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An?lise da express?o do mRNA das enzimas timidina fosforilase e uridina fosforilase 1 e 2 e dos fatores de transcri??o PDEF e ETV4 em tumores de pr?stata e de rim

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Previous issue date: 2014-08-25 / Prostate cancer is the most important urological tumor and the second most common in men. The incidence and mortality of this multifactorial disease are varied and take into account behavioral factors and genetic predisposition. The main predisposing factors are age, race and family history. Among the various histological subtypes, the acinar adenocarcinoma is the most common. The classification of this tumor, from transrectal ultrasonography and biopsy needle, is made for degrees of Gleason score and TNM classification that provides for tumor staging. The prostatic carcinoma has a propensity to metastasize and is regulated by various molecular signaling pathways through genes, proteins, enzymes, receptors and transcription factors. The RCC is the third most common urological tumor. The wide variation in incidence correlates with the geographical area. Risk factors can be various as smoking, genetic diseases and genetic alterations. The vast majority of cases occur in adults and in the renal parenchyma, and comprise five histological subtypes, the clear and sporadic cells being the most common. The histological differentiation is made by Fuhrman grade and staging by TNM classification. As the clinical manifestations are varied, most patients are diagnosed incidentally and by ultrasonography. The enzymes thymidine phosphorylase and uridine phosphorylase 1 and 2 as well as the transcription factors PDEF and ETV4 are reported as components of pathways leading to tumorigenesis and / or metastasis. The objective of this work is to analyze these enzymes and transcription factors and their correlation with clinical and pathological variables in prostate and kidney cancers as well as in bening tissue, by RT-PCR in real time. In prostate cancer, the geometric mean of the relative expression of transcription factors PDEF and ETV were greater in the tumor than in the benign tissues These factors also had a significant correlation between them in tumor tissue and benign tissue. The geometric mean of relative expression of the enzyme thymidine phosphorylase and uridine phosphorylase 1 strongly and significantly correlated between them in benign and in malignant prostate samples. The geometric mean of relative expression of thymidine phosphorylase also correlated moderately and significantly with the ETV4 in benign tissues. The geometric mean of relative expression of uridine phosphorylase in tumor T3 was significantly lower than in T1 and T2 prostate tumors. Kidney carcinoma TNM Classification strongly and significantly correlated with the relative expression of the enzyme thymidine phosphorylase and negatively correlated very strong and significantly with the enzyme uridine phosphorylase. The relative expression of the transcription factor ETV4 correlated negatively and significantly stronger with the TNM classification, and correlated with strength and significance with the relative expression of uridine phosphorylase in tumor tissues of the kidney. / O c?ncer de pr?stata ? o mais importante tumor urol?gico e o segundo mais frequente no homem. As taxas de incid?ncia e de mortalidade desta doen?a multifatorial s?o muito variadas e leva em conta fatores comportamentais e pr?-disposi??o gen?tica. Os principais fatores predisponentes s?o idade avan?ada, ra?a e hist?ria familiar. Dentre os v?rios subtipos histol?gicos, o adenocarcinoma acinar ? o mais frequente. A classifica??o deste tumor, a partir da ultra-sonografia transretal com bi?psia por agulha, ? feita pelos graus de escore de Gleason e pela Classifica??o TNM que fornece o estadiamento do tumor. O carcinoma de pr?stata, al?m de ter grande propens?o em formar met?stases, ? regulado por v?rias vias moleculares de sinaliza??o por meio de genes, prote?nas, enzimas, receptores e fatores de transcri??o. O carcinoma de c?lulas renais ? o terceiro mais comum tumor urol?gico. A grande varia??o na taxa de incid?ncia se correlaciona com a ?rea geogr?fica. Os fatores de risco podem ser v?rios como tabagismo, doen?as gen?ticas e altera??es g?nicas. A grande maioria dos casos ocorre em adultos no par?nquima renal e, al?m de compreender cinco subtipos histol?gicos, o de c?lulas claras e espor?dico ? o mais frequente. A diferencia??o histol?gica ? feita pelo grau de Fuhrman e o estadiamento pela Classifica??o TNM. Como as manifesta??es cl?nicas s?o variadas, a maioria dos pacientes s?o diagnosticados incidentalmente e por ultra-sonografia. As enzimas timidina fosforilase e uridina fosforilase 1 e 2, bem como os fatores de transcri??o PDEF e ETV4, s?o relatados como componentes das vias que levam ? tumorig?nese e/ou a metastiza??o. O objetivo deste trabalho ? analizar estas enzimas e fatores de transcri??o, correlacionando-as com vari?veis cl?nicas e patol?gicas nos tumores de pr?stata e de rim, bem como nos tecidos adjacentes a estes tumores, pela t?cnica de RT-PCR em tempo real. No c?ncer de pr?stata, a m?dia geom?trica da express?o relativa dos fatores de transcri??o PDEF e ETV4 entre os tecidos benignos e tumorais, apresentaram correla??o significativa com uma maior express?o relativa no tumor quando comparado ao seu benigno. Estes fatores tamb?m apresentaram uma correla??o significativa entre eles no tecido tumoral e no tecido benigno. As m?dias geom?tricas da express?o relativa das enzimas timidina fosforilase e uridina fosforilase 1 se correlacionaram fortemente e significativamente entre os tecidos benignos e tumorais da pr?stata. A m?dia geom?trica da express?o relativa da timidina fosforilase tamb?m se correlacionou de forma moderada e significativa com a do ETV4, entre os tecidos benignos. A m?dia geom?trica da express?o relativa da uridina fosforilase nos tumores T3 foi significativamente menor do que nos tumores T1 e T2 da pr?stata. No carcinoma de rim a Classifica??o TNM se correlacionou fortemente e significativamente com a express?o relativa da enzima timidina fosforilase, e se correlacionou de forma negativa, muito forte e significativamente com a enzima uridina fosforilase. A express?o relativa do fator de transcri??o ETV4 se correlacionou de forma negativa, forte e significativamente com a Classifica??o TNM, e se correlacionou de forma forte e significativamente com a express?o relativa de uridina fosforilase nos tecidos tumorais de rim.

Identiferoai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/1788
Date25 August 2014
CreatorsCavazzola, Luciane Rostirola
ContributorsCarvalhal, Gustavo Franco
PublisherPontif?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 SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis
Formatapplication/pdf
Sourcereponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS
Rightsinfo:eu-repo/semantics/openAccess
Relation7620745074616285884, 500, 600, -8624664729441623247

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