Horst Zitzelsberger

Horst Zitzelsberger
Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | HZM · Department of Radiation Sciences

About

201
Publications
15,279
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5,446
Citations
Citations since 2016
58 Research Items
1446 Citations
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2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250

Publications

Publications (201)
Article
Full-text available
Objective HPV-associated head and neck cancer is correlated with favorable prognosis; however, its underlying biology is not fully understood. We propose an explainable convolutional neural network (CNN) classifier, DeepClassPathway, that predicts HPV-status and allows patient-specific identification of molecular pathways driving classifier decisio...
Article
Full-text available
Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) allows spatial analysis of proteins, metabolites, or small molecules from tissue sections. Here, we present the simultaneous generation and analysis of MALDI-MSI, whole-exome sequencing (WES), and RNA-sequencing data from the same formalin-fixed paraffin-embedded (FFP...
Article
Full-text available
Human papillomavirus (HPV)-driven head and neck squamous cell carcinomas (HNSCC) generally have a more favourable prognosis. We hypothesized that HPV-associated HNSCC may be identified by an miRNA-signature according to their specific molecular pathogenesis, and be characterized by a unique transcriptome compared to HPV-negative HNSCC. We performed...
Article
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Purpose To establish stable in vitro growth of keratinocytes from very small biopsy specimens and successfully apply new test systems to determine their radiosensitivity. Materials and Methods Oral mucosa biopsies (diameter: 1.7 mm) from 15 subjects were immobilized with custom-made cups onto culture plates. Outgrowing cells were tested for cytoke...
Article
Purpose: The genetic relatedness between primary and recurrent head and neck squamous cell carcinomas (HNSCC) reflects the extent of heterogeneity and therapy-driven selection of tumor subpopulations. Yet, current treatment of recurrent HNSCC ignores the molecular characteristics of therapy-resistant tumor populations. Experimental design: From...
Article
Full-text available
Resistance against radio(chemo)therapy-induced cell death is a major determinant of oncological treatment failure and remains a perpetual clinical challenge. The underlying mechanisms are manifold and demand for comprehensive, cancer entity- and subtype-specific examination. In the present study, resistance against radiotherapy was systematically a...
Article
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Biomarkers with relevance for loco-regional therapy are needed in Human Papillomavirus negative aka HPV(−) Head and Neck Squamous Cell Carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome-based classifier identifying HPV(−) HNSCC patients at risk for loco-regi...
Article
The clonogenic assay measures the capacity of single cells to form colonies in vitro. It is widely used to identify and quantify self-renewing mammalian cells derived from in vitro cultures as well as from ex vivo tissue preparations of different origins. Varying research questions and the heterogeneous growth requirements of individual cell model...
Article
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Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective al...
Article
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Radiotherapy is an essential component of multi-modality treatment of glioblastoma(GBM). However, treatment failure and recurrence are frequent and give rise to the dismal prognosis of this aggressive type of primary brain tumor. A high level of inherent treatment resistance is considered to be the major underlying reason, stemming from constantly...
Article
Thyroid carcinoma incidence rates in western societies are among the fastest rising, compared to all malignant tumors over the past two decades. While risk factors such as age and exposure to ionizing radiation are known, early-state carcinogenic processes or pre-lesions are poorly understood or unknown. This study aims at the identification and ch...
Article
Purpose The long-term effect of low and moderate doses of ionizing radiation on the lens is still a matter of debate and needs to be evaluated in more detail. Material and Methods We conducted a detailed histological analysis of eyes from B6C3F1 mice cohorts after acute gamma irradiation (⁶⁰Co source; 0.063 Gy/min) at young adult age of 10 weeks w...
Article
Full-text available
Head and neck squamous cell carcinomas (HNSCCs) have poor clinical outcome owing to therapy resistance and frequent recurrences that are among others attributable to tumor cells in partial epithelial‐to‐mesenchymal transition (pEMT). We compared side‐by‐side software‐based and visual quantification of immunohistochemistry (IHC) staining of epitheli...
Article
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Purpose The increasing use of low-dose ionizing radiation in medicine requires a systematic study of its long-term effects on the brain, behaviour and its possible association with neurodegenerative disease vulnerability. Therefore, we analysed the long-term effects of a single low-dose irradiation exposure at 10 weeks of age compared to medium and...
Article
Full-text available
Background The clonogenic assay is a versatile and frequently used tool to quantify reproductive cell survival in vitro. Current state-of-the-art analysis relies on plating efficiency-based calculations which assume a linear correlation between the number of cells seeded and the number of colonies counted. The present study was designed to test the...
Article
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Background The potential benefit of risk stratification using a 4-miRNA signature in combination with MGMT promoter methylation in IDH1/2 wild-type glioblastoma patients was assessed. Methods Primary tumors from 102 patients with comparable treatment from the LMU Munich (n=37), the University Hospital Düsseldorf (n=33) and The Cancer Genome Atlas...
Preprint
Full-text available
Background: The clonogenic assay is a versatile and frequently used tool to quantify reproductive cell survival in vitro. Current state-of-the-art analysis relies on plating efficiency-based calculations which assume a linear correlation between the number of cells seeded and the number of colonies counted. The present study was designed to test th...
Article
Full-text available
Background: We present a functional gene association network of the CLIP2 gene, generated by de-novo reconstruction from transcriptomic microarray data. CLIP2 was previously identified as a potential marker for radiation induced papillary thyroid carcinoma (PTC) of young patients in the aftermath of the Chernobyl reactor accident. Considering the...
Article
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Background: Prognostic models based on high-dimensional omics data generated from clinical patient samples, such as tumor tissues or biopsies, are increasingly used for prognosis of radio-therapeutic success. The model development process requires two independent discovery and validation data sets. Each of them may contain samples collected in a s...
Article
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Background: Definitive chemoradiotherapy (dCRT) is a standard treatment for patients with locally advanced head and neck cancer. There is a clinical need for a stratification of this prognostically heterogeneous group of tumors in order to optimize treatment of individual patients. We retrospectively reviewed all patients with head and neck squamo...
Article
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Breast cancer is the most prevalent malignant disease in women. Amongst other risk factors such as age, life style, genetic factors and hormone status, exposure to ionizing irradiation is a known risk factor. Markers of radiation-associated breast cancer have been now identified at the DNA-, miRNA- and protein levels providing the starting point fo...
Article
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Carcinoma cells undergo epithelial-mesenchymal transition (EMT); however, contributions of EMT heterogeneity to disease progression remain a matter of debate. Here, we addressed the EMT status of ex vivo cultured circulating and disseminated tumor cells (CTCs/DTCs) in a syngeneic mouse model of metastatic breast cancer (MBC). Epithelial-type CTCs w...
Data
Fig. S2. Kaplan–Meier curves for the endpoint overall survival for the pooled HPV‐negative patients of the radio(chemo)therapy‐treated TCGA training and validation set stratified according to the four‐gene classifier.
Data
Table S2. Patient subset of 99 radio(chemo)therapy‐treated HNSCC patients of the TCGA cohort.
Data
Table S5. Gene set enrichment analysis (GSEA): Significantly (FDR < 0.05) up‐regulated sets of genes between the four‐gene signature high and low‐risk groups of the TCGA cohort.
Data
Table S9. Significantly enriched pathways (FDR < 0.05) of first and second neighborhood genes of the four signature genes from the reconstructed GAN.
Data
Table S3. Differences of demographic and histopathological parameters between the TCGA cohort and the LMU‐KKG cohort.
Data
Table S8. Correlation of the second neighborhood genes of the reconstructed gene association network.
Data
Table S1. REporting recommendations for tumour MARKer prognostic studies (REMARK) according to McShane et al. (2005).
Data
Table S6. Gene set enrichment analysis (GSEA): Significantly (FDR < 0.05) down‐regulated sets of genes between the four‐gene signature high and low‐risk groups of the TCGA cohort.
Data
Fig. S1. Schematic workflow for the development of the classifier and the reconstruction of the gene association network with subsequent analyses.
Data
Fig. S3. DNA gains of chromosomal band 16q24.3 are associated with increased mRNA expression levels of the signature genes in radio(chemo)therapy‐treated patients of the TCGA HNSCC cohort.
Data
Table S4. Univariate Cox regression analyses of clinicopathological parameters and the four‐gene classifier with overall survival in the TCGA HNSCC training and validation set and the LMU‐KKG HNSCC cohort.
Data
Table S7. Correlation of the first neighborhood genes of the reconstructed gene association network.
Data
Table S10. Significant results of the sigaR cis‐test.
Article
Full-text available
Locally advanced head and neck squamous cell carcinomas (HNSCC) have limited prognosis due to frequent treatment failure. Currently, TNM-classification and human papillomavirus (HPV) infection are the sole clinical prognosticators of outcome. Tumor heterogeneity and stemness based on epithelial-mesenchymal-transition reportedly associate with thera...
Article
Full-text available
Previously, we have shown that copy number gain of the chromosomal band 16q24.3 is associated with impaired clinical outcome of radiotherapy‐treated head and neck squamous cell carcinoma (HNSCC) patients. We set out to identify a prognostic mRNA signature from genes located on 16q24.3 in radio(chemo)therapy‐treated HNSCC patients of the TCGA (The C...
Article
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Background: Postoperative (chemo) radiation improves tumor control and survival in high-risk patients with head and neck squamous cell carcinoma based on established risk factors. The clinical cooperation group "Personalized Radiotherapy in Head and Neck Cancer" focuses on the identification and validation of new biomarkers, which are aimed at eve...
Article
Full-text available
Because of the increasing application of ionizing radiation in medicine, quantitative data on effects of low-dose radiation are needed to optimize radiation protection, particularly with respect to cataract development. Using mice as mammalian animal model, we applied a single dose of 0, 0.063, 0.125 and 0.5 Gy at 10 weeks of age, determined lens o...
Article
Full-text available
Breast cancer is the second leading cause of cancer death among women worldwide and besides life‐style, age and genetic risk factors, exposure to ionising radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation‐induced double‐strand breaks, are frequently occurring in b...
Article
Full-text available
Activation‐induced cytidine deaminase (AID) is required for the immunoglobulin diversification processes of somatic hypermutation, gene conversion and class‐switch recombination. The targeting of AID's deamination activity is thought to be a combination of cis‐ and trans‐acting elements, but has not been fully elucidated. Deletion analysis of putat...
Article
Full-text available
We did a lifetime study in irradiated and control mice with a follow up time until 24 months post irradiation with repeated in vivo analysis of the lens density and the retina.
Article
In order to deal with endogenous and exogenous factors, including radiation or pathogens, cells evolved different strategies. This includes highly complex processes such as DNA damage response, senescence, cell death, and inflammatory reactions. Recent research indicates an interconnection between the mentioned cellular pathways whilst all of them...
Article
At the adult age of 10 weeks male and female hybrid mice (C57BL/6 × C3H F1) were acutely whole-body irradiated with low doses of ionising radiation (0, 0.063, 0.125 and 0.5 Gy) using a ⁶⁰Co source. Over the following 24 months the mice were examined monthly for lens opacities by Scheimpflug imaging and every four months for retinal effects by OCT (...
Article
At the adult age of 10 weeks male and female hybrid mice (C57BL/6 x C3H F1) were acutely whole-body irradiated with low doses of ionising radiation (0, 0.063, 0.125 and 0.5 Gy) using a Co 60 source. Over the following 24 months the mice were examined monthly for lens opacities by Scheimpflug imaging; and every four months for retinal effects by OCT...
Article
Full-text available
One of the major consequences of the 1986 Chernobyl reactor accident was a dramatic increase in papillary thyroid carcinoma (PTC) incidence, predominantly in patients exposed to the radioiodine fallout at young age. The present study is the first on genomic copy number alterations (CNAs) of PTCs of the Ukrainian American cohort (UkrAm) generated by...