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dc.contributor.authorCebulla, Jana
dc.contributor.authorHuuse-Røneid, Else Marie
dc.contributor.authorPettersen, Kristine
dc.contributor.authorvan der Veen, Anna
dc.contributor.authorKim, Eugene
dc.contributor.authorAndersen, Sonja
dc.contributor.authorPrestvik, Wenche S
dc.contributor.authorBofin, Anna M.
dc.contributor.authorPathak, Arvind P
dc.contributor.authorBjørkøy, Geir
dc.contributor.authorBathen, Tone Frost
dc.contributor.authorMoestue, Siver Andreas
dc.date.accessioned2016-08-31T08:15:30Z
dc.date.accessioned2016-09-06T10:48:10Z
dc.date.available2016-08-31T08:15:30Z
dc.date.available2016-09-06T10:48:10Z
dc.date.issued2015
dc.identifier.citationBritish Journal of Cancer 2015, 112(3):504-513nb_NO
dc.identifier.issn1532-1827
dc.identifier.urihttp://hdl.handle.net/11250/2404545
dc.description.abstractBackground: The phosphoinositide-3 kinase (PI3K) pathway is an attractive therapeutic target. However, difficulty in predicting therapeutic response limits the clinical implementation of PI3K inhibitors. This study evaluates the utility of clinically relevant magnetic resonance imaging (MRI) biomarkers for noninvasively assessing the in vivo response to the dual PI3K/mTOR inhibitor BEZ235 in two ovarian cancer models with differential PI3K pathway activity. Methods: The PI3K signalling activity of TOV-21G and TOV-112D human ovarian cancer cells was investigated in vitro. Cellular and vascular response of the xenografts to BEZ235 treatment (65 mg kg−1, 3 days) was assessed in vivo using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE)-MRI. Micro-computed tomography was performed to investigate changes in vascular morphology. Results: The TOV-21G cells showed higher PI3K signalling activity than TOV-112D cells in vitro and in vivo. Treated TOV-21G xenografts decreased in volume and DW-MRI revealed an increased water diffusivity that was not found in TOV-112D xenografts. Treatment-induced improvement in vascular functionality was detected with DCE-MRI in both models. Changes in vascular morphology were not found. Conclusions: Our results suggest that DW- and DCE-MRI can detect cellular and vascular response to PI3K/mTOR inhibition in vivo. However, only DW-MRI could discriminate between a strong and weak response to BEZ235.nb_NO
dc.language.isoengnb_NO
dc.publisherCancer Research UK - Nature Publishing Group: Open Access Hybrid Model Option Anb_NO
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subjectdiffusion weighted MRI; DCE-MRI; treatment monitoring; biomarker; PI3K inhibition; ADCnb_NO
dc.titleMRI Reveals the in Vivo Cellular and Vascular Response to BEZ235 in Ovarian Cancer Xenografts with Different PI3-Kinase Pathway Activitynb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.date.updated2016-08-31T08:15:30Z
dc.source.volume112nb_NO
dc.source.journalBritish Journal of Cancernb_NO
dc.source.issue3nb_NO
dc.identifier.doi10.1038/bjc.2014.628
dc.identifier.cristin1183726
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.description.localcodeFrom twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/nb_NO


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