Brenig, Bertram B.

[["dc.bibliographiccitation.firstpage","35379"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","35389"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Liu, Wen"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Schmidt, Laura C."],["dc.contributor.author","Roolf, Catrin"],["dc.contributor.author","Pews-Davtyan, Anahit"],["dc.contributor.author","Ruetgen, Barbara C."],["dc.contributor.author","Hammer, Sabine"],["dc.contributor.author","Willenbrock, Saskia"],["dc.contributor.author","Sekora, Anett"],["dc.contributor.author","Rolfs, Arndt"],["dc.contributor.author","Beller, Matthias"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Nolte, Ingo"],["dc.contributor.author","Junghanss, Christian"],["dc.contributor.author","Schuetz, Ekkehard"],["dc.contributor.author","Escobar, Hugo Murua"],["dc.date.accessioned","2018-11-07T10:12:52Z"],["dc.date.available","2018-11-07T10:12:52Z"],["dc.date.issued","2016"],["dc.description.abstract","Protein kinase inhibitors are widely used in chemotherapeutic cancer regimens. Maleimide derivatives such as SB-216763 act as GSK-3 inhibitor targeting cell proliferation, cell death and cell cycle progression. Herein, the two arylindolylmaleimide derivatives PDA-66 and PDA-377 were evaluated as potential chemotherapeutic agents on canine B-cell lymphoma cell lines. Canine lymphoma represents a naturally occurring model closely resembling the human high-grade non-Hodgkin's lymphoma (NHL). PDA-66 showed more pronounced effects on both cell lines. Application of 2.5 mu M PDA-66 resulted in a significant induction of apoptosis (approx. 11 %), decrease of the metabolic activity (approx. 95 %), anti-proliferative effect (approx. 85 %) and cell death within 48h. Agent induced mode of action was characterized by whole transcriptome sequencing, 12 h and 24 h post-agent exposure. Key PDA-66-modulated pathways identified were cell cycle, DNA replication and p53 signaling. Expression analyses indicated that the drug acting mechanism is mediated through DNA replication and cycle arrest involving the spindle assembly checkpoint. In conclusion, both PDA derivatives displayed strong anti-proliferation activity in canine B-cell lymphoma cells. The cell and molecular PDA-induced effect characterization and the molecular characterization of the agent acting mechanism provides the basis for further evaluation of a potential drug for canine lymphoma serving as model for human NHL."],["dc.description.sponsorship","Chinese Scholarship Council (CSC)"],["dc.identifier.doi","10.18632/oncotarget.9297"],["dc.identifier.isi","000377752100139"],["dc.identifier.pmid","27177088"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14133"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40322"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights.access","openAccess"],["dc.title","Characterization of the novel indolylmaleimides' PDA-66 and PDA-377 effect on canine lymphoma cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Taher, Leila"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Liu, Wen"],["dc.contributor.author","Roolf, Catrin"],["dc.contributor.author","Soller, Jan T."],["dc.contributor.author","Rütgen, Barbara C."],["dc.contributor.author","Hammer, Sabine E."],["dc.contributor.author","Chodisetti, Murali"],["dc.contributor.author","Sender, Sina"],["dc.contributor.author","Sterenczak, Katharina A."],["dc.contributor.author","Fuellen, Georg"],["dc.contributor.author","Junghanss, Christian"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Nolte, Ingo"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Murua Escobar, Hugo"],["dc.date.accessioned","2020-12-10T18:10:09Z"],["dc.date.available","2020-12-10T18:10:09Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41598-018-23207-7"],["dc.identifier.eissn","2045-2322"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15424"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73867"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Comparative High-Resolution Transcriptome Sequencing of Lymphoma Cell Lines and de novo Lymphomas Reveals Cell-Line-Specific Pathway Dysregulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cancer Cell International"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Liu, Wen"],["dc.contributor.author","Sender, Sina"],["dc.contributor.author","Kong, Weibo"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Sekora, Anett"],["dc.contributor.author","Bornemann-Kolatzki, Kirsten"],["dc.contributor.author","Schuetz, Ekkehart"],["dc.contributor.author","Junghanss, Christian"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Nolte, Ingo"],["dc.contributor.author","Murua Escobar, Hugo"],["dc.date.accessioned","2020-12-10T18:38:58Z"],["dc.date.available","2020-12-10T18:38:58Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1186/s12935-020-01211-0"],["dc.identifier.eissn","1475-2867"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17242"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77499"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Establishment and characterization of stable red, far-red (fR) and near infra-red (NIR) transfected canine prostate cancer cell lines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["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","11481"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Thiemeyer, Heike; 1Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany; heike.thiemeyer@icloud.com (H.T.); jan.torben.schille@tiho-hannover.de (J.T.S.); eva-maria.packeiser@tiho-hannover.de (E.-M.P.); lisa.harder@tiho-hannover.de (L.K.H.); ingo.nolte@tiho-hannover.de (I.N.)"],["dc.contributor.affiliation","Taher, Leila; 3Institute of Biomedical Informatics, Graz University of Technology, 8010 Graz, Austria; leila.taher@tugraz.at"],["dc.contributor.affiliation","Schille, Jan Torben; 1Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany; heike.thiemeyer@icloud.com (H.T.); jan.torben.schille@tiho-hannover.de (J.T.S.); eva-maria.packeiser@tiho-hannover.de (E.-M.P.); lisa.harder@tiho-hannover.de (L.K.H.); ingo.nolte@tiho-hannover.de (I.N.)"],["dc.contributor.affiliation","Packeiser, Eva-Maria; 1Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany; heike.thiemeyer@icloud.com (H.T.); jan.torben.schille@tiho-hannover.de (J.T.S.); eva-maria.packeiser@tiho-hannover.de (E.-M.P.); lisa.harder@tiho-hannover.de (L.K.H.); ingo.nolte@tiho-hannover.de (I.N.)"],["dc.contributor.affiliation","Harder, Lisa K.; 1Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany; heike.thiemeyer@icloud.com (H.T.); jan.torben.schille@tiho-hannover.de (J.T.S.); eva-maria.packeiser@tiho-hannover.de (E.-M.P.); lisa.harder@tiho-hannover.de (L.K.H.); ingo.nolte@tiho-hannover.de (I.N.)"],["dc.contributor.affiliation","Hewicker-Trautwein, Marion; 4Institute of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany; marion.hewicker-trautwein@tiho-hannover.de"],["dc.contributor.affiliation","Brenig, Bertram; 5Institute of Veterinary Medicine, University of Göttingen, 37077 Göttingen, Germany; bbrenig@gwdg.de"],["dc.contributor.affiliation","Schütz, Ekkehard; 6Chronix Biomedical GmbH, 37079 Göttingen, Germany; esc@chronixbiomedical.de (E.S.); jbeck@chronixbiomedical.de (J.B.)"],["dc.contributor.affiliation","Beck, Julia; 6Chronix Biomedical GmbH, 37079 Göttingen, Germany; esc@chronixbiomedical.de (E.S.); jbeck@chronixbiomedical.de (J.B.)"],["dc.contributor.affiliation","Nolte, Ingo; 1Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany; heike.thiemeyer@icloud.com (H.T.); jan.torben.schille@tiho-hannover.de (J.T.S.); eva-maria.packeiser@tiho-hannover.de (E.-M.P.); lisa.harder@tiho-hannover.de (L.K.H.); ingo.nolte@tiho-hannover.de (I.N.)"],["dc.contributor.affiliation","Murua Escobar, Hugo; 1Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany; heike.thiemeyer@icloud.com (H.T.); jan.torben.schille@tiho-hannover.de (J.T.S.); eva-maria.packeiser@tiho-hannover.de (E.-M.P.); lisa.harder@tiho-hannover.de (L.K.H.); ingo.nolte@tiho-hannover.de (I.N.)"],["dc.contributor.author","Thiemeyer, Heike"],["dc.contributor.author","Taher, Leila"],["dc.contributor.author","Schille, Jan Torben"],["dc.contributor.author","Packeiser, Eva-Maria"],["dc.contributor.author","Harder, Lisa K."],["dc.contributor.author","Hewicker-Trautwein, Marion"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Nolte, Ingo"],["dc.contributor.author","Murua Escobar, Hugo"],["dc.date.accessioned","2021-12-01T09:22:50Z"],["dc.date.available","2021-12-01T09:22:50Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-03T23:17:38Z"],["dc.description.abstract","Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the transcriptional landscape of canine PCa and the identification of diagnostic, prognostic and/or therapeutic biomarkers through a multi-step screening approach. RNA-Sequencing of ten malignant tissues and fine-needle aspirations (FNA), and 14 nonmalignant tissues and FNAs was performed to find differentially expressed genes (DEGs) and deregulated pathways. The 4098 observed DEGs were involved in 49 pathways. These 49 pathways could be grouped into five superpathways summarizing the hallmarks of canine PCa: (i) inflammatory response and cytokines; (ii) regulation of the immune system and cell death; (iii) cell surface and PI3K signaling; (iv) cell cycle; and (v) phagosome and autophagy. Among the highly deregulated, moderately to strongly expressed DEGs that were members of one or more superpathways, 169 DEGs were listed in relevant databases and/or the literature and included members of the PCa pathway, oncogenes, prostate-specific genes, and druggable genes. These genes are novel and promising candidate diagnostic, prognostic and/or therapeutic canine PCa biomarkers."],["dc.description.abstract","Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the transcriptional landscape of canine PCa and the identification of diagnostic, prognostic and/or therapeutic biomarkers through a multi-step screening approach. RNA-Sequencing of ten malignant tissues and fine-needle aspirations (FNA), and 14 nonmalignant tissues and FNAs was performed to find differentially expressed genes (DEGs) and deregulated pathways. The 4098 observed DEGs were involved in 49 pathways. These 49 pathways could be grouped into five superpathways summarizing the hallmarks of canine PCa: (i) inflammatory response and cytokines; (ii) regulation of the immune system and cell death; (iii) cell surface and PI3K signaling; (iv) cell cycle; and (v) phagosome and autophagy. Among the highly deregulated, moderately to strongly expressed DEGs that were members of one or more superpathways, 169 DEGs were listed in relevant databases and/or the literature and included members of the PCa pathway, oncogenes, prostate-specific genes, and druggable genes. These genes are novel and promising candidate diagnostic, prognostic and/or therapeutic canine PCa biomarkers."],["dc.identifier.doi","10.3390/ijms222111481"],["dc.identifier.pii","ijms222111481"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94494"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["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"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Granados-Soler, José Luis"],["dc.contributor.author","Taher, Leila"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Bornemann-Kolatzki, Kirsten"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Nerschbach, Verena"],["dc.contributor.author","Ferreira, Fernando"],["dc.contributor.author","Junginger, Johannes"],["dc.contributor.author","Hewicker-Trautwein, Marion"],["dc.contributor.author","Murua Escobar, Hugo"],["dc.contributor.author","Nolte, Ingo"],["dc.date.accessioned","2022-11-01T10:16:44Z"],["dc.date.available","2022-11-01T10:16:44Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n \n The molecular heterogeneity of feline mammary carcinomas (FMCs) represents a prognostic and therapeutic challenge. RNA-Seq-based comparative transcriptomic profiling serves to identify recurrent and exclusive differentially expressed genes (DEGs) across sample types and molecular subtypes. Using mass-parallel RNA-Seq, we identified DEGs and performed comparative function-based analysis across 15 tumours (four basal-like triple-negative [TN], eight normal-like TN, and three luminal B\n f\n HER2 negative [LB\n f\n HER2−]), two cell lines (CL, TiHo-0906, and TiHo-1403) isolated from the primary tumours (LB\n f\n HER2−) of two cats included in this study, and 13 healthy mammary tissue controls. DEGs in tumours were predominantly upregulated; dysregulation of CLs transcriptome was more extensive, including mostly downregulated genes. Cell-cycle and metabolic-related DEGs were upregulated in both tumours and CLs, including therapeutically-targetable cell cycle regulators (e.g.\n CCNB1\n ,\n CCNB2\n ,\n CDK1\n ,\n CDK4\n ,\n GTSE1\n ,\n MCM4\n , and\n MCM5)\n , metabolic-related genes (e.g.\n FADS2\n and\n SLC16A3\n ), heat-shock proteins (e.g.\n HSPH1, HSP90B1\n , and\n HSPA5\n ), genes controlling centrosome disjunction (e.g.\n RACGAP1\n and\n NEK2\n ), and collagen molecules (e.g.\n COL2A1\n ). DEGs specifically upregulated in basal-like TN tumours were involved in antigen processing and presentation, in normal-like TN tumours encoded G protein-coupled receptors (GPCRs), and in LB\n f\n HER2− tumours were associated with lysosomes, phagosomes, and endosomes formation. Downregulated DEGs in CLs were associated with structural and signalling cell surface components. Hence, our results suggest that upregulation of genes enhancing proliferation and metabolism is a common feature among FMCs and derived CLs. In contrast, the dissimilarities observed in dysregulation of membrane components highlight CLs’ disconnection with the tumour microenvironment. Furthermore, recurrent and exclusive DEGs associated with dysregulated pathways might be useful for the development of prognostically and therapeutically-relevant targeted panels."],["dc.identifier.doi","10.1038/s41598-022-20874-5"],["dc.identifier.pii","20874"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116639"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-605"],["dc.relation.eissn","2045-2322"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Transcription profiling of feline mammary carcinomas and derived cell lines reveals biomarkers and drug targets associated with metabolic and cell cycle pathways"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1655"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Hammer, Susanne Conradine"],["dc.contributor.author","Becker, Annegret"],["dc.contributor.author","Rateitschak, Katja"],["dc.contributor.author","Mohr, Annika"],["dc.contributor.author","Ripoli, Florenza Lueder"],["dc.contributor.author","Hennecke, Silvia"],["dc.contributor.author","Junginger, Johannes"],["dc.contributor.author","Hewicker-Trautwein, Marion"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Ngezahayo, Anaclet"],["dc.contributor.author","Nolte, Ingo"],["dc.contributor.author","Escobar, Hugo Murua"],["dc.date.accessioned","2018-11-07T10:07:25Z"],["dc.date.available","2018-11-07T10:07:25Z"],["dc.date.issued","2016"],["dc.description.abstract","Human and canine mammary tumours show partial claudin expression deregulations. Further, claudins have been used for directed therapeutic approaches. However, the development of claudin targeting approaches requires stable claudin expressing cell lines. This study reports the establishment and characterisation of canine mammary tissue derived cell lines, analysing longitudinally the claudin-1, -3, -4 and -7 expressions in original tissue samples, primary cultures and developed cell lines. Primary cultures were derived from 17 canine mammary tissues: healthy, lobular hyperplasia, simple adenoma, complex adenoma, simple tubular carcinoma, complex carcinoma, carcinoma arising in a benign mixed tumour and benign mixed tissue. Cultivation was performed, if possible, until passage 30. Claudin mRNA and protein expressions were analysed by PCR, QuantiGene Plex Assay, immunocytochemistry and immunofluorescence. Further, cytokeratin expression was analysed immunocytochemically. Cultivation resulted in 11 established cell lines, eight showing epithelial character. In five of the early passages the claudin expressions decreased compared to the original tissues. In general, claudin expressions were diminished during cultivation. Three cell lines kept longitudinally claudin, as well as epithelial marker expressions, representing valuable tools for the development of claudin targeted anti-tumour therapies."],["dc.identifier.doi","10.3390/ijms17101655"],["dc.identifier.isi","000387768300129"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13994"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39276"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Longitudinal Claudin Gene Expression Analyses in Canine Mammary Tissues and Thereof Derived Primary Cultures and Cell Lines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Granados-Soler, José Luis"],["dc.contributor.author","Junginger, Johannes"],["dc.contributor.author","Hewicker-Trautwein, Marion"],["dc.contributor.author","Bornemann-Kolatzki, Kirsten"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Betz, Daniela"],["dc.contributor.author","Schille, Jan Torben"],["dc.contributor.author","Murua Escobar, Hugo"],["dc.contributor.author","Nolte, Ingo"],["dc.date.accessioned","2020-12-10T18:10:11Z"],["dc.date.available","2020-12-10T18:10:11Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41598-018-31682-1"],["dc.identifier.eissn","2045-2322"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15443"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73881"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Granados-Soler, José Luis"],["dc.contributor.author","Bornemann-Kolatzki, Kirsten"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Betz, Daniela"],["dc.contributor.author","Junginger, Johannes"],["dc.contributor.author","Hewicker-Trautwein, Marion"],["dc.contributor.author","Murua Escobar, Hugo"],["dc.contributor.author","Nolte, Ingo"],["dc.date.accessioned","2021-04-14T08:27:35Z"],["dc.date.available","2021-04-14T08:27:35Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41598-020-57942-7"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82340"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2045-2322"],["dc.title","Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]