Schön, Margarete

[["dc.bibliographiccitation.firstpage","410"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","421"],["dc.bibliographiccitation.volume","121"],["dc.contributor.author","Zibert, John R."],["dc.contributor.author","Wallbrecht, Katrin"],["dc.contributor.author","Schon, Margarete"],["dc.contributor.author","Mir, Lluis M."],["dc.contributor.author","Jacobsen, Grete K."],["dc.contributor.author","Trochon-Joseph, Veronique"],["dc.contributor.author","Bouquet, Celine"],["dc.contributor.author","Villadsen, Louise S."],["dc.contributor.author","Cadossi, Ruggero"],["dc.contributor.author","Skov, Lone"],["dc.contributor.author","Schon, Michael P."],["dc.date.accessioned","2018-11-07T09:01:32Z"],["dc.date.available","2018-11-07T09:01:32Z"],["dc.date.issued","2011"],["dc.description.abstract","Dysregulated angiogenesis is a hallmark of chronic inflammatory diseases, including psoriasis, a common skin disorder that affects approximately 2% of the population Studying both human psoriasis in 2 complementary xenotransplantation models and psoriasis-like skin lesions in transgenic mice with epidermal expression of human TGF-beta 1, we have demonstrated that antiangiogenic non-viral somatic gene therapy reduces the cutaneous microvasculature and alleviates chronic inflammatory skin disorders Transient muscular expression of the recombinant disintegrin domain (RDD) of metargidin (also known as ADAM-15) by in vivo electroporation reduced cutaneous angiogenesis and vascularization in all 3 models As demonstrated using red fluorescent protein-coupled RDD, the treatment resulted in muscular expression of the gene product and its deposition within the cutaneous hyperangiogenic connective tissue High-resolution ultrasound revealed reduced cutaneous blood flow in vivo after electroporation with RDD but not with control plasmids In addition, angiogenesis- and inflammation-related molecular markers, keratinocyte proliferation, epidermal thickness, and clinical disease scores were downregulated in all models Thus, non-viral antiangiogenic gene therapy can alleviate psoriasis and may do so in other angiogenesis-related inflammatory skin disorders"],["dc.identifier.doi","10.1172/JCI41295"],["dc.identifier.isi","000285892300042"],["dc.identifier.pmid","21135506"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6284"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24453"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Clinical Investigation Inc"],["dc.relation.issn","0021-9738"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions"],["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","28"],["dc.bibliographiccitation.journal","Cancer Cell International"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Filleur, Stephanie"],["dc.contributor.author","Hirsch, Jennifer"],["dc.contributor.author","Wille, Aline"],["dc.contributor.author","Schön, Margarete"],["dc.contributor.author","Sell, Christian"],["dc.contributor.author","Shearer, Michael H."],["dc.contributor.author","Nelius, Thomas"],["dc.contributor.author","Wieland, Ilse"],["dc.date.accessioned","2019-07-09T11:52:36Z"],["dc.date.available","2019-07-09T11:52:36Z"],["dc.date.issued","2009"],["dc.description.abstract","Background The gene encoding integrator complex subunit 6 (INTS6), previously known as deleted in cancer cells 1 (DICE1, OMIM 604331) was found to be frequently affected by allelic deletion and promoter hypermethylation in prostate cancer specimens and cell lines. A missense mutation has been detected in prostate cancer cell line LNCaP. Together, these results suggest INTS6/DICE1 as a putative tumor suppressor gene in prostate cancer. In this study, we examined the growth inhibitory effects of INTS6/DICE1 on prostate cancer cells. Results Markedly decreased INTS6/DICE1 mRNA levels were detected in prostate cancer cell lines LNCaP, DU145 and PC3 as well as CPTX1532 as compared to a cell line derived from normal prostate tissue, NPTX1532. Exogenous re-expression of INTS6/DICE1 cDNA in androgen-independent PC3 and DU145 cell lines substantially suppressed their ability to form colonies in vitro. This growth inhibition was not due to immediate induction of apoptosis. Rather, prostate cancer cells arrested in G1 phase of the cell cycle. Expression profiling of members of the Wnt signaling pathway revealed up-regulation of several genes including disheveled inhibitor CXXC finger 4 (CXXC4), frizzled homologue 7 (FZD7), transcription factor 7-like 1 (TCF7L1), and down-regulation of cyclin D1. Conclusion These results show for the first time a link between INTS6/DICE1 function, cell cycle regulation and cell-cell communication involving members of the Wnt signaling pathway."],["dc.identifier.doi","10.1186/1475-2867-9-28"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5743"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60236"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.subject.ddc","570"],["dc.title","INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0160096"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Haenssle, Holger Andreas"],["dc.contributor.author","Zibert, John R."],["dc.contributor.author","Schoen, Margarete"],["dc.contributor.author","Hald, Andreas"],["dc.contributor.author","Hansen, Maria H."],["dc.contributor.author","Litman, Thomas"],["dc.contributor.author","Schoen, Michael Peter"],["dc.date.accessioned","2018-11-07T10:08:37Z"],["dc.date.available","2018-11-07T10:08:37Z"],["dc.date.issued","2016"],["dc.description.abstract","The rapid and strong clinical efficacy of the first-in-class, ingenol mebutate, against actinic keratosis (AK) has resulted in its recent approval. We conducted the first comprehensive analysis of the cellular and molecular mode of action of topical ingenol mebutate 0.05% gel in both AK and uninvolved skin of 26 patients in a phase I, single-center, open-label, within-patient comparison. As early as 1 day after application, ingenol mebutate induced profound epidermal cell death, along with a strong infiltrate of CD4(+) and CD8(+) T-cells, neutrophils, and macrophages. Endothelial ICAM-1 activation became evident after 2 days. The reaction pattern was significantly more pronounced in AK compared with uninvolved skin, suggesting a tumor-preferential mode of action. Extensive molecular analyses and transcriptomic profiling of mRNAs and microRNAs demonstrated alterations in gene clusters functionally associated with epidermal development, inflammation, innate immunity, and response to wounding. Ingenol mebutate reveals a unique mode of action linking directly to anti-tumoral effects."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1371/journal.pone.0160096"],["dc.identifier.isi","000383255900002"],["dc.identifier.pmid","27612149"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13695"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39498"],["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","Tumor-Preferential Induction of Immune Responses and Epidermal Cell Death in Actinic Keratoses by Ingenol Mebutate"],["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.firstpage","862"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","JOURNAL OF THE NATIONAL CANCER INSTITUTE"],["dc.bibliographiccitation.lastpage","875"],["dc.bibliographiccitation.volume","100"],["dc.contributor.author","Schoen, Margarete"],["dc.contributor.author","Wienrich, B. Gregor"],["dc.contributor.author","Kneitz, Susanne"],["dc.contributor.author","Sennefelder, Helga"],["dc.contributor.author","Amschler, Katharina"],["dc.contributor.author","Voehringer, Verena"],["dc.contributor.author","Weber, Olaf"],["dc.contributor.author","Stiewe, Thorsten"],["dc.contributor.author","Ziegelbauer, Karl"],["dc.contributor.author","Schoen, Michael Peter"],["dc.date.accessioned","2018-11-07T11:13:55Z"],["dc.date.available","2018-11-07T11:13:55Z"],["dc.date.issued","2008"],["dc.description.abstract","Background Increasing the efficacy of chemotherapeutics by reducing chemoresistance may be a useful strategy in cancer therapy. Constitutive activation of nuclear factor-kappa B (NF-kappa B) is a hallmark of various cancers, including melanoma, which is almost universally resistant to chemotherapy. NF-kappa B is regulated by inhibitory kappa B (I kappa B) proteins, which are in turn phosphorylated by the I kappa B kinase (IKK) complex. Methods The effect on NF-kappa B activity of a novel small-molecule inhibitor of the beta subunit of IKK (KINK-1; kinase inhibitor of nuclear factor-kappa B-1) was assessed by measuring phosphorylation of the alpha subunit of I kappa B by immunoblotting, DNA binding by electrophoretic mobility shift assays, and nuclear translocation of NF-kappa B using immunofluorescence. Regulation of NF-kappa B-dependent gene expression was determined by microarray analysis, real-time and semiquantitative reverse transcription polymerase chain reaction (RT-PCR), and Western blot analyses. The effects of KINK-1 (alone and in combination with cytostatic agents) on melanoma cells were characterized by assessing proliferation, soft agar colony formation, and markers of apoptosis. The antitumoral efficacy of KINK-1 in combination with the cytostatic agents doxorubicin or camptothecin (all injected intraperitoneally) was tested in vivo by measuring lung weight and counting metastases in C57BL6 mice (groups of six) bearing metastases of melanoma cells. All statistical tests were two-sided. Results KINK-1 strongly suppressed both constitutive and induced NF-kappa B activity in melanoma cells. It reduced the expression of NF-kappa B-dependent gene products that regulate proliferation, cytokine production, and antiapoptotic responses but exhibited little antiproliferative or proapoptotic activity at the cellular level. However, KINK-1 markedly increased the activities of some cytostatic agents in vitro and abrogated doxorubicin-induced NF-kappa B activation. Combined treatment of C57BL6 mice that had been injected with melanoma cells with KINK-1 and doxorubicin or camptothecin reduced metastases and pulmonary tumor mass compared with either treatment alone (mean lung weight 19 days after injection of melanoma cells of mice treated with 3 mg/kg KINK-1 alone, 1 mg/kg doxorubicin alone, and 1 mg/kg doxorubicin plus 3 mg/kg KINK-1 = 260 mg, 95% confidence interval (CI) = 216 to 305 mg; 268 mg, 95% CI = 224 to 313 mg; and 181 mg, 95% CI = 171 to 192 mg, respectively, p < .001 from t tests comparing mean lung weight of double-treated mice to that in mice treated with either compound alone). Conclusion Inhibition of constitutive and induced IKK beta-activity through treatment with KINK-1 might increase tumor susceptibility to chemotherapy."],["dc.identifier.doi","10.1093/jnci/djn174"],["dc.identifier.isi","000256979000010"],["dc.identifier.pmid","18544741"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6287"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54008"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press Inc"],["dc.relation.issn","0027-8874"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","KINK-1, a novel small-molecule inhibitor of IKK beta, and the susceptibility of melanoma cells to antitumoral treatment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","49"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuroinflammation"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Ott, Martina"],["dc.contributor.author","Avendaño-Guzmán, Erika"],["dc.contributor.author","Ullrich, Evelyn"],["dc.contributor.author","Dreyer, Carolin"],["dc.contributor.author","Strauss, Judith"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Schön, Margarete"],["dc.contributor.author","Schön, Michael P"],["dc.contributor.author","Bernhardt, Günter"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Wegner, Christiane"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Nessler, Stefan"],["dc.date.accessioned","2019-07-09T11:50:03Z"],["dc.date.available","2019-07-09T11:50:03Z"],["dc.date.issued","2019"],["dc.description.abstract","Abstract Background Quinoline-3-carboxamides, such as laquinimod, ameliorate CNS autoimmunity in patients and reduce tumor cell metastasis experimentally. Previous studies have focused on the immunomodulatory effect of laquinimod on myeloid cells. The data contained herein suggest that quinoline-3-carboxamides improve the immunomodulatory and anti-tumor effects of NK cells by upregulating the adhesion molecule DNAX accessory molecule-1 (DNAM-1). Methods We explored how NK cell activation by laquinimod inhibits CNS autoimmunity in experimental autoimmune encephalomyelitis (EAE), the most utilized model of MS, and improves immunosurveillance of experimental lung melanoma metastasis. Functional manipulations included in vivo NK and DC depletion experiments and in vitro assays of NK cell function. Clinical, histological, and flow cytometric read-outs were assessed. Results We demonstrate that laquinimod activates natural killer (NK) cells via the aryl hydrocarbon receptor and increases their DNAM-1 cell surface expression. This activation improves the cytotoxicity of NK cells against B16F10 melanoma cells and augments their immunoregulatory functions in EAE by interacting with CD155+ dendritic cells (DC). Noteworthy, the immunosuppressive effect of laquinimod-activated NK cells was due to decreasing MHC class II antigen presentation by DC and not by increasing DC killing. Conclusions This study clarifies how DNAM-1 modifies the bidirectional crosstalk of NK cells with CD155+ DC, which can be exploited to suppress CNS autoimmunity and strengthen tumor surveillance."],["dc.identifier.doi","10.1186/s12974-019-1437-0"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15844"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59689"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Laquinimod, a prototypic quinoline-3-carboxamide and aryl hydrocarbon receptor agonist, utilizes a CD155-mediated natural killer/dendritic cell interaction to suppress CNS autoimmunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]