Prostatic Angiogenic Responses In Late Life: Antiangiogenic Therapy Influences And Relation With The Glandular Microenvironment In The Transgenic Adenocarcinoma Of Mouse Prostate (tramp) Model

dc.creatorMontico F.
dc.creatorKido L.A.
dc.creatorHetzl A.C.
dc.creatorCagnon V.H.A.
dc.date2014
dc.date2015-06-25T18:03:02Z
dc.date2015-11-26T15:05:18Z
dc.date2015-06-25T18:03:02Z
dc.date2015-11-26T15:05:18Z
dc.date.accessioned2018-03-28T22:16:05Z
dc.date.available2018-03-28T22:16:05Z
dc.identifier
dc.identifierProstate. John Wiley And Sons Inc., v. , n. , p. - , 2014.
dc.identifier2704137
dc.identifier10.1002/pros.22934
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-84920019048&partnerID=40&md5=6a8e9d6795129566831fdca249415864
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/87967
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/87967
dc.identifier2-s2.0-84920019048
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1257048
dc.descriptionBACKGROUND: Aging is considered one of the main predisposing factors for the development of prostate malignancies. Angiogenesis is fundamental for tumor growth and its inhibition represents a promising therapeutic approach in cancer treatment. Thus, we sought to determine angiogenic responses and the effects of antiangiogenic therapy in the mouse prostate during late life, comparing these findings with the prostatic microenvironment in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model. METHODS: Male mice (52 week-old FVB) were submitted to treatments with SU5416 (6mg/kg; i.p.) and/or TNP-470 (15mg/kg;s.c.). Finasteride was administered (20mg/kg;s.c.), alone or in association to both inhibitors. The dorsolateral prostate was collected for VEGF, HIF-1α, FGF-2 and endostatin immunohistochemical and Western Blotting analyses and for microvessel density (MVD) count. RESULTS: Senescence led to increased MVD and VEGF, HIF-1α and FGF-2 protein levels in the prostatic microenvironment, similarly to what was observed in TRAMP mice prostate. The angiogenic process was impaired in all the treated groups, demonstrating significantly decreased MVD. Antiangiogenic and/or finasteride treatments resulted in decreased VEGF and HIF-1α levels, especially following TNP-470 administration, either alone or associated to SU5416. The combination of these agents resulted in increased endostatin levels, regardless of the presence of finasteride. CONCLUSIONS: Prostatic angiogenesis stimulation during senescence favored the development of neoplastic lesions, considering the pro-angiogenic microenvironment as a common aspect also observed during cancer progression in TRAMP mice. The combined antiangiogenic therapy was more efficient, leading to enhanced imbalance towards angiogenic inhibition in the organ. Finally, finasteride administration might secondarily upregulate the expression of pro-angiogenic factors, pointing to the harmful effects of this therapy.
dc.description
dc.description
dc.description
dc.description
dc.languageen
dc.publisherJohn Wiley and Sons Inc.
dc.relationProstate
dc.rightsfechado
dc.sourceScopus
dc.titleProstatic Angiogenic Responses In Late Life: Antiangiogenic Therapy Influences And Relation With The Glandular Microenvironment In The Transgenic Adenocarcinoma Of Mouse Prostate (tramp) Model
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución