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Anomalies cytogénétiques impliquées dans la carcinogénèse des tumeurs urothéliales et application clinique / Cytogenetic Abnormalities of Urothelial Carcinomas Analysis and Clinical Application for Urine Detection Using CGH ArrayLarré, Stéphane 30 November 2010 (has links)
Les carcinomes urothéliaux représentent la 4ème cause de cancer chez l'homme après les cancers de la prostate, du colon et du poumon. Leur incidence est en augmentation de plus de 50% depuis 25 ans. Ce cancer présente principalement deux formes, une superficielle (70% des cas) de bon pronostic et une invasive (30%) de mauvais pronostic. Les formes superficielles nécessitent une surveillance active rapprochée afin d'identifier les récidives fréquentes et l'évolution vers un stade invasif. Cette surveillance fait principalement appel à la cystoscopie et engendre morbidité et cout importants. Une alternative à la cystoscopie est possible à l'aide de tests de détection urinaire des cellules cancéreuses, mais leur sensibilité jusqu'à présent n'est pas suffisante pour une utilisation en pratique courante. Notre but a été de développer un outil de détection urinaire des tumeurs urothéliales.Matériel, Méthode et RésultatsLes tumeurs urothéliales étant très instables sur le plan génétique, le travail a initialement consisté à faire la synthèse des anomalies cytogénétiques retrouvées dans la littérature. Les anomalies les plus pertinentes ont été sélectionnées et une puce de CGH en a été développée comprenant 341 clones (BAC) répartis sur l'ensemble des chromosomes. Cette puce intitulée BCA-1 a été développée en collaboration avec la société ArrayGenomics (Voisins Le Bretonneux, France). La validité de ce test a été confirmée sur 10 lignées cellulaires tumorales et bénignes.Notre travail a ensuite consisté à étudier la valeur ajoutée de cette puce en pratique clinique. Pour ce faire, une cohorte de 163 patients porteurs de tumeurs urothéliales et de témoins a été constituée. Les urines ont été prélevées et analysées en utilisant la puce BCA-1. Un logiciel a été développé sous filemaker pro afin de permettre une saisie uniforme et détaillée des données cliniques et de prendre en considération le caractère complexe de la prise en charge de ces tumeurs.Le test urinaire utilisant la puce de CGH a montré une excellente performance diagnostique avec une sensibilité de 96% et une spécificité de 98% dans les tumeurs vésicale, et une sensibilité de 100% tumeurs du haut appareil urinaire.Enfin, le test a aussi permit de caractériser le caractère agressif ou non agressif des tumeurs sur le plan cytogénétique. Cette caractérisation est fortement corrélée avec le stade anatomopathologique et un troisième aspect de notre travail a montré que la détermination cytogénétique de l'agressivité des tumeurs prédisait l'évolution défavorable des tumeurs du haut appareil urinaire. Notre travail a permis le développement et l'analyse d'un nouveau test de dépistage urinaire des tumeurs urothéliales permettant le diagnostic urinaire de ces tumeurs et la caractérisation de leur caractère agressif éventuel, ainsi que le développement d'un logiciel de saisie et d'analyse des données cliniques. / Urothelial carcinomas are the 4th cause of cancer in men, following prostate, colon and lung cancer. An increase of 50% in its incidence was observed on the last 25 years. This cancer presents two types, a superficial type (70% of the cases) of good prognosis and an invasive type (30% of the cases) of bad prognosis. Superficial type require an active monitoring to identify recurrences and evolution to an invasive stage. This follow up is performed using cystoscopy and leads to some level of morbidity and a high cost. An alternative to cystoscopy is possible using urine test to detect cancer cells, but they are lacking of sensitivity to be used instead of cystoscopy in clinical practice. Our goal was to develop a urine detection tool of urothélial carcinomas.Material and MethodsUrothelial carcinoma usually present with a high level of genetic instability. We first analyse literature so to identify most relevant cytogenetic abnormalities that occur in urothélial carcinomas. A CGH array chip was designed using 341 clones (BAC) that were selected according to initial analysis. This chip called BCA-1 covers the whole genome and was developed in collaboration with ArrayGenomics (Voisins Le Bretonneux, France).ResultsThis test has shown a good efficacy on a preliminary study of cytogenetic analysis on 10 cancerous and benign bladder cell lines. The Chip was then assessed in clinical practice on a series of 163 patients diagnosed with or without urothelial cancer. Urines were collected and analysed using the BCA-1 chip. A software was designed to favour homogeneous and detailed clinical data collection and take into consideration the complex management of the tumours.The test using the CGH chip as shown an excellent diagnosis performance with a sensitivity of 96% and a specificity of 98% for bladder cancer detection, and a sensitivity of 100% on upper urinary tract detection.Finaly, the test was able to define the grade of the tumour according to cytogenetic loci affected. This grade was strongly correlated with the pathology score and could be used to predict outcomes in upper urinary tract carcinomas. Our work lead to the developpement and the analysis of a new urothélial carcinoma urinary detection test, to the identification of the agressivity of the tumour, and to the development of an analysis and data entry software for clinical details.
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Avaliação de parâmetros fisiológicos e epidemiológicos da população de anta-brasileira (Tapirus terrestris, Linnaeus, 1758) na Mata Atlântica do Parque Estadual Morro do Diabo, Pontal do Paranapanema, São Paulo / Evaluation of physiological and epidemiological parameters of Lowland Tapirs (Tapirus terrestris, Linnaeus, 1758) population in the Atlantic Forest of Morro do Diabo State Park, Pontal do Paranapanema Region, São Paulo StateMay Júnior, Joares Adenilson 20 April 2011 (has links)
Procurou-se avaliar parâmetros fisiológicos de antas (Tapirus terrestris) de vida livre capturadas no Parque Estadual Morro do Diabo, estado de São Paulo, Brasil, entre 1996-2008 pelo Programa Anta Mata Atlântica. Paralelamente, avaliou-se a exposição desses animais a patógenos de interesse em saúde pública e saúde animal. Nesse período foram obtidas amostras de 35 animais. Os valores médios de hemograma e bioquímica sérica foram comparados com os valores de referência do ISIS, através do uso do teste t de Student. Os resultados médios de todos os parâmetros avaliados estavam dento do intervalo de variação descrito para a espécie em cativeiro. Títulos sorológicos incluíram Encefalite Equina Oeste (n=1 animal), Encefalite Equina Leste (n=6), Leptospira interrogans sorovar pomona (n=6), Leptospira interrogans sorovar autumnalis (n=1), Leptospira interrogans sorovar hebdomadi (n=1), Língua Azul (n=5), Rinotraqueíte Infecciosa Bovina (IBR) (n=1). Não foi detectada a presença de anticorpos para Febre Aftosa, Doença de Aujeszky, Parvovirose Suína, Diarréia Viral Bovina, Leucose Bovina, Estomatite Vesicular, Anemia Infecciosa Equina e Brucelose. Todas as capturadas apresentavam alta infestação de carrapatos, identificados como Amblyomma brasiliense, Amblyomma cajennense, Amblyomma coelebs, Amblyomma ovale, Amblyomma naponense, Haemaphysalis juxtakochi e Rhipicephalus (Boophilus) microplus. Alguns animais apresentaram Tunga penetrans e mosca-do-chifre (Haematobia irritans). Oito amostras de urinas de antas de vida livre foram analisadas e descritas pela primeira vez. Os swabs das cavidades naturais apresentaram Staphylococcus aureus em todos os orifícios. Escherichia coli em todos os orifícios, com exceção da orelha. Proteus sp. em todos os orifícios, com exceção do prepúcio. Ânus e vagina presentaram as mesmas bactérias, já prepúcio e ânus se distinguiram pelo Staphylococcus saprophyticus. / It was evaluated physiologic parameters of wild Lowland tapirs (Tapirus terrestris) captured in Morro do Diabo State Park, São Paulo state, Brazil, between 1996 2008 by Atlantic Rainforest Lowland Tapir Program. Together, it was evaluated the expose of these animals to pathogens of public health and animal health interest. During this time it was collected samples from 35 animals. The medium value of blood cells and serum biochemistry were compared with reference values of ISIS, with the t test of Student. All medium values of parameters evaluated were inside of regular range described for the specie in captivity. Serologic titles include West Equine Encephalitis (n= 1 animal), East Equine Encephalitis (n=6), Leptospira interrogans sorovar pomona (n=6), Leptospira interrogans sorovar autumnalis (n=1), Leptospira interrogans sorovar hebdomadi (n=1), Bluetongue (n=5), Infectious Bovine Rhinotraqueitis (IBR) (n=1). It was not detected antibodies to Foot and Mouth Disease, Aujeszky\'s disease, Porcine Parvovirosis, Bovine Viral Diarrhea, Bovine Leucosis, Vesicular Stomatitis, Equine Infectious Anemia and Brucelosis. All captured animals had high level of infestation of ticks, identified as Amblyomma brasiliense, Amblyomma cajennense, Amblyomma coelebs, Amblyomma ovale, Amblyomma naponense, Haemaphysalis juxtakochi and Rhipicephalus (Boophilus) microplus. Some animals had Tunga penetrans and mosca-do-chifre (Haematobia irritans). Eight samples of urine from wild tapirs were analyzed and described first time. The swabs from natural cavity showed Staphylococcus aureus in all of them. Escherichia coli in all cavities, except ears. Proteus sp. in all cavities, except prepucial. Anus and vagina showed the same kinds of bacteria, but prepucial and vagina show the same bacteria, and prepucial and anus to be different because Staphylococcus saprophyticus.
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Avaliação de parâmetros fisiológicos e epidemiológicos da população de anta-brasileira (Tapirus terrestris, Linnaeus, 1758) na Mata Atlântica do Parque Estadual Morro do Diabo, Pontal do Paranapanema, São Paulo / Evaluation of physiological and epidemiological parameters of Lowland Tapirs (Tapirus terrestris, Linnaeus, 1758) population in the Atlantic Forest of Morro do Diabo State Park, Pontal do Paranapanema Region, São Paulo StateJoares Adenilson May Júnior 20 April 2011 (has links)
Procurou-se avaliar parâmetros fisiológicos de antas (Tapirus terrestris) de vida livre capturadas no Parque Estadual Morro do Diabo, estado de São Paulo, Brasil, entre 1996-2008 pelo Programa Anta Mata Atlântica. Paralelamente, avaliou-se a exposição desses animais a patógenos de interesse em saúde pública e saúde animal. Nesse período foram obtidas amostras de 35 animais. Os valores médios de hemograma e bioquímica sérica foram comparados com os valores de referência do ISIS, através do uso do teste t de Student. Os resultados médios de todos os parâmetros avaliados estavam dento do intervalo de variação descrito para a espécie em cativeiro. Títulos sorológicos incluíram Encefalite Equina Oeste (n=1 animal), Encefalite Equina Leste (n=6), Leptospira interrogans sorovar pomona (n=6), Leptospira interrogans sorovar autumnalis (n=1), Leptospira interrogans sorovar hebdomadi (n=1), Língua Azul (n=5), Rinotraqueíte Infecciosa Bovina (IBR) (n=1). Não foi detectada a presença de anticorpos para Febre Aftosa, Doença de Aujeszky, Parvovirose Suína, Diarréia Viral Bovina, Leucose Bovina, Estomatite Vesicular, Anemia Infecciosa Equina e Brucelose. Todas as capturadas apresentavam alta infestação de carrapatos, identificados como Amblyomma brasiliense, Amblyomma cajennense, Amblyomma coelebs, Amblyomma ovale, Amblyomma naponense, Haemaphysalis juxtakochi e Rhipicephalus (Boophilus) microplus. Alguns animais apresentaram Tunga penetrans e mosca-do-chifre (Haematobia irritans). Oito amostras de urinas de antas de vida livre foram analisadas e descritas pela primeira vez. Os swabs das cavidades naturais apresentaram Staphylococcus aureus em todos os orifícios. Escherichia coli em todos os orifícios, com exceção da orelha. Proteus sp. em todos os orifícios, com exceção do prepúcio. Ânus e vagina presentaram as mesmas bactérias, já prepúcio e ânus se distinguiram pelo Staphylococcus saprophyticus. / It was evaluated physiologic parameters of wild Lowland tapirs (Tapirus terrestris) captured in Morro do Diabo State Park, São Paulo state, Brazil, between 1996 2008 by Atlantic Rainforest Lowland Tapir Program. Together, it was evaluated the expose of these animals to pathogens of public health and animal health interest. During this time it was collected samples from 35 animals. The medium value of blood cells and serum biochemistry were compared with reference values of ISIS, with the t test of Student. All medium values of parameters evaluated were inside of regular range described for the specie in captivity. Serologic titles include West Equine Encephalitis (n= 1 animal), East Equine Encephalitis (n=6), Leptospira interrogans sorovar pomona (n=6), Leptospira interrogans sorovar autumnalis (n=1), Leptospira interrogans sorovar hebdomadi (n=1), Bluetongue (n=5), Infectious Bovine Rhinotraqueitis (IBR) (n=1). It was not detected antibodies to Foot and Mouth Disease, Aujeszky\'s disease, Porcine Parvovirosis, Bovine Viral Diarrhea, Bovine Leucosis, Vesicular Stomatitis, Equine Infectious Anemia and Brucelosis. All captured animals had high level of infestation of ticks, identified as Amblyomma brasiliense, Amblyomma cajennense, Amblyomma coelebs, Amblyomma ovale, Amblyomma naponense, Haemaphysalis juxtakochi and Rhipicephalus (Boophilus) microplus. Some animals had Tunga penetrans and mosca-do-chifre (Haematobia irritans). Eight samples of urine from wild tapirs were analyzed and described first time. The swabs from natural cavity showed Staphylococcus aureus in all of them. Escherichia coli in all cavities, except ears. Proteus sp. in all cavities, except prepucial. Anus and vagina showed the same kinds of bacteria, but prepucial and vagina show the same bacteria, and prepucial and anus to be different because Staphylococcus saprophyticus.
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