A5041820221- Carcinogens and Genotoxicity Assessment
- Animal testing and alternatives
- DNA Repair Mechanisms
- Neuroscience and Neuropharmacology Research
- Genetically Modified Organisms Research
- BRCA gene mutations in cancer
- Heme Oxygenase-1 and Carbon Monoxide
- Receptor Mechanisms and Signaling
- Effects and risks of endocrine disrupting chemicals
- Cell Image Analysis Techniques
- Cardiac Arrest and Resuscitation
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- Cannabis and Cannabinoid Research
- Immunotoxicology and immune responses
- Biosimilars and Bioanalytical Methods
- Computational Drug Discovery Methods
- Autophagy in Disease and Therapy
- Cardiac Ischemia and Reperfusion
- Nicotinic Acetylcholine Receptors Study
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Acute Myeloid Leukemia Research
- Genomic variations and chromosomal abnormalities
- Mitochondrial Function and Pathology
Roche (Switzerland)
2013-2023
Roche (Bosnia-Herzegovina)
2013
Bayer (Germany)
2008-2010
Oregon Health & Science University
2003-2008
University Hospital Ulm
1998-2002
The detailed mechanisms of DNA interstrand cross-link (ICL) repair and the involvement Fanconi anemia (FA)/BRCA pathway in this process are not known. Present models suggest that recognition ICL human cells occur primarily during S phase. Here we provide evidence for a refined model which ICLs recognized rapidly incised by ERCC1/XPF independent replication. However, then processed further double-strand breaks (DSB) form exclusively FA fully proficient sensing incision as well subsequent...
Single-stranded oligonucleotides (ON) comprise a promising therapeutic platform that enables selective modulation of currently undruggable targets. The development novel ON drug candidates has demonstrated excellent efficacy, but in certain cases also some safety liabilities were reported. Among them are events thrombocytopenia, which have recently been evident late stage trials with drugs. underlying mechanisms poorly understood and the risk for causing such cannot be sufficiently assessed...
An international expert working group representing 37 organisations (pharmaceutical/biotechnology companies, contract research organisations, academic institutions and regulatory bodies) collaborated in a data sharing exercise to evaluate the utility of two species within general toxicology studies. Anonymised on 172 drug candidates (92 small molecules, 46 monoclonal antibodies, 15 recombinant proteins, 13 synthetic peptides 6 antibody-drug conjugates) were submitted by 18 organisations. The...
Hyperbaric oxygen (HBO) treatment (i.e. exposure to 100% at a pressure of 2.5 ATA for total three 20 min periods) human subjects caused clear and reproducible DNA effects in the comet assay with leukocytes. Interestingly, damage was detected only after first not further treatments under same conditions, indicating an increase antioxidant defences. We now demonstrate that blood taken 24 h HBO is well protected against vitro induction by hydrogen peroxide (H2O2). H2O2 significant chromosome...
Accumulating evidence suggests that HO-1 plays an important role in cellular protection against oxidant-mediated cell injury. Our previous studies on hyperbaric oxygen (HBO; i.e. exposure to pure under high ambient pressure) indicated clearly increased levels of lymphocytes volunteers 24 h after HBO treatment (1 at 1.5 bar). Experiments with the comet assay (alkaline single gel electrophoresis) revealed same cells were almost completely protected induction DNA damage by a repeated or vitro...
Abstract GABA A -α5 subunit-containing receptors have been shown to play a key modulatory role in cognition and represent promising drug target for cognitive dysfunction, as well other disorders. Here we report on the preclinical early clinical profile of novel selective negative allosteric modulator (NAM), basmisanil, which progressed into Phase II trials intellectual disability Down syndrome impairment associated with schizophrenia. Preclinical pharmacology studies showed that basmisanil...
We report on the generation of computer-based models for prediction chromosome-damaging potential chemicals as assessed in vitro chromosome aberration (CA) test. On basis publicly available CA-test results more than 650 chemical substances, half which are drug-like compounds, we generated two different computational models. The first model was realized using (Q)SAR tool MCASE. Results obtained with this indicate a limited performance (53%) assessment (sensitivity), whereas negative compounds...
Heme oxygenase (HO) catalyzes the rate-limiting step in oxidative degradation of heme to biliverdin. The isoform HO-1 is inducible by a variety agents causing stress and has been suggested play an important role cellular protection against oxidant-mediated cell damage. Using treatment cultures with hyperbaric oxygen (HBO) as model for stress, we have shown induction isolated human lymphocytes after single HBO exposure these cells DNA damage subsequent stress. In contrast, V79 Chinese hamster...