Schön, Margarete

[["dc.bibliographiccitation.firstpage","579"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Experimental Dermatology"],["dc.bibliographiccitation.lastpage","584"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Schneider, Philine"],["dc.contributor.author","Schoen, Margarete"],["dc.contributor.author","Pletz, Nadin"],["dc.contributor.author","Seitz, Cornelia S."],["dc.contributor.author","Liu, Ningshu"],["dc.contributor.author","Ziegelbauer, Karl"],["dc.contributor.author","Zachmann, Karolin"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Schoen, Michael Peter"],["dc.date.accessioned","2018-11-07T09:37:04Z"],["dc.date.available","2018-11-07T09:37:04Z"],["dc.date.issued","2014"],["dc.description.abstract","Due to its almost universal resistance to chemotherapy, metastasized melanoma remains a major challenge in clinical oncology. Given that phosphatidyl inositol-3 kinase (PI3K) activation in melanoma cells is associated with poor prognosis, disease progression and resistance to chemotherapy, the PI3K-Akt signalling pathway is a promising therapeutic target for melanoma treatment. We analysed six human melanoma cell lines for their constitutive activation of Akt and then tested two representative lines, A375 and LOX, for their susceptibility to PI3K-inhibition by the highly specific small molecule inhibitor, BAY 80-6946. In addition, the effect of BAY 80-6946 on A375 and LOX melanoma cells was assessed in vivo in a xenotransplantation mouse model. We provide experimental evidence that specifically inhibiting the PI3K pathway and phosphorylation of Akt by this novel compound results in antitumoral activities including inhibition of proliferation, induction of apoptosis and cell cycle arrest in vitro and in vivo. However, the susceptibility did not show a clear-cut pattern and differed between the melanoma cell lines tested, resulting in in vivo growth inhibition of A375 but not LOX melanoma cells. Thus, in some cases BAY 80-6946 or related compounds may be a valuable addition to the therapeutic armamentarium."],["dc.description.sponsorship","Wilhelm Sander Stiftung"],["dc.identifier.doi","10.1111/exd.12470"],["dc.identifier.isi","000340536100013"],["dc.identifier.pmid","24942196"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32754"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1600-0625"],["dc.relation.issn","0906-6705"],["dc.title","The novel PI3 kinase inhibitor, BAY 80-6946, impairs melanoma growth in vivo and in vitro"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Investigative Dermatology"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Pletz, Nadin"],["dc.contributor.author","Schoen, Michael Peter"],["dc.contributor.author","Ziegelbauer, Karl"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Liu, Ningshu"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Schoen, Margarete"],["dc.date.accessioned","2018-11-07T08:52:43Z"],["dc.date.available","2018-11-07T08:52:43Z"],["dc.date.issued","2011"],["dc.format.extent","S37"],["dc.identifier.isi","000294361300222"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22240"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.publisher.place","New york"],["dc.relation.conference","41st Annual Meeting of the European-Society-for-Dermatological-Research"],["dc.relation.eventlocation","Barcelona, SPAIN"],["dc.relation.issn","0022-202X"],["dc.title","Doxorubicin-induced activation of NF-kappa B in melanoma cells is abrogated by specific inhibition of IKK beta, but not IKK alpha"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","301"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Experimental Dermatology"],["dc.bibliographiccitation.lastpage","304"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Pletz, Nadin"],["dc.contributor.author","Schoen, Margarete"],["dc.contributor.author","Ziegelbauer, Karl"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Liu, Ningshu"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Schoen, Michael Peter"],["dc.date.accessioned","2018-11-07T09:11:39Z"],["dc.date.available","2018-11-07T09:11:39Z"],["dc.date.issued","2012"],["dc.description.abstract","Drug resistance is arguably the most important challenge in cancer therapy. Here, doxorubicin induced profound of NF-kappa B activation in melanoma cells with a maximum (3.5-fold) at concentrations relevant in vivo. This was followed by transcriptional induction of several gene products involved in tumor progression. A novel IKKa inhibitor (BAY32-5915) was identified and characterized, and doxorubicin-induced NF-kappa B activation was assessed following inhibition of IKKa or IKK beta by small-molecular compounds. While the IKKa inhibitor did not affect doxorubicin-induced NF-kappa B activation, this process was completely abrogated when the IKK beta inhibitor, KINK-1, was used. Moreover, inhibition of IKK beta, but not IKKa, led to significantly increased apoptosis in response to doxorubicin. Our results indicate that the net outcome of chemotherapy is difficult to predict and may even involve mechanisms conferring chemoresistance. In case of doxorubicin-induced NF-kappa B activation, blocking IKK beta, but not IKK alpha, by small molecules can antagonize this activity and, thus, increase chemosensitivity."],["dc.identifier.doi","10.1111/j.1600-0625.2012.01440.x"],["dc.identifier.isi","000301532600012"],["dc.identifier.pmid","22320445"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26770"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1600-0625"],["dc.relation.issn","0906-6705"],["dc.title","Doxorubicin-induced activation of NF-kappa B in melanoma cells is abrogated by inhibition of IKK beta, but not by a novel IKK alpha inhibitor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","91"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Experimental Dermatology"],["dc.bibliographiccitation.lastpage","98"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Schill, Tillmann"],["dc.contributor.author","Schoen, Michael Peter"],["dc.contributor.author","Pletz, Nadin"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Schoen, Margarete"],["dc.date.accessioned","2018-11-07T09:14:03Z"],["dc.date.available","2018-11-07T09:14:03Z"],["dc.date.issued","2012"],["dc.description.abstract","Given that metastasized melanoma is a fatal disease in most cases, it is tempting to develop strategies to a priori prevent metastasis. We have stimulated the pulmonary innate immune system by macrophage-activating lipopeptide-2 (MALP-2), a specific agonist at Toll-like receptor (TLR) 2/6, and investigated its impact on experimental melanoma metastasis. In C57BL/6 mice, intratracheal application of MALP-2 induced a profound influx of neutrophils and macrophages into the lung, which peaked after 24 h (sixfold increase) and returned to baseline within 72 h. Further analysis revealed that MALP-2 also markedly induced VCAM-1 expression on pulmonary blood vessels. In vitro experiments demonstrated that this adhesion molecule mediates binding of B16F10 melanoma cells. Furthermore, in vivo or in vitro treatment with MALP-2 did not significantly affect the ability of immune cells to lyse melanoma cells. As a consequence, notwithstanding the profound pulmonary immune response induction and in contrast to conclusions drawn from some previous publications, the net extent of experimental metastasis did not change significantly, regardless of the application regimen of MALP-2 prior to, concomitant with or after tumor cell inoculation. Melanoma cells stably transfected with green fluorescent protein allowed tracking of early events after tumor cell dissemination and showed that MALP-2-mediated TLR2/6 activation did not interfere with pulmonary melanoma cell arrest. Likewise, boosting the immune induction after establishment of metastases did not change the clinical outcome. These unexpected results vividly counsel caution regarding predictions of immunomodulating therapies, as multiple intertwined effects may influence the net outcome."],["dc.identifier.doi","10.1111/j.1600-0625.2011.01386.x"],["dc.identifier.isi","000298917000003"],["dc.identifier.pmid","22044500"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27311"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0906-6705"],["dc.title","Stimulation of pulmonary immune responses by the TLR2/6 agonist MALP-2 and effect on melanoma metastasis to the lung"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]