Latest Publications

@article{kahounova_circulating_2023,

title = {Circulating tumor cell-derived preclinical models: current status and future perspectives.},

author = {Zuzana Kahounová and Markéta Pícková and Stanislav Drápela and Jan Bouchal and Eva Szczyrbová and Jiří Navrátil and Karel Souček},

doi = {10.1038/s41419-023-06059-6},

issn = {2041-4889},

year  = {2023},

date = {2023-08-01},

journal = {Cell death & disease},

volume = {14},

number = {8},

pages = {530},

abstract = {Despite the advancements made in the diagnosis and treatment of cancer, the stages associated with metastasis remain largely incurable and represent the primary cause of cancer-related deaths. The dissemination of cancer is facilitated by circulating tumor cells (CTCs), which originate from the primary tumor or metastatic sites and enter the bloodstream, subsequently spreading to distant parts of the body. CTCs have garnered significant attention in research due to their accessibility in peripheral blood, despite their low abundance. They are being extensively studied to gain a deeper understanding of the mechanisms underlying cancer dissemination and to identify effective therapeutic strategies for advanced stages of the disease. Therefore, substantial efforts have been directed towards establishing and characterizing relevant experimental models derived from CTCs, aiming to provide relevant tools for research. In this review, we provide an overview of recent progress in the establishment of preclinical CTC-derived models, such as CTC-derived xenografts (CDX) and cell cultures, which show promise for the study of CTCs. We discuss the advantages and limitations of these models and conclude by summarizing the potential future use of CTCs and CTC-derived models in cancer treatment decisions and their utility as precision medicine tools.},

note = {Place: England},

keywords = {*Neoplastic Cells, Cell Culture Techniques, Circulating, Heterografts, Heterologous, Humans, Precision Medicine, Transplantation},

pubstate = {published},

tppubtype = {article}

}

@article{mccarrick_vitro_2019,

title = {In vitro and in vivo genotoxicity of oxygenated polycyclic aromatic hydrocarbons.},

author = {Sarah McCarrick and Virginia Cunha and Ondřej Zapletal and Jan Vondráček and Kristian Dreij},

doi = {10.1016/j.envpol.2018.12.092},

issn = {1873-6424 0269-7491},

year  = {2019},

date = {2019-03-01},

journal = {Environmental pollution (Barking, Essex : 1987)},

volume = {246},

pages = {678–687},

abstract = {Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are a group of environmental pollutants found in complex mixtures together with PAHs. In contrast to the extensively studied PAHs, which have been established to have mutagenic and carcinogenic properties, much less is known about the effects of oxy-PAHs. The present work aimed to investigate the genotoxic potency of a set of environmentally relevant oxy-PAHs along with environmental soil samples in human bronchial epithelial cells (HBEC). We found that all oxy-PAHs tested induced DNA strand breaks in a dose-dependent manner and some of the oxy-PAHs further induced micronuclei formation. Our results showed weak effects in response to the oxy-PAH containing subfraction of the soil sample. The genotoxic potency was confirmed in both HBEC and HepG2 cells following exposure to oxy-PAHs by an increased level of phospho-Chk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro. We further exposed zebrafish embryos to single oxy-PAHs or a binary mixture with PAH benzo[a]pyrene (B[a]P) and found the mixture to induce comparable or greater effects on the induction of DNA strand breaks compared to the sum of that induced by B[a]P and oxy-PAHs alone. In conclusion, oxy-PAHs were found to elicit genotoxic effects at similar or higher levels to that of B[a]P which indicates that oxy-PAHs may contribute significantly to the total carcinogenic potency of environmental PAH mixtures. This emphasizes further investigations of these compounds as well as the need to include oxy-PAHs in environmental monitoring programs in order to improve health risk assessment.},

note = {Place: England},

keywords = {*DNA Damage, Animals, Cell Culture Techniques, Cell Survival/drug effects/genetics, Comet assay, Embryonic Development/drug effects/genetics, Environmental Monitoring/*methods, Epithelial Cells/drug effects/pathology, Genotoxicity, Hep G2 Cells, Humans, Micronucleus assay, Mutagens/analysis/*toxicity, Oxygen/chemistry, Oxygenated PAH, Polycyclic Aromatic Hydrocarbons/analysis/*toxicity, Zebrafish, Zebrafish/embryology},

pubstate = {published},

tppubtype = {article}

}

@article{hyzdalova_aryl_2018,

title = {Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation.},

author = {Martina Hýžd'alová and Jakub Pivnicka and Ondrej Zapletal and Gerardo Vázquez-Gómez and Jason Matthews and Jirí Neca and Katerina Pencíková and Miroslav Machala and Jan Vondrácek},

doi = {10.1093/toxsci/kfy153},

issn = {1096-0929 1096-6080},

year  = {2018},

date = {2018-10-01},

journal = {Toxicological sciences : an official journal of the Society of Toxicology},

volume = {165},

number = {2},

pages = {447–461},

abstract = {Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that interact in a complex manner with both the aryl hydrocarbon receptor (AhR) and estrogen receptors (ER). Their potential endocrine-disrupting activities may depend on both inhibitory AhR-ER cross-talk and on AhR-dependent metabolic production of estrogenic PAH metabolites. Here, we analyzed the impact of AhR on estrogen-like effects of PAHs, such as benzo[a]pyrene (BaP), in particular, on control of cell cycle progression/cell proliferation. Using AhR knockout variant of estrogen-sensitive human breast cancer MCF-7 cells (MCF-7 AhRKO cells), we observed that the AhR-dependent control of cytochrome P450 family 1 (CYP1) expression played a major role in formation of estrogenic BaP metabolites, most notably 3-OH-BaP, which contributed to the ER-dependent induction of cell cycle progression/cell proliferation. Both BaP metabolism and the BaP-induced S-phase transition/cell proliferation were inhibited in MCF-7 AhRKO cells, whereas these cells remained sensitive towards both endogenous estrogen 17β-estradiol or hydroxylated BaP metabolites. BaP was found to increase the activity of ER-dependent luciferase reporter gene in wild-type MCF-7 cells; however, unlike its hydroxylated metabolite, BaP failed to stimulate luciferase activity in MCF-7 AhRKO cells. Similarly, estrogen-like effects of other known estrogenic PAHs, such as benz[a]anthracene or 3-methylcholanthrene, were diminished in MCF-7 AhRKO cells. Ectopic expression of human CYP1A1 and CYP1B1 enzymes partly restored both BaP metabolism and its effects on cell proliferation. Taken together, our data suggest that the AhR-dependent metabolism of PAHs contributes significantly to the impact of PAHs on cell proliferation in estrogen-sensitive cells.},

note = {Place: United States},

keywords = {Aryl Hydrocarbon/genetics/*metabolism, Cell Culture Techniques, Cell Cycle/drug effects/genetics, Cell Proliferation/*drug effects/genetics, Cytochrome P-450 CYP1A1/genetics/metabolism, Cytochrome P-450 CYP1B1/genetics/metabolism, Endocrine Disruptors/metabolism/*toxicity, Estrogen/genetics/metabolism, Gene Expression/drug effects, Gene Knockdown Techniques, Genes, Genetic Vectors, Humans, MCF-7 Cells, Plasmids, Polycyclic Aromatic Hydrocarbons/metabolism/*toxicity, Receptors, Reporter, Transfection},

pubstate = {published},

tppubtype = {article}

}