Küffer, Stefan

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","ENDOCRINE CONNECTIONS"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Kirchner, Matthias"],["dc.contributor.author","Geissler, Franziska"],["dc.contributor.author","Bugert, Peter"],["dc.contributor.author","Spahn, Martin"],["dc.contributor.author","Kneitz, Burkhard"],["dc.contributor.author","Riedmiller, Hubertus"],["dc.contributor.author","Sauer, Christian"],["dc.contributor.author","Kueffer, Stefan"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Bolenz, Christian"],["dc.contributor.author","Michel, Maurice Stephan"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Stroebel, Philipp"],["dc.date.accessioned","2018-11-07T09:04:21Z"],["dc.date.available","2018-11-07T09:04:21Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Insulin-like growth factor 2 (IGF2) is the predominant IGF in adults and regulates cell growth. In contrast to normal tissues, where IGF2 is imprinted and only expressed from the paternal allele, loss of imprinting (LOI) and biallelic IGF2 expression are observed in many cancers including prostate cancer (PCa). We here studied whether LOI of IGF2 in normal circulating peripheral blood lymphocytes can predict increased PCa risk. Samples and methods: We analyzed IGF2 protein levels, IGF2 820G/A genotype and imprinting status, as well as methylation status of the IGF2 imprinting control region (ICR) in 113 blood samples of patients with a history of radical prostatectomy (RPE) for PCa by ELISA, restriction-fragment length polymorphism, and bisulfite-DNA sequencing. Results were compared to 249 male blood donors with unknown prostate specific antigen (PSA) status. Results: The 820G/A genotype was enriched in the RPE group and was associated with younger age at cancer diagnosis. LOI in patients was only slightly more frequent than in controls, but IGF2 levels were significantly higher and uncoupled from the imprinting status. Analysis of the IGF2/H19 ICR revealed marked hypermethylation. Conclusions: The IGF 820G/A genotype is associated with PCa diagnosis at younger age. Increased IGF2 in patients with PCa appears to be the result of impaired imprinting in non-neoplastic cells rather than a paracrine tumor product. Uncoupling of IGF2 protein levels from imprinting status (not LOI alone) and hypermethylation of the ICR characterized PCa patients and could have the potential to indicate persons at risk in screening programs."],["dc.identifier.doi","10.1530/EC-12-0054"],["dc.identifier.isi","000209773300005"],["dc.identifier.pmid","23781309"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25099"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bioscientifica Ltd"],["dc.relation.issn","2049-3614"],["dc.title","Relaxed imprinting of IGF2 in peripheral blood cells of patients with a history of prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","300"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Medicine"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Müller, Denise"],["dc.contributor.author","Mazzeo, Paolo"],["dc.contributor.author","Koch, Raphael"],["dc.contributor.author","Bösherz, Mark-Sebastian"],["dc.contributor.author","Welter, Stefan"],["dc.contributor.author","von Hammerstein-Equord, Alexander"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Cordes, Lucia"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Küffer, Stefan"],["dc.date.accessioned","2021-11-25T11:03:44Z"],["dc.date.accessioned","2022-08-18T12:36:39Z"],["dc.date.available","2021-11-25T11:03:44Z"],["dc.date.available","2022-08-18T12:36:39Z"],["dc.date.issued","2021-11-16"],["dc.date.updated","2022-07-29T12:17:26Z"],["dc.description.abstract","Background Multi-omics studies have shown a high and lack of common driver mutations in most thymomas (TH) and thymic carcinomas (TC) that hamper the development of novel treatment approaches. However, deregulation of apoptosis has been proposed as a common hallmark of TH and TC. BH3 profiling can be utilized to study the readiness of living cancer cells to undergo apoptosis and their dependency on pro-survival BCL-2 family proteins. Methods We screened a cohort of 62 TH and TC patient samples for expression of BCL-2 family proteins and used the TC cell line 1889c and native TH for dynamic BH3 profiling and treatment with BH3 mimetics. Results Immunohistochemical overexpression of MCL-1 and BCL-xL was a strong prognostic marker of TH and TC, and BH3 profiling indicated a strong dependency on MCL-1 and BCL-xL in TH. Single inhibition of MCL-1 resulted in increased binding of BIM to BCL-xL as an escape mechanism that the combined inhibition of both factors could overcome. Indeed, the inhibition of MCL-1 and BCL-xL in combination induced apoptosis in a caspase-dependent manner in untreated and MCL-1-resistant 1889c cells. Conclusion TH and TC are exquisitely dependent on the pro-survival factors MCL-1 and BCL-xL, making them ideal candidates for co-inhibition by BH3 mimetics. Since TH show a heterogeneous dependency on BCL-2 family proteins, upfront BH3 profiling could select patients and tailor the optimal therapy with the least possible toxicity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.citation","BMC Medicine. 2021 Nov 16;19(1):300"],["dc.identifier.doi","10.1186/s12916-021-02158-3"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/93525"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112954"],["dc.language.iso","en"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.subject","MCL-1"],["dc.subject","BCL-xL"],["dc.subject","BH3 mimetics"],["dc.subject","Thymoma"],["dc.subject","Thymic carcinoma"],["dc.title","Functional apoptosis profiling identifies MCL-1 and BCL-xL as prognostic markers and therapeutic targets in advanced thymomas and thymic carcinomas"],["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","256"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular Oncology"],["dc.bibliographiccitation.lastpage","266"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Gutting, Tobias"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Sauer, Christian"],["dc.contributor.author","Michel, Maurice S."],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Ströbel, Philipp"],["dc.date.accessioned","2020-12-10T14:05:58Z"],["dc.date.available","2020-12-10T14:05:58Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1002/1878-0261.12164"],["dc.identifier.issn","1574-7891"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69728"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Insulin-like growth factor 2 expression in prostate cancer is regulated by promoter-specific methylation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]