumor escape in patients with radioresistant HNSCC cancers