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000154244 0247_ $$2ISSN$$a1687-8469
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000154244 037__ $$aDKFZ-2020-00680
000154244 041__ $$aeng
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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.$$c2019
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000154244 520__ $$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.
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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
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