{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:49:23Z","timestamp":1769906963175,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T00:00:00Z","timestamp":1577059200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Oncology"],"published-print":{"date-parts":[[2019,12,23]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Malignant 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.<jats:italic>Materials and Methods<\/jats:italic>. 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.<jats:italic>Results<\/jats:italic>. 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.<jats:italic>Conclusion<\/jats:italic>. 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.<\/jats:p>","DOI":"10.1155\/2019\/2902985","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T23:30:42Z","timestamp":1577143842000},"page":"1-11","source":"Crossref","is-referenced-by-count":5,"title":["Screening of Pleural Mesothelioma Cell Lines for Kinase Activity May Identify New Mechanisms of Therapy Resistance in Patients Receiving Platin-Based Chemotherapy"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-3206","authenticated-orcid":true,"given":"Sabrina","family":"Borchert","sequence":"first","affiliation":[{"name":"Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia-Maria","family":"Suckrau","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4399-8646","authenticated-orcid":true,"given":"Michael","family":"Wessolly","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Mairinger","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Balazs","family":"Hegedus","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Thoracical Endoscopy, Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Hager","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Herold","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wildfried E. 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