A5058275183- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Carcinogens and Genotoxicity Assessment
- Radiomics and Machine Learning in Medical Imaging
- Circular RNAs in diseases
- Nanoparticles: synthesis and applications
- DNA Repair Mechanisms
- Air Quality and Health Impacts
- RNA modifications and cancer
- bioluminescence and chemiluminescence research
- Effects and risks of endocrine disrupting chemicals
- Molecular Biology Techniques and Applications
- Microplastics and Plastic Pollution
- Animal testing and alternatives
- Heavy Metal Exposure and Toxicity
- CRISPR and Genetic Engineering
- Cancer Diagnosis and Treatment
- Virus-based gene therapy research
- Pesticide Exposure and Toxicity
- Healthcare and Environmental Waste Management
- Genomics, phytochemicals, and oxidative stress
- Pesticide and Herbicide Environmental Studies
- Histone Deacetylase Inhibitors Research
- Immunotherapy and Immune Responses
- Sirtuins and Resveratrol in Medicine
AcXys Technologies (France)
2017-2023
Leiden University Medical Center
2014-2017
Chemical exposure of cells may damage biomolecules, cellular structures, and organelles thereby jeopardizing homeostasis. A multitude defense mechanisms have evolved that can recognize specific types damaged molecules will initiate distinct programs aiming to remove the inflicted prevent havoc. As a consequence, quantitative assessment activity stress responses serve as sensitive reporter for induction damage. We previously developed ToxTracker assay, mammalian stem cell-based genotoxicity...
Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms still poorly understood. Furthermore, effects related nanoparticles (NPs) of Ni have not been fully elucidated. The aim this study was investigate genotoxicity and mutagenicity NiO NPs compare effect soluble from NiCl2 . We employed different models; i.e., exposure (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay γ-H2AX staining); (2) six mouse embryonic...
Breast cancer is a heterogeneous disease with highly variable clinical outcome in which both genetic and epigenetic changes have critical roles. We investigated tumor expression levels of histone-modifying enzymes LSD1, HDAC2 SIRT1 relation patient survival relapse retrospective cohort 460 breast patients. Additionally, we correlated differentiation cell proliferation. Immunohistochemical staining for was performed on tissue microarrays corresponding normal formalin-fixed paraffin-embedded...
An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding physiochemical characteristics Co metal NPs oxides combination with assessment mechanisms may facilitate decisions grouping during risk The aim this study was to gain mechanistic insights correlation between NP reactivity three Co-based (Co, CoO, Co3O4) by using various tools characterization,...
Abstract ToxTracker is a mammalian cell reporter assay that predicts the genotoxic properties of compounds with high accuracy. By evaluating induction various genes play key role in relevant cellular pathways, it provides insight into chemical mode‐of‐action (MoA), thereby supporting discrimination direct‐acting genotoxicants and cytotoxic chemicals. A comprehensive interlaboratory validation trial was conducted, which principles outlined OECD Guidance Document 34 were followed, primary...
Millions of people in the world perform welding as their primary occupation resulting exposure to metal-containing nanoparticles fumes generated. Even though health effects including airway diseases are well-known, there is currently a lack studies investigating how different set-ups and conditions affect toxicity generated fume. The aim this study was investigate nine types fume particles via active gas shielded metal arc (GMAW) chromium-containing stainless steel under and, furthermore,...
Colon cancer prognosis and treatment are currently based on a classification system still showing large heterogeneity in clinical outcome, especially TNM stages II III. Prognostic biomarkers for metastasis risk warranted as development of distant recurrent disease mainly accounts the high lethality rates colon cancer. miRNAs have been proposed potential Furthermore, verified standard normalization amount input material PCR-based relative quantification miRNA expression is lacking.A selection...
Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not other subtypes. We evaluated tumor expression FAS, a key receptor T-cell mediated apoptosis, as possible explanation for this differential value TILs. Furthermore, we relevance both an independent biomarker and relation to CD8-positive presence. The study cohort consisted 667 patients treated LUMC between 1997 2009. FAS was determined using...
The increased use of nanoparticles (NPs) requires efficient testing their potential toxic effects. A promising approach is to reporter cell lines quickly assess the activation cellular stress response pathways. This study aimed ToxTracker investigate (geno)toxicity various metal- or metal oxide NPs and draw general conclusions on NP-induced effects, in combination with our previous findings. tested this (n = 18) also included quantum dots (QDs) different sizes. results showed a large...
The ongoing developments in chemical risk assessment have led to new concepts building on integration of sophisticated nonanimal models for hazard characterization. Here we explore a pragmatic approach implementing such concepts, using case study three triazole fungicides, namely, flusilazole, propiconazole, and cyproconazole. strategy applied starts with evaluating the overall level concern by comparing exposure estimates toxicological potential, followed combination silico tools...
Abstract Understanding the mode-of-action (MOA) of genotoxic compounds and differentiating between direct DNA interaction indirect genotoxicity is crucial for their reliable safety assessment. ToxTracker a stem cell-based reporter assay that detects activation various cellular responses are associated with cancer. consists 6 different GFP cell lines can detect induction damage, oxidative stress, protein damage in single test. The thereby provide insight into MOA compounds. Genotoxicity...
ToxTracker is an in vitro mammalian stem cell-based reporter assay that detects activation of specific cellular signaling pathways (DNA damage, oxidative stress, and/or protein damage) upon chemical exposure using flow cytometry. Here we used quantitative methods to empirically analyze historical control data, and dose-response data across a wide range reference chemicals. First, analyzed define fold-change threshold for identification significant positive response. Next, the benchmark dose...
In vitro (geno)toxicity assessment of electronic vapour products (EVPs), relative to conventional cigarette, currently uses assays, including the micronucleus and Ames tests. Whilst informative on induction a finite endpoint risk posed by test articles, such assays could benefit from mechanistic supplementation. The ToxTracker Aneugen Clastogen Evaluation analysis can indicate activation reporters associated with (geno)toxicity, DNA damage, oxidative stress, p53-related stress response...
Antimony (Sb) and its compounds are negative in gene mutation assays bacteria cultured mammalian cells but positive some for clastogenicity and/or DNA damage. In order to better understand the modes of action antimony genotoxicity, we assessed reporter activation by new expanded ToxTracker assay. evaluates biomarkers different cellular defense mechanisms using a series green fluorescent protein reporters inserted into mouse embryonic stem cell lines. The assay responds to: 1) damage...
Cobalt metal and cobalt sulfate are carcinogenic in rodents following inhalation exposure. The pre-carcinogenic effects associated with exposure to these substances include oxidative stress genotoxicity. Some, but not all, induce vitro clastogenicity or an increase micronuclei. As a result, classified genotoxic carcinogens, having major impacts on their risk assessment, e.g. assumption of non-thresholded dose response. Here, we investigated the potential nine cause genotoxicity using...
Abstract Welding fumes induce lung toxicity and are carcinogenic to humans but the molecular mechanisms have yet be clarified. The aim of this study was evaluate stainless mild steel particles generated via gas–metal arc welding using primary human small airway epithelial cells (hSAEC) ToxTracker reporter murine stem cells, which track activation six cancer-related pathways. Metal content (Fe, Mn, Ni, Cr) relatively homogenous across particle size. were not cytotoxic in activated...
Aneuploidy is characterized by the presence of an abnormal number chromosomes and a common hallmark cancer. However, exposure to aneugenic compounds does not necessarily lead Aneugenic are mainly identified using in vitro micronucleus assay but this cannot standardly discriminate between aneugens clastogens be used identify exact mode-of-action (MOA) aneugens; tubulin stabilization, destabilization, or inhibition mitotic kinases. To improve classification substances determine their MOA, we...
<p>Supplementary File S1. Read counts and library sizes</p>