A5021923559- Head and Neck Cancer Studies
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Nasal Surgery and Airway Studies
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Reconstructive Facial Surgery Techniques
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Virus-based gene therapy research
- Ferroptosis and cancer prognosis
- Bioinformatics and Genomic Networks
- Ear Surgery and Otitis Media
- Salivary Gland Tumors Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Head and Neck Surgical Oncology
- Ear and Head Tumors
- Hearing Loss and Rehabilitation
- Virology and Viral Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer Immunotherapy and Biomarkers
- Sinusitis and nasal conditions
- Meningioma and schwannoma management
- Ubiquitin and proteasome pathways
- Dental Implant Techniques and Outcomes
Heidelberg University
2014-2023
University Hospital Heidelberg
2014-2023
Medical University of Vienna
2021-2022
German Cancer Research Center
2011-2021
Universitäts-HNO-Klinik Heidelberg
2019-2021
DKFZ-ZMBH Alliance
2020
Deutschen Konsortium für Translationale Krebsforschung
2019
National Center for Tumor Diseases
2011-2013
Hôpital Beaujon
2010
Université Paris Cité
2010
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...
Oncolytic measles viruses (MV) derived from the live attenuated vaccine strain have been engineered for increased tumor-cell specificity, and are currently under investigation in clinical trials including a phase I study glioblastoma multiforme (GBM). Recent preclinical studies shown that cellular tropism of several can be controlled by inserting microRNA-target sequences into their genomes, thereby inhibiting spread tissues expressing cognate microRNAs. Since neuron-specific microRNA-7 is...
Oncolytic measles viruses (MV) derived from the live attenuated vaccine strain have been engineered for increased antitumor activity, and are currently under investigation in clinical phase 1 trials. Approaches with other viral vectors shown that insertion of immunomodulatory transgenes enhances therapeutic potency. In this study, we MV expression cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). For first time, efficacy adaptive immune response context oncolysis could be...
Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as promising biomarker early diagnosis or unfavorable prognosis. However, the in carcinomas derived from mucosal epithelia, including head neck squamous cell carcinoma (HNSCC), its mode action has not been addressed so far. Stable clones tumor lines were generated with shRNA-mediated silencing ectopic overexpression to characterize impact on...
Genomic sequencing projects unraveled the mutational landscape of head and neck squamous cell carcinoma (HNSCC) provided a comprehensive catalog somatic mutations. However, limited number significant cancer-related genes obtained so far only partially explains biological complexity HNSCC hampers development novel diagnostic biomarkers therapeutic targets. We pursued multiscale omics approach based on whole-exome sequencing, global DNA methylation gene expression profiling data derived from...
Malignant progression exhibits a tightly orchestrated balance between immune effector response and tolerance. However, underlying molecular principles that drive the establishment maintenance of tumor phenotype remain to be elucidated.We trained novel classifier based on cell subsets related programmed death-ligand 1 (PD-L1) interferon γ (IFNγ) expression, which revealed distinct subgroups with higher (cluster A) or lower (subcluster B3) cytotoxic phenotypes. Integrative analysis multi-omics...
Background: Head and neck squamous cell carcinomas (HNSCC) are phenotypically molecularly heterogeneous frequently develop therapy resistance. Reliable patient-derived 3D tumor models urgently needed to further study the complex pathogenesis of these tumors overcome treatment failure. Methods: We developed a three-dimensional organotypic co-culture (3D-OTC) model for HNSCC that maintains architecture composition individual tumor. A dermal equivalent (DE), composed healthy human-derived...
Abstract Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) result from interaction exogenous environmental exposures endogenous cellular processes. Each these processes leaves characteristic pattern mutations on tumor genome providing unique opportunity to decipher specific signatures mutational operative during HNC pathogenesis address their prognostic value. Computational analysis whole exome sequencing data HIPO‐HNC (Heidelberg Center for...
First-line treatment of recurrent and/or refractory head and neck squamous cell carcinoma (HNSCC) is based on platinum, 5-fluorouracil (5-FU) the monoclonal antiEGFR antibody cetuximab. However, in most cases this chemoimmunotherapy does not cure disease, more than 50% HNSCC patients are dying because local recurrence tumors. In majority cases, overexpress epidermal growth factor receptor (EGFR), its presence associated with a poor outcome. study, we engineered an EGFR-targeted oncolytic...
While genetic alterations in Epidermal growth factor receptor (EGFR) and PI3K are common head neck squamous cell carcinomas (HNSCC), their impact on oncogenic signaling cancer drug sensitivities remains elusive. To determine consequences the transcriptional network, pathway activities of EGFR, PI3K, 12 additional pathways were inferred 498 HNSCC samples The Cancer Genome Atlas using PROGENy. More than half HPV-negative showed a activation EGFR or PI3K. An amplification mutation PI3KCA...
Advanced pancreatic cancer is characterized by few treatment options and poor outcomes. Oncolytic virotherapy chemotherapy involve complementary pharmacodynamics could synergize to improve therapeutic efficacy. Likewise, multimodality may cause additional toxicity, new agents have be safe. Balancing both aims, we generated an oncolytic measles virus for 5-fluorouracil-based chemovirotherapy of with enhanced tumor specificity through microRNA-regulated vector tropism. The resulting encodes a...
Background During mammalian protein N-glycosylation, 20% of all dolichol-linked oligosaccharides (LLO) appear as free (fOS) bearing the di-N-acetylchitobiose (fOSGN2), or a single N-acetylglucosamine (fOSGN), moiety at their reducing termini. After sequential trimming by cytosolic endo β-N-acetylglucosaminidase (ENGase) and Man2c1 mannosidase, fOS are transported into lysosomes. Why cells generate such large quantities remains unexplored, but fOSGN2 could be liberated from LLO...
Primary surgical treatment of nasal vestibule cancertherapeutic outcome and reconstructive strategies* Objective: The strategy squamous cell carcinoma the (SCCNV) is controversial.The objective this study to investigate role surgery, which preferred option at our institution. Design:This was a monocentric prospective patients that were diagnosed with SCCNV between 2005 2013.Material Methods: Twenty-six included.Tumors staged using UICC (7th edition) TNM classification cavity cancer proposed...
Abstract Background Despite new radiotherapeutic strategies, radioresistance in head and neck squamous cell carcinoma (HNSCC) remains a major problem. Preclinical model systems are needed to identify resistance mechanisms this heterogeneous entity. Methods We elucidated the interplay among mitogen‐activated protein kinase (MAPK)‐inhibition, radiation, p53 mutations vitro novel ex vivo derived from vital human HNSCC samples. lines (p53WT/mut) were treated with (MEK)‐inhibitor PD‐0325901...
An inverse correlation between expression of the aldehyde dehydrogenase 1 subfamily A2 (ALDH1A2) and gene promoter methylation has been identified as a common feature oropharyngeal squamous cell carcinoma (OPSCC). Moreover, low ALDH1A2 was associated with an unfavorable prognosis OPSCC patients, however causal link reduced function treatment failure not addressed so far.Serial sections from tissue microarrays patients primary (n = 101) were stained by immunohistochemistry for key regulators...
Molecular mechanisms of intrinsic or acquired radioresistance serve as critical barrier for curative therapy head and neck squamous cell carcinoma (HNSCC) remain a major obstacle progression-free disease-specific survival. HNSCC lines were treated with protocol fractionated irradiation (IR, 4× 2Gy) alone in combination antagonists estrogen receptor signaling viability was determined by colony-forming assay (CFA). Expression submaxillary gland androgen-regulated protein 3A (SMR3A) 2 (ESR2)...
Lip, oral cavity, and pharynx cancers (ICD-10: C00-C14) describe a heterogeneous group of tumors with strong variations in incidence, mortality, survival by entity.This work provides detailed overview epidemiologic measures for these tumor entities, taking into account heterogeneity age, sex, location, stage.Incidence mortality data Germany the years 1999-2016 were extracted from interactive database Center Cancer Registry Data (ZfKD). Age stage distributions five-year relative calculated on...
Glyoxalase 1 is a key enzyme in the detoxification of reactive metabolites such as methylglyoxal and induced expression has been demonstrated for several human malignancies. However, regulation clinical relevance context head neck squamous cell carcinoma not addressed so far.Argpyrimidine modification surrogate accumulation tumor cells was assessed by immunohistochemical staining tissue microarrays with specimens from oropharyngeal patients (n = 154). Prognostic values distinct patterns were...
Salvage surgery of recurrent hypopharyngeal and laryngeal squamous cell carcinoma (SCC) results in limited local control survival rates. As a result recent technological progress, radiotherapy (RT) has become valuable, potentially curative therapeutic option. Thus, we aimed to determine prognostic factors for outcome order optimize patient selection salvage after failure first-line treatment with alone this special cohort.Seventy-five patients (85% male, median age 64 years) underwent RT...