Rosenberger, Albert

[["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","959"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","JNCI Journal of the National Cancer Institute"],["dc.bibliographiccitation.lastpage","971"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Truong, T."],["dc.contributor.author","Hung, R. J."],["dc.contributor.author","Amos, Christopher I."],["dc.contributor.author","Wu, X."],["dc.contributor.author","Bickeböller, H."],["dc.contributor.author","Rosenberger, A."],["dc.contributor.author","Sauter, W."],["dc.contributor.author","Illig, T."],["dc.contributor.author","Wichmann, H.- E."],["dc.contributor.author","Risch, A."],["dc.contributor.author","Dienemann, H."],["dc.contributor.author","Kaaks, R."],["dc.contributor.author","Yang, P."],["dc.contributor.author","Jiang, R."],["dc.contributor.author","Wiencke, J. K."],["dc.contributor.author","Wrensch, M."],["dc.contributor.author","Hansen, Helen"],["dc.contributor.author","Kelsey, K. T."],["dc.contributor.author","Matsuo, K."],["dc.contributor.author","Tajima, K."],["dc.contributor.author","Schwartz, A. G."],["dc.contributor.author","Wenzlaff, A."],["dc.contributor.author","Seow, A."],["dc.contributor.author","Ying, C."],["dc.contributor.author","Staratschek-Jox, A."],["dc.contributor.author","Nurnberg, P."],["dc.contributor.author","Stoelben, E."],["dc.contributor.author","Wolf, J."],["dc.contributor.author","Lazarus, P."],["dc.contributor.author","Muscat, J. E."],["dc.contributor.author","Gallagher, C. J."],["dc.contributor.author","Zienolddiny, S."],["dc.contributor.author","Haugen, A."],["dc.contributor.author","van der Heijden, H. F. M."],["dc.contributor.author","Kiemeney, L. A."],["dc.contributor.author","Isla, D."],["dc.contributor.author","Mayordomo, J. I."],["dc.contributor.author","Rafnar, T."],["dc.contributor.author","Stefansson, K."],["dc.contributor.author","Zhang, Z.-F."],["dc.contributor.author","Chang, S.-C."],["dc.contributor.author","Kim, J. H."],["dc.contributor.author","Hong, Y.-C."],["dc.contributor.author","Duell, E. J."],["dc.contributor.author","Andrew, Angeline S."],["dc.contributor.author","Lejbkowicz, F."],["dc.contributor.author","Rennert, G."],["dc.contributor.author","Muller, H."],["dc.contributor.author","Brenner, H."],["dc.contributor.author","Le Marchand, L."],["dc.contributor.author","Benhamou, S."],["dc.contributor.author","Bouchardy, C."],["dc.contributor.author","Teare, M. D."],["dc.contributor.author","Xue, X."],["dc.contributor.author","McLaughlin, J."],["dc.contributor.author","Liu, G."],["dc.contributor.author","McKay, J. D."],["dc.contributor.author","Brennan, P."],["dc.contributor.author","Spitz, M. R."],["dc.date.accessioned","2019-07-09T11:52:53Z"],["dc.date.available","2019-07-09T11:52:53Z"],["dc.date.issued","2010"],["dc.description.abstract","Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case–control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10226), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10210) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 1028) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 1025; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusions In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology."],["dc.identifier.doi","10.1093/jnci/djq178"],["dc.identifier.fs","575235"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6100"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60298"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","113"],["dc.bibliographiccitation.journal","BMC cancer"],["dc.bibliographiccitation.lastpage","9"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Mittelstrass, Kirstin"],["dc.contributor.author","Sauter, Wiebke"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Illig, Thomas"],["dc.contributor.author","Timofeeva, Maria"],["dc.contributor.author","Klopp, Norman"],["dc.contributor.author","Dienemann, Hendrik"],["dc.contributor.author","Meese, Eckart"],["dc.contributor.author","Sybrecht, Gerhard"],["dc.contributor.author","Woelke, Gabi"],["dc.contributor.author","Cebulla, Mathias"],["dc.contributor.author","Degen, Maria"],["dc.contributor.author","Morr, Harald"],["dc.contributor.author","Drings, Peter"],["dc.contributor.author","Groeschel, Andreas"],["dc.contributor.author","Grosse Kreymborg, Karsten"],["dc.contributor.author","Haeußinger, Karl"],["dc.contributor.author","Hoeffken, Gerd"],["dc.contributor.author","Schmidt, Christine"],["dc.contributor.author","Jilge, Bettina"],["dc.date.accessioned","2019-07-10T08:12:55Z"],["dc.date.available","2019-07-10T08:12:55Z"],["dc.date.issued","2008"],["dc.description.abstract","The polymorphism SNP309 (rs2279744) in the promoter region of the MDM2 gene has been shown to alter protein expression and may play a role in the susceptibility to lung cancer. The MDM2 protein is a key inhibitor of p53 and several mechanisms of MDM2/p53 interactions are presently known: modulating DNA-repair, cell-cycle control, cell growth and apoptosis. We used 635 Caucasian patients diagnosed with lung cancer before 51 years of age and 1300 healthy gender and age frequency matched population Caucasian controls to investigate the association between the MDM2 SNP309 and the risk of developing early onset lung cancer. Conditional logistic models were applied to assess the genotype-phenotype association, adjusted for smoking. Compared to the GG genotype, the adjusted ORs for the TG and TT genotype were 0.9 (95% CI: 0.71.5) and 1.0 (95% CI: 0.71.5), respectively. Also no association was found for histological subtypes of lung cancer. The strength of this study is that within young cases the genetic component to develop lung cancer may be greater. Our results indicate that the MDM2 SNP309 is not significantly associated with lung carcinogenesis but point towards gender-specific differences."],["dc.identifier.fs","185630"],["dc.identifier.ppn","576814873"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4330"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61076"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-2 (MDM2) gene"],["dc.title.alternative","Research article"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]