Roßmann, Laura

[["dc.bibliographiccitation.firstpage","780"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","780"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Stark, Nadine"],["dc.contributor.author","Schulz-Heddergott, Ramona"],["dc.contributor.author","Erytch, Norman"],["dc.contributor.author","Edmunds, Shelley"],["dc.contributor.author","Roßmann, Laura"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Concin, Nicole"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2020-12-10T18:09:42Z"],["dc.date.available","2020-12-10T18:09:42Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41418-018-0190-8"],["dc.identifier.eissn","1476-5403"],["dc.identifier.issn","1350-9047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73731"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation.iserratumof","/handle/2/43281"],["dc.title","Correction: Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","erratum_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","300"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","316"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Stark, Nadine"],["dc.contributor.author","Schulz-Heddergott, Ramona"],["dc.contributor.author","Erytch, Norman"],["dc.contributor.author","Edmunds, Shelley"],["dc.contributor.author","Rossmann, Laura"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Concin, Nicole"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2018-11-07T10:27:41Z"],["dc.date.available","2018-11-07T10:27:41Z"],["dc.date.issued","2017"],["dc.description.abstract","All current regimens for treating ovarian cancer center around carboplatin as standard first line. The HSP90 inhibitor ganetespib is currently being assessed in advanced clinical oncology trials. Thus, we tested the combined effects of ganetespib and carboplatin on a panel of 15 human ovarian cancer lines. Strikingly, the two drugs strongly synergized in cytotoxicity in tumor cells lacking wild-type p53. Mechanistically, ganetespib and carboplatin in combination, but not individually, induced persistent DNA damage causing massive global chromosome fragmentation. Live-cell microscopy revealed chromosome fragmentation occurring to a dramatic degree when cells condensed their chromatin in preparation for mitosis, followed by cell death in mitosis or upon aberrant exit from mitosis. HSP90 inhibition caused the rapid decay of key components of the Fanconi anemia pathway required for repair of carboplatin-induced interstrand crosslinks (ICLs), as well as of cell cycle checkpoint mediators. Overexpressing FancA rescued the DNA damage induced by the drug combination, indicating that FancA is indeed a key client of Hsp90 that enables cancer cell survival in the presence of ICLs. Conversely, depletion of nuclease DNA2 prevented chromosomal fragmentation, pointing to an imbalance of defective repair in the face of uncontrolled nuclease activity as mechanistic basis for the observed premitotic DNA fragmentation. Importantly, the drug combination induced robust antitumor activity in xenograft models, again accompanied with depletion of FancA. In sum, our findings indicate that ganetespib strongly potentiates the antitumor efficacy of carboplatin by causing combined inhibition of DNA repair and cell cycle control mechanisms, thus triggering global chromosome disruption, aberrant mitosis and cell death."],["dc.identifier.doi","10.1038/cdd.2016.124"],["dc.identifier.isi","000395789500012"],["dc.identifier.pmid","27834954"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43281"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.haserratum","/handle/2/73731"],["dc.relation.issn","1476-5403"],["dc.relation.issn","1350-9047"],["dc.title","Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1220"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","1233"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Kaiser, Tina K."],["dc.contributor.author","Li, Hu"],["dc.contributor.author","Roßmann, Laura"],["dc.contributor.author","Reichardt, Sybille D."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Feldmann, Claus"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2021-04-14T08:27:15Z"],["dc.date.available","2021-04-14T08:27:15Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Glucocorticoids (GCs) are widely used to treat acute graft‐versus‐host disease (aGvHD) due to their immunosuppressive activity, but they also reduce the beneficial graft‐versus‐leukemia (GvL) effect of the allogeneic T cells contained in the graft. Here, we tested whether aGvHD therapy could be improved by delivering GCs with the help of inorganic–organic hybrid nanoparticles (IOH‐NPs) that preferentially target myeloid cells. IOH‐NPs containing the GC betamethasone (BMP‐NPs) efficiently reduced morbidity, mortality, and tissue damage in a totally MHC mismatched mouse model of aGvHD. Therapeutic activity was lost in mice lacking the GC receptor (GR) in myeloid cells, confirming the cell type specificity of our approach. BMP‐NPs had no relevant systemic activity but suppressed cytokine and chemokine gene expression locally in the small intestine, which presumably explains their mode of action. Most importantly, BMP‐NPs delayed the development of an adoptively transferred B cell lymphoma better than the free drug, although the overall incidence was unaffected. Our findings thus suggest that employing IOH‐NPs could diminish the risk of relapse associated with GC therapy of aGvHD patients while still allowing to efficiently ameliorate the disease."],["dc.description.abstract","Clinical symptoms and histological hallmarks of acute graft‐versus‐host disease in mice are ameliorated by glucocorticoids when specifically delivered to macrophages with the help of nanoparticles. In addition, this therapeutic intervention improves the graft‐versus‐leukemia effect compared to the free drug, and thus presumably reduces the risk of relapse. image"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1002/eji.201948464"],["dc.identifier.eissn","1521-4141"],["dc.identifier.issn","0014-2980"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82221"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Glucocorticoids delivered by inorganic–organic hybrid nanoparticles mitigate acute graft‐versus‐host disease and sustain graft‐versus‐leukemia activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","15437"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","15450"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Baake, Tina"],["dc.contributor.author","Jörß, Katharina"],["dc.contributor.author","Suennemann, Jennifer"],["dc.contributor.author","Roßmann, Laura"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Reichardt, Holger M."],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Reichardt, Sybille D."],["dc.date.accessioned","2019-07-09T11:45:14Z"],["dc.date.available","2019-07-09T11:45:14Z"],["dc.date.issued","2018"],["dc.description.abstract","Graft-versus-host disease (GvHD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), which is caused by allogeneic T cells recognizing molecules of the recipient as foreign. Endogenous glucocorticoids (GC) released from the adrenal gland are crucial in regulating such inflammatory diseases. Here we demonstrate that genetically engineered mice, that are largely unresponsive to GC, suffer from aggravated clinical symptoms and increased mortality after HSCT, effects that could be tempered by neutralization of IL-6. Interestingly, selective ablation of the GC receptor (GR) in recipient myeloid cells resulted in fulminant disease as well. While histopathological analysis of the jejunum failed to reveal any differences between sick mice of both genotypes, systemic IL-6 and TNFα secretion was strongly increased in transplanted mice lacking the GR in myeloid cells briefly before the majority of them succumbed to the disease. Collectively, our findings reveal an important role of the GR in recipient cells in limiting the cytokine storm caused by GvHD induction."],["dc.identifier.doi","10.18632/oncotarget.24602"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15071"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59189"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.ddc","610"],["dc.title","The glucocorticoid receptor in recipient cells keeps cytokine secretion in acute graft-versus-host disease at bay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]