Schütz, Ekkehard

[["dc.bibliographiccitation.artnumber","54"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cancer Cell International"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Packeiser, Eva-Maria"],["dc.contributor.author","Taher, Leila"],["dc.contributor.author","Kong, Weibo"],["dc.contributor.author","Ernst, Mathias"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Hewicker-Trautwein, Marion"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Murua Escobar, Hugo"],["dc.contributor.author","Nolte, Ingo"],["dc.date.accessioned","2022-04-01T10:03:07Z"],["dc.date.accessioned","2022-08-18T12:37:01Z"],["dc.date.available","2022-04-01T10:03:07Z"],["dc.date.available","2022-08-18T12:37:01Z"],["dc.date.issued","2022-02-02"],["dc.date.updated","2022-07-29T12:17:32Z"],["dc.description.abstract","Abstract\r\n \r\n Background\r\n Canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) are typically characterized by metastasis and chemoresistance. Cell lines are important model systems for developing new therapeutic strategies. However, as they adapt to culturing conditions and undergo clonal selection, they can diverge from the tissue from which they were originally derived. Therefore, a comprehensive characterization of cell lines and their original tissues is paramount.\r\n \r\n \r\n Methods\r\n This study compared the transcriptomes of nine canine cell lines derived from PAC, PAC metastasis and TCC to their respective original primary tumor or metastasis tissues. Special interests were laid on cell culture-related differences, epithelial to mesenchymal transition (EMT), the prostate and bladder cancer pathways, therapeutic targets in the PI3K-AKT signaling pathway and genes correlated with chemoresistance towards doxorubicin and carboplatin.\r\n \r\n \r\n Results\r\n Independent analyses for PAC, PAC metastasis and TCC revealed 1743, 3941 and 463 genes, respectively, differentially expressed in the cell lines relative to their original tissues (DEGs). While genes associated with tumor microenvironment were mostly downregulated in the cell lines, patient-specific EMT features were conserved. Furthermore, examination of the prostate and bladder cancer pathways revealed extensive concordance between cell lines and tissues. Interestingly, all cell lines preserved downstream PI3K-AKT signaling, but each featured a unique therapeutic target signature. Additionally, resistance towards doxorubicin was associated with G2/M cell cycle transition and cell membrane biosynthesis, while carboplatin resistance correlated with histone, m- and tRNA processing.\r\n \r\n \r\n Conclusion\r\n Comparative whole-transcriptome profiling of cell lines and their original tissues identifies models with conserved therapeutic target expression. Moreover, it is useful for selecting suitable negative controls, i.e., cell lines lacking therapeutic target expression, increasing the transfer efficiency from in vitro to primary neoplasias for new therapeutic protocols. In summary, the dataset presented here constitutes a rich resource for canine prostate and bladder cancer research."],["dc.identifier.citation","Cancer Cell International. 2022 Feb 02;22(1):54"],["dc.identifier.doi","10.1186/s12935-021-02422-9"],["dc.identifier.pii","2422"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/106087"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112958"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.publisher","BioMed Central"],["dc.relation.eissn","1475-2867"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Prostate cancer"],["dc.subject","Metastasis"],["dc.subject","Bladder cancer"],["dc.subject","TCC"],["dc.subject","Cell line"],["dc.subject","Dog"],["dc.subject","Gene expression"],["dc.subject","In vitro model"],["dc.subject","Targeted therapy"],["dc.title","RNA-seq of nine canine prostate cancer cell lines reveals diverse therapeutic target signatures"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","12673"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Kong, Weibo; 1Department of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany; weibo.kong@outlook.com (W.K.); Sina.Sender@med.uni-rostock.de (S.S.); Simon.VillaPerez@med.uni-rostock.de (S.V.-P.); Yixuan.Ma@med.uni-rostock.de (Y.M.); anett.sekora@med.uni-rostock.de (A.S.); christian.junghanss@med.uni-rostock.de (C.J.)"],["dc.contributor.affiliation","Sender, Sina; 1Department of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany; weibo.kong@outlook.com (W.K.); Sina.Sender@med.uni-rostock.de (S.S.); Simon.VillaPerez@med.uni-rostock.de (S.V.-P.); Yixuan.Ma@med.uni-rostock.de (Y.M.); anett.sekora@med.uni-rostock.de (A.S.); christian.junghanss@med.uni-rostock.de (C.J.)"],["dc.contributor.affiliation","Taher, Leila; 4Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, 18057 Rostock, Germany; leila.taher@tugraz.at"],["dc.contributor.affiliation","Villa-Perez, Simon; 1Department of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany; weibo.kong@outlook.com (W.K.); Sina.Sender@med.uni-rostock.de (S.S.); Simon.VillaPerez@med.uni-rostock.de (S.V.-P.); Yixuan.Ma@med.uni-rostock.de (Y.M.); anett.sekora@med.uni-rostock.de (A.S.); christian.junghanss@med.uni-rostock.de (C.J.)"],["dc.contributor.affiliation","Ma, Yixuan; 1Department of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany; weibo.kong@outlook.com (W.K.); Sina.Sender@med.uni-rostock.de (S.S.); Simon.VillaPerez@med.uni-rostock.de (S.V.-P.); Yixuan.Ma@med.uni-rostock.de (Y.M.); anett.sekora@med.uni-rostock.de (A.S.); christian.junghanss@med.uni-rostock.de (C.J.)"],["dc.contributor.affiliation","Sekora, Anett; 1Department of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany; weibo.kong@outlook.com (W.K.); Sina.Sender@med.uni-rostock.de (S.S.); Simon.VillaPerez@med.uni-rostock.de (S.V.-P.); Yixuan.Ma@med.uni-rostock.de (Y.M.); anett.sekora@med.uni-rostock.de (A.S.); christian.junghanss@med.uni-rostock.de (C.J.)"],["dc.contributor.affiliation","Ruetgen, Barbara C.; 6Department for Pathobiology, Clinical Pathology, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria; Barbara.Ruetgen@vetmeduni.ac.at"],["dc.contributor.affiliation","Brenig, Bertram; 7Department of Animal Sciences, Faculty of Agricultural Sciences, University of Goettingen, 37077 Goettingen, Germany; bbrenig@gwdg.de (B.B.); ekkehard.schuetz@agr.uni-goettingen.de (E.S.)"],["dc.contributor.affiliation","Beck, Julia; 8Chronix Biomedical Goettingen, 37079 Goettingen, Germany; jbeck@chronixbiomedical.de"],["dc.contributor.affiliation","Schuetz, Ekkehard; 7Department of Animal Sciences, Faculty of Agricultural Sciences, University of Goettingen, 37077 Goettingen, Germany; bbrenig@gwdg.de (B.B.); ekkehard.schuetz@agr.uni-goettingen.de (E.S.)"],["dc.contributor.affiliation","Junghanss, Christian; 1Department of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany; weibo.kong@outlook.com (W.K.); Sina.Sender@med.uni-rostock.de (S.S.); Simon.VillaPerez@med.uni-rostock.de (S.V.-P.); Yixuan.Ma@med.uni-rostock.de (Y.M.); anett.sekora@med.uni-rostock.de (A.S.); christian.junghanss@med.uni-rostock.de (C.J.)"],["dc.contributor.affiliation","Nolte, Ingo; 2Small Animal Clinic, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; ingo.nolte@gmx.net"],["dc.contributor.affiliation","Murua Escobar, Hugo; 1Department of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany; weibo.kong@outlook.com (W.K.); Sina.Sender@med.uni-rostock.de (S.S.); Simon.VillaPerez@med.uni-rostock.de (S.V.-P.); Yixuan.Ma@med.uni-rostock.de (Y.M.); anett.sekora@med.uni-rostock.de (A.S.); christian.junghanss@med.uni-rostock.de (C.J.)"],["dc.contributor.author","Kong, Weibo"],["dc.contributor.author","Sender, Sina"],["dc.contributor.author","Taher, Leila"],["dc.contributor.author","Villa-Perez, Simon"],["dc.contributor.author","Ma, Yixuan"],["dc.contributor.author","Sekora, Anett"],["dc.contributor.author","Ruetgen, Barbara C."],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Schuetz, Ekkehard"],["dc.contributor.author","Murua Escobar, Hugo"],["dc.contributor.author","Junghanss, Christian"],["dc.contributor.author","Nolte, Ingo"],["dc.date.accessioned","2022-01-11T14:05:54Z"],["dc.date.available","2022-01-11T14:05:54Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-03T19:45:35Z"],["dc.description.abstract","Bruton’s tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) in the B-cell receptor (BCR) signaling pathway are considered potential therapeutic targets for the treatment of B-cell lymphomas, among which, diffuse large B-cell lymphoma (DLBCL) is the most common type. Herein, we comparatively evaluated the single and combined application of the BTK inhibitor ibrutinib and the selective PI3Kγ inhibitor AS-605240 in the canine DLBCL cell line CLBL-1. For further comparison, key findings were additionally analyzed in canine B-cell leukemia GL-1 and human DLBCL cell line SU-DHL-4. While ibrutinib alone induced significant anti-proliferative effects on all cell lines in a dose-dependent manner, AS-605240 only induced anti-proliferative effects at high concentrations. Interestingly, ibrutinib and AS-605240 acted synergistically, reducing cell proliferation and increasing apoptosis/necrosis in all cell lines and inducing morphological changes in CLBL-1. Moreover, the combined application of ibrutinib and AS-605240 reduced relative phosphorylation and, in some instances, the levels of the BTK, AKT, GSK3β, and ERK proteins. Comparative variant analysis of RNA-seq data among canine B- and T-lymphoid cell lines and primary B-cell lymphoma samples revealed potentially high-impact somatic variants in the genes that encode PI3K, which may explain why AS-605240 does not singly inhibit the proliferation of cell lines. The combination of ibrutinib and AS-605240 represents a promising approach that warrants further in vivo evaluation in dogs, potentially bearing significant value for the treatment of human DLBCL."],["dc.description.abstract","Bruton’s tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) in the B-cell receptor (BCR) signaling pathway are considered potential therapeutic targets for the treatment of B-cell lymphomas, among which, diffuse large B-cell lymphoma (DLBCL) is the most common type. Herein, we comparatively evaluated the single and combined application of the BTK inhibitor ibrutinib and the selective PI3Kγ inhibitor AS-605240 in the canine DLBCL cell line CLBL-1. For further comparison, key findings were additionally analyzed in canine B-cell leukemia GL-1 and human DLBCL cell line SU-DHL-4. While ibrutinib alone induced significant anti-proliferative effects on all cell lines in a dose-dependent manner, AS-605240 only induced anti-proliferative effects at high concentrations. Interestingly, ibrutinib and AS-605240 acted synergistically, reducing cell proliferation and increasing apoptosis/necrosis in all cell lines and inducing morphological changes in CLBL-1. Moreover, the combined application of ibrutinib and AS-605240 reduced relative phosphorylation and, in some instances, the levels of the BTK, AKT, GSK3β, and ERK proteins. Comparative variant analysis of RNA-seq data among canine B- and T-lymphoid cell lines and primary B-cell lymphoma samples revealed potentially high-impact somatic variants in the genes that encode PI3K, which may explain why AS-605240 does not singly inhibit the proliferation of cell lines. The combination of ibrutinib and AS-605240 represents a promising approach that warrants further in vivo evaluation in dogs, potentially bearing significant value for the treatment of human DLBCL."],["dc.identifier.doi","10.3390/ijms222312673"],["dc.identifier.pii","ijms222312673"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97773"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","BTK and PI3K Inhibitors Reveal Synergistic Inhibitory Anti-Tumoral Effects in Canine Diffuse Large B-Cell Lymphoma Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]