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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
Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/1714 |
Date | 15 March 2011 |
Creators | Moreira, Carla Costa |
Contributors | Silva, Vin?cius Duval da |
Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, BR, Faculdade de Medicina |
Source Sets | IBICT Brazilian ETDs |
Language | Portuguese |
Detected Language | English |
Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
Format | application/pdf |
Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
Rights | info:eu-repo/semantics/openAccess |
Relation | 7620745074616285884, 500, 600, -8624664729441623247 |
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