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.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.artnumber","1589"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Ripoli, Florenza Lueder"],["dc.contributor.author","Hammer, Susanne Conradine"],["dc.contributor.author","Mohr, Annika"],["dc.contributor.author","Willenbrock, Saskia"],["dc.contributor.author","Hewicker-Trautwein, Marion"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Escobar, Hugo Murua"],["dc.contributor.author","Nolte, Ingo"],["dc.date.accessioned","2018-11-07T10:09:08Z"],["dc.date.available","2018-11-07T10:09:08Z"],["dc.date.issued","2016"],["dc.description.abstract","Mammary gland tumors are one of the most common neoplasms in female dogs, and certain breeds are prone to develop the disease. The use of biomarkers in canines is still restricted to research purposes. Therefore, the necessity to analyze gene profiles in different mammary entities in large sample sets is evident in order to evaluate the strength of potential markers serving as future prognostic factors. The aim of the present study was to analyze the gene expression of 16 target genes (BRCA1, BRCA2, FOXO3, GATA4, HER2, HMGA1, HMGA2, HMGB1, MAPK1, MAPK3, MCL1, MYC, PFDN5, PIK3CA, PTEN, and TP53) known to be involved in human and canine mammary neoplasm development. Expression was analyzed in 111 fresh frozen (FF) and in 170 formalin-fixed, paraffin-embedded (FFPE) specimens of neoplastic and non-neoplastic canine mammary tissues using a multiplexed branched-DNA (b-DNA) assay. TP53, FOXO3, PTEN, and PFDN5 expression revealed consistent results with significant low expression in malignant tumors. The possibility of utilizing them as predictive factors as well as for assisting in the choice of an adequate gene therapy may help in the development of new and improved approaches in canine mammary tumors."],["dc.identifier.doi","10.3390/ijms17091589"],["dc.identifier.isi","000385525500202"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13977"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39600"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1422-0067"],["dc.rights.access","openAccess"],["dc.title","Multiplex Gene Expression Profiling of 16 Target Genes in Neoplastic and Non-Neoplastic Canine Mammary Tissues Using Branched-DNA Assay"],["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.artnumber","e0131280"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Hennecke, Silvia"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Bornemann-Kolatzki, Kirsten"],["dc.contributor.author","Neumann, Stephan"],["dc.contributor.author","Escobar, Hugo Murua"],["dc.contributor.author","Nolte, Ingo"],["dc.contributor.author","Hammer, Susanne Conradine"],["dc.contributor.author","Hewicker-Trautwein, Marion"],["dc.contributor.author","Junginger, Johannes"],["dc.contributor.author","Kaup, Franz-Josef"],["dc.contributor.author","Brenig, Bertram"],["dc.contributor.author","Schuetz, Ekkehard"],["dc.date.accessioned","2018-11-07T09:55:07Z"],["dc.date.available","2018-11-07T09:55:07Z"],["dc.date.issued","2015"],["dc.description.abstract","Background A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. Methods Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores <= -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry. Results The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p < 0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion. Conclusions A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer-driver gene."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.1371/journal.pone.0131280"],["dc.identifier.isi","000358153000106"],["dc.identifier.pmid","26132936"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12021"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36681"],["dc.notes","Silvia Hennecke (University of Göttingen) is the submitting author of this article."],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights.access","openAccess"],["dc.title","Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors"],["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"]]