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The study was approved by Ethics Committee of La Paz University Hospital (PI-2295). All animal experiments were conducted in accordance with the European Directive 2010\/63\/EU on the protection of animals used for scientific purposes and with Spanish legislation (Royal Decree 53\/2013). All procedures were reviewed and approved by the Spanish National Cancer Research Centre (CNIO) Animal Care and Use Committee, the Ethics Committee of the Instituto de Salud Carlos III (ISCIII), and the Comunidad de Madrid (PROEX 258.7\/22). 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