A5088881605- DNA Repair Mechanisms
- Cannabis and Cannabinoid Research
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Ubiquitin and proteasome pathways
- Bee Products Chemical Analysis
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Cancer therapeutics and mechanisms
- Fatty Acid Research and Health
- Chemotherapy-induced organ toxicity mitigation
- Bipolar Disorder and Treatment
- Cancer Cells and Metastasis
- Silk-based biomaterials and applications
- Genomics and Rare Diseases
- Multiple Myeloma Research and Treatments
- Trace Elements in Health
- PARP inhibition in cancer therapy
- Polysaccharides and Plant Cell Walls
- Protein Degradation and Inhibitors
- Cellular Mechanics and Interactions
- thermodynamics and calorimetric analyses
- 3D Printing in Biomedical Research
Palacký University Olomouc
2016-2025
Institute of Molecular and Translational Medicine
2016-2025
Masaryk Memorial Cancer Institute
2021
Regional Centre of Advanced Technologies and Materials
2021
Danish Cancer Society
2021
Research on repurposing the old alcohol-aversion drug disulfiram (DSF) for cancer treatment has identified inhibition of NPL4, an adaptor p97/VCP segregase essential turnover proteins involved in multiple pathways, as unsuspected cell vulnerability. While we reported that NPL4 is targeted by anticancer metabolite DSF, bis-diethyldithiocarbamate-copper complex (CuET), exact, apparently multifaceted mechanism(s) through which CuET-induced aggregation kills cells remains to be fully elucidated....
PARP inhibitors (PARPi), known for their ability to induce replication gaps and accelerate forks, have become potent agents in anticancer therapy. However, the molecular mechanism underlying PARPi-induced fork acceleration has remained elusive. Here, we show that first effect on DNA is an increased rate, followed by a secondary reduction origin activity. Through systematic knockdown of human polymerases, identify POLA1 as mediator acceleration. This depends both polymerase α primase...
Abstract Despite several approved therapeutic modalities, multiple myeloma (MM) remains an incurable blood malignancy and only a small fraction of patients achieves prolonged disease control. The common anti-MM treatment targets proteasome with specific inhibitors (PI). resulting interference protein degradation is particularly toxic to MM cells as they typically accumulate large amounts proteins. However, often acquire resistance PIs through aberrant expression or mutations subunits such...
Disulfiram (DSF), an established alcohol-aversion drug, is a candidate for repurposing in cancer treatment. DSF's antitumor activity supported by preclinical studies, case reports, and small clinical trials; however, ongoing trials of advanced-stage patients encounter variable results. Here, we show that one reason the inconsistent effects DSF may reflect interference other drugs. Using high-throughput screening automated microscopy, identify cannabidiol, abundant component marijuana plant...
Abstract Despite proteotoxic stress and heat shock being implicated in diverse pathologies, currently no methodology to inflict defined, subcellular thermal damage exists. Here, we present such a single-cell method compatible with laser-scanning microscopes, adopting the plasmon resonance principle. Dose-defined causes protein compartments, rapid heat-shock chaperone recruitment, ensuing engagement of ubiquitin–proteasome system, providing unprecedented insights into spatiotemporal response...
Cannabinoids, a class of compounds derived from Cannabis sativa L., have recently become more widely accessible for public consumption in the form diverse cannabis products, parallel with weakening measures that so far restricted their availability. The US Food and Drug Administration has approved several cannabis-derived drugs management various diseases as well chemotherapy-induced nausea vomiting. Besides attenuation adverse effects chemotherapy, numerous reports about...
Replication stress (RS) fuels genomic instability and cancer development may contribute to aging, raising the need identify factors involved in cellular responses such stress. Here, we present a strategy for identification of affecting maintenance common fragile sites (CFSs), which are loci that particularly sensitive RS suffer from increased breakage rearrangements tumors. A DNA probe designed match high flexibility island sequence typical commonly expressed CFS (FRA16D) was used as...
Abstract During metastasis, cancer cells navigate through harsh conditions, including various mechanical forces in the bloodstream, highlighting need to understand impact of and shear stresses on cells. To overcome current methodological limitations such research, here we present a new device that replicates similar conditions by applying stress cultured The provides less complex, easily accessible alternative traditional microfluidics while generating fluid values comparable those human...
Abstract Despite proteotoxic stress and heat shock are implicated in diverse pathologies, currently no methodology to inflict defined, subcellular thermal damage exists. Here, we present a protocol for such single-cell method compatible with laser-scanning microscopes, adopting the plasmon resonance principle. The is based on modified microscopic cell culture plates, pre-coated by layer of anisotropic silver NPs allowing excitation through targeted irradiation conventional lasers used laser...
Abstract Cannabinoids including cannabidiol belong between constituents of cannabis sp. (marijuana plant). Purified or as a part products, the compounds are frequently used by cancer patients to attenuate chemotherapy-induced side effects such pain, nausea, and vomiting. The presence products on public market expands each year while illegality status weakens in an increasing number countries. U.S. Food Drug Administration has approved several cannabis-based drugs for seizures induced...
Abstract Due to malignant transformation, cancer cells are characterized by elevated levels of genotoxic, replication or proteotoxic stresses, which makes them vulnerable various external conditions, including increased temperature. Thus, hyperthermia represents a very effective therapeutic modality usually combined with standard chemotherapy radiation. Moreover, the temperature is often used in experimental studies related protein aggregation, cellular heat shock response and other...
Abstract CFS’s are genomic loci present in higher vertebrates that particularly sensitive to various forms of replication stress and suffer from increased breakage rearrangements tumors. They have rather enigmatic evolutionary role employ DNA repair checkpoint mechanisms promoting their stability. We used an original approach for identification associated factors based on probe designed match the high flexibility island sequences typically some highly expressed CFS’s. This was as affinity...