Hahn, Heidi Eva

[["dc.bibliographiccitation.artnumber","e93555"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Koenig, Simone"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Theiss-Suennemann, Jennifer"],["dc.contributor.author","Herrmann, Markus"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Schwendener, Reto"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T09:41:53Z"],["dc.date.available","2018-11-07T09:41:53Z"],["dc.date.issued","2014"],["dc.description.abstract","Basal cell carcinoma (BCC) belongs to the group of non-melanoma skin tumors and is the most common tumor in the western world. BCC arises due to mutations in the tumor suppressor gene Patched1 (Ptch). Analysis of the conditional Ptch knockout mouse model for BCC reveals that macrophages and dendritic cells (DC) of the skin play an important role in BCC growth restraining processes. This is based on the observation that a clodronate-liposome mediated depletion of these cells in the tumor-bearing skin results in significant BCC enlargement. The depletion of these cells does not modulate Ki67 or K10 expression, but is accompanied by a decrease in collagen-producing cells in the tumor stroma. Together, the data suggest that cutaneous macrophages and DC in the tumor microenvironment exert an antitumor effect on BCC."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [FOR942 HA 2197/5-2]"],["dc.identifier.doi","10.1371/journal.pone.0093555"],["dc.identifier.isi","000334101100104"],["dc.identifier.pmid","24691432"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10067"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33833"],["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 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Depletion of Cutaneous Macrophages and Dendritic Cells Promotes Growth of Basal Cell Carcinoma in Mice"],["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","9113"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","9124"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Tolosa, Ezequiel J."],["dc.contributor.author","Cuvelier, Nicole"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Fernandez-Zapico, Martin E."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2019-07-09T11:41:58Z"],["dc.date.available","2019-07-09T11:41:58Z"],["dc.date.issued","2015-04-20"],["dc.description.abstract","Mice with heterozygous loss of the tumor suppressor Patched1 (Ptch) develop rhabdomyosarcoma (RMS)-like tumors. However, Ptch transcripts are consistently overexpressed in these tumors. We have recently shown that the upregulated transcripts are derived from the mutated Ptch allele thus leading to the hypothesis that the wild-type allele is repressed during RMS development. Here we describe epigenetic changes taking place at the Ptch locus during RMS development. We showed a lower degree of DNA-methylation in methylation-sensitive CpG regions of the Ptch promoter in RMS compared to normal muscle from heterozygous Ptch animals. In agreement with these results, treatment of heterozygous Ptch mice with the DNA demethylating agent 5-aza-2-deoxycytidine (5-aza-dC) between embryonic days E9.5-E11.5 significantly accelerated RMS formation. Since Ptch promoter methylation occurs after/around E13.5, the window for RMS initiation during embryogenesis, these results provide additional evidence that Ptch promoter hypomethylation may contribute to RMS formation. We have also demonstrated increased trimethylation of histone H3 lysine 4 (H3K4me3) and preferential binding of Gli1, a known Ptch activator, to the mutant locus in RMS. Together, these findings support an alternative model for RMS formation in heterozygous Ptch mice including loss of methylation and concomitant occupancy by activating histone marks of mutant Ptch."],["dc.identifier.doi","10.18632/oncotarget.3272"],["dc.identifier.pmid","25823816"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12644"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58561"],["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.title","Overexpression of mutant Ptch in rhabdomyosarcomas is associated with promoter hypomethylation and increased Gli1 and H3K4me3 occupancy."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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.firstpage","887"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","895"],["dc.bibliographiccitation.volume","69"],["dc.contributor.author","Ecke, Ines"],["dc.contributor.author","Petry, Frauke"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Tauber, Svantje"],["dc.contributor.author","Moenkemeyer, Sven"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Kimmina, Sarah"],["dc.contributor.author","Pirngruber, Judith"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Wojnowski, Leszek"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Witt, Olaf"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:32:54Z"],["dc.date.available","2018-11-07T08:32:54Z"],["dc.date.issued","2009"],["dc.description.abstract","Patched (etch) heterozygous mice develop medulloblastoma (MB) and rhabdomyosarcoma (RMS) resembling the corresponding human tumors. We have previously shown that epigenetic silencing of the intact Ptch allele contributes to tumor formation in this model. Here, we investigated whether targeting of epigenetic silencing mechanisms could be useful in the treatment of Ptch-associated cancers. A reduction of endogenous DNA methyltransferasel (Dnmt1) activity significantly reduced tumor incidence in heterozygous Ptch knockout mice. A combined treatment with the Dnmt inhibitor 5-aza-2'deoxycytidine (5-aza-dC) and the histone deacetlyase (HDAC) inhibitor valproic acid (VPA) efficiently prevented MB and RMS formation, whereas monotherapies with either drug were less effective. Wild-type Ptch expression was efficiently reactivated in tumors by 5-aza-dC/VPA combination therapy. This was associated with reduced methylation of the Pitch promoter and induction of historic hyperacetylation suggesting inhibition of HDACs is vivo. However, the treatment was not effective in clinically overt, advanced stage tumors. This is a first in vivo demonstration that targeting of Dnmt and HDAC activities is highly effective in preventing formation of Ptch-associated tumors. The results suggest a novel clinical strategy for consolidation therapy of corresponding tumors in humans after completion of conventional treatment. Our data also suggest that epigenetic therapy may be less effective in treating advanced stages of tumors, at least in this tumor model. [Cancer Res 2009;69(3):887-95]"],["dc.identifier.doi","10.1158/0008-5472.CAN-08-0946"],["dc.identifier.isi","000263048700023"],["dc.identifier.pmid","19155313"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6234"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17446"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","0008-5472"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Antitumor Effects of a Combined 5-Aza-2 ' Deoxycytidine and Valproic Acid Treatment on Rhabdomyosarcoma and Medulloblastoma in Ptch Mutant Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Journal of Skin Cancer"],["dc.bibliographiccitation.lastpage","11"],["dc.bibliographiccitation.volume","2012"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Becker, Marco"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Schulz-Schaeffer, Walter"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2019-07-09T11:54:04Z"],["dc.date.available","2019-07-09T11:54:04Z"],["dc.date.issued","2012"],["dc.description.abstract","Basal cell carcinoma (BCC) is the most common human tumor. Mutations in the hedgehog (HH) receptor Patched (PTCH) are the main cause of BCC. Due to their high and increasing incidence, BCC are becoming all the more important for the health care system. Adequate animal models are required for the improvement of current treatment strategies. A good model should reflect the situation in humans (i.e., BCC initiation due to Ptch mutations on an immunocompetent background) and should allow for (i) BCC induction at a defined time point, (ii) analysis of defined BCC stages, and (iii) induction of BCC in 100% of animals. In addition, it should be easy to handle. Here, we compare several currently existing conventional and conditional Ptch knockout mousemodels for BCC and their potential use in preclinical research. In addition, we provide new data using conditional Ptchf lox/ f lox mice and the K5-Cre-ERT+/− driver."],["dc.identifier.doi","10.1155/2012/907543"],["dc.identifier.fs","592804"],["dc.identifier.pmid","23024864"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8397"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60564"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2090-2905"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Patched Knockout Mouse Models of Basal Cell Carcinoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]