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2. Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas

Author

Fischer, Anja, Albert, Thomas K., Moreno, Natalia, Interlandi, Marta, Mormann, Jana, Glaser, Selina, Patil, Paurnima, de Faria, Flavia W., Richter, Mathis, Verma, Archana, Balbach, Sebastian T., Wagener, Rabea, Bens, Susanne, Dahlum, Sonja, Göbel, Carolin, Münter, Daniel, Inserte, Clara, Graf, Monika, Kremer, Eva, Melcher, Viktoria, Di Stefano, Gioia, Santi, Raffaella, Chan, Alexander, Dogan, Ahmet, Bush, Jonathan, Hasselblatt, Martin, Cheng, Sylvia, Spetalen, Signe, Fosså, Alexander, Hartmann, Wolfgang, Herbrüggen, Heidi, Robert, Stella, Oyen, Florian, Dugas, Martin, Walter, Carolin, Sandmann, Sarah, Varghese, Julian, Rossig, Claudia, Schüller, Ulrich, Tzankov, Alexandar, Pedersen, Martin B., d’Amore, Francesco A., Mellgren, Karin, Kontny, Udo, Kancherla, Venkatesh, Veloza, Luis, Missiaglia, Edoardo, Fataccioli, Virginie, Gaulard, Philippe, Burkhardt, Birgit, Soehnlein, Oliver, Klapper, Wolfram, de Leval, Laurence, Siebert, Reiner, and Kerl, Kornelius

Published
2024
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3. Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases

Author

Wu, Zhichao, Dazelle, Karen, Abdullaev, Zied, Chung, Hye-Jung, Dahiya, Sonika, Wood, Matthew, Lee, Han, Lucas, Calixto-Hope G., Mao, Qinwen, Robinson, Lorraina, Fernandes, Igor, McCord, Matthew, Pytel, Peter, Conway, Kyle S., Yoda, Rebecca, Eschbacher, Jennifer M., Maher, Ossama M., Hasselblatt, Martin, Mobley, Bret C., Raisanen, Jack M., Hatanpaa, Kimmo J., Byers, Joshua, Lehman, Norman L., Cimino, Patrick J., Pratt, Drew, Quezado, Martha, and Aldape, Kenneth

Published
2024
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4. EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics

Author

Hench, Jürgen, Hultschig, Claus, Brugger, Jon, Mariani, Luigi, Guzman, Raphael, Soleman, Jehuda, Leu, Severina, Benton, Miles, Stec, Irenäus Maria, Hench, Ivana Bratic, Hoffmann, Per, Harter, Patrick, Weber, Katharina J, Albers, Anne, Thomas, Christian, Hasselblatt, Martin, Schüller, Ulrich, Restelli, Lisa, Capper, David, Hewer, Ekkehard, Diebold, Joachim, Kolenc, Danijela, Schneider, Ulf C., Rushing, Elisabeth, della Monica, Rosa, Chiariotti, Lorenzo, Sill, Martin, Schrimpf, Daniel, von Deimling, Andreas, Sahm, Felix, Kölsche, Christian, Tolnay, Markus, and Frank, Stephan

Published
2024
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5. Prostaglandin E2 controls the metabolic adaptation of T cells to the intestinal microenvironment

Author

Villa, Matteo, Sanin, David E., Apostolova, Petya, Corrado, Mauro, Kabat, Agnieszka M., Cristinzio, Carmine, Regina, Annamaria, Carrizo, Gustavo E., Rana, Nisha, Stanczak, Michal A., Baixauli, Francesc, Grzes, Katarzyna M., Cupovic, Jovana, Solagna, Francesca, Hackl, Alexandra, Globig, Anna-Maria, Hässler, Fabian, Puleston, Daniel J., Kelly, Beth, Cabezas-Wallscheid, Nina, Hasselblatt, Peter, Bengsch, Bertram, Zeiser, Robert, Sagar, Buescher, Joerg M., Pearce, Edward J., and Pearce, Erika L.

Published
2024
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6. The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece

Author

Maria Filippidou, Stavros Glentis, Ilona Binenbaum, Martin Sill, Kleoniki Roka, Antonia Vlachou, Georgia Avgerinou, Jonas Ecker, Florian Selt, Martin Hasselblatt, Mirjam Blattner-Johnson, Kathrin Schramm, Clio Trougkou, Dimitrios Doganis, Nikolaos Katzilakis, Vita Ridola, Evgenia Papakonstantinou, Vassilios Papadakis, Emmanouel Hatzipantelis, Eleftheria Kokkinou, Roser Pons, Christina Kanaka-Gantenbein, Dominik Sturm, Steffen Hirsch, Nicola Dikow, Kristian W. Pajtler, Cornelis M. van Tilburg, Michael C. Frühwald, Till Milde, Olaf Witt, David T.W. Jones, Andreas Von Deimling, Felix Sahm, Kalliopi Stefanaki, Stefan M. Pfister, and Antonis Kattamis

Subjects
Paediatrics, Brain tumours, Classification, Diagnosis, DNA methylation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: The recently published WHO classification of central nervous system (CNS) tumours recognizes DNA methylation profiling as a desirable and, for some diagnoses, essential diagnostic tool adjunctive to conventional histopathology. DNA methylation profiling is not routinely available in many countries, including Greece. Methods: In this collaborative study, we report the DNA methylation results in a series of children and adolescents with CNS tumours in Greece (2018–2023). In total, 130 tumour samples were analyzed using the latest applicable version of the Heidelberg brain tumour classifier. Results: Upon initial analysis, 80 % (104/130) achieved calibrated scores (Cs) ≥ 0.9 and matched an established methylation class family/subclass. Among them, methylation results confirmed (90/104, 86.5 %), refined (50/104, 48 %) or changed (10/104, 9.6 %) the histological diagnosis. Only four results were regarded as non-contributing (4/104, 3.9 %). Twenty-six tumour samples received Cs < 0.9. Despite low scores, methylation results supported the initial diagnosis with lower confidence in 38.5 % (10/26) and established the diagnosis in two tumours with non-conclusive histopathology. Additional t-distributed stochastic neighbour embedding (t-SNE) analysis allowed the possible classification of twelve tumours. Nine more samples reached high Cs using the newer brain tumour classifiers, since available. Samples co-tested in Greece demonstrated excellent test reproducibility, supporting the analysis' local implementation. Methylome profiling impacted the clinical management of 40 % of patients, modifying stratification, prognosis, or treatment approach. Conclusions: This study supports the need to integrate methylome analysis into routine diagnostics in our country and highlights the importance of collaboration between European pediatric oncology centres.

Published
2024
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8. Leptomeningeal Dissemination in Choroid Plexus Tumors: Magnetic Resonance Imaging Appearance and Risk Factors

Author

Daniel Nunes do Espirito Santo, Monika Warmuth-Metz, Camelia-Maria Monoranu, Martin Hasselblatt, Christian Thomas, Torsten Pietsch, Jürgen Krauß, Tilmann Schweitzer, Brigitte Bison, Matthias Eyrich, Uwe Kordes, Denise Obrecht-Sturm, Mirko Pham, and Annika Quenzer

Subjects
choroid plexus tumor, metastasis, MRI, morphology, cysts, imaging, Pediatrics, RJ1-570
Abstract

Background: Intracranial choroid plexus tumors (CPT) are rare and primarily affect young children. Leptomeningeal dissemination (LMD) has been reported not only in high-grade choroid plexus carcinoma (CPC) but also in lower histological grades; however, a systematic evaluation of CPT-specific imaging characteristics remains lacking. Methods: We analyzed the imaging characteristics of LMD in a single-center pediatric cohort of 22 CPT patients (thirteen choroid plexus papilloma (CPP), six atypical choroid plexus papilloma (aCPP), three CPC), comparing LMD features with those of the primary tumor. Additionally, we examined the correlation between resection status and LMD development during follow-up. Results: At diagnosis, we observed true LMD in three (two CPCs, one CPP) and pseudo-LMD in one case (CPP). During follow-up, two CPP patients developed cystic LMD, and one aCPP patient developed a solid metastasis. LMD had characteristics of the primary tumor in 3/4 cases. Incomplete resection was associated with a higher risk of LMD (p = 0.025). Conclusions: LMD can occur in both high- and lower-grade CPT, presenting at diagnosis as well as in relapsed lower-grade cases. Notable MR-imaging features include pseudo-LMD at diagnosis and cystic LMD in relapsed CPP cases. Incomplete tumor resection may increase the risk of LMD, although further validation is needed.

Published
2025
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10. High-dimensional profiling reveals Tc17 cell enrichment in active Crohn's disease and identifies a potentially targetable signature.

Author

Globig, A-M, Hipp, AV, Otto-Mora, P, Heeg, M, Mayer, LS, Ehl, S, Schwacha, H, Bewtra, M, Tomov, V, Thimme, R, Hasselblatt, P, and Bengsch, B

Subjects
CD8-Positive T-Lymphocytes, Humans, Crohn Disease, Interleukin-17, Lymphocyte Count, Th17 Cells, Prevention, Crohn's Disease, Biodefense, Vaccine Related, Digestive Diseases, Clinical Research, Inflammatory Bowel Disease, Autoimmune Disease, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Inflammatory and immune system, Good Health and Well Being
Abstract

The immune-pathology in Crohn's disease is linked to dysregulated CD4+ T cell responses biased towards pathogenic TH17 cells. However, the role of CD8+ T cells able to produce IL-17 (Tc17 cells) remains unclear. Here we characterize the peripheral blood and intestinal tissue of Crohn's disease patients (n = 61) with flow and mass cytometry and reveal a strong increase of Tc17 cells in active disease, mainly due to induction of conventional T cells. Mass cytometry shows that Tc17 cells express a distinct immune signature (CD6high, CD39, CD69, PD-1, CD27low) which was validated in an independent patient cohort. This signature stratifies patients into groups with distinct flare-free survival associated with differential CD6 expression. Targeting of CD6 in vitro reduces IL-17, IFN-γ and TNF production. These results identify a distinct Tc17 cell population in Crohn's disease with proinflammatory features linked to disease activity. The Tc17 signature informs clinical outcomes and may guide personalized treatment decisions.

Published
2022

11. Current Molecular and Clinical Landscape of ATRT – The Link to Future Therapies

Author

Gastberger K, Fincke VE, Mucha M, Siebert R, Hasselblatt M, and Frühwald MC

Subjects
swi/snf related matrix associated, actin dependent regulator of chromatin, subfamily b, member 1, smarcb1, atypical teratoid rhabdoid tumor, atrt, central nervous system, cns, treatment, pediatric, cell cycle, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Katharina Gastberger,1,2 Victoria E Fincke,1,2 Marlena Mucha,1,2 Reiner Siebert,3 Martin Hasselblatt,4 Michael C Frühwald1,2 1Pediatrics and Adolescent Medicine, Swabian Children’s Cancer Center, University Medical Center Augsburg, Augsburg, Germany; 2Bavarian Cancer Research Center (BZKF), Augsburg, Germany; 3Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany; 4Institute of Neuropathology, University Hospital Münster, Münster, GermanyCorrespondence: Michael C Frühwald, EU-RHAB Center, Swabian Children’s Cancer Center, Pediatrics and Adolescent Medicine, University Medical Center Augsburg, and Bavarian Cancer Research Center (BZKF), Stenglinstr. 2, Augsburg, 86156, Germany, Tel +49 821 400 9340, Fax +49 821 400 179201, Email michael.fruehwald@uk-augsburg.deAbstract: ATRT is a highly aggressive and rare pediatric CNS tumor of very young children. Its genetic hallmark is bi-allelic inactivation of SMARCB1 encoding INI1. Rarely SMARCA4 encoding BRG1 is affected. Up to 30% are associated with constitutional heterozygous pathogenic variants in one of the two genes, giving rise to the Rhabdoid-Tumor-Predisposition-Syndromes (RTPS) 1 and 2. Characteristic DNA methylation profiles distinguish ATRT from other SMARCB1-deficient entities. Three distinct subtypes ATRT-MYC, -TYR, and -SHH are on record. ATRT-SHH may be further divided into the subgroups ATRT-SHH1A, -SHH1B, and -SHH2. The cure of ATRT remains challenging, notwithstanding an increasing understanding of molecular pathomechanisms and genetic background. The implementation of multimodal institutional treatment protocols has improved prognosis. Regardless of treatment approaches, clinical risk factors such as age, metastases, and DNA methylation subtype affect survival probability. We provide a critical appraisal of current conventional multimodal regimens and emerging targeted treatment approaches investigated in clinical trials and entity-specific registries. Intense treatment approaches featuring radiotherapy (RT) and high-dose chemotherapy (HDCT) face the difficulty of balancing tumor control and treatment-related toxicity. Current approaches focus on minimizing radiation fields by proton beam therapy or to withhold RT in HDCT-only approaches. Still, a 40– 75% relapse rate upon first-line treatment reveals the need for novel treatment strategies in primary and even more in recurrent/refractory (r/r) disease. Among targeted treatments, immune checkpoint inhibitors and epigenetically active agents appear most promising. Success remains limited in single agent approaches. We hypothesize that mechanism-informed combination therapy will enhance response, as the low mutational burden of ATRT may contribute to acquiring resistance to single targeted agents. As DNA methylation group-specific gene expression profiles appear to influence response to distinct agents, the future treatment of ATRT should respect clinical and biological heterogeneity in risk group adjusted treatment protocols.Keywords: SWI/SNF related matrix associated, actin dependent regulator of chromatin, subfamily b, member 1, SMARCB1, atypical teratoid rhabdoid tumor, ATRT, central nervous system, CNS, treatment, pediatric, cell cycle

Published
2023

12. Central role of Tim17 in mitochondrial presequence protein translocation

Author

Fielden, Laura F., Busch, Jakob D., Merkt, Sandra G., Ganesan, Iniyan, Steiert, Conny, Hasselblatt, Hanna B., Busto, Jon V., Wirth, Christophe, Zufall, Nicole, Jungbluth, Sibylle, Noll, Katja, Dung, Julia M., Butenko, Ludmila, von der Malsburg, Karina, Koch, Hans-Georg, Hunte, Carola, van der Laan, Martin, and Wiedemann, Nils

Published
2023
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13. Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics

Author

Johann, Pascal D., Altendorf, Lea, Efremova, Emma-Maria, Holsten, Till, Steinbügl, Mona, Nemes, Karolina, Eckhardt, Alicia, Kresbach, Catena, Bockmayr, Michael, Koch, Arend, Haberler, Christine, Antonelli, Manila, DeSisto, John, Schuhmann, Martin U., Hauser, Peter, Siebert, Reiner, Bens, Susanne, Kool, Marcel, Green, Adam L., Hasselblatt, Martin, Frühwald, Michael C., and Schüller, Ulrich

Published
2023
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14. Genetic and epigenetic characterization of posterior pituitary tumors

Author

Schmid, Simone, Solomon, David A, Perez, Eilis, Thieme, Anne, Kleinschmidt-DeMasters, Bette K, Giannini, Caterina, Reinhardt, Annekathrin, Asa, Sylvia L, Mete, Ozgur, Stichel, Damian, Siewert, Christin, Dittmayer, Carsten, Hasselblatt, Martin, Paulus, Werner, Nagel, Christoph, Harter, Patrick N, Schittenhelm, Jens, Honegger, Jürgen, Rushing, Elisabeth, Coras, Roland, Pfister, Stefan M, Buslei, Rolf, Koch, Arend, Perry, Arie, Jones, David TW, von Deimling, Andreas, Capper, David, and Lopes, M Beatriz

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Human Genome, Cancer, Aetiology, 2.1 Biological and endogenous factors, Adenoma, Oxyphilic, Epigenesis, Genetic, Granular Cell Tumor, Humans, Pituitary Neoplasms, Pituicytoma, Spindle cell oncocytoma, Granular cell tumor, Posterior pituitary gland neoplasms, Molecular neuropathology, Brain tumor, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.

Published
2021

15. Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials

Author

Dignass, Axel, Stremmel, Wolfgang, Horyński, Marek, Poyda, Oleksandr, Armerding, Peter, Fellermann, Klaus, Langhorst, Jost, Kuehbacher, Tanja, Uebel, Peter, Stein, Juergen, Novacek, Gottfried, Avalueva, Elena, Oliinyk, Oleksandr, Hasselblatt, Peter, Dorofeyev, Andrey, Heinemann, Heidrun, Mueller, Ralph, Greinwald, Roland, and Reinisch, Walter

Published
2024
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17. Accessibility and centralizers for partially hyperbolic flows

Author

Fisher, Todd and Hasselblatt, Boris

Subjects
Mathematics - Dynamical Systems, 37D30
Abstract

Stable accessibility for partially hyperbolic diffeomorphisms is central to their ergodic theory, and we establish its \(C^1\)-density among 1. all, 2. volume-preserving, 3. symplectic, and 4. contact partially hyperbolic flows. As applications, we obtain in each of these 4 categories \(C^1\)-density of \(C^1\)-stable topological transitivity, ergodicity, and triviality of the centralizer., Comment: 15 pages, 3 figures

Published
2020
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18. IDH-mutant astrocytomas with primitive neuronal component have a distinct methylation profile and a higher risk of leptomeningeal spread

Author

Hinz, Felix, Friedel, Dennis, Korshunov, Andrey, Ippen, Franziska M., Bogumil, Henri, Banan, Rouzbeh, Brandner, Sebastian, Hasselblatt, Martin, Boldt, Henning B., Dirse, Vaidas, Dohmen, Hildegard, Aronica, Eleonora, Brodhun, Michael, Broekman, Marike L. D., Capper, David, Cherkezov, Asan, Deng, Maximilian Y., van Dis, Vera, Felsberg, Jörg, Frank, Stephan, French, Pim J., Gerlach, Rüdiger, Göbel, Kirsten, Goold, Eric, Hench, Jürgen, Kantelhardt, Sven, Kohlhof-Meinecke, Patricia, Krieg, Sandro, Mawrin, Christian, Morrison, Gillian, Mühlebner, Angelika, Ozduman, Koray, Pfister, Stefan M., Poliani, Pietro Luigi, Prinz, Marco, Reifenberger, Guido, Riemenschneider, Markus J., Sankowski, Roman, Schrimpf, Daniel, Sill, Martin, Snuderl, Matija, Verdijk, Robert M., Voisin, Mathew R., Wesseling, Pieter, Wick, Wolfgang, Reuss, David E., von Deimling, Andreas, Sahm, Felix, Maas, Sybren L. N., and Suwala, Abigail K.

Published
2025
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19. MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas

Author

Sigaud, Romain, Albert, Thomas K., Hess, Caroline, Hielscher, Thomas, Winkler, Nadine, Kocher, Daniela, Walter, Carolin, Münter, Daniel, Selt, Florian, Usta, Diren, Ecker, Jonas, Brentrup, Angela, Hasselblatt, Martin, Thomas, Christian, Varghese, Julian, Capper, David, Thomale, Ulrich W., Hernáiz Driever, Pablo, Simon, Michèle, Horn, Svea, Herz, Nina Annika, Koch, Arend, Sahm, Felix, Hamelmann, Stefan, Faria-Andrade, Augusto, Jabado, Nada, Schuhmann, Martin U., Schouten-van Meeteren, Antoinette Y. N., Hoving, Eelco, Brummer, Tilman, van Tilburg, Cornelis M., Pfister, Stefan M., Witt, Olaf, Jones, David T. W., Kerl, Kornelius, and Milde, Till

Published
2023
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20. Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1

Author

Suwala, Abigail K, Stichel, Damian, Schrimpf, Daniel, Maas, Sybren LN, Sill, Martin, Dohmen, Hildegard, Banan, Rouzbeh, Reinhardt, Annekathrin, Sievers, Philipp, Hinz, Felix, Blattner-Johnson, Mirjam, Hartmann, Christian, Schweizer, Leonille, Boldt, Henning B, Kristensen, Bjarne Winther, Schittenhelm, Jens, Wood, Matthew D, Chotard, Guillaume, Bjergvig, Rolf, Das, Anirban, Tabori, Uri, Hasselblatt, Martin, Korshunov, Andrey, Abdullaev, Zied, Quezado, Martha, Aldape, Kenneth, Harter, Patrick N, Snuderl, Matija, Hench, Jürgen, Frank, Stephan, Acker, Till, Brandner, Sebastian, Winkler, Frank, Wesseling, Pieter, Pfister, Stefan M, Reuss, David E, Wick, Wolfgang, von Deimling, Andreas, Jones, David TW, and Sahm, Felix

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Human Genome, Brain Cancer, Neurosciences, Cancer, Rare Diseases, Genetics, 2.1 Biological and endogenous factors, Aetiology, Brain Neoplasms, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 7, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variations, DNA Methylation, Female, Gene Deletion, Glial Fibrillary Acidic Protein, Glioblastoma, Humans, Male, Middle Aged, Neuroectodermal Tumors, Primitive, PTEN Phosphohydrolase, Retinoblastoma Binding Proteins, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, GBM, PNET, DNA methylation, Phenotype, Classification, Plasticity, Neurology & Neurosurgery
Abstract

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.

Published
2021

21. Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology

Author

Sturm, Dominik, Capper, David, Andreiuolo, Felipe, Gessi, Marco, Kölsche, Christian, Reinhardt, Annekathrin, Sievers, Philipp, Wefers, Annika K., Ebrahimi, Azadeh, Suwala, Abigail K., Gielen, Gerrit H., Sill, Martin, Schrimpf, Daniel, Stichel, Damian, Hovestadt, Volker, Daenekas, Bjarne, Rode, Agata, Hamelmann, Stefan, Previti, Christopher, Jäger, Natalie, Buchhalter, Ivo, Blattner-Johnson, Mirjam, Jones, Barbara C., Warmuth-Metz, Monika, Bison, Brigitte, Grund, Kerstin, Sutter, Christian, Hirsch, Steffen, Dikow, Nicola, Hasselblatt, Martin, Schüller, Ulrich, Koch, Arend, Gerber, Nicolas U., White, Christine L., Buntine, Molly K., Kinross, Kathryn, Algar, Elizabeth M., Hansford, Jordan R., Gottardo, Nicholas G., Schuhmann, Martin U., Thomale, Ulrich W., Hernáiz Driever, Pablo, Gnekow, Astrid, Witt, Olaf, Müller, Hermann L., Calaminus, Gabriele, Fleischhack, Gudrun, Kordes, Uwe, Mynarek, Martin, Rutkowski, Stefan, Frühwald, Michael C., Kramm, Christof M., von Deimling, Andreas, Pietsch, Torsten, Sahm, Felix, Pfister, Stefan M., and Jones, David. T. W.

Published
2023
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22. Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1

Author

Sievers, Philipp, Sill, Martin, Blume, Christina, Tauziede-Espariat, Arnault, Schrimpf, Daniel, Stichel, Damian, Reuss, David E, Dogan, Helin, Hartmann, Christian, Mawrin, Christian, Hasselblatt, Martin, Stummer, Walter, Schick, Uta, Hench, Jürgen, Frank, Stephan, Ketter, Ralf, Schweizer, Leonille, Schittenhelm, Jens, Puget, Stéphanie, Brandner, Sebastian, Jaunmuktane, Zane, Küsters, Benno, Abdullaev, Zied, Pekmezci, Melike, Snuderl, Matija, Ratliff, Miriam, Herold-Mende, Christel, Unterberg, Andreas, Aldape, Kenneth, Ellison, David W, Wesseling, Pieter, Reifenberger, Guido, Wick, Wolfgang, Perry, Arie, Varlet, Pascale, Pfister, Stefan M, Jones, David TW, von Deimling, Andreas, and Sahm, Felix

Subjects
Human Genome, Brain Disorders, Pediatric, Cancer, Genetics, Rare Diseases, Brain Cancer, Aetiology, 2.1 Biological and endogenous factors, Brain Neoplasms, Child, Chromosomal Proteins, Non-Histone, Cohort Studies, DNA Methylation, DNA Mutational Analysis, DNA, Neoplasm, DNA-Binding Proteins, Disease Progression, Epigenesis, Genetic, Female, Genome-Wide Association Study, Humans, Immunohistochemistry, Male, Meningioma, Mutation, Neoplasm Recurrence, Local, Treatment Outcome, Young Adult, Brain tumor, Clear cell, SMARCE1, DNA methylation profile, German Consortium “Aggressive Meningiomas”, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Clear cell meningioma represents an uncommon variant of meningioma that typically affects children and young adults. Although an enrichment of loss-of-function mutations in the SMARCE1 gene has been reported for this subtype, comprehensive molecular investigations are lacking. Here we describe a molecularly distinct subset of tumors (n = 31), initially identified through genome-wide DNA methylation screening among a cohort of 3093 meningiomas, of which most were diagnosed histologically as clear cell meningioma. This cohort was further supplemented by an additional 11 histologically diagnosed clear cell meningiomas for analysis (n = 42). Targeted DNA sequencing revealed SMARCE1 mutations in 33/34 analyzed samples, accompanied by a nuclear loss of expression determined via immunohistochemistry and a decreased SMARCE1 transcript expression in the tumor cells. Analysis of time to progression or recurrence of patients within the clear cell meningioma group (n = 14) in comparison to those with meningioma WHO grade 2 (n = 220) revealed a similar outcome and support the assignment of WHO grade 2 to these tumors. Our findings indicate the existence of a highly distinct epigenetic signature of clear cell meningiomas, separate from all other variants of meningiomas, with recurrent mutations in the SMARCE1 gene. This suggests that these tumors may arise from a different precursor cell population than the broad spectrum of the other meningioma subtypes.

Published
2021

23. Orbit Growth Of Contact Structures After Surgery

Author

Foulon, Patrick, Hasselblatt, Boris, and Vaugon, Anne

Subjects
Mathematics - Dynamical Systems, Mathematics - Symplectic Geometry
Abstract

Investigation of the effects of a contact surgery construction and of invariance of contact homology reveals a rich new field of inquiry at the intersection of dynamical systems and contact geometry. We produce contact 3-flows not topologically orbit-equivalent to any algebraic flow, including examples on many hyperbolic 3-manifolds, and we show how the surgery produces dynamical complexity for any Reeb flow compatible with the resulting contact structure. This includes exponential complexity when neither the surg-ered flow nor the surgered manifold are hyperbolic. We also demonstrate the use in dynamics of contact homology, a powerful tool in contact geometry.

Published
2019

24. Centralizers of hyperbolic and kinematic-expansive flows

Author

Bakker, Lennard, Fisher, Todd, and Hasselblatt, Boris

Subjects
Mathematics - Dynamical Systems, 37D20, 37C10, 37C20
Abstract

We show generic $C^\infty$ hyperbolic flows (Axiom A and no cycles, but not transitive Anosov) commute with no $C^\infty$-diffeomorphism other than a time-t map of the flow itself. Kinematic expansivity, a substantial weakening of expansivity, implies that $C^0$ flows have quasi-discrete $C^0$-centralizer, and additional conditions broader than transitivity then give discrete $C^0$-centralizer. We also prove centralizer-rigidity: a diffeomorphism commuting with a generic hyperbolic flow is determined by its values on any open set., Comment: 18 pages

Published
2019

25. Advancing biology-based therapeutic approaches for atypical teratoid rhabdoid tumors.

Author

Hoffman, Lindsey M, Richardson, Elizabeth Anne, Ho, Ben, Margol, Ashley, Reddy, Alyssa, Lafay-Cousin, Lucie, Chi, Susan, Slavc, Irene, Judkins, Alexander, Hasselblatt, Martin, Bourdeaut, Franck, Frühwald, Michael C, Vibhakar, Rajeev, Bouffet, Eric, and Huang, Annie

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Genetics, Human Genome, Orphan Drug, Cancer, Aetiology, 2.1 Biological and endogenous factors, Epigenomics, Humans, Neoplasms, Neuroepithelial, Rhabdoid Tumor, SMARCB1 Protein, ATRT, enhancer, epigenomics, rhabdoid tumors, subgroup-specific therapeutics, ATRT, enhancer, epigenomics, rhabdoid tumors, Neurosciences, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant central nervous system cancer arising in infants and younger children, historically considered to be homogeneous, monogenic, and incurable. Recent use of intensified therapies has modestly improved survival for ATRT; however, a majority of patients will still succumb to their disease. While ATRTs almost universally exhibit loss of SMARCB1 (BAF47/INI1/SNF5), recent whole genome, transcriptome, and epigenomic analyses of large cohorts reveal previously underappreciated molecular heterogeneity. These discoveries provide novel insights into how SMARCB1 loss drives oncogenesis and confer specific therapeutic vulnerabilities, raising exciting prospects for molecularly stratified treatment for patients with ATRT.

Published
2020

26. Interferon-Driven Immune Dysregulation in Common Variable Immunodeficiency–Associated Villous Atrophy and Norovirus Infection

Author

Strohmeier, Valentina, Andrieux, Geoffroy, Unger, Susanne, Pascual-Reguant, Anna, Klocperk, Adam, Seidl, Maximilian, Marques, Otavio Cabral, Eckert, Marleen, Gräwe, Katja, Shabani, Michelle, von Spee-Mayer, Caroline, Friedmann, David, Harder, Ina, Gutenberger, Sylvia, Keller, Baerbel, Proietti, Michele, Bulashevska, Alla, Grimbacher, Bodo, Provaznik, Jan, Benes, Vladimir, Goldacker, Sigune, Schell, Christoph, Hauser, Anja E., Boerries, Melanie, Hasselblatt, Peter, and Warnatz, Klaus

Published
2023
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27. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

Author

Gornet, Jean-Marc, Beaugerie, Laurent, Shaji, Sebastian, Peyrin-Biroulet, Laurent, Reimund, Jean-Marie, Hebuterne, Xavier, Amiot, Aurélien, Armelao, Franco, Blanc, Pierre, Papi, Claudio, De Chambrun, Guillaume Pineton, Roblin, Xavier, Chu, Karmiris, Konstantinos, Shariq, Sohail, Viazis, Nikolaos, Limdi, Jimmy, Eder H, Piotr, Michalopoulos, Georgios, Bell, Andrew, Biancone, Livia, Dewitte, Marie, Mazhar, Zia, Franchimont, Denis, Nancey, Stephane, Macaigne, Gilles, Principi, Maria Beatrice, Fumery, Mathurin, Parkes, Gareth, Valats, Jean-Christophe, Doherty, Glen, Bouguen, Guillaume, Molnar, Tamás, Tsai, Hersin, Gangi, Mohsin, Pedersen, Natalia, Heluwaert, Frédéric, Shenderey, Richard, Zeissig, Sebastian, Butterworth, Jeffrey, Castiglione, Fabiana, Corless, Lynsey, Zallot, Camille, Baert, Filip, Singh, Salil, Sonwalkar, Sunil, Clayton, Elizabeth, Rahier, Jean-François, Vani, Deven, Bellaiche, Guy, De Vos, Martine, Kirchgesner, Julien, Kopylov, Uri, Lobaton, Triana, Locher, Christophe, Mantzaris, Gerassimos, Abouda, George, Smith, Katie, Sprakes, Michael, Theodoropoulou, Angeliki, Wesley, Emma, Bonnet, Joëlle, Elphick, David, Gilletta, Cyrielle, Gordon, John, Laharie, David, Nakad, Antoine, Orlando, Ambrogio, Dubois, Patrick, Hasselblatt, Peter, Michiels, Christophe, Preston, Cathryn, Staicu, Anca, Vuitton, Lucine, Kaassis, Mehdi, Speight, Ally, Ghosh, Deb, Löwenberg, Mark, Mathieu, Nicolas, Pelletier, Anne-Laure, Phillips, Anne, Magro, Fernando, Altwegg, Romain, Avni, Irit, biron, Landy, Jonathon, Nachury, Maria, Shenoy, Achuth, Trang, Caroline, Abitbol, Vered, Bamias, Georgios, Farkas, Klaudia, Maaser, Christian, Shitrit, Ariella, Siegmund, Britta, Filippi, Jérôme, O'morain, Colm, Yanai, Henit, Costes, Laurent, Hobday, David, Szepes, Zoltán, Calabrese, Emma, Dallal, Helen, Fung, Michael, Ramadas, Arvind, Baburajan, Bijay, Koss, Konrad, Barberis, Christophe, Buisson, Anthony, Amil, Morgane, Balestrieri, Paola, Johnson, Matthew, Tzouvala, Maria, Viennot, Stéphanie, Nagy, Ferenc, Thompson, Nick, Alric, Laurent, Samuel, Sunil, Bourrier, Anne, Chanteloup, Elise, Del Tedesco, Emilie, Harbord, Marcus, Lobo, Alan, Myers, Sally, Pollok, Richard, Ahmad, Tariq, Chaudhary, Rakesh, Karakoidas, Christos, Soliman, Ashraf, Stefanescu, Carmen, Theocharis, Georgios, Branden, Stijn Vanden, Beltran, Belén, Bouhnik, Yoram, Bourreille, Arnaud, Branco, Joana, Colleypriest, Ben, Eliakim, Rami, Knight, Paul, O'toole, Aoibhlinn, Robles, Virgina, Triantafyllou, Konstantinos, Bosca, Marta Maia, Lambrecht, Guy, Mosquera, Lucia Marquez, Panter, Simon, Pappa, Aikaterini, Simon, Marion, Sivaji, Ganesh, Bellanger, Christophe, Belle, Arthur, Borruel, Natalia, Egan, Laurence, Peeters, Harald, Sharpstone, Daniel, Arasaradnam, Ramesh, Benitez, José Manuel, Dahlerup, Jens Frederik, Giouleme, Olga, Gisbert, Javier P., Helwig, Ulf, Minguez, Miguel, Tsironi, Eftychia, Variola, Angela, Allen, Patrick, Boivineau, Lucille, Cole, Andy, Dib, Nina, Gomollon, Fernando, Johnston, Richard, Katsanos, Konstantinos, Kennedy, Nick, Kiszka-Kanowitz, Marianne, Marin-Jimenez, Ignacio, Miheller, Pál, Nos, Pilar, Saraj, Othman, Vinter-Jensen, Lars, Zittan, Eran, Baudry, Clotilde, Calvet, Xavier, Cazelles-Boudier, Marie-Christine, Coenegrachts, Jean-Louis, Cullen, Garret, Daperno, Marco, Dhar, Anjan, Gerard, Romain, Jensen, Nanna, Maharshak, Nitsan, Mcalindon, Mark, Mcloughlin, Simon, Parkes, Miles, Patel, Kamal, Peixoto, Armando, Polymeros, Dimitrios, Portela, Francisco, Rocca, Rodolfo, Seksik, Philippe, Subramanian, Sreedhar, Tennenbaum, Ruth, Atreya, Raja, Bachmann, Oliver, Berger, Arthur, Bor, Renáta, Buckley, Maire, Carpio, Daniel, Chaparro, María, Costa, Francesco, Domenech, Eugeni, Esteve, Maria, Foley, Stephen, Guardiola, Jordi, Koutroubakis, Ioannis, Kuehbacher, Tanja, Landman, Cécilia, Lavagna, Alessandro, Manceñido, Noemí, Mañosa, Míriam, Martín-Arranz, Maria Dolores, Plastaras, Laurianne, Scribano, Maria Lia, Sengupta, Subhasish, Teich, Nils, Tran-Minh, My-Linh, Zampeli, Evanthia, Amininejad, Leila, Arroyo, Teresa, Attar, Alain, Backman, Ann-Sofie, Bálint, Anita, Beckly, John, Ben Horin, Shomron, Bernardo, Sónia, Caillo, Ludovic, Caron, Bénédicte, Shanika de Silva, María, FábiáN, Anna, Fiorino, Gionata, Gutierrez, Ana, Lahat, Adi, Masmoudi, Mohamed, Mendolaro, Marco, Muls, Vinciane, Poullenot, Florian, Probert, Christopher, Reenaers, Catherine, Rutka, Mariann, Sarwari, Zaman, Sayer, Joanne, Sicilia, Beatriz, Sousa, Helena, van Kemseke, Catherine, Zabana, Yamile, Astegiano, Marco, Banim, Paul, Bettenworth, Dominik, Boualit, Médina, Brodersen, Jacob Broder, Christidou, Angeliki, Cooney, Rachel, Pinto, João Cortez, Cravo, Portugal Marília, Cremer, Anneline, Danese, Silvio, di Sabatino, Antonio, Fallingborg, Jan, Ferronato, Antonio, Planella, Esther Garcia, Gupta, Sanjay, Halfvarson, Jonas, Israeli, Eran, Kestenbaum, Samantha, Larsen, Lone, Macken, Elisabeth, Mathou, Nicoletta, Milassin, Ágnes, Pofelski, Joanna, Ricci, Chiara, Rodriguez-Moranta, Francisco, Schmidt-Lauber, Martin, Shaw, Ian, Soares, Marta, Soliman, Heithem, Triantos, Christos, Zografos, Konstantinos, Agrawal, Anurag, Armuzzi, Alessandro, Aubourg, Alexandre, Acosta, Manuel Barreiro-de, Barrio, Jesús, Bergemalm, Daniel, Bermejo, Fernando, Bodini, Giorgia, Bohr, Johan, Bossuyt, Peter, Christodoulou, Dimitrios, Claessens, Christophe, Collins, Paul, de Francisco, Ruth, Garcia, Santiago, Georgopoulos, Sotirios, Goutorbe, Felix, Kalantzis, Chrisostomos, Kourikou, Anastasia, Mace, Vincent, Malamut, Georgia, Ministro, Paula, Larmurier, Isabelle Nion, Ricart, Elena, Serrero, Mélanie, Sheridan, Juliette, Weimers, Petra, Andersen, Vibeke, Arroja, Bruno, Bokemeyer, Bernd, Bujanda, Luis, Degand, Thibault, Eriksson, Carl, Garceau, Cécile, Glerup, Henning, Goren, Idan, Jackson, Lucina, Koch, Stéphane, Mesonero, Francisco, Ordas, Ingrid, Riviere, Pauline, Saibeni, Simone, Soares, João, Tavernier, Noémie, Theede, Klaus, Ungar, Bella, Bästlein, Elke, Gasbarrini, Antonio, Protopapas, Andreas, Reindl, Wolfgang, Bossa, Fabrizio, Hart, Ailsa, Heil, Franz-Josef, O'Connor, Anthony, Oldenburg, Bas, Pastorelli, Luca, Stephen patchett, Ramakrishnan, Subramaniam, de Caestecker, John, Echarri, Ana, Kevans, David, Büning, Jürgen, Coelho, Rosa, Jansen, Jeroen, Koslowski, Benjamin, Wells, Christopher, Ceballos, Daniel, König, Ingrid, Padmanabhan, Hari, Patani, Timi, Qureshi, Raheel, Zagorowicz, Edyta, Allez, Matthieu, Archavlis, Emmanouil, Bonnet, Delphine, Guidi, Luisa, Mcnamara, Deirdre, Vernia, Piero, Weidenhiller, Michael, Alon, Lang, Boysen, Trine, Delattre, Charlotte, Farrell, Richard, Krüger, Rolf-Achim, Paupard, Thierry, Vind, Ida, Caprioli, Flavio, Gancho, Vladimir, Quentin, Vincent, Avidan, Benjamin, D’Haens, Geert, Mccarthy, Jane, Snook, Jonathon, Soufleris, Konstantinos, Zerbib, Frank, Carter, Dan, Depla, Annekatrien, Eisenbach, Thomas, Fries, Walter, Grammatikos, Nikolaos, Ilegems, Saskia, Lopez-Sanroman, Antonio, Moreau, Jacques, Riegler, Gabriele, Rietdijk, Svend, Rocha, Marta, Rosa, Isabelle, Ryan, Barbara, Yeremenko, Yelena, Boruchowicz, Arnaud, Damião, Filipe, Laoudi, Foteini, Lügering, Andreas, Macarri, Giampiero, Thomopoulos, Konstantinos, Barros, Luísa, Blixt, Thomas, Garros, Aurélien, Khorrami, Sam, Sokol, Harry, Sturm, Andreas, Livovsky, Dan, Maul, Jochen, Miks, Heinrich, Papadopoulos, Vasileios, Schmidt, Carsten, Snir, Yifat, Svenningsen, Lise, Ahmed, Wafaa, Broitman, Yelena, Cuillerier, Emmanuel, Kant, Prashant, Leyden, Jan, Lichtenstein, Lev, Lopes, Susana, Martineau, Chloé, Mulcahy, Hugh, Schweitzer, Axel, Van Schaik, Fiona, Banai, Hagar, Danion, Pauline, Dulery, Charlotte, Fidder, Herma, Gay, Claire, Hagege, Hervé, Harnois, Florence, Jørgensen, Søren Peter, Müller-Ziehm, Jens, Oikonomou, Michail, Palmela, Carolina, Schulze/Röske, Jörg, Smith, Mark, Thurm, Tamar, Bresso, Francesca, Brixi, Hedia, Jones, John, Macmathuna, Padraig, Painchart, Claire, Ron, Yulia, Vester-Andersen, Marianne, Alexandrino, Gonçalo, Börner, Norbert, Cardoso, Mariana, Chagas, Cristina, Dignaß, Axel, Dotan, Iris, Hedin, Charlotte, Karatzas, Pantelis, Kasapidis, Panagiotis, Palatka, Károly, Sakizlis, Georgios, Wilson, Ana, Bosanko, Nick, Caldeira, Paulo, Gagniere, Charlotte, Libier, Louise, Meunier, Camille, Moog, Gero, Pasquion, Audrey, Pica, Roberta, Akbar, Ayesha, Arab, Nadia, Cadiot, Guillaume, Carvalho, João, Charpignon, Claire, Fellermann, Laus, Fishman, Sigal, Fraser, Gerald, Gluck, Nathan, Hoesl, Mark, Kierkus, Jarosław, Klopocka, Maria, Arranz, Eduardo Martin, Menchen, Luis, Nikolaus, Susanna, Petrache, Anca, Ponsioen, Cyriel, Riestra, Sabino, Robledo, Pilar, Rodriguez, Cristina, Samer, Misheal, Tischer, Matthias, Wypych, Joanna, Baudon, Julien, Bezzio, Cristina, Boschetti, Gilles, Burisch, Johan, Creed, Tom, Demarzo, Maria Giulia, Festa, Stefano, Figueroa, Andrés, Julsgaard, Mette, Navarro, Pablo, Perez-Galindo, Pablo, Rouillon, Cléa, Sablich, Emanuele, Tosca, Joan, Vidon, Mathias, Vidon, Marine, Vitte, René-Louis, Wampach, Anne, Baumann, Cédric, Urmes, Isabelle Clerc, Rousseau, Hélène, Borie, Marc, Uzzan, Mathieu, Chatten, Kelly, Peter, Rimmer, Tariq, Iqbal, Cossignani, Marta, Cañete, Fiorella, Holvoet, Tom, Krasz, Susanne, Dias, Sandra, Abalia, Hadas, Abaza, Aziza, Abramovich, Gal, Ackzell, Ingrid, Adams, Carol, Addleton, Catherine, Alfambra, Erika, Algaba, Alicia, Allcock, Clare, Allison, Joanna, Amouriaux, Karine, Anderson, Julie, Anderson, Emma, Appelmans, Saskia, Armstrong, Lisa, Atkins, Stacey, Attaran-Bandarabadi, Masoumeh, Bailey, Yvonne, Bardot, Stephanie, Beck, Natasha, Bennett, Lillie, Bergfeld, Jonathan Phil, Berkane, Ramdane, Boey, Hanne, Bowlas, Louise, Bradley-Potts, Joanne, Brear, Tracy, Bretlander-Peters, Nicole, Brown, Ellen, Brown, Johanna, Buckingham, Elizabeth, Buellens, Katrien, Bull, Rhian, Burke, Maura, Burns, Leighanne, Burton, Julie, Bwalya, Agness, Cabanas, Karine, Callaghan, Muriel, Camou, Océane, Campbell, Debbie, Capoferro, Elvira, Carnahan, Mandy, Carnio, Cornelia, Carter, Anne, Clack, Concetta Casali, Chedouba, Leïla, Cipriano, Bessie, Claeys, Sophie, Closset, Manon, Coban, Dilek, Cococcia, Sara, Coe, Carolann, Cole, Helen, Collet, Emilie, Collins, Kayleigh, Combes, Isabelle, Connor, Emma, Constantin, Kathryn, Cooke, Susan, Cornet, Nathanaëlle, Corrihons, Estelle, Corsino, Pilar, Cortaville, Rosie, Cotterill, Donna, Cowton, Amanda, Cox, Harriet, Cripps, Viktoria, Crowder, Amanda, Cukier, Tzufit, Daniel, Amelia, Dawe, Chris, de Haan, Jose, Croix, Rosanna de la, Dejonckheere, Evva, Villanegro, Juan Delare, Delaval, Guillaume, Delliponti, Mariangela, Delommez, Aude, Detry, Emilie, Dhanaratne, Melanie, Galan, Laura Diez, Dodel, Marie, Dooks, Emma, Du Cheyron, Joseph, Duane, Linda, Vulgo Cochran, Jennifer Dulling, Dyer, Simona, Dymond, Harvey, Ekblad, Charlotte, Elliott, Kerry, Emmerson, Ingrid, Eugene-Jolchine, Irène, Fleming, Lorna, Fletcher, Eve, Ford, Sarah, Forshaw, Greg, Foulds, Angela, Francois, Caroline, Fuge, Nicole, Gafni, Gal, Ganon, Miri, Nuñez, Olga Garcia, Ramirez, Laura Garcia, Gelder, Sophie, Gettkowski, Raimonda, Gilardi, Daniela, Giuffrida, Paolo, Gobert, Vincent, Godden, Jo, Godwin, Nuala, Goulden, Kay, Graham, Sharon, Green, Charlotte, Green, Marie, Gueye, Aboubakar, Guler, Tuba, Gustavsson, Ida, Hadjisavvas, Helena, Hammonds, Fiona, Hantzi, Christina, Hauke, Marion, Haydock, Julie, Hayes, Orla, Nislev, Lizette Helbo, Hochstodter, Jessica, Hogg, Ashleigh, Hölbing, Manuela, Holland, Maureen, Holsbergen, Maartje, Howard, Linda, Hoyda, Aviya, Hull, Robert, Irish, Jane, Jackson, Wendy, Janssen, Wendy, Jeffrey, Lesley, Jourdan, Sofia, Jutrowska, Izabela, Kaniel, Chava, Karezos, Theofilos, Kelly, Niamh, Kelly, Jessica, Kennedy, Mary, Kennedy, Una, Kibaru, Joyce, Kirkman, Gemma, Klaproth, Janine, Kneese, Corinna, Koch, Andrea, Kokke, Kathleen, Koppelow, Martha, Krause, Sabine, Krauspe, Sabine, Kwakkenbos, Petra, Labarile, Nunzia, Lang, Hannah, Lassailly, Marianne, Leconte, Martine, Lepczynski, Linda, Levell, Emma, Levhar, Nina, Lindhort, Kerstin, Lisle, Jessica, Cauce, Beatriz Lopez, Lorenz, Gabriele, Lovati, Ambra, Lowry, Tracey, Lund, Margareta, Vorderbrügge, Anne Lutz, Maansson, Suzanne, Madapathage, Videsheka, Cheviakoff, Maelys, Magness, Alison, Manley, Orla, Manyoni, Catherine, Marg, Ingke, Marra, Antonella, Martins, Carole, Massella, Arianna, Mathias, Aurore, Mervyn, Danielle, Minsart, Charlotte, Mitchell, Sally, Monks, Kathleen, Montero, Mélanie, Moore, Alson, Moser, Maren, Moss, Alison, Mullen, Angela, Murciano, M. Francisca, Naylor, Deanna, Nehus, Ansgar, Nicholson, Anne, Nöding, Sarah, Nolan, Sinead, Nörenberg, Janet, Northcott, Clare, O'Connell, Jim, O’Kelly, Alison, Orbach-Zingboim, Noam, Orobitg, Judit, Otieno, Charlene, Owen, Charlotte, Patch, Sarah, Pauker, Maor, Pauli, Renate, Pearson, Harriet, Peggy, Falgon, Petit, Séverine, Petrissans, Christine, Piergallini, Simona, Pippard, Lucy, Pitt, Laura, Pócsik, Gabriella, Poher, Yoann, Pomes, Chloé, Pritchard, Lucy, Puchades, Laura, Quaid, Sheena, Rana, Aleem, Raynard, Dana, Reilly, Mykla, Reinert, Sonja, Reinknecht, Manuela, Renner, Baerbel, Reynolds, Rob, Rizzuto, Giulia, Robinson, Matthew, Robrechts, Joke, Rodriguez, Eva M., Rosenblum, Efrat, Russel, Tamlyn, Sadare, Ibiyemi, Salama, Noa, Schakel, Toos, Schauer, Anja, Schiavoni, Elisa, Shaw, Caroline, Shelton, Sarah, Sicart, Virginie, Siouville, Elodie, Smith, Orla, Soude, Théo, Stephenson, Sophie, Stephenson, Elaine, Steppe, Marjan, Sterkx, An, Stickley, Jo, Sugrue, Kathleen, Swietec, Natalia, Tasiaux, Charlotte, Thamu, Bhavneet, Thomas, Susane, Tobi, Ogwa, Touabi, Kahina, Tovi, Shifra, Tregonning, Julie, Turchini, Laura, Unkhoff, Julia, Unruh, Olesya, Uzun, Nurcan, Van Aert, Frauke, Bergh, Sandrine Vanden, Vandenbroucke, Louise, Vansteenkiste, Laura, Vardit, Shay, Vergriete, Valentin, Walker, Elaine, Warner, Eleanor, Watchorn, Olivia, Watson, Ekaterina, Wauthier, Marie-Claire, Weetman, Belgium Maria, Weston, Margaret, West-Petroschka, Wiebke, Wienecke, Susann, Wierling, Kerstin, Wiestler, Miriam, Wilcox, Rebecca, Wilhelmsen, Elva, Williams, Angharad, Williamson, Georgina, Wilson, Deborah, Wistance, Kate, Wortmann, Nicolas, Wurie, Subie, Yadgar, Karin, Young, Gail, Young, Megan, Aucouturier, Julien, Bertin, Marie- Jo, Bougrine, Hasnae, Coisnon, Marie, Defrance, Antoine, Gutierrez, Kati, Harouz, Amel, Jerber, Laure, Khlifi, Aida, Kirati, Amina, Liworo, Nasaladjine, Logoltat, Maude, Mailhat, Charlotte, M'Bayi, Chancely, Medane, Yasmina, Merkhoufa, Dalal, Elhad, Saouda Mohamed, Monthe, Bertille, Moyon, Fanny, Rabiega, Pascaline, Sekela, Jennifer, Thilloy, Charlotte, Hamamouche, Naima, Partisotti, Frederic, Blandin, Patrick, Mokhtari, Hocine, Coutard, Laure, and Doherty, Glen A.

Published
2023
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28. Author Correction: Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology

Author

Sturm, Dominik, Capper, David, Andreiuolo, Felipe, Gessi, Marco, Kölsche, Christian, Reinhardt, Annekathrin, Sievers, Philipp, Wefers, Annika K., Ebrahimi, Azadeh, Suwala, Abigail K., Gielen, Gerrit H., Sill, Martin, Schrimpf, Daniel, Stichel, Damian, Hovestadt, Volker, Daenekas, Bjarne, Rode, Agata, Hamelmann, Stefan, Previti, Christopher, Jäger, Natalie, Buchhalter, Ivo, Blattner-Johnson, Mirjam, Jones, Barbara C., Warmuth-Metz, Monika, Bison, Brigitte, Grund, Kerstin, Sutter, Christian, Hirsch, Steffen, Dikow, Nicola, Hasselblatt, Martin, Schüller, Ulrich, Koch, Arend, Gerber, Nicolas U., White, Christine L., Buntine, Molly K., Kinross, Kathryn, Algar, Elizabeth M., Hansford, Jordan R., Gottardo, Nicholas G., Schuhmann, Martin U., Thomale, Ulrich W., Hernáiz Driever, Pablo, Gnekow, Astrid, Witt, Olaf, Müller, Hermann L., Calaminus, Gabriele, Fleischhack, Gudrun, Kordes, Uwe, Mynarek, Martin, Rutkowski, Stefan, Frühwald, Michael C., Kramm, Christof M., von Deimling, Andreas, Pietsch, Torsten, Sahm, Felix, Pfister, Stefan M., and Jones, David. T. W.

Published
2024
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29. DNA methylation-based classification of sinonasal tumors

Author

Philipp Jurmeister, Stefanie Glöß, Renée Roller, Maximilian Leitheiser, Simone Schmid, Liliana H. Mochmann, Emma Payá Capilla, Rebecca Fritz, Carsten Dittmayer, Corinna Friedrich, Anne Thieme, Philipp Keyl, Armin Jarosch, Simon Schallenberg, Hendrik Bläker, Inga Hoffmann, Claudia Vollbrecht, Annika Lehmann, Michael Hummel, Daniel Heim, Mohamed Haji, Patrick Harter, Benjamin Englert, Stephan Frank, Jürgen Hench, Werner Paulus, Martin Hasselblatt, Wolfgang Hartmann, Hildegard Dohmen, Ursula Keber, Paul Jank, Carsten Denkert, Christine Stadelmann, Felix Bremmer, Annika Richter, Annika Wefers, Julika Ribbat-Idel, Sven Perner, Christian Idel, Lorenzo Chiariotti, Rosa Della Monica, Alfredo Marinelli, Ulrich Schüller, Michael Bockmayr, Jacklyn Liu, Valerie J. Lund, Martin Forster, Matt Lechner, Sara L. Lorenzo-Guerra, Mario Hermsen, Pascal D. Johann, Abbas Agaimy, Philipp Seegerer, Arend Koch, Frank Heppner, Stefan M. Pfister, David T. W. Jones, Martin Sill, Andreas von Deimling, Matija Snuderl, Klaus-Robert Müller, Erna Forgó, Brooke E. Howitt, Philipp Mertins, Frederick Klauschen, and David Capper

Subjects
Science
Abstract

Sinonasal tumour diagnosis can be complicated by the heterogeneity of disease and classification systems. Here, the authors use machine learning to classify sinonasal undifferentiated carcinomas into 4 molecular classe with differences in differentiation state and clinical outcome.

Published
2022
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30. Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors

Author

Lena Blümel, Nan Qin, Johannes Berlandi, Eunice Paisana, Rita Cascão, Carlos Custódia, David Pauck, Daniel Picard, Maike Langini, Kai Stühler, Frauke-Dorothee Meyer, Sarah Göbbels, Bastian Malzkorn, Max C. Liebau, João T. Barata, Astrid Jeibmann, Kornelius Kerl, Serap Erkek, Marcel Kool, Stefan M. Pfister, Pascal D. Johann, Michael C. Frühwald, Arndt Borkhardt, Guido Reifenberger, Claudia C. Faria, Ute Fischer, Martin Hasselblatt, Jasmin Bartl, and Marc Remke

Subjects
Cytology, QH573-671
Abstract

Abstract Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor in infants that is characterized by loss of nuclear expression of SMARCB1 or SMARCA4 proteins. Recent studies show that AT/RTs comprise three molecular subgroups, namely AT/RT-TYR, AT/RT-MYC and AT/RT-SHH. The subgroups show distinct expression patterns of genes involved in ciliogenesis, however, little is known about the functional roles of primary cilia in the biology of AT/RT. Here, we show that primary cilia are present across all AT/RT subgroups with specific enrichment in AT/RT-TYR patient samples. Furthermore, we demonstrate that primary ciliogenesis contributes to AT/RT biology in vitro and in vivo. Specifically, we observed a significant decrease in proliferation and clonogenicity following disruption of primary ciliogenesis in AT/RT cell line models. Additionally, apoptosis was significantly increased via the induction of STAT1 and DR5 signaling, as detected by proteogenomic profiling. In a Drosophila model of SMARCB1 deficiency, concomitant knockdown of several cilia-associated genes resulted in a substantial shift of the lethal phenotype with more than 20% of flies reaching adulthood. We also found significantly extended survival in an orthotopic xenograft mouse model of AT/RT upon disruption of primary ciliogenesis. Taken together, our findings indicate that primary ciliogenesis or its downstream signaling contributes to the aggressiveness of AT/RT and, therefore, may constitute a novel therapeutic target.

Published
2022
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31. Exhaustion of CD39-Expressing CD8+ T Cells in Crohn’s Disease Is Linked to Clinical Outcome

Author

Globig, Anna-Maria, Mayer, Lena Sophie, Heeg, Maximilian, Andrieux, Geoffroy, Ku, Manching, Otto-Mora, Patricia, Hipp, Anna Veronika, Zoldan, Katharina, Pattekar, Ajinkya, Rana, Nisha, Schell, Christoph, Boerries, Melanie, Hofmann, Maike, Neumann-Haefelin, Christoph, Kuellmer, Armin, Schmidt, Arthur, Boettler, Tobias, Tomov, Vesselin, Thimme, Robert, Hasselblatt, Peter, and Bengsch, Bertram

Published
2022
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32. ATRT–SHH comprises three molecular subgroups with characteristic clinical and histopathological features and prognostic significance

Author

Federico, Aniello, Thomas, Christian, Miskiewicz, Katarzyna, Woltering, Niklas, Zin, Francesca, Nemes, Karolina, Bison, Brigitte, Johann, Pascal D., Hawes, Debra, Bens, Susanne, Kordes, Uwe, Albrecht, Steffen, Dohmen, Hildegard, Hauser, Peter, Keyvani, Kathy, van Landeghem, Frank K. H., Lund, Eva Løbner, Scheie, David, Mawrin, Christian, Monoranu, Camelia-Maria, Parm Ulhøi, Benedicte, Pietsch, Torsten, Reinhard, Harald, Riemenschneider, Markus J., Sehested, Astrid, Sumerauer, David, Siebert, Reiner, Paulus, Werner, Frühwald, Michael C., Kool, Marcel, and Hasselblatt, Martin

Published
2022
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33. High-dimensional profiling reveals Tc17 cell enrichment in active Crohn’s disease and identifies a potentially targetable signature

Author

A.-M. Globig, A. V. Hipp, P. Otto-Mora, M. Heeg, L. S. Mayer, S. Ehl, H. Schwacha, M. Bewtra, V. Tomov, R. Thimme, P. Hasselblatt, and B. Bengsch

Subjects
Science
Abstract

The T cell compartment in patients with Crohn's disease is dysregulated. Here the authors use cytometric profiling to reveal an enrichment of distinct Tc17 cells during active Crohn's disease and may suggest CD6 as a potential target for therapeutic studies.

Published
2022
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36. Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial

Author

Afzali, Anita, Aitova, Lilia, Aldeguer i Mante, Xavier, Allez, Matthieu, Altorjay, István, Argüelles Arias, Federico, Armuzzi, Alessandro, Augustyn, Monika, Bafutto, Mauro, Barrio, Jesus, Begun, Jakob, Behrend, Clint, Bezemer, Geert, Bonnaud, Guillaume, Brankovic, Marija, Byung, Ik Jang, Calvet Calvo, Xavier, Chachu, Karen, Chebli, Julio Maria Fonseca, Cheon, Jae Hee, Cichoz-Lach, Halina, Clark, Larry, Cummings, Fraser, Dalal, Kunal, Danese, Silvio, De Boer, Nanne, De Lourdes Ferrari, Maria, Désilets, Etienne, Dugalic, Predrag, Duvall, George, Fedorishina, Olga, Filip, Rafal, Flores, Cristina, Fogel, Ronald, Fon, James, Frankel, Michael, Friedenberg, Keith, Fries, Walter, Galina, Vassileva, Gietka, Piotr, Goel, Rishi, Hasselblatt, Peter, Herfarth, Hans, Herszényi, László, Hindryckx, Pieter, Hoentjen, Frank, Horjus Talabur Horje, Carmen, Iduru, Satish, Irving, Peter, Isfort, Robert, Jairath, Vipul, Jones, Michael, Kalimullina, Dilara, Katz, Jeffry, Kaur, Manreet, Khurana, Sunil K, Kim, Joo Sung, Kim, Youngho, Kleczkowski, Dariusz, Knezevic, Slavko, Knoll, Aaron, Korman, Louis Y, Kotzev, Iskren, Kulyapin, Andrey, Lee, Kang Moon, Leemreis, Desiree, Leszczyszyn, Jaroslaw, Limdi, Jimmy, Lissauer, Jack, Loftus, Edward, Malecka-Panas, Ewa, Marshall, John, Mihály, Emese, Milan, Lukas, Monteleone, Giovanni, Nagorni, Aleksandar, Owczarek, Danuta, Palekar, Nichole, Panaccione, Remo, Park, Young Soo, Park, Sang Hyoung, Parra, Rogério, Patai, Árpád, Patel, Kamal, Patel, Bhaktasharan, Pershko, Anatoly, Petrova, Elina, Pineton de Chambrun, Guillaume, Randall, Charles, Riestra Menendez, Sabino, Ritter, Timothy, Rivero, Montserrat, Roblin, Xavier, Rocca, Rodolfo, Romatowski, Jacek, Rydzewska, Grazyna, Saibeni, Simone, Salzberg, Bruce, Sarles, Harry, Saunders, John, Savarino, Edoardo Vincenzo, Serclova, Zuzana, Shchukina, Oksana, Siegel, Jonathan, Soofi, Najm, Sparrow, Miles, Stokesberry, David, Suiter, Daniel, Svorcan, Petar, Tkachev, Alexander, Tsonev, Nikolay, Tünde, Kristóf, Ulbrych, Jan, Vanasek, Tomas, Varga, Márta, Vermeire, Severine, Vicente Lidon, Raquel, Weiss, Michael L, Wesley, Emma, Winstead, Nathaniel, Wojcik, Katarzyna, Wypych, Joanna, Zaltman, Cyrla, Zdena, Zadorova, Sands, Bruce E, Irving, Peter M, Hoops, Timothy, Izanec, James L, Gao, Long-Long, Gasink, Christopher, Greenspan, Andrew, Hanauer, Stephen B, Kuehbacher, Tanja, Lewis, James D, Loftus, Edward V, Jr, Mihaly, Emese, Scherl, Ellen, Shchukina, Oksana B, and Sandborn, William J

Published
2022
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37. Leptomeningeal Dissemination in Choroid Plexus Tumors: Magnetic Resonance Imaging Appearance and Risk Factors.

Author

Nunes do Espirito Santo, Daniel, Warmuth-Metz, Monika, Monoranu, Camelia-Maria, Hasselblatt, Martin, Thomas, Christian, Pietsch, Torsten, Krauß, Jürgen, Schweitzer, Tilmann, Bison, Brigitte, Eyrich, Matthias, Kordes, Uwe, Obrecht-Sturm, Denise, Pham, Mirko, and Quenzer, Annika

Abstract

Background: Intracranial choroid plexus tumors (CPT) are rare and primarily affect young children. Leptomeningeal dissemination (LMD) has been reported not only in high-grade choroid plexus carcinoma (CPC) but also in lower histological grades; however, a systematic evaluation of CPT-specific imaging characteristics remains lacking. Methods: We analyzed the imaging characteristics of LMD in a single-center pediatric cohort of 22 CPT patients (thirteen choroid plexus papilloma (CPP), six atypical choroid plexus papilloma (aCPP), three CPC), comparing LMD features with those of the primary tumor. Additionally, we examined the correlation between resection status and LMD development during follow-up. Results: At diagnosis, we observed true LMD in three (two CPCs, one CPP) and pseudo-LMD in one case (CPP). During follow-up, two CPP patients developed cystic LMD, and one aCPP patient developed a solid metastasis. LMD had characteristics of the primary tumor in 3/4 cases. Incomplete resection was associated with a higher risk of LMD (p = 0.025). Conclusions: LMD can occur in both high- and lower-grade CPT, presenting at diagnosis as well as in relapsed lower-grade cases. Notable MR-imaging features include pseudo-LMD at diagnosis and cystic LMD in relapsed CPP cases. Incomplete tumor resection may increase the risk of LMD, although further validation is needed. [ABSTRACT FROM AUTHOR]

Published
2025
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38. Activation of Wnt/β-catenin signaling is critical for the tumorigenesis of choroid plexus.

Author

Ho, Kim Hoa, Trapp, Marleen, Guida, Catello, Ivanova, Ekaterina L, Jaime-Soguero, Anchel De, Jabali, Ammar, Thomas, Christian, Salasova, Alena, Bernatík, Ondřej, Salio, Chiara, Horschitz, Sandra, Hasselblatt, Martin, Sassoè-Pognetto, Marco, Čajánek, Lukáš, Ishikawa, Hiroshi, Schroten, Horst, Schwerk, Christian, Acebrón, Sergio P, Angel, Peter, and Koch, Philipp

Published
2025
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40. Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial

Author

Aguilar, Humberto, Ahmad, Tariq, Akriviadis, Evangelos, Aldeguer Mante, Xavier, Allez, Matthieu, Altorjay, Istvan, Ananthakrishnan, Ashwin, Andersen, Vibeke, Andreu Garcia, Montserrat, Armuzzi, Alessandro, Aumais, Guy, Avni-Biron, Irit, Axler, Jeffrey, Ayub, Kamran, Jr., Baert, Filip, Bafutto, Mauro, Bamias, George, Bassan, Isaac, Baum, Curtis, Beaugerie, Laurent, Behm, Brian, Bekal, Pradeep, Bennett, Michael, Bermejo San Jose, Fernando, Bernstein, Charles, Bettenworth, Dominik, Bhaskar, Sudhir, Biancone, Livia, Bilir, Bahri, Blaeker, Michael, Bloom, Stuart, Bohman, Verle, Jr., Bosques Padilla, Francisco Javier, Bossuyt, Peter, Bouhnik, Yoram, Bouma, Gerd, Bourdages, Raymond, Brand, Stephan, Bressler, Brian, Brückner, Markus, Buening, Carsten, Carbonnel, Franck, Caves, Thomas, Chapman, Jonathon, Cheon, Jae Hee, Chiba, Naoki, Chioncel, Camelia, Christodoulou, Dimitrios, Clodi, Martin, Cohen, Albert, Corazza, Gino Roberto, Corlin, Richard, Cosintino, Rocco, Cummings, Fraser, Dalal, Robin, Danese, Silvio, De Maeyer, Marc, De Magalhães Francesconi, Carlos Fernando, De Silva, Aminda, Debinski, Henry, Desreumaux, Pierre, Dewit, Olivier, D'Haens, Geert, Di Felice Boratto, Sandra, Ding, John Nik, Dixon, Tyler, Dryden, Gerald, Jr., Du Vall, George Aaron, Ebert, Matthias, Echarri Piudo, Ana, Ehehalt, Robert, Elkhashab, Magdy, Ennis, Craig, Etzel, Jason, Fallingborg, Jan, Feagan, Brian, Fejes, Roland, Ferraz de Campos Mazo, Daniel, Ferreira de Almeida Borges, Valéria, Fischer, Andreas, Fixelle, Alan, Fleisher, Mark, Fowler, Sharyle, Freilich, Bradley, Friedenberg, Keith, Fries, Walter, Fulop, Csaba, Fumery, Mathurin, Fuster, Sergio, G Kiss, Gyula, Garcia Lopez, Santiago, Gassner, Sonja, Gill, Kanwar, Gilletta de Saint Joseph, Cyrielle, Ginsburg, Philip, Gionchetti, Paolo, Goldin, Eran, Goldis, Adrian-Eugen, Gomez Jaramillo, Hector Alejandro, Gonciarz, Maciej, Gordon, Glenn, Green, Daniel, Grimaud, Jean-Charles, Guajardo Rodriguez, Rogelio, Gurzo, Zoltan, Gutierrez, Alexandra, Gyökeres, Tibor, Hahm, Ki Baik, Hanauer, Stephen, Hanson, John, Harlan III, William, Hasselblatt, Peter, Hayee, Buhussain, Hebuterne, Xavier, Hendy, Peter, Heyman, Melvin, Higgins, Peter, Hilal, Raouf, Hindryckx, Pieter, Hoentjen, Frank, Hoffmann, Peter, Holtkamp-Endemann, Frank, Holtmann, Gerald, Horvat, Gyula, Howaldt, Stefanie, Huber, Samuel, Ibegbu, Ikechukwu, Iborra Colomino, Maria Isabel, Irving, Peter, Isaacs, Kim, Jagarlamudi, Kiran, Jain, Rajesh, Jankiel Miszputen, Sender, Jansen, Jeroen, Jones, Jennifer, Juillerat, Pascal, Karagiannis, John, Karyotakis, Nicholas, Kaser, Arthur, Katz, Lior, Katz, Seymour, Katz, Leo, Kaur, Nirmal, Kazenaite, Edita, Khanna, Reena, Khurana, Sunil, Kim, Joo Sung, Kim, Young-Ho, Kim, Sung Kook, Kim, Dongwoo, Klaus, Jochen, Kleczkowski, Dariusz, Kohout, Pavel, Korczowski, Bartosz, Kouklakis, Georgios, Koutroubakis, Ioannis, Krause, Richard, Kristof, Tunde, Kronborg, Ian, Krummenerl, Annette, Kupcinskas, Limas, Laborda Molteni, Jorge, Laharie, David, Lahat-zok, Adi, Lee, Jonghun, Lee, Kang-Moon, Leong, Rupert, Levine, Henry, Limdi, Jimmy, Lindsay, James, Lodhia, Nilesh, Loftus, Edward, Longman, Randy, Lopez Serrano, Pilar, Louis, Edouard, Louzada Pereira, Maria Helena, Lowe, John, Lueth, Stefan, Lukas, Milan, Maconi, Giovanni, Macrae, Finlay, Madi-Szabo, Laszlo, Mahadevan-Velayos, Uma, Malluta, Everson Fernando, Mana, Fazia, Mannon, Peter, Mantzaris, Gerasimos, Marin Jimenez, Ignacio, Martin Arranz, Maria Dolores, Mateescu, Radu-Bogdan, Mazzoleni, Felipe, Meder, Agnieszka, Melzer, Ehud, Mertens, Jessica, Mimidis, Konstantinos, Mitchell, Brent, Molnar, Tamas, Moore, Gregory, Morales Garza, Luis Alonso, Mountifield, Reme, Muls, Vinciane, Murray, Charles, Nagy, Bela, Neurath, Markus, Nguyen, Augustin, Panaccione, Remo, Pandak, William, Panes Diaz, Julian, Park, Jihye, Pastorelli, Luca, Patel, Bhaktasharan, Peck-Radosavljevic, Markus, Pecsi, Gyula, Peerani, Farhad, Perez Gisbert, Javier, Pesta, Martin, Petryka, Robert, Peyrin-Biroulet, Laurent, Phillips, Raymond, Pierik, Marieke, Pratha, Vijayalakshmi, Prochazka, Vlastimil, Racz, Istvan, Radford-Smith, Graham, Ramos Castañeda, Daniel, Ramos Júnior, Odery, Regula, Jaroslaw, Reimund, Jean-Marie, Robbins, Bryan, Roblin, Xavier, Rogai, Francesca, Rogler, Gerhard, Rozciecha, Jerzy, Rubin, David, Ruiz Flores, Azalia Yuriria, Rupinski, Maciej, Rydzewska, Grazyna, Saha, Sumona, Saibeni, Simone, Salamon, Agnes, Sallo, Zoltan, Salzberg, Bruce, Samuel, Douglas, Samuel, Sunil, Sandborn, William, Savarino, Edoardo Vincenzo, Schirbel, Anja, Schnabel, Robert, Schreiber, Stefan, Scott, John, Sedghi, Shahriar, Seibold, Frank, Seidelin, Jakob, Seidler, Ursula, Shaban, Ahmad, Shafran, Ira, Sheikh, Aasim, Sherman, Alex, Shirin, Haim, Smolinski, Patryk, Song, Geun Am, Soufleris, Konstantinos, Speight, Alexander, Staessen, Dirk, Stallmach, Andreas, Staun, Michael, Stein, Daniel, Steinhart, Hillary, Stifft, Jonathas, Stokesberry, David, Sturm, Andreas, Sultan, Keith, Szekely, Gyorgy, Tagore, Kuldeep, Tanno, Hugo, Thin, Lena, Thiwan, Syed, Thomas, Carlton, Tichy, Michal, Toth, Gabor Tamas, Tulassay, Zsolt, Ulbrych, Jan, Valentine, John, Varga, Marta, Vasconcellos, Eduardo, Vaughn, Byron, Velasco, Brenda, Velazquez, Francisco, Vermeire, Severine, Villa, Erica, Vincze, Aron, Vogelsang, Harald, Volfova, Miroslava, Vuitton, Lucine, Vyhnalek, Petr, Wahab, Peter, Walldorf, Jens, Waterman, Mattitiahu, Weber, John, Weiss, L. Michael, Wiechowska-Kozlowska, Anna, Wiesner, Elise, Witthoeft, Thomas, Wohlman, Robert, Wozniak-Stolarska, Barbara, Yacyshyn, Bruce, Ye, Byong-Duk, Younes, Ziad, Yukie Sassaki, Lígia, Zaltman, Cyrla, Zeuzem, Stefan, Hart, Ailsa, Long, Millie, Loftus, Edward V, Jr, Ostad-Saffari, Elham, Scalori, Astrid, Oh, Young S, Tole, Swati, Chai, Akiko, Pulley, Jennifer, Lacey, Stuart, and Sandborn, William J

Published
2022
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41. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study

Author

Aboo, Nazimuddin, Ahmad, Tariq, Aldeguer Mante, Xavier, Allez, Matthieu, Almer, Sven, Altwegg, Romain, Andreu Garcia, Montserrat, Arasaradnam, Ramesh, Ardizzone, Sandro, Armuzzi, Alessandro, Arnott, Ian, Aumais, Guy, Avni-Biron, Irit, Barrow, Peter, Beales, Ian, Bermejo San Jose, Fernando, Bezuidenhout, Abraham, Biancone, Livia, Blaeker, Michael, Bloom, Stuart, Bokemeyer, Bernd, Bossa, Fabrizio, Bossuyt, Peter, Bouguen, Guillaume, Bouhnik, Yoram, Bouma, Gerd, Bourdages, Raymond, Bourreille, Arnaud, Boustiere, Christian, Brabec, Tomas, Brand, Stephan, Buening, Carsten, Buisson, Anthony, Cadiot, Guillaume, Calvet Calvo, Xavier, Carbonnel, Franck, Carpio, Daniel, Cheon, Jae Hee, Chiba, Naoki, Chioncel, Camelia, Cimpoeru, Nicoleta-Claudia, Clodi, Martin, Corazza, Gino Roberto, Cosintino, Rocco, Cotter, Jose, Creed, Thomas, Cummings, Fraser, Danese, Silvio, de' Angelis, Gian Luigi, De Maeyer, Marc, Desai, Milind, Desilets, Etienne, Desreumaux, Pierre, Dewit, Olivier, D'Haens, Geert, Dinter, Johanna, Dobru, Ecaterina Daniela, Douda, Tomas, Dumitrascu, Dan Lucian, Ebert, Matthias, Echarri Piudo, Ana, Elkhashab, Magdy, Eun, Chang Soo, Feagan, Brian, Fejes, Roland, Fidalgo, Catarina, Fishman, Sigal, Flourié, Bernard, Fowler, Sharyle, Fries, Walter, Fulop, Csaba, Fumery, Mathurin, G Kiss, Gyula, Gassner, Sonja, Gaya, Daniel, Germanà, Bastianello, Gheorghe, Liliana Simona, Gilletta de Saint Joseph, Cyrielle, Gionchetti, Paolo, Goldis, Adrian-Eugen, Gonçalves, Raquel, Grimaud, Jean-Charles, Gyökeres, Tibor, Hagege, Herve, Haidar, Andrei, Hartmann, Heinz, Hasselblatt, Peter, Hayee, Buhussain, Hebuterne, Xavier, Hellström, Per, Hindryckx, Pieter, Hlavova, Helena, Hoentjen, Frank, Howaldt, Stefanie, Hrdlicka, Ludek, Huh, Kyu Chan, Iborra Colomino, Maria Isabel, Ionita-Radu, Florentina, Irving, Peter, Jahnsen, Jørgen, Jang, ByungIk, Jansen, Jeroen, Jeon, Seong Woo, Jover Martinez, Rodrigo, Juillerat, Pascal, Karlén, Per, Kaser, Arthur, Keil, Radan, Kejariwal, Deepak, Keret, Dan, Khanna, Reena, Kim, Dongwoo, Kim, Duk Hwan, Kim, Hyo-Jong, Kim, Hyun-Soo, Kim, Joo Sung, Kim, Kueongok, Kim, Kyung-Jo, Kim, Sung Kook, Kim, Young-Ho, Klaus, Jochen, Kohn, Anna, Kojecky, Vladimir, Koo, Ja Seol, Kozak, Robert, Kremer, Milan, Kristof, Tunde, Kruger, Frederik, Laharie, David, Lahat-zok, Adi, Landa, Evgeny, Lee, Jonghun, Lee, Kang-Moon, Lee, Kook Lae, Lee, YooJin, Lenze, Frank, Lim, Wee Chian, Limdi, Jimmy, Lindsay, James, Lopez Serrano, Pilar, Louis, Edouard, Lueth, Stefan, Lukas, Milan, Maconi, Giovanni, Mana, Fazia, Mann, Steven, Mansfield, John, Marchi, Santino, Marino, Marco, Marshall, John, Martin Arranz, Maria Dolores, Mateescu, Radu-Bogdan, McLaughlin, John, McLaughlin, Simon, Melzer, Ehud, Mertens, Jessica, Mitrut, Paul, Molnar, Tamas, Muls, Vinciane, Munuswamy, Pushpakaran, Murray, Charles, Naftali, Timna, Naidoo, Visvakuren, Nanabhay, Yusuf, Negreanu, Lucian, Nguyen, Augustin, Ochsenkuehn, Thomas, Orlando, Ambrogio, Panaccione, Remo, Panes Diaz, Julian, Paritsky, Maya, Park, Dong Il, Park, Jihye, Pastorelli, Luca, Peck-Radosavljevic, Markus, Peerani, Farhad, Perez Gisbert, Javier, Peyrin-Biroulet, Laurent, Picon, Laurence, Pierik, Marieke, Ponich, Terry, Portela, Francisco, Prins, Maartens Jeroen, Racz, Istvan, Rahman, Khan Fareed, Reimund, Jean-Marie, Reinshagen, Max, Roblin, Xavier, Rocca, Rodolfo, Rogai, Francesca, Rogler, Gerhard, Salamon, Agnes, Salazar, Ennaliza, Sallo, Zoltan, Samuel, Sunil, Sans Cuffi, Miquel de los Santos, Savarino, Edoardo Vincenzo, Savarino, Vincenzo, Savoye, Guillaume, Schreiber, Stefan, Seicean, Andrada, Selinger, Christian, Serra, David Martins, Shim, Hang Hock, Shin, SungJae, Siegmund, Britta, Siffledeen, Jesse, Simmonds, Wayne, Smid, Jan, Sollano, Jose, Song, Geun Am, Speight, Alexander, Sporea, Ioan, Staessen, Dirk, Stancu, George, Steel, Alan, Stepek, David, Stoica, Victor, Sturm, Andreas, Szekely, Gyorgy, Tan, Teck Kiang, Taxonera Samso, Carlos, Thomson, John, Tichy, Michal, Toth, Gabor Tamas, Tulassay, Zsolt, Vangeli, Marcello, Varga, Marta, Vieira, Ana, Viennot, Stephanie, Villa, Erica, Vitek, Petr, Vogelsang, Harald, Vyhnalek, Petr, Wahab, Peter, Walldorf, Jens, Ye, Byong Duk, Ziady, Christopher, Colombel, Jean-Frederic, Gisbert, Javier P, Hayee, Bu'hussain, Reinisch, Walter, Tyrrell, Helen, Oh, Young S, Tole, Swati, Chai, Akiko, Chamberlain-James, Kirsten, and Tang, Meina Tao

Published
2022
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42. GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity

Author

Heitzeneder, Sabine, Bosse, Kristopher R., Zhu, Zhongyu, Zhelev, Doncho, Majzner, Robbie G., Radosevich, Molly T., Dhingra, Shaurya, Sotillo, Elena, Buongervino, Samantha, Pascual-Pasto, Guillem, Garrigan, Emily, Xu, Peng, Huang, Jing, Salzer, Benjamin, Delaidelli, Alberto, Raman, Swetha, Cui, Hong, Martinez, Benjamin, Bornheimer, Scott J., Sahaf, Bita, Alag, Anya, Fetahu, Irfete S., Hasselblatt, Martin, Parker, Kevin R., Anbunathan, Hima, Hwang, Jennifer, Huang, Min, Sakamoto, Kathleen, Lacayo, Norman J., Klysz, Dorota D., Theruvath, Johanna, Vilches-Moure, José G., Satpathy, Ansuman T., Chang, Howard Y., Lehner, Manfred, Taschner-Mandl, Sabine, Julien, Jean-Phillipe, Sorensen, Poul H., Dimitrov, Dimiter S., Maris, John M., and Mackall, Crystal L.

Published
2022
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44. OS-083 Highly multiplexed spatial analysis of acute pediatric hepatitis of unknown origin indicates a characteristic immune infiltrate as a possible post-acute sequel of COVID-19

Author

Röttele, Felix, primary, Zollner, Andreas, additional, Yuksel, Muhammed, additional, Arıkan, Cigdem, additional, Mogler, Carolin, additional, Aberle, Judith, additional, Aberle, Stephan, additional, Wölfle, Lena, additional, Maier, Felix, additional, Lurz, Eberhart, additional, Hasselblatt, Peter, additional, Hofmann, Maike, additional, Thimme, Robert, additional, Müller, Thomas, additional, Vogel, Georg-Friedrich, additional, and Bengsch, Bertram, additional

Published
2024
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45. Clinical response to nivolumab in an INI1-deficient pediatric chordoma correlates with immunogenic recognition of brachyury

Author

Laura M. Williamson, Craig M. Rive, Daniela Di Francesco, Emma Titmuss, Hye-Jung E. Chun, Scott D. Brown, Katy Milne, Erin Pleasance, Anna F. Lee, Stephen Yip, Daniel G. Rosenbaum, Martin Hasselblatt, Pascal D. Johann, Marcel Kool, Melissa Harvey, David Dix, Daniel J. Renouf, Robert A. Holt, Brad H. Nelson, Martin Hirst, Steven J. M. Jones, Janessa Laskin, Shahrad R. Rassekh, Rebecca J. Deyell, and Marco A. Marra

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Poorly differentiated chordoma (PDC) is a recently recognized subtype of chordoma characterized by expression of the embryonic transcription factor, brachyury, and loss of INI1. PDC primarily affects children and is associated with a poor prognosis and limited treatment options. Here we describe the molecular and immune tumour microenvironment profiles of two paediatric PDCs produced using whole-genome, transcriptome and whole-genome bisulfite sequencing (WGBS) and multiplex immunohistochemistry. Our analyses revealed the presence of tumour-associated immune cells, including CD8+ T cells, and expression of the immune checkpoint protein, PD-L1, in both patient samples. Molecular profiling provided the rationale for immune checkpoint inhibitor (ICI) therapy, which resulted in a clinical and radiographic response. A dominant T cell receptor (TCR) clone specific for a brachyury peptide–MHC complex was identified from bulk RNA sequencing, suggesting that targeting of the brachyury tumour antigen by tumour-associated T cells may underlie this clinical response to ICI. Correlative analysis with rhabdoid tumours, another INI1-deficient paediatric malignancy, suggests that a subset of tumours may share common immune phenotypes, indicating the potential for a therapeutically targetable subgroup of challenging paediatric cancers.

Published
2021
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47. GOPC:ROS1 and other ROS1 fusions represent a rare but recurrent drug target in a variety of glioma types

Author

Sievers, Philipp, Stichel, Damian, Sill, Martin, Schrimpf, Daniel, Sturm, Dominik, Selt, Florian, Ecker, Jonas, Kazdal, Daniel, Miele, Evelina, Kranendonk, Mariëtte E. G., Tops, Bastiaan B. J., Kohlhof-Meinecke, Patricia, Beschorner, Rudi, Kramm, Christof M., Hasselblatt, Martin, Reifenberger, Guido, Capper, David, Wesseling, Pieter, Stenzinger, Albrecht, Milde, Till, Korshunov, Andrey, Witt, Olaf, Pfister, Stefan M., Wick, Wolfgang, von Deimling, Andreas, Jones, David T. W., and Sahm, Felix

Published
2021
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48. MiR-100 overexpression attenuates high fat diet induced weight gain, liver steatosis, hypertriglyceridemia and development of metabolic syndrome in mice

Author

Christian Smolka, Delia Schlösser, Catherine Hohnloser, Xavier Bemtgen, Caterina Jänich, Laura Schneider, Julien Martin, Dietmar Pfeifer, Martin Moser, Peter Hasselblatt, Christoph Bode, Sebastian Grundmann, and Franziska Pankratz

Subjects
miR-100, CD36, Fatty acid uptake, Liver steatosis, Metabolic syndrome, Therapeutics. Pharmacology, RM1-950, Biochemistry, QD415-436
Abstract

Abstract Background Diet-induced obesity can result in the development of a diverse spectrum of cardiovascular and metabolic diseases, including type 2 diabetes, dyslipidemia, non-alcoholic liver steatosis and atherosclerotic disease. MicroRNAs have been described to be important regulators of metabolism and disease development. Methods In the current study, we investigated the effects of ubiquitous miR-100 overexpression on weight gain and the metabolic phenotype in a newly generated transgenic mouse strain under normal chow and high fat diet and used microarray expression analysis to identify new potential target genes of miR-100. Results While transgenic overexpression of miR-100 did not significantly affect weight and metabolism under a normal diet, miR-100 overexpressing mice showed a reduced weight gain under a high fat diet compared to wildtype mice, despite an equal calorie intake. This was accompanied by less visceral and subcutaneous fat development and lover serum LDL cholesterol. In addition, transgenic miR-100 mice were more glucose tolerant and insulin sensitive and demonstrated increased energy expenditure under high fat diet feeding. A comprehensive gene expression profiling revealed the differential expression of several genes involved in lipid storage- and metabolism, among them CD36 and Cyp4A14. Our data showed a direct regulation of CD36 by miR-100, leading to a reduced fatty acid uptake in primary hepatocytes overexpressing miR-100 and the downregulation of several downstream mediators of lipid metabolism such as ACC1, FABP4, FAS and PPARγ in the liver. Conclusions Our findings demonstrate a protective role of miR-100 in high fat diet induced metabolic syndrome and liver steatosis, partially mediated by the direct repression of CD36 and attenuation of hepatic lipid storage, implicating miR-100 as a possible therapeutic target in liver steatosis.

Published
2021
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