Meetronomic chemotherapy following the maximum tolerated dose is an effective anti-tumour therapy affecting angiogenesis, tumour dissemination and cancer stem cells

In this article, the effectiveness of a multi-targeted chemo-switch (C-S) schedule that combines metronomic chemotherapy (MET) after treatment with the maximum tolerated dose (MTD) is reported. This schedule was tested with gemcitabine in two distinct human pancreatic adenocarcinoma orthotopic model...

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Detalles Bibliográficos
Autores: Vives, Marta, Ginestà, Mireia M., Gracova, Kristina, Graupera i Garcia-Milà, Mariona, Casanovas i Casanovas, Oriol, Capellá, G. (Gabriel), Serrano Piñol, M. Teresa, Laquente, Berta, Viñals Canals, Francesc
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/120265
Acceso en línea:https://hdl.handle.net/2445/120265
Access Level:acceso abierto
Palabra clave:Quimioteràpia del càncer
Medicaments antineoplàstics
Angiogènesi
Cèl·lules mare
Cèl·lules canceroses
Cancer chemotherapy
Antineoplastic agents
Neovascularization
Stem cells
Cancer cells
Descripción
Sumario:In this article, the effectiveness of a multi-targeted chemo-switch (C-S) schedule that combines metronomic chemotherapy (MET) after treatment with the maximum tolerated dose (MTD) is reported. This schedule was tested with gemcitabine in two distinct human pancreatic adenocarcinoma orthotopic models and with cyclophosphamide in an orthotopic ovarian cancer model. In both models, the C-S schedule had the most favourable effect, achieving at least 80% tumour growth inhibition without increased toxicity. Moreover, in the pancreatic cancer model, although peritoneal metastases were observed in control and MTD groups, no dissemination was observed in the MET and C-S groups. C-S treatment caused a decrease in angiogenesis, and its effect on tumour growth was similar to that produced by the MTD followed by anti-angiogenic DC101 treatment. C-S treatment combined an increase in thrombospondin-1 expression with a decrease in the number of CD133+ cancer cells and triple-positive CD133+/CD44+/CD24+ cancer stem cells (CSCs). These findings confirm that the C-S schedule is a challenging clinical strategy with demonstrable inhibitory effects on tumour dissemination, angiogenesis and CSCs.