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dc.contributor.authorHernandez-Agudo, Elena 
dc.contributor.authorMondejar, Tamara
dc.contributor.authorSoto-Montenegro, Maria Luisa
dc.contributor.authorMegias Vazquez, Diego 
dc.contributor.authorMouron, Silvana Andrea 
dc.contributor.authorSanchez, Jesus
dc.contributor.authorHidalgo, Manuel
dc.contributor.authorLopez-Casas, Pedro Pablo
dc.contributor.authorMulero Francisca, Francisca 
dc.contributor.authorDesco, Manuel 
dc.contributor.authorQuintela Fandino, Miguel Angel 
dc.date.accessioned2019-10-30T11:48:43Z
dc.date.available2019-10-30T11:48:43Z
dc.date.issued2016-05
dc.identifier.citationMol Oncol. 2016;10(5):704-18.es_ES
dc.identifier.issn15747891es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8537
dc.descriptionThis work was supported by the following sources: Fondo de Investigacion Sanitaria (Ministry of Health, Spain; numbers FIS PI10/0288, FIS PI13/00430, FIS PI 11/00616, CPII14/00005 and FIS PI14/00860; the first two awarded to MQF and the last three to MD), and "Fondo Europeo de Desarrollo Regional (FEDER) - Una manera de hacer Europa". MQF is a recipient of a 2010 Beca-Retorno from the AECC Scientific Foundation. Rosae Foundation and AVON Espana S.A.U. contributed to this work with unrestricted donations. Dovitinib was kindly provided by Novartis.es_ES
dc.description.abstractBACKGROUND: Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with (18)F-misonidazole ([18F]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib. METHODS: Two patient-derived pancreas xenografts (PDXs; Panc215 and Panc286) and the spontaneous breast cancer model MMTV-PyMT were used. Animals were treated during 1 week of WoO treatment with vehicle or dovitinib, preceded and followed by [18F]-FMISO-PET, [18F]-FDG-PET, and histologic assessment (dextran extravasation, hypoxia and microvessel staining, and necrosis, cleaved caspase-3 and Ki67 measurements). After WoO treatment, gemcitabine (pancreas)/adriamycin (breast) or vehicle was added and animals were treated until the humane endpoint. Tumor growth inhibition (TGI) and survival were the parameters studied. RESULTS: [18F]-FMISO SUV did not change after dovitinib-WoO treatment compared to vehicle-WoO (0.54 vs. 0.6) treatment in Panc215, but it decreased significantly in Panc286 (0.58 vs. 1.18; P < 0.05). In parallel, 10-KDa perivascular dextran extravasation was not reduced with dovitinib or vehicle-WoO treatment in Panc215, but it was reduced in Panc286. Whereas the addition of dovitinib to gemcitabine was indifferent in Panc215, it increased TGI in Panc286 (TGI switched from -59% to +49%). [18F]-FMISO SUV changes were accompanied by an almost 100% increase in interstitial gemcitabine delivery (665-1260 ng/mL). The results were validated in the PyMT model. CONCLUSIONS: [18F]-FMISO accurately monitored vascular re-normalization and improved interstitial chemotherapy delivery.es_ES
dc.description.sponsorshipThis work was supported by the following sources: Fondo de Investigacion Sanitaria (Ministry of Health, Spain; numbers FIS PI10/0288, FIS PI13/00430, FIS PI 11/00616, CPII14/00005 and FIS PI14/00860; the first two awarded to MQF and the last three to MD), and "Fondo Europeo de Desarrollo Regional (FEDER) - Una manera de hacer Europa". MQF is a recipient of a 2010 Beca-Retorno from the AECC Scientific Foundation. Rosae Foundation and AVON Espana S.A.U. contributed to this work with unrestricted donations. Dovitinib was kindly provided by Novartis.es_ES
dc.language.isoenges_ES
dc.publisherWiley es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject(18)F-misonidazole-PETes_ES
dc.subjectAntiangiogenicses_ES
dc.subjectBiomarkeres_ES
dc.subjectBreast canceres_ES
dc.subjectPancreatic canceres_ES
dc.subjectVascular normalizationes_ES
dc.subject.meshAngiogenesis Inhibitors es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntimetabolites, Antineoplastic es_ES
dc.subject.meshBenzimidazoles es_ES
dc.subject.meshBreast es_ES
dc.subject.meshBreast Neoplasms es_ES
dc.subject.meshCell Hypoxia es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshDeoxycytidine es_ES
dc.subject.meshFemale es_ES
dc.subject.meshFluorine Radioisotopes es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Nude es_ES
dc.subject.meshMisonidazole es_ES
dc.subject.meshNeovascularization, Pathologices_ES
dc.subject.meshPancreas es_ES
dc.subject.meshPancreatic Neoplasms es_ES
dc.subject.meshPositron-Emission Tomography es_ES
dc.subject.meshQuinolones es_ES
dc.titleMonitoring vascular normalization induced by antiangiogenic treatment with (18)F-fluoromisonidazole-PETes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID26778791es_ES
dc.format.volume10es_ES
dc.format.number5es_ES
dc.format.page704-18es_ES
dc.identifier.doi10.1016/j.molonc.2015.12.011es_ES
dc.contributor.funderUnión Europea 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderMinisterio de Sanidad y Consumo (España) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1878-0261es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.molonc.2015.12.011es_ES
dc.identifier.journalMolecular oncologyes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Investigación Clínica de Cáncer de Mamaes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/PI10/0288es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/PI13/00430es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/PI11/00616es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/CPII14/00005es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/PI14/00860es_ES
dc.rights.accessRightsopen accesses_ES


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