Latest Publications

@article{prochazkova_specific_2020,

title = {Specific alterations of sphingolipid metabolism identified in EpCAM-positive cells isolated from human colon tumors.},

author = {Jiřina Procházková and Josef Slavík and Jan Bouchal and Monika Levková and Zlata Hušková and Jiří Ehrmann and Petra Ovesná and Zdeněk Kolář and Pavel Skalický and Nicol Straková and Ondřej Zapletal and Alois Kozubík and Jiřina Hofmanová and Jan Vondráček and Miroslav Machala},

doi = {10.1016/j.bbalip.2020.158742},

issn = {1879-2618 1388-1981},

year  = {2020},

date = {2020-09-01},

journal = {Biochimica et biophysica acta. Molecular and cell biology of lipids},

volume = {1865},

number = {9},

pages = {158742},

note = {Place: Netherlands},

keywords = {80 and over, Adult, Aged, B4GALTs, Colon adenocarcinoma, Colorectal Neoplasms/*metabolism, EPCAM-positive cells, Epithelial Cell Adhesion Molecule/*metabolism, Female, Galactosyltransferases/genetics, Humans, Lactosylceramide, Male, Middle Aged, Sphingolipid metabolism, Sphingolipids/*metabolism},

pubstate = {published},

tppubtype = {article}

}

@article{nekvindova_hepatocellular_2020,

title = {Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450.},

author = {Jana Nekvindova and Alena Mrkvicova and Veronika Zubanova and Alena Hyrslova Vaculova and Pavel Anzenbacher and Pavel Soucek and Lenka Radova and Ondrej Slaby and Igor Kiss and Jan Vondracek and Alena Spicakova and Lucia Bohovicova and Pavel Fabian and Zdenek Kala and Vladimir Palicka},

doi = {10.1016/j.bcp.2020.113912},

issn = {1873-2968 0006-2952},

year  = {2020},

date = {2020-07-01},

journal = {Biochemical pharmacology},

volume = {177},

pages = {113912},

abstract = {Hepatocellular carcinoma (HCC) remains a highly prevalent and deadly disease, being among the top causes of cancer-related deaths worldwide. Despite the fact that the liver is the major site of biotransformation, studies on drug metabolizing enzymes in HCC are scarce. It is known that malignant transformation of hepatocytes leads to a significant alteration of their metabolic functions and overall deregulation of gene expression. Advanced stages of the disease are thus frequently associated with liver failure, and severe alteration of drug metabolism. However, the impact of dysregulation of metabolic enzymes on therapeutic efficacy and toxicity in HCC patients is largely unknown. Here we demonstrate a significant down-regulation in European Caucasian patients of cytochromes P450 (CYPs), the major xenobiotic-metabolizing enzymes, in HCC tumour samples as compared to their surrounding non-cancerous (reference) tissue. Moreover, we report for the first time the association of the unique CYP profiles with specific transcriptome changes, and interesting correlations with expression levels of nuclear receptors and with the histological grade of the tumours. Integrated analysis has suggested certain co-expression profiles of CYPs with lncRNAs that need to be further characterized. Patients with large tumours with down-regulated CYPs could be more vulnerable to drug toxicity; on the other hand, such tumours would eliminate drugs more slowly and should be more sensitive to pharmacotherapy (except in the case of pro-drugs where activation is necessary).},

note = {Place: England},

keywords = {*Gene Expression Regulation, *Transcriptome, Adult, Aged, Carcinoma, Cohort Studies, CYP, Cytochrome P-450 Enzyme System/*genetics, Cytochrome P450, Cytoplasmic and Nuclear/genetics/metabolism, Drug metabolism, Enzymologic, Female, Gene Expression, Gene Expression Profiling, Hepatocellular carcinoma, Hepatocellular/*enzymology/pathology, Hepatocytes/metabolism, Humans, Inactivation, Liver Neoplasms/*enzymology/pathology, Liver/metabolism, Male, Metabolic/genetics, Middle Aged, Neoplasm Grading, Non-coding RNA, Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{soucek_presence_2018,

title = {Presence of growth/differentiation factor-15 cytokine in human follicular fluid, granulosa cells, and oocytes.},

author = {Karel Souček and Alice Malenovská and Zuzana Kahounová and Ján Remšík and Zuzana Holubcová and Tomáš Soukup and Daniela Kurfürstová and Jan Bouchal and Tereza Suchánková and Eva Slabáková and Aleš Hampl},

doi = {10.1007/s10815-018-1230-5},

issn = {1573-7330 1058-0468},

year  = {2018},

date = {2018-08-01},

journal = {Journal of assisted reproduction and genetics},

volume = {35},

number = {8},

pages = {1407–1417},

abstract = {PURPOSE: The purpose of the study was to determine whether the GDF-15 is present in follicular fluid; to evaluate if there is a relation between follicular and serum levels of GDF-15 and fertility status of study subjects; and to test whether granulosa cells, oocytes, or both produce GDF-15. METHODS: This study used follicular fluid (FF, serum, and oocytes obtained under informed consent from women undergoing oocyte retrieval for in vitro fertilization. It also used ovaries from deceased preterm newborns. Collection of FF and blood at the time of oocyte retrieval, ELISA and western blot were performed to determine levels and forms of GDF-15. Concentrations of GDF-15 in FF and serum, its expression in ovarian tissue, and secretion from granulosa cells were analyzed. RESULTS: GDF-15 concentration in FF ranged from 35 to 572 ng/ml, as determined by ELISA. Western blot analysis revealed the GDF-15 pro-dimer only in FF. Both normal healthy and cancerous granulosa cells secreted GDF-15 into culture media. Primary oocytes displayed cytoplasmic GDF-15 positivity in immunostained newborn ovaries, and its expression was also observed in fully grown human oocytes. CONCLUSIONS: To the best of our knowledge, this is the first documentation of cytokine GDF-15 presence in follicular fluid. Its concentration was not associated with donor/patient fertility status. Our data also show that GDF-15 is expressed and inducible in both normal healthy and cancerous granulosa cells, as well as in oocytes.},

note = {Place: Netherlands},

keywords = {Adult, Cell Differentiation/*genetics, Developmental, Female, Fertilization in Vitro, Follicular fluid, Follicular Fluid/*metabolism, Follicular granulosa cells, Gene Expression Regulation, Granulosa Cells/*metabolism, Growth Differentiation Factor 15/*genetics/isolation & purification, Growth/differentiation factor-15, Humans, IVF, Oocyte Retrieval, Oocytes/metabolism},

pubstate = {published},

tppubtype = {article}

}

@article{soucek_growthdifferentiation_2010,

title = {Growth/differentiation factor-15 is an abundant cytokine in human seminal plasma.},

author = {Karel Soucek and Eva Slabáková and Petra Ovesná and Alice Malenovská and Alois Kozubík and Ales Hampl},

doi = {10.1093/humrep/deq264},

issn = {1460-2350 0268-1161},

year  = {2010},

date = {2010-12-01},

journal = {Human reproduction (Oxford, England)},

volume = {25},

number = {12},

pages = {2962–2971},

abstract = {BACKGROUND: Transforming growth factor-β cytokines have various biological effects in female reproductive tissue, including modulation of inflammatory response and induction of immune tolerance to seminal antigens in the reproductive tract. However, no studies have analyzed the presence of growth/differentiation factor-15 (GDF-15/macrophage inhibitory cytokine-1) in seminal fluid or demonstrated the quantity and form of GDF-15, its possible role or the relationship between its concentration and semen quality. METHODS: The form and the concentration of GDF-15 were determined in 53 seminal plasma samples of both fertile and infertile men by ELISA and western blot. The sperm cells of three volunteers were treated with recombinant GDF-15, and cell viability and apoptosis were assessed by flow cytometry. The effect of GDF-15 on vaginal epithelial cells and peripheral blood mononuclear cells (PBMCs) was analyzed by quantitative RT-PCR. RESULTS: The GDF-15 concentration in seminal plasma ranged from 0.2 to 6.6 μg/ml as determined by ELISA. Western blot analysis revealed that GDF-15 is present in the active form. In vitro cultivation of sperm cells with GDF-15 did not affect their viability or rates of apoptosis; however, it did inhibit proliferation of PBMCs and induce expression of FOXP3 in CD4+CD25+ cells. CONCLUSIONS: To the best of our knowledge, this is the first demonstration that GDF-15 is an abundant cytokine in seminal plasma, although its concentration is not associated with semen quality or the fertility/infertility status of the donors. Moreover, our data show that GDF-15 displays immunosuppressive characteristics.},

note = {Place: England},

keywords = {Adult, Apoptosis/drug effects, CD4-Positive T-Lymphocytes/metabolism, Cell Proliferation/drug effects, Cell Survival/drug effects, Epithelial Cells/metabolism, Female, Forkhead Transcription Factors/biosynthesis, Growth Differentiation Factor 15/*physiology, Humans, Interleukin-2 Receptor alpha Subunit/metabolism, Leukocytes, Male, Middle Aged, Mononuclear/drug effects, Semen Analysis, Semen/*metabolism, Spermatozoa},

pubstate = {published},

tppubtype = {article}

}