A5034606670- Sarcoma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Cardiac tumors and thrombi
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- Chromatin Remodeling and Cancer
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Histone Deacetylase Inhibitors Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Cancer-related gene regulation
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Prostate Cancer Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Veterinary Oncology Research
- DNA Repair Mechanisms
- Polyamine Metabolism and Applications
- Vitamin K Research Studies
Hopp Children's Cancer Center Heidelberg
2021-2025
German Cancer Research Center
2021-2025
National Center for Tumor Diseases
2024-2025
Heidelberg University
2021-2025
University Hospital Heidelberg
2024-2025
Deutschen Konsortium für Translationale Krebsforschung
2021-2025
Children's Cancer Center
2025
Seirei Hamamatsu General Hospital
2024
Ludwig-Maximilians-Universität München
2015-2022
Kanagawa Academy of Science and Technology
1993
Ewing sarcoma is an undifferentiated small-round-cell sarcoma. Although molecular detection of pathognomonic EWSR1-ETS fusions such as EWSR1-FLI1 enables definitive diagnosis, substantial confusion can arise if diagnostics are unavailable. Diagnosis based on the conventional immunohistochemical marker CD99 unreliable due to its abundant expression in morphological mimics. To identify novel diagnostic markers for sarcoma, we performed comparative analyses 768 tumors representing 21 entities...
Ewing sarcoma (EwS) is an aggressive cancer characterized by chromosomal translocations generating fusions of the EWSR1 gene with ETS transcription factors (in 85% FLI1). EWSR1-FLI1 induces expression via binding to enhancer-like GGAA-microsatellites, whose activity correlates number consecutive GGAA-repeats. Herein we investigate role secretory neuropeptide CALCB (calcitonin-related polypeptide β) in EwS, which signals CGRP (calcitonin gene-related peptide) receptor complex, containing...
Abstract Pediatric malignancies including Ewing sarcoma (EwS) feature a paucity of somatic alterations except for pathognomonic driver-mutations that cannot explain overt variations in clinical outcome. Here, we demonstrate EwS how cooperation dominant oncogenes and regulatory germline variants determine tumor growth, patient survival drug response. Binding the oncogenic EWSR1-FLI1 fusion transcription factor to polymorphic enhancer-like DNA element controls expression MYBL2 mediating these...
Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family transcription factors (in 85% FLI1). EWSR1-FLI1 can induce target genes using GGAA-microsatellites as enhancers.Here, we show that hijacks developmental factor SOX6 - a physiological driver proliferation progenitors binding to intronic GGAA-microsatellite, which...
Epithelioid sarcoma (EpS) is a high-grade malignancy of unknown histogenesis first described in 1970 [1], characterized by high rates relapse and metastasis, with 5-year survival 60%-75% [2]. The only Food Drug Administration (FDA)-approved targeted therapy, the enhancer zeste homology 2 (EZH2) inhibitor tazemetostat, achieved transient responses 15% patients To establish solid mechanistic basis, we investigated role SWI/SNF related BAF chromatin remodeling complex subunit B1 (SMARCB1) via...
Ewing sarcoma (EwS) cell line culture largely relies on standard techniques, which do not recapitulate physiological conditions. Here, we report a feasible and cost-efficient EwS technique with increased relevance employing an advanced medium composition, reduced fetal calf serum, spheroidal growth. Improved reflection of the transcriptional activity related to proliferation, hypoxia, differentiation in patient tumors was detected cells grown this refined vitro condition. Moreover,...
Abstract Tumor cells often cope with elevated levels of replication stress (RS) causing increased dependency on ATR-CHK1 signalling. We previously presented RRM2, the regulatory component ribonucleotide reductase (RNR) enzyme, as novel in neuroblastoma, keeping its role RS resistance. identified strong synergism for combined RRM2-CHK1 inhibition using iron chelator triapine and prexasertib respectively. To obtain direct RNR targeting, we evaluated a inhibitor, TAS1553, specifically...
Desmoplastic small round cell tumor (DSRCT) is an aggressive cancer that predominantly affects adolescents and young adults, typically developing at sites lined by mesothelium [1, 2]. DSRCT genetically defined a chromosomal translocation fuses the N-terminus of EWS RNA binding protein 1 (EWSR1) to C-terminus Wilms (WT1), forming EWSR1::WT1 [3]. This fusion encodes potent transcription factor only known driver oncogenic transformation in [4]. The lack comprehensive understanding biology...
Up to 30-40% of Ewing sarcoma (EwS) patients with non-metastatic disease develop local or metastatic relapse within a time span 2-10 years. This is in part caused by the absence prognostic biomarkers that can identify high-risk and thus assign them risk-adapted monitoring treatment regimens. Since cancer stemness has been associated tumour poor patient outcomes, we investigated current study potential SOX2 (sex determining region Y box 2) - major transcription factor involved development...
Abstract Chromosomal instability (CIN) is a hallmark of cancer 1 . Yet, many childhood cancers, such as Ewing sarcoma (EwS), feature remarkably ‘silent’ genomes with minimal CIN 2 Here, we show in the EwS model how uncoupling mitosis and cytokinesis via targeting protein regulator (PRC1) or its activating polo-like kinase (PLK1) can be employed to induce fatal genomic tumor regression. We find that EwS-specific oncogenic transcription factor EWSR1-FLI1 hijacks PRC1 , which physiologically...
Glyoxalase I (EC 4.4.1.5) catalyzes the transformation of methylglyoxal and glutathione to S-lactoylglutathione. We have isolated human cDNA clones encoding glyoxalase from a phorbol myristate acetate-treated U937 library. This encodes protein 184 amino acids with calculated M(r) 20,719. The acid composition deduced sequence agreed that reported for purified erythrocytes. Escherichia coli cells carrying expression vector this acquired resistance cell lysate showed high activity I. exhibited...
Ewing sarcoma (EwS) is an aggressive cancer displaying undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, aimed at validating the specificity both in far larger independent cohort EwS (including EWSR1-ERG-positive cases) Furthermore,...
Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis Variable gene Expressions in Numerous tissues) that automatizes the systematic fast identification CSG-encoded highly affine to...
Abstract The diagnosis of canine intestinal lymphoma by morphological examination is challenging, especially when endoscopic tissue specimens are used. utility detection antigen receptor gene rearrangement polymerase chain reaction ( PARR ) in has been well established, but its usefulness to distinguish enteritis and remains unclear. In this retrospective study we assessed clonality 29 primary lymphoma, 14 15 healthy control cases analysis, using formalin‐fixed, paraffin‐embedded...
In prostate adenocarcinoma (PCa), distinction between indolent and aggressive disease is challenging. Around 50% of PCa are characterized by TMPRSS2‐ERG (T2E)‐fusion oncoproteins defining two molecular subtypes (T2E‐positive/negative). However, current prognostic tests do not differ both subtypes, which might affect outcome prediction. To investigate gene‐signatures associated with metastasis in T2E‐positive T2E‐negative independently, we integrated tumor transcriptomes clinicopathological...
Soft-tissue sarcomas are rare, heterogeneous, and often aggressive mesenchymal cancers. Many of them associated with poor outcome, partially because biomarkers that can identify high-risk patients lacking. Studies on limited by small sample-sizes rendering the identification difficult when focusing individual cohorts. However, increasing number publicly available 'omics' data opens inroads to overcome this obstacle. Here, we combine transcriptome analyses, immunohistochemistry, functional...
Abstract Drug resistance is one of the major factors associated with poor outcome cancer patients. Treatment Ewing sarcoma (EwS), an aggressive neoplasm mainly affecting children, adolescents and young adults, therapy failure tumor relapse in 30-80% cases. Thus, it supports need to explore mechanisms modulating drug activity. Here, we describe a novel mechanism sensitivity based on role EWS::FLI1 R-loop metabolism. Our results demonstrate that promotes formation favoring interaction between...
ABSTRACT Chromosome 8 (chr8) gains are common in cancer. However, their potential contribution to tumor heterogeneity is largely unexplored. Ewing sarcoma (EwS) characterized by pathognomonic FET::ETS fusions but a general paucity of other recurrent somatic mutations that could explain the observed clinical diversity. In EwS, chr8 second most genetic alteration rendering EwS an ideal model investigate relevance otherwise silent genomic context. Here, we report gain-driven gene expression...
ABSTRACT Cell lines have been essential for major discoveries in cancer including Ewing sarcoma (EwS). EwS is a highly aggressive pediatric bone or soft-tissue characterized by oncogenic EWSR1-ETS fusion transcription factors converting polymorphic GGAA-microsatellites (mSats) into neo-enhancers. However, further detailed mechanistic evaluation of gene regulation hindered the limited number well-characterized cell line models. Here, we present Sarcoma Line Atlas (ESCLA) comprising 18 with...