Dittmann, Kai

[["dc.bibliographiccitation.artnumber","396"],["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Geyer, Natalie"],["dc.contributor.author","Ridzewski, Rosalie"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Kuzyakova, Maria"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Fulda, Simone"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2019-07-09T11:50:33Z"],["dc.date.available","2019-07-09T11:50:33Z"],["dc.date.issued","2018"],["dc.description.abstract","Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with poor prognosis. RMS frequently show Hedgehog (HH) pathway activity, which is predominantly seen in the embryonal subtype (ERMS). They also show activation of Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling. Here we compared the therapeutic effectiveness and the impact on HH target gene expression of Smoothened (SMO) antagonists with those of the PI3K inhibitor pictilisib in ERMS with and without mutations in the HH receptor Patched1 (PTCH). Our data demonstrate that growth of ERMS showing canonical Hh signaling activity due to Ptch germline mutations is efficiently reduced by SMO antagonists. This goes along with strong downregulation of the Hh target Gli1. Likewise Ptch mutant tumors are highly responsive toward the PI3K inhibitor pictilisib, which involves modulation of AKT and caspase activity. Pictilisib also modulates Hh target gene expression, which, however, is rather not correlated with its antitumoral effects. In contrast, sporadic ERMS, which usually express HH target genes without having PTCH mutation, apparently lack canonical HH signaling activity. Thus, stimulation by Sonic HE (SHH) or SAG (Smoothened agonist) or inhibition by SMO antagonists do not modulate HH target gene expression. In addition, SMO antagonists do not provoke efficient anticancer effects and rather exert off-target effects. In contrast, pictilisib and other PI3K/AKT/mTOR inhibitors potently inhibit cellular growth. They also efficiently inhibit HH target gene expression. However, of whether this is correlated with their antitumoral effects it is not clear. Together, these data suggest that PI3K inhibitors are a good and reliable therapeutic option for all ERMS, whereas SMO inhibitors might only be beneficial for ERMS driven by PTCH mutations."],["dc.identifier.doi","10.3389/fonc.2018.00396"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15965"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59798"],["dc.language.iso","en"],["dc.subject.ddc","610"],["dc.title","Different Response of Ptch Mutant and Ptch Wildtype Rhabdomyosarcoma Toward SMO and PI3K Inhibitors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e52898"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Marklein, Diana"],["dc.contributor.author","Graab, Ulrike"],["dc.contributor.author","Naumann, Ivonne"],["dc.contributor.author","Yan, T."],["dc.contributor.author","Ridzewski, Rosalie"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Wojnowski, Leszek"],["dc.contributor.author","Fulda, Simone"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T09:02:08Z"],["dc.date.available","2018-11-07T09:02:08Z"],["dc.date.issued","2012"],["dc.description.abstract","We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX). We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines."],["dc.description.sponsorship","DFG [GRK 1034, WO505/3-1]; Deutsche Krebshilfe [109837 (KoSAR)]"],["dc.identifier.doi","10.1371/journal.pone.0052898"],["dc.identifier.isi","000313872600033"],["dc.identifier.pmid","23300809"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8548"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24607"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","PI3K Inhibition Enhances Doxorubicin-Induced Apoptosis in Sarcoma 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.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Ridzewski, Rosalie"],["dc.contributor.author","Rettberg, Diana"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Cuvelier, Nicole"],["dc.contributor.author","Fulda, Simone"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2021-06-01T10:48:45Z"],["dc.date.available","2021-06-01T10:48:45Z"],["dc.date.issued","2015"],["dc.identifier.doi","10.3389/fonc.2015.00130"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86047"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","2234-943X"],["dc.title","Hedgehog Inhibitors in Rhabdomyosarcoma: A Comparison of Four Compounds and Responsiveness of Four Cell Lines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]