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Título:	Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model
Autor/a:	Laquente, Berta; Lacasa Salavert, Cristina; Ginestà, Mireia M.; Casanovas i Casanovas, Oriol; Figueras i Amat, Agnès; Galán, Maica; García Ribas, Ignacio; Germà Lluch, José Ramón; Capellá, G. (Gabriel); Viñals Canals, Francesc
Abstract:	Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action toward proliferative cells. In this article, we aim to investigate the potential antitumor and antiangiogenic effect of gemcitabine following a metronomic schedule that involves the regular administration of cytotoxic drugs at doses lower than standard treatment. In vitro results showed that human endothelial cells are more sensitive to gemcitabine (IC50 3 nmol/L) than pancreatic tumor cells (IC50 20 nmol/L). For in vivo studies, we used an orthotopic implantation model of human pancreatic carcinoma in nude mice. Gemcitabine was administered i.p. following a low-dose schedule (1 mg/kg/d for a month) and compared with the conventional schedule (100 mg/kg days 0, 3, 6, and 9 postimplantation). Metronomic treatment effect on established tumor was equivalent to standard administration. The measure of CD31 endothelial marked area allowed us to show an in vivo antiangiogenic effect of this drug that was further enhanced by using metronomic administration. This effect correlated with an induction of thrombospondin-1, a natural inhibitor of angiogenesis. Our results allow us to hypothesize that, in addition to a direct antiproliferative or cytotoxic antiendothelial cell effect, a secondary effect involving thrombospondin-1 induction might provide an explanation for the specificity of the effects of metronomic gemcitabine treatment.
Materia(s):	-Medicaments antineoplàstics -Quimioteràpia del càncer -Càncer de pàncrees -Angiogènesi -Antineoplastic agents -Cancer chemotherapy -Pancreas cancer -Neovascularization
Derechos:	(c) American Association for Cancer Research, 2008
Tipo de documento:	Artículo Artículo - Versión aceptada
Editor:	American Association for Cancer Research
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