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","341"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Genetics in Medicine"],["dc.bibliographiccitation.lastpage","351"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Schröder, Simone"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Bader, Ingrid"],["dc.contributor.author","Bevot, Andrea"],["dc.contributor.author","Biskup, Saskia"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Christoph Korenke, G."],["dc.contributor.author","Kottke, Raimund"],["dc.contributor.author","Mayr, Johannes A."],["dc.contributor.author","Preisel, Martin"],["dc.contributor.author","Toelle, Sandra P."],["dc.contributor.author","Wente-Schulz, Sarah"],["dc.contributor.author","Wortmann, Saskia B."],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Boltshauser, Eugen"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2021-04-14T08:31:50Z"],["dc.date.available","2021-04-14T08:31:50Z"],["dc.date.issued","2020"],["dc.description.abstract","Purpose\r\n\r\nThis study aimed to delineate the genetic basis of congenital ocular motor apraxia (COMA) in patients not otherwise classifiable.\r\nMethods\r\n\r\nWe compiled clinical and neuroimaging data of individuals from six unrelated families with distinct clinical features of COMA who do not share common diagnostic characteristics of Joubert syndrome or other known genetic conditions associated with COMA. We used exome sequencing to identify pathogenic variants and functional studies in patient-derived fibroblasts.\r\nResults\r\n\r\nIn 15 individuals, we detected familial as well as de novo heterozygous truncating causative variants in the Suppressor of Fused (SUFU) gene, a negative regulator of the Hedgehog (HH) signaling pathway. Functional studies showed no differences in cilia occurrence, morphology, or localization of ciliary proteins, such as smoothened. However, analysis of expression of HH signaling target genes detected a significant increase in the general signaling activity in COMA patient–derived fibroblasts compared with control cells. We observed higher basal HH signaling activity resulting in increased basal expression levels of GLI1, GLI2, GLI3, and Patched1. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign.\r\nConclusion\r\n\r\nTaken together, our data imply that the clinical phenotype associated with heterozygous truncating germline variants in SUFU is a forme fruste of Joubert syndrome."],["dc.identifier.doi","10.1038/s41436-020-00979-w"],["dc.identifier.pmid","33024317"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83726"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/80"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1530-0366"],["dc.relation.issn","1098-3600"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","CC BY 4.0"],["dc.title","Heterozygous truncating variants in SUFU cause congenital ocular motor apraxia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9295"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","21"],["dc.contributor.affiliation","Brandes, Nadine; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, nadine.brandes@med.uni-goettingen.de"],["dc.contributor.affiliation","Mitkovska, Slavica Hristomanova; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, s.hristomanovamitk@stud.uni-goettingen.de"],["dc.contributor.affiliation","Botermann, Dominik Simon; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, dominik.botermann@med.uni-goettingen.de"],["dc.contributor.affiliation","Maurer, Wiebke; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, wiebke.maurer@stud.uni-goettingen.de"],["dc.contributor.affiliation","Müllen, Anna; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, anna.muellen@stud.uni-goettingen.de"],["dc.contributor.affiliation","Scheile, Hanna; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, hannarabe@gmx.de"],["dc.contributor.affiliation","Zabel, Sebastian; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, sebastian.zabel@live.de"],["dc.contributor.affiliation","Frommhold, Anke; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, anke.frommhold@med.uni-goettingen.de"],["dc.contributor.affiliation","Heß, Ina; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, ihess@gwdg.de"],["dc.contributor.affiliation","Hahn, Heidi; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, hhahn@gwdg.de"],["dc.contributor.affiliation","Uhmann, Anja; \t\t \r\n\t\t Tumor Genetics Group, Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37079 Göttingen, Germany, auhmann@gwdg.de"],["dc.contributor.author","Brandes, Nadine"],["dc.contributor.author","Mitkovska, Slavica Hristomanova"],["dc.contributor.author","Botermann, Dominik Simon"],["dc.contributor.author","Maurer, Wiebke"],["dc.contributor.author","Müllen, Anna"],["dc.contributor.author","Scheile, Hanna"],["dc.contributor.author","Zabel, Sebastian"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Heß, Ina"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Uhmann, Anja"],["dc.date.accessioned","2021-04-14T08:24:51Z"],["dc.date.available","2021-04-14T08:24:51Z"],["dc.date.issued","2020"],["dc.date.updated","2022-09-06T08:37:10Z"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/ijms21239295"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81445"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Spreading of Isolated Ptch Mutant Basal Cell Carcinoma Precursors Is Physiologically Suppressed and Counteracts Tumor Formation in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e61034"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Michel, Kai D."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:26:05Z"],["dc.date.available","2018-11-07T09:26:05Z"],["dc.date.issued","2013"],["dc.description.abstract","Hedgehog (Hh) signaling modulates T cell development and function but its exact role remains a matter of debate. To further address this issue we made use of conditional knock-out mice in which the Hh receptor Patched1 (Ptch) is inactivated in the T cell lineage. Thymocyte development was moderately compromised by the deletion of Ptch as characterized by reduced numbers of CD4 and CD8 single-positive cells. In contrast, peripheral T cells were not affected. Proliferation and IFN gamma secretion by Ptch-deficient T cells were indistinguishable from controls irrespectively of whether we used strong or suboptimal conditions for stimulation. Analysis of CTL and T-reg cell functions did not reveal any differences between both genotypes, and T cell apoptosis induced by glucocorticoids or gamma-irradiation was also similar. Surprisingly, absence of Ptch did not lead to an activation of canonic Hh signaling in peripheral T cells as indicated by unaltered expression levels of Gli1 and Gli2. To test whether we could uncover any role of Ptch in T cells in vivo we subjected the mutant mice to three different disease models, namely allogeneic bone marrow transplantation mimicking graft-versus-host disease, allergic airway inflammation as a model of asthma and growth of adoptively transferred melanoma cells as a means to test tumor surveillance by the immune system. Nonetheless, we were neither able to demonstrate any difference in the disease courses nor in any pathogenic parameter in these three models of adaptive immunity. We therefore conclude that the Hh receptor Ptch is dispensable for T cell function in vitro as well as in vivo."],["dc.identifier.doi","10.1371/journal.pone.0061034"],["dc.identifier.isi","000317898000092"],["dc.identifier.pmid","23577186"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8912"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30214"],["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-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","The Hedgehog Receptor Patched1 in T Cells Is Dispensable for Adaptive Immunity 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.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.firstpage","1"],["dc.bibliographiccitation.journal","Sarcoma"],["dc.bibliographiccitation.lastpage","7"],["dc.bibliographiccitation.volume","2012"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Niemann, Hannah"],["dc.contributor.author","Lammering, Bérénice"],["dc.contributor.author","Henkel, Cornelia"],["dc.contributor.author","Heß, Ina"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Schraepler, Anke"],["dc.contributor.author","Schulz-Schaeffer, Walter"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2019-07-09T11:53:34Z"],["dc.date.available","2019-07-09T11:53:34Z"],["dc.date.issued","2012"],["dc.description.abstract","Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Aberrant Hedgehog (Hh) signaling is characteristic of the embryonal subtype (ERMS) and of fusion-negative alveolar RMS. In the mouse, ERMS-like tumors can be induced by mutations in the Hh receptor Patched1 (Ptch). As in humans these tumors show increased Hh pathway activity. Here we demonstrate that the treatment with the active form of vitamin D3, calcitriol, inhibits Hh signaling and proliferation of murine ERMS in vivo and in vitro. Concomitantly, calcitriol activates vitamin D receptor (Vdr) signaling and induces tumor differentiation. In addition, calcitriol inhibits ERMS growth in Ptch-mutant mice, which is, however, a rather late response. Taken together, our results suggest that exogenous supply of calcitriol could be beneficial in the treatment of RMS, especially in those which are associated with aberrant Hh signaling activity."],["dc.identifier.doi","10.1155/2012/357040"],["dc.identifier.fs","585079"],["dc.identifier.pmid","22550417"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7722"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60449"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in the Patched Mouse Model of Embryonal Rhabdomyosarcoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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.artnumber","13377"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Botermann, Dominik S."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2022-01-11T14:08:09Z"],["dc.date.available","2022-01-11T14:08:09Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-03T23:24:46Z"],["dc.description.abstract","In the Ptch+/- mouse model for embryonal rhabdomyosarcoma (ERMS), we recently showed that oncogenic (onc) H-, K- or NRAS mutations do not influence tumor growth when induced at the advanced, full-blown tumor stage. However, when induced at the invisible ERMS precursor stage at 4 weeks of age, tumor development was enforced upon oncHRAS and oncKRAS but not by oncNRAS, which instead initiated tumor differentiation. These data indicate that oncRAS-associated processes differ from each other in dependency on the isoform and their occurrence during tumor development. Here, we investigated the outcome of oncNRAS induction at an earlier ERMS precursor stage at 2 weeks of age. In this setting, oncNRAS accelerates tumor growth because it significantly shortens the ERMS-free survival and increases the ERMS incidence. However, it does not seem to alter the differentiation of the tumors. It is also not involved in tumor initiation. Together, these data show that oncNRAS mutations can accelerate tumor growth when targeting immature ERMS precursors within a specific time window, in which the precursors are permissive to the mutation and show that oncNRAS-associated processes differ from each other in dependency on their occurrence during tumor development."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/ijms222413377"],["dc.identifier.pii","ijms222413377"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97949"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Oncogenic NRAS Accelerates Rhabdomyosarcoma Formation When Occurring within a Specific Time Frame during Tumor Development in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","24928"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Pyczek, Joanna"],["dc.contributor.author","Buslei, Rolf"],["dc.contributor.author","Schult, David"],["dc.contributor.author","Hoelsken, Annett"],["dc.contributor.author","Buchfelder, Michael"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Uhmann, Anja"],["dc.date.accessioned","2018-11-07T10:15:25Z"],["dc.date.available","2018-11-07T10:15:25Z"],["dc.date.issued","2016"],["dc.description.abstract","Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors."],["dc.identifier.doi","10.1038/srep24928"],["dc.identifier.isi","000374642300002"],["dc.identifier.pmid","27109116"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13312"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40804"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland"],["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"]]