Schildhaus, Hans-Ulrich

[["dc.bibliographiccitation.firstpage","6105"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","Clinical Cancer Research"],["dc.bibliographiccitation.lastpage","6116"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Wozniak, Agnieszka"],["dc.contributor.author","Rutkowski, Piotr"],["dc.contributor.author","Schoffski, Patrick"],["dc.contributor.author","Ray-Coquard, Isabelle"],["dc.contributor.author","Hostein, Isabelle"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Le Cesne, Axel"],["dc.contributor.author","Bylina, Elzbieta"],["dc.contributor.author","Limon, Janusz"],["dc.contributor.author","Blay, Jean-Yves"],["dc.contributor.author","Siedlecki, Janusz A."],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Sciot, Raf"],["dc.contributor.author","Coindre, Jean-Michel"],["dc.contributor.author","Debiec-Rychter, Maria"],["dc.date.accessioned","2018-11-07T09:31:58Z"],["dc.date.available","2018-11-07T09:31:58Z"],["dc.date.issued","2014"],["dc.description.abstract","Purpose: Although the mutational status in gastrointestinal stromal tumors (GIST) can predict the response to treatment with tyrosine kinase inhibitors, the role of tumor genotype as a prognostic factor remains controversial. The ConticaGIST study sought to determine the pathologic and molecular factors associated with disease-free survival (DFS) in patients with operable, imatinib-naive GIST. Experimental Design: Clinicopathologic and molecular data from 1,056 patients with localized GIST who underwent surgery with curative intention (R0/R1) and were registered in the European ConticaGIST database were prospectively obtained and reviewed. Risk of tumor recurrence was stratified using the modified NIH criteria. The median follow-up was 52 months. Results: On testing for potential prognostic parameters, the following were associated with inferior DFS on multivariable Cox model analysis: primary nongastric site, size > 10 cm, mitotic index > 10 mitoses per 50 high power field, and the KIT exon 9 duplication [hazard ratio (HR), 1.47; 95% confidence interval (CI), 0.9-2.5; P = 0.037] and KIT exon 11 deletions involving codons 557 and/or 558 [KITdel-inc557/558; HR, 1.45; 95% CI, 1.0-2.2; P = 0.004]. Conversely, PDGFRA exon 18 mutations were indicators of better prognosis [HR, 0.23; 95% CI, 0.1-0.6; P = 0.002]. KITdel-inc557/558 were an adverse indicator only in GIST localized in the stomach (P < 0.001) but not in tumors with nongastric origin. In gastric GIST, all other mutations presented remarkably superior 5-year DFS. Conclusions: In conclusion, tumor genotype is an independent molecular prognostic variable associated with gastric GIST and should be used for optimizing tailored adjuvant imatinib treatment. (C) 2014 AACR."],["dc.identifier.doi","10.1158/1078-0432.CCR-14-1677"],["dc.identifier.isi","000346417400027"],["dc.identifier.pmid","25294914"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31643"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1557-3265"],["dc.relation.issn","1078-0432"],["dc.title","Tumor Genotype Is an Independent Prognostic Factor in Primary Gastrointestinal Stromal Tumors of Gastric Origin: A European Multicenter Analysis Based on ConticaGIST"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Modern Pathology"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Schildhaus, H-U"],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Buttner, R."],["dc.contributor.author","Tancheva-Poor, I."],["dc.contributor.author","Wardelmann, Eva"],["dc.date.accessioned","2018-11-07T09:44:20Z"],["dc.date.available","2018-11-07T09:44:20Z"],["dc.date.issued","2014"],["dc.format.extent","28A"],["dc.identifier.isi","000331502200099"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34370"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.publisher.place","New york"],["dc.relation.conference","103rd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP)"],["dc.relation.eventlocation","San Diego, CA"],["dc.relation.issn","1530-0285"],["dc.relation.issn","0893-3952"],["dc.title","Validation of Break Apart FISH Probes for the Detection of COL1A1-PDGFB Rearrangements in Dermatofibrosarcoma Protuberans"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Laboratory Investigation"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Schildhaus, H-U"],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Buttner, R."],["dc.contributor.author","Tancheva-Poor, I."],["dc.contributor.author","Wardelmann, Eva"],["dc.date.accessioned","2018-11-07T09:44:19Z"],["dc.date.available","2018-11-07T09:44:19Z"],["dc.date.issued","2014"],["dc.format.extent","28A"],["dc.identifier.isi","000331155800099"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34365"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.publisher.place","New york"],["dc.relation.conference","103rd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP)"],["dc.relation.eventlocation","San Diego, CA"],["dc.relation.issn","1530-0307"],["dc.relation.issn","0023-6837"],["dc.title","Validation of Break Apart FISH Probes for the Detection of COL1A1-PDGFB Rearrangements in Dermatofibrosarcoma Protuberans"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","206"],["dc.bibliographiccitation.journal","Human Pathology"],["dc.bibliographiccitation.lastpage","214"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Huss, Sebastian"],["dc.contributor.author","Pasternack, Helen"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Heitkoetter, Birthe"],["dc.contributor.author","Hartmann, Wolfgang"],["dc.contributor.author","Trautmann, Marcel"],["dc.contributor.author","Gevensleben, Heidrun"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Wardelmann, Eva"],["dc.date.accessioned","2018-11-07T10:25:18Z"],["dc.date.available","2018-11-07T10:25:18Z"],["dc.date.issued","2017"],["dc.description.abstract","In KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GISTs), BRAF mutations are regarded as alternative pathogenic events driving tumorigenesis. In our study, we aimed at analyzing a large cohort (n = 444) of GISTs for BRAF mutations using molecular and immunohistochemical methods. More than 3000 GIST samples from caucasian patients were available in our GIST and Sarcoma Registry NRW. Of these, we selected 172 wt-GISTs to evaluate the frequency of BRAF mutations. Furthermore, 272 GISTs with a representative KIT and PDGFRA mutational status were selected. BRAF mutational status was evaluated by high-resolution melting analysis, Sanger sequencing, and VE1 immunohistochemistry. A BRAF mutation (p.V600E) was found in 7 cases (3.9%) of the wt-GIST cohort. In 2 cases, multiple synchronous tumors harbored the same somatic BRAF mutation. VE1 immunohistochemical staining had a sensitivity of 81.8% and a specificity of 97.5% to detect BRAF p.V600E mutations. Analyzing our cases and the cases reported in the literature (n = 37), the percentage of intermediate and high-risk BRAF-mutated wt-GISTs (17/31; 54.8%) was comparable to that recorded for large GIST cohorts irrespective of the mutational status. BRAF mutations are rare events in wt-GISTs, and VE1 immunohistochemistry appears to be a valuable pre-screening tool for the detection of BRAF p.V600E mutations. BRAF mutations in GISTs do not seem to have a prognostic value per se. However, as BRAF inhibition represents a therapeutic option to control disease, we suggest the assessment of the BRAF mutational status, especially in the setting of advanced GIST disease. (C) 2017 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.humpath.2017.01.005"],["dc.identifier.isi","000400230800027"],["dc.identifier.pmid","28159677"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42831"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1532-8392"],["dc.relation.issn","0046-8177"],["dc.title","Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","59"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Journal of Pathology"],["dc.bibliographiccitation.lastpage","71"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Angelika Ihle, Michaela"],["dc.contributor.author","Merkelbach‐Bruse, Sabine"],["dc.contributor.author","Hartmann, Wolfgang"],["dc.contributor.author","Bauer, Sebastian"],["dc.contributor.author","Ratner, Nancy"],["dc.contributor.author","Sonobe, Hiroshi"],["dc.contributor.author","Nishio, Jun"],["dc.contributor.author","Larsson, Olle"],["dc.contributor.author","Åman, Pierre"],["dc.contributor.author","Pedeutour, Florence"],["dc.contributor.author","Taguchi, Takahiro"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Schildhaus, Hans‐Ulrich"],["dc.date.accessioned","2020-12-10T14:05:57Z"],["dc.date.available","2020-12-10T14:05:57Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1002/cjp2.v2.2"],["dc.identifier.eissn","2056-4538"],["dc.identifier.issn","2056-4538"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69719"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1985"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Molecular Cancer Therapeutics"],["dc.bibliographiccitation.lastpage","1996"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Mühlenberg, Thomas"],["dc.contributor.author","Ketzer, Julia"],["dc.contributor.author","Heinrich, Michael C."],["dc.contributor.author","Grunewald, Susanne"],["dc.contributor.author","Marino-Enriquez, Adrian"],["dc.contributor.author","Trautmann, Marcel"],["dc.contributor.author","Hartmann, Wolfgang"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Treckmann, Jürgen"],["dc.contributor.author","Worm, Karl"],["dc.contributor.author","Bertram, Stefanie"],["dc.contributor.author","Herold, Thomas"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Glimm, Hanno"],["dc.contributor.author","Stenzinger, Albrecht"],["dc.contributor.author","Brors, Benedikt"],["dc.contributor.author","Horak, Peter"],["dc.contributor.author","Hohenberger, Peter"],["dc.contributor.author","Fröhling, Stefan"],["dc.contributor.author","Fletcher, Jonathan A."],["dc.contributor.author","Bauer, Sebastian"],["dc.date.accessioned","2020-12-10T18:37:47Z"],["dc.date.available","2020-12-10T18:37:47Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1158/1535-7163.MCT-18-1224"],["dc.identifier.eissn","1538-8514"],["dc.identifier.issn","1535-7163"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77089"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","KIT-Dependent and KIT-Independent Genomic Heterogeneity of Resistance in Gastrointestinal Stromal Tumors — TORC1/2 Inhibition as Salvage Strategy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2578"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","2588"],["dc.bibliographiccitation.volume","137"],["dc.contributor.author","Sievers, Elisabeth"],["dc.contributor.author","Trautmann, Marcel"],["dc.contributor.author","Kindler, Dagmar"],["dc.contributor.author","Huss, Sebastian"],["dc.contributor.author","Gruenewald, Inga"],["dc.contributor.author","Dirksen, Uta"],["dc.contributor.author","Renner, Marcus"],["dc.contributor.author","Mechtersheimer, Gunhild"],["dc.contributor.author","Pedeutour, Florence"],["dc.contributor.author","Aman, Pierre"],["dc.contributor.author","Nishio, Jun"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Kirfel, Jutta"],["dc.contributor.author","Schirmacher, Peter"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Hartmann, Wolfgang"],["dc.date.accessioned","2018-11-07T09:48:44Z"],["dc.date.available","2018-11-07T09:48:44Z"],["dc.date.issued","2015"],["dc.description.abstract","Liposarcomas (LS) are the most common malignant mesenchymal tumors, with an overall long-term mortality rate of 60%. LS comprise three major subtypes, i.e., well-differentiated/dedifferentiated liposarcoma (WDLS/DDLS), myxoid/round cell liposarcoma (MLS) and pleomorphic liposarcoma (PLS). Aiming at the preclinical identification of novel therapeutic options, we here investigate the functional significance of SRC in primary human LS and in LS-derived cell lines. Immunohistochemical and Western blot analyses reveal relevant levels of activated p-(Tyr416)-SRC in LS of the different subtypes with particular activation in MLS and PLS. Dysregulation of the SRC modifiers CSK and PTP1B was excluded as major reason for the activation of the kinase. Consistent siRNA-mediated knockdown of SRC or inhibition by the SRC inhibitor Dasatinib led to decreased proliferation of LS cell lines of the different subtypes, with MLS cells reacting particularly sensitive in MTT assays. Flow cytometric analyses revealed that this effect was due to a significant decrease in mitotic activity and an induction of apoptosis. SRC inhibition by Dasatinib resulted in dephosphorylation of SRC itself, its interacting partners FAK and IGF-IR as well as its downstream target AKT. Consistent with a particular role of SRC in cell motility, Dasatinib reduced the migratory and invasive potential of MLS cells in Boyden chamber and Matrigel chamber assays. In summary, we provide evidence that SRC activation plays an important role in LS biology and therefore represents a potential therapeutic target, particularly in MLS and PLS."],["dc.description.sponsorship","Deutsche Krebshilfe (KoSar-Sarcoma Net)"],["dc.identifier.doi","10.1002/ijc.29645"],["dc.identifier.isi","000362843000006"],["dc.identifier.pmid","26084847"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35366"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1097-0215"],["dc.relation.issn","0020-7136"],["dc.title","SRC inhibition represents a potential therapeutic strategy in liposarcoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","573"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Human Pathology"],["dc.bibliographiccitation.lastpage","582"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Kuenstlinger, Helen"],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Huss, Sebastian"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.date.accessioned","2018-11-07T09:43:24Z"],["dc.date.available","2018-11-07T09:43:24Z"],["dc.date.issued","2014"],["dc.description.abstract","The mutational status of KIT and PDGFRA is highly relevant for prognosis and therapy prediction in gastrointestinal stromal tumors (GIST). PDGFRA exon 18 mutations have direct therapeutic implications since it is crucial to distinguish mutations associated with sensitivity to tyrosine kinase inhibitors from those causing primary resistance, eg, the most common exon 18 mutation p.D842V. In response to a growing demand for reliable, faster and more sensitive methods we established and validated a high-resolution melting (BRM) assay for PDGFRA exon 18. A total of 159 GIST samples were comparatively analyzed by FIRM and direct Sanger sequencing. We demonstrate that BRM provides highly reliable mutational results with higher sensitivity and shorter time to diagnosis compared to Sanger sequencing. We determined the sensitivity threshold of FIRM at 6% of mutated alleles. PDGFRA exon 18 wild-type status and the most common p.D842V resistance mutation (together representing >90% of the cases) can be detected specifically by FIRM. Other rare mutations can be pre-screened by FIRM and afterwards determined precisely by DNA sequencing. In this way we detected four novel mutations in PDGFRA exon 18, two of which were associated with an aggressive clinical course. Including these new mutations, we provide a comprehensive overview of all 60 currently known subtypes of PDGFRA exon 18 mutations in GIST. Seven of them (accounting for about 75% of all exon 18-mutated GISTs) are reported to be resistant to imatinib. However, there are at least 10 other mutations which are regarded as sensitive to tyrosine kinase inhibitors. (C) 2014 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Novartis Oncology"],["dc.identifier.doi","10.1016/j.humpath.2013.10.025"],["dc.identifier.isi","000331854400017"],["dc.identifier.pmid","24444465"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34178"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1532-8392"],["dc.relation.issn","0046-8177"],["dc.title","High-resolution melting analysis is a sensitive diagnostic tool to detect imatinib-resistant and imatinib-sensitive PDGFRA exon 18 mutations in gastrointestinal stromal tumors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]