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dc.contributor.authorLópez-Valero, Israel
dc.contributor.authorSaiz-Ladera, Cristina
dc.contributor.authorTorres, Sofía
dc.contributor.authorHernández-Tiedra, Sonia
dc.contributor.authorGarcía-Taboada, Elena
dc.contributor.authorRodríguez-Fornés, Fátima
dc.contributor.authorBarba, Marina
dc.contributor.authorDávila, David
dc.contributor.authorSalvador-Tormo, Nélida
dc.contributor.authorGuzmán, Manuel
dc.contributor.authorSepúlveda, Juan M.
dc.contributor.authorSanchez-Gomez, Pilar 
dc.contributor.authorLorente, Mar
dc.contributor.authorVelasco, Guillermo
dc.identifier.citationBiochemical Pharmacology Volume 157, November 2018, Pages 266-274es_ES
dc.description.abstractGlioblastoma multiforme (GBM) is the most frequent and aggressive type of brain tumor due, at least in part, to its poor response to current anticancer treatments. These features could be explained, at least partially, by the presence within the tumor mass of a small population of cells termed Glioma Initiating Cells (GICs) that has been proposed to be responsible for the relapses occurring in this disease. Thus, the development of novel therapeutic approaches (and specifically those targeting the population of GICs) is urgently needed to improve the survival of the patients suffering this devastating disease. Previous observations by our group and others have shown that Δ9-Tetrahydrocannabinol (THC, the main active ingredient of marijuana) and other cannabinoids including cannabidiol (CBD) exert antitumoral actions in several animal models of cancer, including gliomas. We also found that the administration of THC (or of THC + CBD at a 1:1 ratio) in combination with temozolomide (TMZ), the benchmark agent for the treatment of GBM, synergistically reduces the growth of glioma xenografts. In this work we investigated the effect of the combination of TMZ and THC:CBD mixtures containing different ratios of the two cannabinoids in preclinical glioma models, including those derived from GICs. Our findings show that TMZ + THC:CBD combinations containing a higher proportion of CDB (but not TMZ + CBD alone) produce a similar antitumoral effect as the administration of TMZ together with THC and CBD at a 1:1 ratio in xenografts generated with glioma cell lines. In addition, we also found that the administration of TMZ + THC:CBD at a 1:1 ratio reduced the growth of orthotopic xenografts generated with GICs derived from GBM patients and enhanced the survival of the animals bearing these intracranial xenografts. Remarkably, the antitumoral effect observed in GICs-derived xenografts was stronger when TMZ was administered together with cannabinoid combinations containing a higher proportion of CBD. These findings support the notion that the administration of TMZ together with THC:CBD combinations - and specifically those containing a higher proportion of CBD - may be therapeutically explored to target the population of GICs in GBM.es_ES
dc.description.sponsorshipThis work has been funded by the PI15/00339 grant, integrated into the State Plan for R & D + I2013-2016 and funded by the Instituto de Salud Carlos III (ISCIII) (Spain) and the European Regional Development Fund (ERDF) and by grants from Spanish Ministry of Economy and Competitiveness (MINECO)/ISCIII and ERDF (PS09/01401; PI12/02248,to GV), GW Pharma Ltd. (UK), Comunidad de Madrid (Spain) (S2011/BMD-2308 to MG), Fundación Mutua Madrileña (Spain) (AP101042012 to GV), Fundació La Marató de TV3 (Spain) (201334031 to GV), Voices Against Brain Cancer (US), and donations by The Medical Cannabis Bike Tour Foundation (The Netherlands) and Jeff Ditchfield. Israel López-Valero was supported by a predoctoral P-FIS contract from Instituto de Salud Carlos III (ISCIII) and Cristina Sáiz was supported by a “Juan de la Cierva formación” contract of the Spanish Ministry of Economy and Competitiveness.es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectCombinational therapieses_ES
dc.subjectGlioma Initiating Cellses_ES
dc.subjectTumor xenograftses_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols es_ES
dc.subject.meshBrain Neoplasms es_ES
dc.subject.meshCannabidiol es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshDronabinol es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGlioblastoma es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice, Nude es_ES
dc.subject.meshNeoplastic Stem Cells es_ES
dc.subject.meshTemozolomide es_ES
dc.subject.meshTumor Cells, Culturedes_ES
dc.subject.meshXenograft Model Antitumor Assays es_ES
dc.titleTargeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomidees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderFundación Mutua Madrileñaes_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderGW Pharma Ltd. (UK)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderFundació La Marató de TV3es_ES
dc.contributor.funderVoices Against Brain Cancer (US)es_ES
dc.contributor.funderThe Medical Cannabis Bike Tour Foundation (The Netherlands)es_ES
dc.identifier.journalBiochemical Pharmacologyes_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional