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dc.contributor.author Török, Szilvia
dc.contributor.author Vegvari A
dc.contributor.author Rezeli M
dc.contributor.author Fehniger TE
dc.contributor.author Tóvári, József
dc.contributor.author Paku, Sándor
dc.contributor.author Laszlo, Viktoria
dc.contributor.author Hegedűs, Balázs
dc.contributor.author Rózsás, Anita
dc.contributor.author Döme, Balázs
dc.contributor.author Marko-Varga G
dc.date.accessioned 2018-06-12T11:13:56Z
dc.date.available 2018-06-12T11:13:56Z
dc.date.issued 2015
dc.identifier 84921667759
dc.identifier.citation pagination=1148-1163; journalVolume=172; journalIssueNumber=4; journalTitle=BRITISH JOURNAL OF PHARMACOLOGY;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/5545
dc.identifier.uri doi:10.1111/bph.12990
dc.description.abstract BACKGROUND AND PURPOSE: The clinical impact of antiangiogenic agents remains controversial. Therefore, elucidating the pharmacological properties of these compounds is a pivotal issue. EXPERIMENTAL APPROACH: In our study, malignant and normal tissues of sunitinib-treated tumour-bearing mice were analysed by matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). The expressions of sunitinib's key target angiogenic receptors were studied by immunofluorescent labelling. KEY RESULTS: Sunitinib and its fragment ions were ubiquitously detected by MALDI-MS in malignant and normal tissues. Major metabolites were identified in blood and solid tissues, while minor drug metabolites were traceable only in blood. Tumour growth and intratumoural VEGFR-2 expressions were significantly reduced in sunitinib-treated mice, while the expression of the other targeted receptors (VEGFR-2, PDGFR- alpha/-beta or FGFR-1) remained unaffected. Within tumour tissue, the near proximity of sunitinib metabolites with the precursor ion suggested the in situ processing of the drug. There were intratumoural areas where the signal intensity of sunitinib correlated with VEGFR-2 expression. CONCLUSIONS AND IMPLICATIONS: This is the first study that demonstrates MALDI-MSI as a versatile platform to study the intratumoural localization of an unlabeled antiangiogenic drug. The combination of MALDI-MSI and immunofluorescence analysis can provide further insights into the molecular interaction of drug compounds and their targets within tumour tissue.
dc.relation.ispartof urn:issn:0007-1188
dc.title Localization of sunitinib, its metabolites and its target receptors in tumour bearing mice: a MALDI mass spectrometry imaging study
dc.type Journal Article
dc.date.updated 2018-06-06T12:26:04Z
dc.language.rfc3066 en
dc.identifier.mtmt 2807854
dc.identifier.wos 000348507700015
dc.identifier.pubmed 25363319
dc.contributor.department SE/AOK/I/I. Sz. Patológiai és Kísérleti Rákkutató Intézet
dc.contributor.department SE/AOK/K/Mellkassebészeti Klinika
dc.contributor.department SE/AOK/I/IISZPI/MTA-SE Molekuláris Onkológia Kutatócsoport
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote B. D. and G. M. V. contributed equally as senior authors to this study.


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