Made available in DSpace on 2015-04-14T13:35:37Z (GMT). No. of bitstreams: 1 444782.pdf: 1327290 bytes, checksum: 51c0bcf62b76809d6ed98fd7aca7d6b9 (MD5) Previous issue date: 2011-03-15 / The Wilms Tumors (WT) is the most frequent renal tumors of children, and although curable, fatal outcomes may occur. A number a genetic alterations have been suggested as associated factors but still, the exact pathogenesis of WT remains to be fully characterized. Tissue factor (TF) is a glycoprotein which happens to be a key receptor for factor VII/VIIa and is the primary initiator of blood coagulation. Also important, TF has been associated with processes that lead to angiogenesis. It is widely expressed among cells and tissues and recent evidences pointed out an important role for TF in cancer progression and metastasis. Recent evidences suggested that TF may have a role in WT since its immunodetection was associated with poor prognosis. In the present investigation the differential expression of TF was assessed in WT using real-time PCR of RNA retrieved from paraffin sections using microdissection. Different histological components of WT - (blastema, epithelial and stromal) were analysed and the results revealed that TF in blastema and epithelial components was upregulated (14.38 and 16.02-fold respectively, P<0.001). Stroma and control non neoplasic tissues expressed similar levels of expression (P>0.05). TF expression in metastatic lesions from WT was also singificantly upregulated compared to non metastatic lesions. Microvessel density was positively correlated with TF expression (r=0.721). As described for other tumors, TF seems to play a role in malignancy or WT. Further investigations are warranted to better understand the pathways by which TF exerts its effects on tumor progression. Noteworthy, pharmacological strategies that aim at controlling angiogenesis through regulation of TF may be very promising / Esta pesqusisa teve como objetivo demonstrar a express?o diferencial do fator tecidual (FT) em tumor de Wilms (TW), atrav?s de um estudo do tipo transversal. O TW ? a neoplasia renal maligna mais comum na inf?ncia. Os estudos sobre angiog?nese em neoplasias malignas pedi?tricas apresentam poss?veis vias de terapias antiangiog?nicas, com menor agressividade e melhor especificidade tumoral. E, entre os fatores angiog?nicos poss?veis, foi estudo o Fator Tecidual (FT), prote?na transmebrana com sua principal fun??o no processo de hemostasia, mas que demonstra ter importante papel nos processos patol?gicos de tumorig?nese, angiog?nese e microambiente tumoral favor?vel ? dissemina??o neopl?sica. Sua express?o vem sendo associada ?s met?stases e piora no progn?stico. Contuto, s? a partir da pesquisa de Maciel et al (1) que a associa??o do FT com TW foi observada, onde se encontrou, utilizando imunoistoqu?mica, a correla??o positiva entre a express?o do FT, recidiva tumoral e ?bito. Ent?o, a partir desses dados iniciais, a presente pesquisa analisou uma amostra com 27 esp?cimes fixadas em parafina de TW e 26 controles (?rea sem TW), para demonstrar a express?o diferencial do FT em TW, atrav?s da t?cnica de quantifica??o de ?cidos nucl?icos (RNAm) por Rea??o Cadeia de DNA Polimerase em Tempo Real (RT-PCR), avaliar a express?o do FT em diferentes componentes tumorais, com a densidade microvascular (DMV) do TW e a ocorr?ncia de met?stases. Foi observado aumento da express?o diferencial do FT no TW, sua maior varia??o do FT foi encontrada nos componentes blastematoso e epitelial, enquanto no componente estromal apresentou varia??o m?nima em rela??o ao tecido n?o tumoral, em les?es metast?ticas o FT se mostrou significativamente mais elevado, sugerindo um papel importante para essa prote?na no processo de dissemina??o dessas c?lulas malignas, o aumento da DMV apresentou associa??o positiva com a express?o do FT. Os resultados apresentados corroboram os achados de Maciel et al (1) de forma mais concisa e quantitativa, enfatizando a import?ncia do FT na biologia do TW

Thesis (Ph. D.)--University of Virginia, 2008. / Title from title page. Includes bibliographical references. Also available online through Digital Dissertations.

Made available in DSpace on 2013-08-07T19:04:23Z (GMT). No. of bitstreams: 1 000401330-Texto+Completo-0.pdf: 5353673 bytes, checksum: 3c1d547acc29764200b6affc9d492d2d (MD5) Previous issue date: 2007 / Wilms tumor is the most common solid renal malignancy in childhood. Even among patients with favorable histology and staging, some recur and eventually die from the disease. Novel prognostic factors could be especially useful in the management of these children. Tissue factor (TF), a protein linked to the extrinsic coagulation pathway, is highly expressed in various tumors, and has been associated to the development of metastases and to a poor prognosis. Our study describes, for the first time, the expression of TF in paraffin-fixed specimens of Willms tumors from 41 patients treated at Hospital São Lucas da PUCRS and Hospital da Criança Conceição, Porto Alegre. The immunohistochemical expression of TF was compared to microvascular density (MVD) and to other established prognostic criteria, such as age, staging, histology, tumor recurrence, overall and cancer-specific mortality. Increased TF expression was correlated to a higher risk of tumor recurrence and death. However, there was no significant correlation between TF expression and other established prognostic factors. Likewise, TF expression was not correlated to an increased MVD. In multivariate analysis TF expression remain as a independent prognostic factor to a higher risk of death. / O Tumor de Wilms (TW) é o tumor sólido renal mais comum na criança. Apesar do bom prognóstico na maioria dos casos, muitos pacientes com doença de histologia favorável apresentam recidiva e evoluem para óbito. Tem-se buscado na biologia molecular a identificação de fatores de prognóstico mais efetivos para estas crianças. O fator tecidual (FT), uma proteína de membrana celular ligada ao desencadeamento da cascata da coagulação parece ser fundamental para a progressão de neoplasias malignas através da ativação do processo de angiogênese. A expressão do FT foi associada ao desenvolvimento de metástases e a um pior prognóstico em vários tipos tumorais. Descrevemos pela primeira vez a expressão do FT em espécimes fixados em parafina de tumores de Wilms obtidos de 41 pacientes operados no Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul e no Hospital da Criança Conceição de Porto Alegre e comparamos a intensidade da sua expressão com a densidade microvascular (DMV), critérios de prognóstico estabelecidos (idade, estagiamento e histologia), recidivas tumorais e sobrevida geral. Encontramos correlação positiva entre a expressão do FT e a recidiva dos tumores e entre a expressão do FT e o óbito. Não encontramos correlação significativa entre a expressão de FT e os outros fatores de prognóstico estabelecidos, bem como com a DMV. Na análise multivariada o FT permanece como um fator independente de prognóstico para uma maior mortalidade.

Nephroblastoma is the most prevalent pediatric kidney tumor, which occurs primarily in younger children with the average age at diagnosis of 42,5 months for girls and 36,5 months for boys. Even though its treatment is currently very succesful and the overall survival rate reaches over 90 %, there are still more things to be discovered and improved. An important role for the right choice of treatment plays not only the histology of tumor, but also the chromosomal changes present at tumor. Some of them (for example 1q gain, simultaneous deletion of 1p and 16q, TP53 deletion) were confirmed as negative prognostic markers because they are associated with an increased risk of relapse or with anaplastic type of nephroblastoma that is included in a high risk group. These changes are therefore used together with the tumor histology for stratification of nephroblastomas. Some of these changes were found in a heterogeneous state (only in a part of the cells) in nephroblastoma, which also complicates the treatment of the patient and which cannot be solved when only one sample is taken from the tumor. In this work we concentrated on the detection of chromosomal changes present in nephroblastomas of 44 patients and their associations with clinical data. We have proved some of the known associations (22q...

El siguiente trabajo propone un análisis del diario íntimo de Teresa Wilms Montt, escrito entre 1912 y 1921. A partir de un marco teórico psicoanalítico y desde una perspectiva de género, se buscó investigar la configuración del yo femenino en la escritura del diario, así como los rasgos y conflictos psicológicos expuestos en el relato.

Wilms tumör (WT) är en malign snabbväxande tumör och den vanligaste solida buktumören hos barn under sex år. En kombination av operation, cytostatika och strålbehandling har lett till att 90 % av barnen idag blir helt botade. Enligt ett enhetligt europeiskt morfologiskt klassifikationssystem och behandlingsprotokoll behandlas alla barnpatienter med WT med cytostatika pre-operativt innan nefrektomi. Den histologiska tumörtypen, klassad efter operation, är helt avgörande för vidarebehandling av WT. Tumören består av tre celltyper, stromala epiteliala och blastemala, där de blastemala har en stor likhet med mesenkymala celler i njuren hos embryot. Tumörer med mer än 2/3 blastem klassificeras som högrisktumörer som följs upp med ytterligare, extra intensiv kemoterapi. I dagsläget görs en histologisk bedömning av tumörens riskgrupp endast på hematoxylin-eosin färgning. Proteinet SIX1 har nyligen rapporterats fungera som lämplig biomarkör för blastem. Med hjälp av immunohistokemi undersöktes i detta arbete om SIX1-färgning på blastem kan tillämpas kliniskt för säkrare riskbedömning av WT. Efter omfattande utvecklingsarbete med testning av olika varianter av förbehandling och detektionsmetod kunde ett fullgott protokoll för kliniskt bruk utformas. Detta kommer nu att implementeras inom klinisk patologi i Skåne. / Wilms tumor (WT) is a malign fast growing tumor and the most common solid abdominal tumor amongst children under the age of 6. A combination of surgery, chemotherapy and radiotherapy has led to a 90 % cured rate among children affected by WT. According to a uniform European morphological classification system and treatment protocol, all WTs receive pre-operative chemotherapy prior to nephrectomy. Histological tumor type, determined after surgery, is crucial for further treatment of WT. The tumor consists of three cell types: stromal elements, epithelial elements and blastema, of which the blastema has a great similarity to embryonic mesenchymal cells. Tumors that consist of more than 2/3 blastema are classified as high risk tumors, recieving additional intensive chemotherapy. Today, an assesment of WT histology is performed on hematoxylin-eosin stained specimens only. Recently, the SIX1 protein has been reported to function as a suitable biomarker for blastema. Using immunohistochemistry, it was investigated if SIX1 detection could be applied clinically for classification of WT. After several modifications of pre-treatment and primary antibody detection methodology, a clinically robust immunohistochemical staining protocol was finally developed. This will now be implemented in the clinic.

Made available in DSpace on 2015-04-14T13:34:29Z (GMT). No. of bitstreams: 1 401330.pdf: 5353673 bytes, checksum: 3c1d547acc29764200b6affc9d492d2d (MD5) Previous issue date: 2008-01-18 / O Tumor de Wilms (TW) ? o tumor s?lido renal mais comum na crian?a. Apesar do bom progn?stico na maioria dos casos, muitos pacientes com doen?a de histologia favor?vel apresentam recidiva e evoluem para ?bito. Tem-se buscado na biologia molecular a identifica??o de fatores de progn?stico mais efetivos para estas crian?as. O fator tecidual (FT), uma prote?na de membrana celular ligada ao desencadeamento da cascata da coagula??o parece ser fundamental para a progress?o de neoplasias malignas atrav?s da ativa??o do processo de angiog?nese. A express?o do FT foi associada ao desenvolvimento de met?stases e a um pior progn?stico em v?rios tipos tumorais. Descrevemos pela primeira vez a express?o do FT em esp?cimes fixados em parafina de tumores de Wilms obtidos de 41 pacientes operados no Hospital S?o Lucas da Pontif?cia Universidade Cat?lica do Rio Grande do Sul e no Hospital da Crian?a Concei??o de Porto Alegre e comparamos a intensidade da sua express?o com a densidade microvascular (DMV), crit?rios de progn?stico estabelecidos (idade, estagiamento e histologia), recidivas tumorais e sobrevida geral. Encontramos correla??o positiva entre a express?o do FT e a recidiva dos tumores e entre a express?o do FT e o ?bito. N?o encontramos correla??o significativa entre a express?o de FT e os outros fatores de progn?stico estabelecidos, bem como com a DMV. Na an?lise multivariada o FT permanece como um fator independente de progn?stico para uma maior mortalidade.

Tesis para optar al grado de Doctor en Literatura Hispanoamericana y Chilena

Informe de Seminario para optar al grado de Licenciado en Lengua y Literatura Hispánica mención Literatura / Autor no autoriza el acceso a texto completo de su documento. / El presente informe aborda la vida y obra de Teresa Wilms consignada en los textos recopilatorios a cargo de Ruth González-Vergara, con el propósito de reflexionar en torno a la relación que existe entre la escritura autobiográfica de Wilms y el contexto histórico y “personal” que rodean su obra autobiográfica y literaria, además de caracterizar el sujeto femenino que se constituye en la escritura de los diarios y cuáles son los recursos utilizados. La aproximación teórico-crítica que se hará de los textos contempla, por un lado, la lectura de los diarios de Teresa Wilms con características particulares del género autobiográfico; la autobiografía y el diario íntimo, además, considera las reflexiones previas realizadas en torno a la obra y vida de Teresa Wilms por diversos autores. A lo largo de la revisión bibliográfica y el análisis de los diarios encontramos que éste tipo de escritura se constituye como una respuesta al contexto que circunda a la autora y su obra, con lo que los diarios se convierten en “obras abiertas” que dialogan, directa e indirectamente con el entorno. Palabras Clave: Teresa Wilms Montt, escritura autobiográfica, diario íntimo, espacio público/ espacio privado, rol de la mujer.

La tumeur de Wilms (TW) est un cancer du rein retrouvé principalement chez les enfants âgés de 2 à 4 ans. Elle représente 90% des cancers pédiatriques du rein. Le taux de survie des TW est supérieur à 90%. Ce dernier est rendu possible grâce à une stratification des patients en fonction du risque de récidive. Les TW sont classées dans différents groupes de risque selon le stade, l’histologie, la taille de la tumeur et la perte d’hétérozygotie aux loci 1p et 16q. Deux régions sont importantes dans la génétique des TW, WT1 et WT2. WT1 est un gène qui code pour un facteur de transcription important dans différentes phases du développement rénal. Des anomalies de WT1 sont retrouvées dans certains syndromes humains tels que WAGR et Denys-Drash qui sont associés à l’émergence de TW. WT2 est un locus présent dans la région chromosomique 11p15 où une perte d'hétérozygotie conduit à une disomie uniparentale. Ceci entraîne un risque accru de TW dû à une surexpression de IGF2 qui est liée à la prolifération d’organes et de membres. Malgré ce portrait génétique, il n’existe pas de sous-groupes moléculaires qui permettent une classification des TW comme on observe chez d’autres cancers de l’enfant, notamment la leucémie. Nous proposons de déterminer une stratification de sous-groupes groupes moléculaire à l’aide d’une signature moléculaire basée sur des profils d’expression qui améliorait la classification des TW dans leurs groupes de risque adéquat. Pour vérifier cette hypothèse, nous avons analysé le transcriptome d’une cohorte de 130 patients atteint d’une TW. Grâce à un regroupement hiérarchique du profil d’expression des échantillons, nous avons identifié deux sous-groupes potentiels de TW. Un de ces sous-groupes est défini par une sous-expression de WT1 et une surexpression de gènes du début du développement musculaire chez les enfants et montrerait un risque plus fort de rechute. Ces résultats montrent que des outils de regroupement basés sur une signature moléculaire permettraient d’identifier des sous-groupes moléculaires chez les TW. / Wilms' tumor (TW) is a kidney cancer found mainly in children aged from 2 to 4 years old. It represents 90% of pediatric kidney cancers. The TW survival rate is over 90%. The latter is made possible by stratifying patients according to the risk of relapse. TW are classified into different risk groups according to stage, histology, tumor size and more recently the loss of heterozygosity at loci 1p and 16q. Two regions are important in the genetics of WT, WT1 and WT2. WT1 is a gene that encodes an important transcription factor in different phases of renal development. WT1 abnormalities are found in some human syndromes such as WAGR and Denys-Drash which are associated with the emergence of TW. WT2 is a locus present in the chromosomal region 11p15 where a loss of heterozygosity leads to a uniparental disomy. This leads to an increased risk of WT due to an overexpression of IGF2 which is linked to the proliferation of organs and members. Despite this genetic portrait, there are no molecular subgroups which allow classification of TW as observed in other childhood cancers, including leukemia. We propose to determine a stratification of WT using a molecular signature based on expression profiles in their proper risk group. To test this hypothesis, we analyzed the transcriptome of a cohort of 130 WT patients. The hierarchical clustering of the of the sample’s expressions profiles identified two potential WT subgroups. One of these subgroups can be described by a lower expression of WT1 and overexpression of genes for early muscle development in children and show a higher risk of relapse. These results show that clustering tools based on a molecular signature could allow treatment adjustment (i.e. precision medicine) and thus increase the survival rate.