A5045047262- Head and Neck Cancer Studies
- Lung Cancer Treatments and Mutations
- Cancer-related gene regulation
- RNA modifications and cancer
- S100 Proteins and Annexins
- Skin and Cellular Biology Research
- Lymphatic System and Diseases
- Cutaneous lymphoproliferative disorders research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- NF-κB Signaling Pathways
- Cancer Cells and Metastasis
- Ferroptosis and cancer prognosis
- Advanced Glycation End Products research
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Salivary Gland Tumors Diagnosis and Treatment
- Immune Cell Function and Interaction
- Hepatocellular Carcinoma Treatment and Prognosis
- Immune Response and Inflammation
- Cancer-related Molecular Pathways
Heidelberg University
2016-2025
University Hospital Heidelberg
2016-2025
German Cancer Research Center
2016-2025
DKFZ-ZMBH Alliance
2009-2023
Essen University Hospital
2021-2022
Universitäts-HNO-Klinik Heidelberg
2021
Deutschen Konsortium für Translationale Krebsforschung
2019
Hess (United States)
2016
University Medical Center
2015
Tel Aviv Sourasky Medical Center
2014
Abstract Due to the dependency on aromatic precursors, growth of Salmonella typhimurium aroA- is limited in immunocompetent mice. Here we show that H-21-A beta-/- mice (lacking MHC class II molecules and thus devoid mature CD4+ TCR-alpha beta cells), TCR-beta-/- (devoid IFN-gamma R-/- (unresponsive IFN-gamma) are highly susceptible S. infection compared with heterozygous controls. In contrast, 2m-deficient surface I conventional CD8+ T cells) or TCR-delta-/- TCR-gamma delta were equally as...
A broad range of experimental and clinical evidence has highlighted the central role chronic inflammation in promoting tumor development. However, molecular mechanisms converting a transient inflammatory tissue reaction into tumor-promoting microenvironment remain largely elusive. We show that mice deficient for receptor advanced glycation end-products (RAGE) are resistant to DMBA/TPA-induced skin carcinogenesis exhibit severe defect sustaining during promotion phase. Accordingly, RAGE is...
Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA RNA status, gene expression patterns, mutated candidate genes may facilitate patient treatment decision. We characterize with different (E6*I) status from 290 consecutively recruited patients by profiling targeted sequencing 50 genes. show that tumors transcriptionally inactive (DNA+ RNA-) are similar to HPV-negative (DNA-) regarding frequency TP53 mutations (47%, 8/17 43%, 72/167, respectively). also find an...
Aggressive and metastatic cancers show enhanced metabolic plasticity1, but the precise underlying mechanisms of this remain unclear. Here we how two NOP2/Sun RNA methyltransferase 3 (NSUN3)-dependent modifications-5-methylcytosine (m5C) its derivative 5-formylcytosine (f5C) (refs.2-4)-drive translation mitochondrial mRNA to power metastasis. Translation mitochondrially encoded subunits oxidative phosphorylation complex depends on formation m5C at position 34 in tRNAMet. m5C-deficient human...
The incidence rate of human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Despite good prognosis, recurrence can decrease health-related quality life and increase mortality, so post-treatment monitoring important for patient outcomes. One potential biomarker HPV cell-free DNA (cfDNA) from blood plasma. Plasma samples at start treatment during follow-up 27 OPSCC patients were analyzed cfDNA six high-risk types using a multiplex digital PCR assay....
Abstract Purpose: S100 proteins comprise a family of calcium-modulated that have recently been associated with epithelial tumors. We examined the expression two members this family, S100A8 and S100A9, together receptor RAGE (receptor for advanced glycation end products) in human prostate adenocarcinomas prostatic intraepithelial neoplasia. Experimental Design: Tissue specimens 75 patients organ-confined cancer different grades were analyzed by immunohistochemistry S100A8, RAGE. In addition,...
Abstract The receptor for advanced glycation end products (RAGE) is a single transmembrane of the immunoglobulin superfamily that mainly expressed on immune cells, neurons, activated endothelial and vascular smooth muscle bone forming variety cancer cells. RAGE multifunctional binds broad repertoire ligands mediates responses to cell damage stress conditions. It activates programs responsible acute chronic inflammation, implicated in number pathological diseases, including diabetic...
Death rates from hepatocellular carcinoma (HCC) are steadily increasing, yet therapeutic options for advanced HCC limited. We identify a subset of mouse and human HCCs harboring VEGFA genomic amplification, displaying distinct biologic characteristics. Unlike common tumor amplifications, this one seems to work via heterotypic paracrine interactions; stromal VEGF receptors (VEGFR), responding VEGF-A, produce hepatocyte growth factor (HGF) that reciprocally affects cells. VEGF-A inhibition...
Glioblastoma spheroid cultures are enriched in tumor stem-like cells and therefore may be more representative of the respective primary tumors than conventional monolayer cultures. We exploited glioma culture model to find novel tumor-relevant genes.We carried out array-based comparative genomic hybridization derived from 20 glioblastomas. Microarray-based gene expression analysis was applied determine genes with differential compared normal brain tissue nonneoplastic spheroids The protein...
The nuclear factor-kappaB (NF-kappaB) signaling pathway has been recently shown to participate in inflammation-induced cancer progression. Here, we describe a detailed analysis of the NF-kappaB-dependent gene regulatory network well-established Mdr2 knockout mouse model inflammation-associated liver carcinogenesis. Expression profiling NF-kappaB-deficient and NF-kappaB-proficient hepatocellular carcinoma (HCC) revealed comprehensive list known novel putative NF-kappaB target genes, including...
High-risk types of human papilloma virus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). Strikingly, patients HPV-positive OPSCC highly curable ionizing radiation and have better survival compared HPV-negative patients, but the underlying molecular mechanisms remain poorly understood. We applied an array-based approach to monitor global changes in CpG island hypermethylation between OPSCCs identified a specific pattern differentially methylated regions...
The expression of MMP13 (collagenase-3), a member the matrix metalloproteinase family, is increased in vivo as well cultured osteosarcoma cell lines by parathyroid hormone (PTH), major regulator calcium homeostasis. Binding sites for AP-1 and Cbfa/Runt transcription factors close proximity have been identified cis-acting elements murine rat mmp13 promoter required PTH-induced expression. cooperative function these response to PTH osteoblastic cells suggests direct interaction between...
Abstract Recently, we described phorbol ester–induced expression of the brain and skin serine proteinase Bssp/kallikrein 6 (Klk6), mouse orthologue human KLK6, in back advanced tumor stages a well-established multistage model. Here, show KLK6 up-regulation squamous tumors patients other epithelial tissues. Ectopic Klk6 keratinocyte cell lines induces spindle-like morphology associated with accelerated proliferation, migration, invasion capacity. We found reduced E-cadherin protein levels...
The receptor for advanced glycation endproducts (RAGE) is a multiligand and member of the immunoglobulin superfamily. RAGE mainly involved in tissue damage chronic inflammatory disorders, sustaining response upon engagement with damage-associated molecular pattern molecules (DAMPs) such as S100 proteins high-mobility group box 1 (HMGB1). Enhanced expression its ligands has been demonstrated distinct tumors several studies support crucial role tumor progression metastasis by still unknown...
Recurrent gain on chromosome 3q26 encompassing the gene locus for transcription factor SOX2 is a frequent event in human squamous cell carcinoma, including head and neck carcinoma (HNSCC). Numerous studies demonstrated that expression function related to distinct aspects of tumor pathophysiology. However, underlying molecular mechanisms are not well understood, correlation between clinical outcome revealed conflicting data. Transcriptional profiling after silencing HNSCC line identified set...
Mucosal melanoma of the head and neck is a rare aggressive tumor entity with poor prognosis. The standard treatment radical resection, or without adjuvant radiation, where conventional chemotherapies in advanced stage recurrent diseases have shown little benefit. Overexpression programmed cell death ligand 1 (PD-L1) common feature human cancer. Although PD-L1 an acknowledged prognostic biomarker for dismal prognosis other tumors neck, expression clinical relevance mucosal not been addressed...
Background Although the mitogen-activated protein kinases (MAPK) pathway is hyperactive in head and neck cancer (HNC), inhibition of MEK1/2 HNC patients has not shown clinically meaningful activity. Therefore, we aimed to characterize effect on tumor microenvironment (TME) MAPK-driven HNC, elucidate tumor-host interaction mechanisms facilitating immune escape treatment, apply rationale-based therapy combination immunotherapy inhibitor induce clearance. Methods Mouse syngeneic tumors...
Abstract Background The prognostic significance of tumour budding (TB) and minimal cell nest size (MCNS) was shown in human papillomavirus (HPV)-negative head neck squamous carcinomas (HNSCC). However, the optimisation cutpoints, impact HPV-positive HNSCC, comparison with other histopathological grading systems are insufficiently investigated. Methods TB MCNS were analysed digitally 1 10 high-power fields (HPF) 331 HPV-negative cases from TCGA. Optimising cutpoints a new cellular...