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dc.contributor.authorBorgan, Eldrid
dc.contributor.authorLindholm, Evita Maria
dc.contributor.authorMoestue, Siver Andreas
dc.contributor.authorMælandsmo, Gunhild
dc.contributor.authorLingjærde, Ole Christian
dc.contributor.authorGribbestad, Ingrid S
dc.contributor.authorBørresen-Dale, Anne-Lise
dc.contributor.authorEngebråten, Olav
dc.contributor.authorSørlie, Therese
dc.date.accessioned2018-08-15T13:27:26Z
dc.date.available2018-08-15T13:27:26Z
dc.date.issued2012-10-23
dc.description.abstract<p>Antiangiogenic therapy with bevacizumab has shown varying results in breast cancer clinical trials. Identifying robust biomarkers for selecting patients who may benefit from such treatment and for monitoring response is important for the future use of bevacizumab.</p> <p>Two established xenograft models representing basal‐like and luminal‐like breast cancer were used to study bevacizumab treatment response on the metabolic and gene expression levels. Tumor samples were obtained from mice treated with bevacizumab, doxorubicin or a combination of the two drugs, and high resolution magic angle spinning magnetic resonance spectroscopy and gene expression microarray analysis was performed.</p> <p>Combination treatment with bevacizumab showed the strongest growth inhibiting effect in basal‐like tumors, and this was reflected by a significant change in the metabolomic and transcriptomic profiles. In the luminal‐like xenografts, addition of bevacizumab did not improve the effect of doxorubicin. On the global transcriptomic level, the largest gene expression changes were observed for the most efficient treatment in both models. Glycerophosphocholine showed opposite response in the treated xenografts compared with untreated controls; lower in basal‐like and higher in luminal‐like tumors. Comparing combination therapy with doxorubicin monotherapy in basal‐like xenografts, 14 genes showed significant differential expression, including very low density lipoprotein receptor (VLDLR) and hemoglobin, theta 1 (HBQ1). Bevacizumab‐treated tumors were associated with a more hypoxic phenotype, while no evidence was found for associations between bevacizumab treatment and vascular invasion or tumor grade.</p> <p>This study underlines the importance of characterizing biological differences between subtypes of breast cancer to identify personalized biomarkers for improved patient stratification and evaluation of response to therapy.</p>en_US
dc.description.sponsorshipThe South-Eastern Norway Regional Health Authority Monica Nordal memorial funden_US
dc.descriptionSource at <a href=https://doi.org/10.1016/j.molonc.2012.10.005> https://doi.org/10.1016/j.molonc.2012.10.005</a>. Accepted manuscript version, licensed <a href=http://creativecommons.org/licenses/by-nc-nd/4.0/> CC BY-NC-ND 4.0.</a>en_US
dc.identifier.citationBorgan, E., Lindholm, E.M., Moestue, S.A., Mælandsmo, G.M., Lingjærde, O.C., Gribbestad, I.S., ... Sørlie, T. (2013). Subtype-specific response to bevacizumab is reflected in the metabolome and transcriptome of breast cancer xenografts. Molecular Oncology, 7(1), 130-142. https://doi.org/10.1016/j.molonc.2012.10.005en_US
dc.identifier.cristinIDFRIDAID 963385
dc.identifier.doi10.1016/j.molonc.2012.10.005
dc.identifier.issn1574-7891
dc.identifier.issn1878-0261
dc.identifier.urihttps://hdl.handle.net/10037/13411
dc.language.isoengen_US
dc.publisherWiley Open Accessen_US
dc.relation.journalMolecular Oncology
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/KREFT/193375/Norway/Molecular and biological characterization of cancer metastases//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/KREFT/193387/Norway/Understanding Breast Cancer Genomics; Towards combined molecular profiles for better diagnosis and treatment//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/YFF/163027/Norway/Molecular portraits of breast cancer: Translating genomics to the clinical practice//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FUGE/183379/Norway/Advanced MR imaging, MR metabolomics, proteomics and genetic mapping of breast cancer - Clinical tools for personalized patient treatment//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FUGE/183621/Norway/Towards personalized therapy for breast cancer//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectBevacizumaben_US
dc.subjectXenograften_US
dc.subjectbreast canceren_US
dc.subjectTranscriptomicsen_US
dc.subjectMetabolomicsen_US
dc.titleSubtype-specific response to bevacizumab is reflected in the metabolome and transcriptome of breast cancer xenograftsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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