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","2179"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Molecular Cancer Therapeutics"],["dc.bibliographiccitation.lastpage","2188"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Niemann, Hannah"],["dc.contributor.author","Lammering, Berenice"],["dc.contributor.author","Henkel, Cornelia"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Fritsch, Anne"],["dc.contributor.author","Pruefer, Nicole"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Schraepler, Anke"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Pietsch, Torsten"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:50:18Z"],["dc.date.available","2018-11-07T08:50:18Z"],["dc.date.issued","2011"],["dc.description.abstract","Activation of the Hedgehog (Hh)-signaling pathway due to deficiency in the Hh receptor Patched1 (Ptch) is the pivotal defect leading to formation of basal cell carcinoma (BCC). Recent reports provided evidence of Ptch-dependent secretion of vitamin D(3)-related compound, which functions as an endogenous inhibitor of Hh signaling by repressing the activity of the signal transduction partner of Ptch, Smoothened (Smo). This suggests that Ptch-deficient tumor cells are devoid of this substance, which in turn results in activation of Hh-signaling. Here, we show that the application of the physiologically active form of vitamin D(3), calcitriol, inhibits proliferation and growth of BCC of Ptch mutant mice in vitro and in vivo. This is accompanied by the activation of the vitamin D receptor (Vdr) and induction of BCC differentiation. In addition, calcitriol inhibits Hh signaling at the level of Smo in a Vdr-independent manner. The concomitant antiproliferative effects on BCC growth are stronger than those of the Hh-specific inhibitor cyclopamine, even though the latter more efficiently inhibits Hh signaling. Taken together, we show that exogenous supply of calcitriol controls the activity of 2 independent pathways, Hh and Vdr signaling, which are relevant to tumorigenesis and tumor treatment. These data suggest that calcitriol could be a therapeutic option in the treatment of BCC, the most common tumor in humans. Mol Cancer Ther; 10(11); 2179-88. (C) 2011 AACR."],["dc.identifier.doi","10.1158/1535-7163.MCT-11-0422"],["dc.identifier.isi","000296791300032"],["dc.identifier.pmid","21878656"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21665"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1535-7163"],["dc.title","Antitumoral Effects of Calcitriol in Basal Cell Carcinomas Involve Inhibition of Hedgehog Signaling and Induction of Vitamin D Receptor Signaling and Differentiation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2739"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","2748"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Koenig, Simone"],["dc.contributor.author","Wijgerde, Mark"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Brembeck, Felix H."],["dc.contributor.author","Carstens, Per-Ole"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Klingler, Stefan"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Aberger, Fritz"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:44:23Z"],["dc.date.available","2018-11-07T08:44:23Z"],["dc.date.issued","2010"],["dc.description.abstract","Basal cell carcinoma (BCC) is the most common skin tumor in humans. Although BCCs rarely metastasize, they can cause significant morbidity due to local aggressiveness. Approximately 20% of BCCs show signs of spontaneous regression. The understanding of molecular events mediating spontaneous regression has the potential to reduce morbidity of BCC and, potentially, other tumors, if translated into tumor therapies. We show that BCCs induced in conditional Ptch(flox/flox)ERT(2+/-) knockout mice regress with time and show a more differentiated phenotype. Differentiation is accompanied by Wnt5a expression in the tumor stroma, which is first detectable at the fully developed tumor stage. Coculture experiments revealed that Wnt5a is upregulated in tumor-adjacent macrophages by soluble signals derived from BCC cells. In turn, Wnt5a induces the expression of the differentiation marker K10 in tumor cells, which is mediated by Wnt/Ca(2+) signaling in a CaMKII-dependent manner. These data support a role of stromal Wnt5a in BCC differentiation and regression, which may have important implications for development of new treatment strategies for this tumor. Taken together, our results establish BCC as an easily accessible model of tumor regression. The regression of BCC despite sustained Hedgehog signaling activity seems to be mediated by tumor-stromal interactions via Wnt5a signaling. Cancer Res; 70(7); 2739-48. (C) 2010 AACR."],["dc.identifier.doi","10.1158/0008-5472.CAN-09-3743"],["dc.identifier.isi","000278486000019"],["dc.identifier.pmid","20233865"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20187"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","0008-5472"],["dc.title","Tumor Stroma-Derived Wnt5a Induces Differentiation of Basal Cell Carcinoma of Ptch-Mutant Mice via CaMKII"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Oncogene"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Cuvelier, Nicole"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Simon-Keller, Katja"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Geyer, Natalie"],["dc.contributor.author","Botermann, Dominik S."],["dc.contributor.author","Elmer, Dominik P."],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2021-07-05T15:00:28Z"],["dc.date.available","2021-07-05T15:00:28Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS , KRAS , or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh -driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse."],["dc.description.abstract","Abstract A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS , KRAS , or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh -driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse."],["dc.identifier.doi","10.1038/s41388-021-01904-4"],["dc.identifier.pii","1904"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87833"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.relation.eissn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","Context-dependent modulation of aggressiveness of pediatric tumors by individual oncogenic RAS isoforms"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Genetics"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Pyczek, Joanna"],["dc.contributor.author","Khizanishvili, Natalia"],["dc.contributor.author","Kuzyakova, Maria"],["dc.contributor.author","Zabel, Sebastian"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Boukamp, Petra"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2020-12-10T18:44:24Z"],["dc.date.available","2020-12-10T18:44:24Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.3389/fgene.2019.01185"],["dc.identifier.eissn","1664-8021"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16829"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78434"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Regulation and Role of GLI1 in Cutaneous Squamous Cell Carcinoma Pathogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Anticancer Research"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Niemann, Hannah"],["dc.contributor.author","Lammering, Berenice"],["dc.contributor.author","Henkel, Cornelia"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Fritsch, Anne"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Schraepler, Anke"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Pietsch, Torsten"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:57:14Z"],["dc.date.available","2018-11-07T08:57:14Z"],["dc.date.issued","2011"],["dc.format.extent","1499"],["dc.identifier.isi","000290292000081"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23344"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Int Inst Anticancer Research"],["dc.publisher.place","Athens"],["dc.relation.issn","0250-7005"],["dc.title","ANTITUMOR EFFECTS OF CALCITRIOL IN PATCHED1-ASSOCIATED BASAL CELL CARCINOMA INVOLVES INHIBITION OF HEDGEHOG SIGNALING AND INDUCTION OF DIFFERENTIATION"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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.firstpage","134"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","U256"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Pelczar, Penelope"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","van Dop, Willemijn A."],["dc.contributor.author","Heijmans, Jarom"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Gruber, Wolfgang"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Guijarro, Maria V."],["dc.contributor.author","Hernando, Eva"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Wojnowski, Leszek"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Taguchi, Takahiro"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Hogendoorn, Pancras Cornelis Wilhelmus"],["dc.contributor.author","Antonescu, Cristina R."],["dc.contributor.author","Rubin, Brian P."],["dc.contributor.author","Schulz-Schaeffer, Walter Joachim"],["dc.contributor.author","Aberger, Fritz"],["dc.contributor.author","van den Brink, Gijs R."],["dc.contributor.author","Hahn, Heidi Eva"],["dc.date.accessioned","2018-11-07T09:30:42Z"],["dc.date.available","2018-11-07T09:30:42Z"],["dc.date.issued","2013"],["dc.description.abstract","BACKGROUND & AIMS: A fraction of gastrointestinal stromal tumor (GIST) cells overexpress the platelet-derived growth factor receptor (PDGFR) A, although most overexpress KIT. It is not known if this is because these receptor tyrosine kinases have complementary oncogenic potential, or because of heterogeneity in the cellular origin of GIST. Little also is known about why Hedgehog (HH) signaling is activated in some GIST. HH binds to and inactivates the receptor protein patched homolog (PTCH). METHODS: Ptch was conditionally inactivated in mice (to achieve constitutive HH signaling) using a Cre recombinase regulated by the lysozyme M promoter. Cre-expressing cells were traced using R26R-LacZ reporter mice. Tumors were characterized by in situ hybridization, immunohistochemistry, immunoblot, and quantitative reverse-transcriptase polymerase chain reaction analyses. Cell transformation was assessed by soft agar assay. RESULTS: Loss of Ptch from lysozyme M-expressing cells resulted in the development of tumors of GIST-like localization and histology; these were reduced when mice were given imatinib, a drug that targets KIT and PDGFRA. The Hh signaling pathway was activated in the tumor cells, and Pdgfr alpha, but not Kit, was overexpressed and activated. Lineage tracing revealed that Cre-expressing intestinal cells were Kit-negative. These cells sometimes expressed Pdgfr alpha and were located near Kit-positive interstitial cells of Cajal. In contrast to KIT, activation of PDGFRA increased anchorage-independent proliferation and was required for tumor formation in mice by cells with activated HH signaling. CONCLUSIONS: Inactivation of Ptch in mice leads to formation of GIST-like tumors that express Pdgfr alpha, but not Kit. Activation of Pdgfr alpha signaling appears to facilitate tumorigenesis."],["dc.identifier.doi","10.1053/j.gastro.2012.09.061"],["dc.identifier.isi","000312965100034"],["dc.identifier.pmid","23041331"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31367"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","0016-5085"],["dc.title","Inactivation of Patched1 in Mice Leads to Development of Gastrointestinal Stromal-Like Tumors That Express Pdgfr alpha but Not Kit"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2620"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Investigative Dermatology"],["dc.bibliographiccitation.lastpage","2629"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Koenig, Simone"],["dc.contributor.author","Zabel, Sebastian"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T09:34:46Z"],["dc.date.available","2018-11-07T09:34:46Z"],["dc.date.issued","2014"],["dc.description.abstract","The development of basal cell carcinoma (BCC), the most frequently diagnosed tumor among persons with European ancestry, is closely linked to mutations in the Hedgehog (Hh) receptor and tumor suppressor Patched1 (Ptch). Using Ptch(flox/flox)CD4Cre(+/-) mice, in which Ptch was ablated in CD4Cre-expressing cells, we demonstrate that the targeted cells can give rise to BCC after treatment with DMBA (7,12-dimethylbenz(a)anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate), but not after wounding of the skin. In addition, in this model, BCC are not caused by malfunctioning of Ptch-deficient T cells, as BCC did not develop when bone marrow (BM) of Ptch(flox/flox)CD4Cre(+/-) mice was transplanted into Ptch wild-type mice. Instead, lineage-tracing experiments and flow cytometric analyses suggest that the tumors are initiated from rare Ptch-deficient stem cell-like cells of the epidermis that express CD4. As DMBA/TPA is a prerequisite for BCC development in this model, the initiated cells need a second stimulus for expansion and tumor formation. However, in contrast to papilloma, this stimulus seems to be unrelated to alterations in the Ras signaling cascade. Together, these data suggest that biallelic loss of Ptch in CD4(+) cells does not suffice for BCC formation and that BCC formation requires a second so far unknown event, at least in the Ptch(flox/flox)CD4Cre(+/-) BCC mouse model."],["dc.identifier.doi","10.1038/jid.2014.157"],["dc.identifier.isi","000342200400023"],["dc.identifier.pmid","24662765"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32249"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1523-1747"],["dc.relation.issn","0022-202X"],["dc.title","DMBA/TPA Treatment Is Necessary for BCC Formation from Patched Deficient Epidermal Cells in Ptch(flox/flox)CD4Cre(+/-) Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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"]]