000164093 001__ 164093
000164093 005__ 20230915090549.0
000164093 0247_ $$2doi$$a10.1111/nan.12780
000164093 0247_ $$2pmid$$apmid:34837233
000164093 0247_ $$2ISSN$$a0305-1846
000164093 0247_ $$2ISSN$$a1365-2990
000164093 0247_ $$2altmetric$$aaltmetric:117751411
000164093 037__ $$aDZNE-2022-00756
000164093 041__ $$aEnglish
000164093 082__ $$a610
000164093 1001_ $$aJohn, Peter$$b0
000164093 245__ $$aAKT1E17K -mutated meningioma cell lines respond to treatment with the AKT inhibitor AZD5363.
000164093 260__ $$aOxford [u.a.]$$bWiley-Blackwell$$c2022
000164093 3367_ $$2DRIVER$$aarticle
000164093 3367_ $$2DataCite$$aOutput Types/Journal article
000164093 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1671620302_26519
000164093 3367_ $$2BibTeX$$aARTICLE
000164093 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000164093 3367_ $$00$$2EndNote$$aJournal Article
000164093 520__ $$aMeningiomas are the most frequent primary brain tumours. Recently, knowledge about the molecular drivers underlying aggressive meningiomas has been expanded. A hotspot mutation in the AKT1 gene (AKT1E17K ), which is found in meningiomas at the convexity and especially at the skull base, has been associated with earlier tumour recurrence.Here, we analysed the effects of the AKT1E17K mutation and treatment response to the Akt inhibitor AZD5363 in transgenic meningioma cell clones and mouse xenografts modelling convexity or skull base meningiomas.We show that the AKTE17K mutation significantly enhances meningioma cell proliferation and colony size in vitro, resulting in significantly shortened survival times of mice carrying convexity or skull base AKT1E17K xenografts. Treatment of mutant cells or xenografts (150 mg/kg/d) with AZD5363 revealed a significant decrease in cell proliferation and colony size and a prolongation of mouse survival. Western blots revealed activation of AKT1 kinase (phosphorylation at Ser273 and Thr308) by the E17K mutation in human meningioma samples and in our in vitro and in vivo models.Our data suggest that AKT1E17K mutated meningiomas are a promising selective target for AZD5363.
000164093 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0
000164093 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000164093 650_7 $$2Other$$aAKT1
000164093 650_7 $$2Other$$ameningioma
000164093 650_7 $$2Other$$atargeted therapy
000164093 650_7 $$2NLM Chemicals$$aEnzyme Inhibitors
000164093 650_7 $$2NLM Chemicals$$aPyrimidines
000164093 650_7 $$2NLM Chemicals$$aPyrroles
000164093 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aProto-Oncogene Proteins c-akt
000164093 650_7 $$0WFR23M21IE$$2NLM Chemicals$$acapivasertib
000164093 650_2 $$2MeSH$$aAnimals
000164093 650_2 $$2MeSH$$aCell Line, Tumor
000164093 650_2 $$2MeSH$$aCell Proliferation: drug effects
000164093 650_2 $$2MeSH$$aEnzyme Inhibitors: pharmacology
000164093 650_2 $$2MeSH$$aHumans
000164093 650_2 $$2MeSH$$aMeningeal Neoplasms: genetics
000164093 650_2 $$2MeSH$$aMeningeal Neoplasms: pathology
000164093 650_2 $$2MeSH$$aMeningioma: genetics
000164093 650_2 $$2MeSH$$aMeningioma: pathology
000164093 650_2 $$2MeSH$$aMice
000164093 650_2 $$2MeSH$$aProto-Oncogene Proteins c-akt: antagonists & inhibitors
000164093 650_2 $$2MeSH$$aProto-Oncogene Proteins c-akt: genetics
000164093 650_2 $$2MeSH$$aPyrimidines: pharmacology
000164093 650_2 $$2MeSH$$aPyrroles: pharmacology
000164093 650_2 $$2MeSH$$aSkull Base Neoplasms: genetics
000164093 650_2 $$2MeSH$$aSkull Base Neoplasms: pathology
000164093 7001_ $$aWaldt, Natalie$$b1
000164093 7001_ $$aLiebich, Josephine$$b2
000164093 7001_ $$aKesseler, Christoph$$b3
000164093 7001_ $$aSchnabel, Stefan$$b4
000164093 7001_ $$0P:(DE-2719)2810456$$aAngenstein, Frank$$b5$$udzne
000164093 7001_ $$aSandalcioglu, I Erol$$b6
000164093 7001_ $$aScherlach, Cordula$$b7
000164093 7001_ $$00000-0001-5441-1962$$aSahm, Felix$$b8
000164093 7001_ $$aKirches, Elmar$$b9
000164093 7001_ $$00000-0002-6677-3124$$aMawrin, Christian$$b10
000164093 773__ $$0PERI:(DE-600)2008293-9$$a10.1111/nan.12780$$gVol. 48, no. 2$$n2$$pe12780$$tNeuropathology & applied neurobiology$$v48$$x0305-1846$$y2022
000164093 8564_ $$uhttps://pub.dzne.de/record/164093/files/DZNE-2022-00756.pdf$$yOpenAccess
000164093 8564_ $$uhttps://pub.dzne.de/record/164093/files/DZNE-2022-00756.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000164093 909CO $$ooai:pub.dzne.de:164093$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000164093 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810456$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b5$$kDZNE
000164093 9131_ $$0G:(DE-HGF)POF4-351$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vBrain Function$$x0
000164093 9141_ $$y2022
000164093 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-02-03
000164093 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000164093 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2021-02-03$$wger
000164093 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-02-03
000164093 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000164093 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-02-03
000164093 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNEUROPATH APPL NEURO : 2021$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-16
000164093 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bNEUROPATH APPL NEURO : 2021$$d2022-11-16
000164093 9201_ $$0I:(DE-2719)1310004$$kAG Angenstein$$lFunctional Neuroimaging$$x0
000164093 980__ $$ajournal
000164093 980__ $$aVDB
000164093 980__ $$aUNRESTRICTED
000164093 980__ $$aI:(DE-2719)1310004
000164093 9801_ $$aFullTexts