Latest Publications

@article{hofmanova_complex_2021,

title = {Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells.},

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

doi = {10.3390/ijms22136650},

issn = {1422-0067},

year  = {2021},

date = {2021-06-01},

journal = {International journal of molecular sciences},

volume = {22},

number = {13},

abstract = {The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM(+) cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.},

note = {Place: Switzerland},

keywords = {*Gene Expression Regulation, *Lipid Metabolism, Adenocarcinoma/enzymology/genetics/*metabolism, Aged, Colonic Neoplasms/enzymology/genetics/*metabolism, colorectal carcinoma, desaturation, EpCAM, Epithelial Cells, Epithelial Cells/enzymology/metabolism, Fatty Acid Desaturases/genetics/metabolism, Fatty Acid Elongases/genetics/metabolism, Fatty Acid Synthases/genetics/metabolism, fatty acid synthesis, Fatty Acids/*metabolism, Female, Humans, lipidomics, Lipogenesis, lysophospholipids, Male, Neoplastic, Phospholipids, Phospholipids/*metabolism, Stearoyl-CoA Desaturase/genetics/metabolism},

pubstate = {published},

tppubtype = {article}

}

@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{kahounova_generation_2018,

title = {Generation of human iPSCs from human prostate cancer-associated fibroblasts IBPi002-A.},

author = {Zuzana Kahounová and Eva Slabáková and Lucia Binó and Ján Remšík and Radek Fedr and Jan Bouchal and Daniela Kurfűrstová and Radek Vrtěl and Vladimír Študent and Lucie Jurečková and Volodymyr Porokh and Aleš Hampl and Karel Souček},

doi = {10.1016/j.scr.2018.11.006},

issn = {1876-7753 1873-5061},

year  = {2018},

date = {2018-12-01},

journal = {Stem cell research},

volume = {33},

pages = {255–259},

abstract = {A human induced pluripotent stem cell line was generated from cancer-associated fibroblasts of a 68-years old patient with diagnosed prostate adenocarcinoma (PCa). The fibroblast cell line was reprogrammed with Epi5™ Episomal iPSC Reprogramming Kit. Pluripotency of the derived transgene-free iPS cell line was confirmed both in vitro by detecting expression of factors of pluripotency on a single-cell level, and also in vivo using teratoma formation assay. This new iPS cell line may be used for differentiation into different prostate-specific cell types in differentiation studies.},

note = {Place: England},

keywords = {Aged, Cancer-Associated Fibroblasts/*metabolism, Fibroblasts/*metabolism, Humans, Induced Pluripotent Stem Cells/*metabolism, Male, Prostatic Neoplasms/*genetics},

pubstate = {published},

tppubtype = {article}

}