Efeitos da finasterida sobre culturas de células epiteliais prostáticas normais e tumorais em diferentes sistemas in vitro
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Data
2013-02-25
Autores
Moroz, Andrei [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
O câncer de próstata (CaP) é importante causa de morte no mundo. Além do óbvio impacto na vida pessoal do paciente e na sua família, no Brasil esta doença gera custos altíssimos para o Sistema Único de Saúde (SUS), desde o diagnóstico até o óbito. As terapias disponíveis, além de causarem complicações e efeitos colaterais indesejáveis, não proporcionam sobrevida alta ao paciente. Além disso, os casos de cura são restritos aos diagnosticados precocemente, e com intervenção rápida, antes que o tumor se torne resistente à castração química. Neste sentido, estratégias preventivas são desejáveis para a diminuição da incidência e óbitos e, dentre elas, o uso da finasterida, um fármaco inibitório da enzima 5-α-redutase, foi proposto como potencial agente quimiopreventivo após estudo conduzido pelo Prostate Cancer Prevention Trial, que demonstrou significante diminuição na incidência de CaP no grupo de pacientes tratados, em comparação ao grupo controle. No entanto, mesmo com resultados promissores, foi detectado aumento, também significante, do número de casos de cânceres mais agressivos (alto grau) no grupo de pacientes que recebeu finasterida, em comparação aos pacientes do grupo controle. Após intenso debate entre urologistas, biologistas e cancerologistas, ainda não há consenso sobre a natureza artefatual ou de real indução de cânceres mais agressivos pela finasterida. O órgão regulatório americano Food and Drugs Administration (FDA) declarou que o aumento dos casos agressivos pela finasterida não deve ser negligenciado, e recentemente proibiu o uso deste fármaco como quimiopreventivo para o CaP. Uma vez que casos agressivos de câncer estão comumente relacionados à superexpressão de enzimas...
Prostate cancer (PCa) is an important death cause in Brazil and other countries. Besides the obvious impact at patient’s life, and their relatives, this disease consumes exorbitant resources from the Sistema Único de Saúde (SUS), from diagnosis to death. The available therapies not only cause undesirable complications and side effects, but also are inefficient at providing good survival expectancies for those affected. Moreover, the cure is only possible when the tumors are readily found and when the intervention is fast enough to prevent that the tumor become castration-resistant. In this sense, preventive strategies are desirable in order to lower incidence and death, and amongst them, finasteride (Fin) treatment, an inhibitor of the 5-alpha reductase enzyme, was proposed as a potential chemopreventive agent after the study conducted by the Prostate Cancer Prevention Trial reported a significant lower incidence of PCa cases on Fin-treated patients, when compared to control patients. However, even though these results were promising, this study also reported a significant increase on more aggressive, high-grade PCa, amongst Fin-treated patients, compared to those not exposed to Fin. After an intense debate about factual or artifactual Fin-induced high-grade PCa cases, between urologists, biologists and oncologists, there are still no decisive conclusions on this matter. The regulatory USA organ, Food and Drugs Administration (FDA), has recently declared that the higher incidence of a more serious form of PCa at the Fin-treated patients must not be neglected, and prohibited its use as a chemopreventive agent. Given that the aggressive cancer cases are commonly associated with the super-expression of matrix metalloproteinases (MMPs) enzymes, with consequently higher invasion and migration potential of tumor... (Complete abstract click electronic access below)
Prostate cancer (PCa) is an important death cause in Brazil and other countries. Besides the obvious impact at patient’s life, and their relatives, this disease consumes exorbitant resources from the Sistema Único de Saúde (SUS), from diagnosis to death. The available therapies not only cause undesirable complications and side effects, but also are inefficient at providing good survival expectancies for those affected. Moreover, the cure is only possible when the tumors are readily found and when the intervention is fast enough to prevent that the tumor become castration-resistant. In this sense, preventive strategies are desirable in order to lower incidence and death, and amongst them, finasteride (Fin) treatment, an inhibitor of the 5-alpha reductase enzyme, was proposed as a potential chemopreventive agent after the study conducted by the Prostate Cancer Prevention Trial reported a significant lower incidence of PCa cases on Fin-treated patients, when compared to control patients. However, even though these results were promising, this study also reported a significant increase on more aggressive, high-grade PCa, amongst Fin-treated patients, compared to those not exposed to Fin. After an intense debate about factual or artifactual Fin-induced high-grade PCa cases, between urologists, biologists and oncologists, there are still no decisive conclusions on this matter. The regulatory USA organ, Food and Drugs Administration (FDA), has recently declared that the higher incidence of a more serious form of PCa at the Fin-treated patients must not be neglected, and prohibited its use as a chemopreventive agent. Given that the aggressive cancer cases are commonly associated with the super-expression of matrix metalloproteinases (MMPs) enzymes, with consequently higher invasion and migration potential of tumor... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Próstata - Câncer, Celulas epiteliais - Cultura e meios de cultura, Câncer - Quimioterapia, Medicamentos - Efeitos fisiológicos, Cancer - Chemotherapy, Prostate - Cancer
Como citar
MOROZ, Andrei. Efeitos da finasterida sobre culturas de células epiteliais prostáticas normais e tumorais em diferentes sistemas in vitro. 2013. 91 f. Tese (doutorado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Instituto de Biociências de Botucatu, 2013.