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dc.contributor.authorMuñoz Martínez, Raquel 
dc.contributor.authorHileeto, Denise
dc.contributor.authorCruz Muñoz, William
dc.contributor.authorWood, Geoffrey A.
dc.contributor.authorXu, Ping
dc.contributor.authorMan, Shan
dc.contributor.authorViloria Petit, Alicia
dc.contributor.authorKerbel, Robert S.
dc.date.accessioned2020-06-05T12:27:36Z
dc.date.available2020-06-05T12:27:36Z
dc.date.issued2019
dc.identifier.citationPLoS ONE, 2019, vol. 14, n. 9. 28 p.es
dc.identifier.issn1932-6203es
dc.identifier.urihttp://uvadoc.uva.es/handle/10324/40999
dc.descriptionProducción Científicaes
dc.description.abstractMetronomic chemotherapy using the 5-FU prodrug uracil-tegafur (UFT) and cyclophosphamide (CTX) was previously shown to only modestly delay primary tumor growth, but nevertheless markedly suppressed the development of micro-metastasis in an orthotopic breast cancer xenograft model, using the metastatic variant of the MDA-MB-231 cell line, 231/LM2-4. Furthermore, a remarkable prolongation of survival, with no toxicity, was observed in a model of postsurgical advanced metastatic disease. A question that has remained unanswered is the seemingly selective anti-metastatic mechanisms of action responsible for this treatment. We assessed the in vivo effect of metronomic UFT, CTX or their combination, on vascular density, collagen deposition and c-Met (cell mediators or modulators of tumor cell invasion or dissemination) via histochemistry/immunohistochemistry of primary tumor sections. We also assessed the effect of continuous exposure to low and non-toxic doses of active drug metabolites 5-fluorouracil (5-FU), 4-hydroperoxycyclophosphamide (4-HC) or their combination, on 231/LM2-4 cell invasiveness in vitro. In the in vivo studies, a significant reduction in vascular density and p-Met[Y1003] levels was associated with UFT+CTX treatment. All treatments reduced intratumoral collagen deposition. In the in vitro studies, a significant reduction of collagen IV invasion by all treatments was observed. The 3D structures formed by 231/LM2-4 on Matrigel showed a predominantly Mass phenotype under treated conditions and Stellate phenotype in untreated cultures. Taken together, the results suggest the low-dose metronomic chemotherapy regimens tested can suppress several mediators of tumor invasiveness highlighting a new perspective for the anti-metastatic efficacy of metronomic chemotherapy.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.publisherPLOSes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.classificationBreast canceres
dc.subject.classificationCáncer de mamaes
dc.subject.classificationChemotherapyes
dc.subject.classificationQuimioterapiaes
dc.subject.classificationUracil-tegafures
dc.subject.classificationTegafur-uraciloes
dc.subject.classificationCyclophosphamidees
dc.subject.classificationCiclofosfamidaes
dc.titleSuppressive impact of metronomic chemotherapy using UFT and/or cyclophosphamide on mediators of breast cancer dissemination and invasiones
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© 2019 PLOSes
dc.identifier.doi10.1371/journal.pone.0222580es
dc.relation.publisherversionhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222580es
dc.peerreviewedSIes
dc.description.projectCanadian Institutes of Health Research (grant 364411)es
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones


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