000154244 001__ 154244 000154244 005__ 20240229120023.0 000154244 0247_ $$2doi$$a10.1155/2019/2902985 000154244 0247_ $$2pmid$$apmid:31929796 000154244 0247_ $$2pmc$$apmc:PMC6942867 000154244 0247_ $$2ISSN$$a1687-8450 000154244 0247_ $$2ISSN$$a1687-8469 000154244 0247_ $$2altmetric$$aaltmetric:74047354 000154244 037__ $$aDKFZ-2020-00680 000154244 041__ $$aeng 000154244 082__ $$a610 000154244 1001_ $$00000-0002-0447-3206$$aBorchert, Sabrina$$b0 000154244 245__ $$aScreening of Pleural Mesothelioma Cell Lines for Kinase Activity May Identify New Mechanisms of Therapy Resistance in Patients Receiving Platin-Based Chemotherapy. 000154244 260__ $$aNew York, NY$$bHindawi Publ. Corp.$$c2019 000154244 3367_ $$2DRIVER$$aarticle 000154244 3367_ $$2DataCite$$aOutput Types/Journal article 000154244 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1585306247_8314 000154244 3367_ $$2BibTeX$$aARTICLE 000154244 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000154244 3367_ $$00$$2EndNote$$aJournal Article 000154244 520__ $$aMalignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumor associated with a dismal prognosis. Multimodal therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons underlying the rather poor efficacy of platinum compounds remain largely unknown. Kinase activity might influence cellular response to these regimens.For this exploratory study, we screened MPM cell lines (NCI-H2452, NCI-H2052, and MSTO-211H) differing in response to cisplatin and benign control fibroblasts (MRC-5) for overall phosphorylation patterns as well as kinase activity with respect to cellular response to cisplatin-based therapeutics. We analysed the cell lines for cellular kinases in a high-throughput manner using the highly innovative technique PamGene. Cell state analysis including apoptosis, necrosis, and cell viability was performed by using enzyme activity and fluorescent-based assays.Cisplatin alters cellular phosphorylation patterns affecting cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis. In cisplatin-responsive cell lines, phosphorylation of AKT1 and GSK3B was decreased but could not be influenced in cisplatin-resistant NCI-H2452 cells. Cisplatin-responsive cell lines showed increased phosphorylation levels of JNK1/2/3 but decreased phosphorylation in cisplatin-resistant NCI-H2452 cells.Kinase phosphorylation and activity might play a crucial role in cellular response to cytostatic agents. Cisplatin influences phosphorylation patterns with distinct features in cisplatin-resistant cells. These alterations exert a significant impact on cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis of the respective tumor cells. Based on our results, the induction of p38 or JNK1/3, or inhibition of AKT1 by, for example, BIA-6, might offer a positive synergistic effect by induction of an apoptotic response to cisplatin-based treatment, thus potentially enhancing the clinical outcome of MPM patients. 000154244 536__ $$0G:(DE-HGF)POF3-899$$a899 - ohne Topic (POF3-899)$$cPOF3-899$$fPOF III$$x0 000154244 588__ $$aDataset connected to CrossRef, PubMed, 000154244 7001_ $$aSuckrau, Pia-Maria$$b1 000154244 7001_ $$00000-0002-4399-8646$$aWessolly, Michael$$b2 000154244 7001_ $$0P:(DE-HGF)0$$aMairinger, Elena$$b3 000154244 7001_ $$aHegedus, Balazs$$b4 000154244 7001_ $$0P:(DE-HGF)0$$aHager, Thomas$$b5 000154244 7001_ $$0P:(DE-He78)0ecb73a869d20caca507c5781ffc8b11$$aHerold, Thomas$$b6 000154244 7001_ $$aEberhardt, Wildfried E E$$b7 000154244 7001_ $$aWohlschlaeger, Jeremias$$b8 000154244 7001_ $$aAigner, Clemens$$b9 000154244 7001_ $$0P:(DE-HGF)0$$aBankfalvi, Agnes$$b10 000154244 7001_ $$0P:(DE-HGF)0$$aSchmid, Kurt Werner$$b11 000154244 7001_ $$aWalter, Robert F H$$b12 000154244 7001_ $$00000-0003-1067-0051$$aMairinger, Fabian D$$b13 000154244 773__ $$0PERI:(DE-600)2461349-6$$a10.1155/2019/2902985$$gVol. 2019, p. 1 - 11$$p2902985 $$tJournal of oncology$$v2019$$x1687-8469$$y2019 000154244 909CO $$ooai:inrepo02.dkfz.de:154244$$pVDB 000154244 9101_ $$0I:(DE-588b)2036810-0$$60000-0002-0447-3206$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000154244 9101_ $$0I:(DE-588b)2036810-0$$60000-0002-4399-8646$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ 000154244 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ 000154244 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ 000154244 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0ecb73a869d20caca507c5781ffc8b11$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ 000154244 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ 000154244 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ 000154244 9101_ $$0I:(DE-588b)2036810-0$$60000-0003-1067-0051$$aDeutsches Krebsforschungszentrum$$b13$$kDKFZ 000154244 9131_ $$0G:(DE-HGF)POF3-899$$1G:(DE-HGF)POF3-890$$2G:(DE-HGF)POF3-800$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0 000154244 9141_ $$y2019 000154244 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ ONCOL : 2017 000154244 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000154244 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000154244 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000154244 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central 000154244 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal 000154244 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ 000154244 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review 000154244 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ 000154244 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000154244 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000154244 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List 000154244 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000154244 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000154244 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine 000154244 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000154244 9201_ $$0I:(DE-He78)L401-20160331$$kL401$$lDKTK Essen$$x0 000154244 980__ $$ajournal 000154244 980__ $$aVDB 000154244 980__ $$aI:(DE-He78)L401-20160331 000154244 980__ $$aUNRESTRICTED