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22 results on '"Navrátilová, Jarmila"'

5. Infrared Laser Desorption of Intact Nanoparticles for Digital Tissue Imaging

Author

Stiborek, Marek, primary, Jindřichová, Lenka, additional, Meliorisová, Stanislava, additional, Bednařík, Antonín, additional, Prysiazhnyi, Vadym, additional, Kroupa, Jiří, additional, Houška, Pavel, additional, Adamová, Barbora, additional, Navrátilová, Jarmila, additional, Kanický, Viktor, additional, and Preisler, Jan, additional

Published
2022
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8. Synergistic cytotoxicity of perifosine and ABT‐737 to colon cancer cells.

Author

Adamová, Barbora, Říhová, Kamila, Pokludová, Jana, Beneš, Petr, Šmarda, Jan, and Navrátilová, Jarmila

Subjects
COLON cancer, PI3K/AKT pathway, DRUG efficacy, CELL culture, CELLULAR therapy
Abstract

An acidic environment and hypoxia within the tumour are hallmarks of cancer that contribute to cell resistance to therapy. Deregulation of the PI3K/Akt pathway is common in colon cancer. Numerous Akt‐targeted therapies are being developed, the activity of Akt‐inhibitors is, however, strongly pH‐dependent. Combination therapy thus represents an opportunity to increase their efficacy. In this study, the cytotoxicity of the Akt inhibitor perifosine and the Bcl‐2/Bcl‐xL inhibitor ABT‐737 was tested in colon cancer HT‐29 and HCT‐116 cells cultured in monolayer or in the form of spheroids. The efficacy of single drugs and their combination was analysed in different tumour‐specific environments including acidosis and hypoxia using a series of viability assays. Changes in protein content and distribution were determined by immunoblotting and a "peeling analysis" of immunohistochemical signals. While the cytotoxicity of single agents was influenced by the tumour‐specific microenvironment, perifosine and ABT‐737 in combination synergistically induced apoptosis in cells cultured in both 2D and 3D independently on pH and oxygen level. Thus, the combined therapy of perifosine and ABT‐737 could be considered as a potential treatment strategy for colon cancer. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Lactic Acidosis Interferes With Toxicity of Perifosine to Colorectal Cancer Spheroids: Multimodal Imaging Analysis

Author

Pavlatovská, Barbora, primary, Machálková, Markéta, additional, Brisudová, Petra, additional, Pruška, Adam, additional, Štěpka, Karel, additional, Michálek, Jan, additional, Nečasová, Tereza, additional, Beneš, Petr, additional, Šmarda, Jan, additional, Preisler, Jan, additional, Kozubek, Michal, additional, and Navrátilová, Jarmila, additional

Published
2020
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13. Drug Penetration Analysis in 3D Cell Cultures Using Fiducial-Based Semiautomatic Coregistration of MALDI MSI and Immunofluorescence Images

Author

Machálková, Markéta, primary, Pavlatovská, Barbora, additional, Michálek, Jan, additional, Pruška, Adam, additional, Štěpka, Karel, additional, Nečasová, Tereza, additional, Radaszkiewicz, Katarzyna Anna, additional, Kozubek, Michal, additional, Šmarda, Jan, additional, Preisler, Jan, additional, and Navrátilová, Jarmila, additional

Published
2019
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15. MALDI MS Imaging at Acquisition Rates Exceeding 100 Pixels per Second

Author

Bednařík, Antonín, primary, Machálková, Markéta, additional, Moskovets, Eugene, additional, Coufalíková, Kateřina, additional, Krásenský, Pavel, additional, Houška, Pavel, additional, Kroupa, Jiří, additional, Navrátilová, Jarmila, additional, Šmarda, Jan, additional, and Preisler, Jan, additional

Published
2018
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16. Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization

Author

Kučírková, Tereza, primary, Stiborek, Marek, additional, Dúcka, Monika, additional, Navrátilová, Jarmila, additional, Bogdanović Pristov, Jelena, additional, Popović-Bijelić, Ana, additional, Vojvodić, Snežana, additional, Preisler, Jan, additional, Kanický, Viktor, additional, Šmarda, Jan, additional, Spasojević, Ivan, additional, and Beneš, Petr, additional

Published
2018
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21. Lactic Acidosis Interferes With Toxicity of Perifosine to Colorectal Cancer Spheroids: Multimodal Imaging Analysis

Author

Pavlatovská, Barbora, Machálková, Markéta, Brisudová, Petra, Pruska, Adam, Štěpka, Karel, Michálek, Jan, Nečasová, Tereza, Beneš, Petr, Šmarda, Jan, Preisler, Jan, Kozubek, Michal, and Navrátilová, Jarmila

Subjects
Alkalization, Mass spectrometry imaging, Tumor environment, Lactic acidosis, Signal co-registration, Perifosine, Colorectal cancer, 3. Good health, Akt kinase
Abstract

Colorectal cancer (CRC) is a disease with constantly increasing incidence and high mortality. The treatment efficacy could be curtailed by drug resistance resulting from poor drug penetration into tumor tissue and the tumor-specific microenvironment, such as hypoxia and acidosis. Furthermore, CRC tumors can be exposed to different pH depending on the position in the intestinal tract. CRC tumors often share upregulation of the Akt signaling pathway. In this study, we investigated the role of external pH in control of cytotoxicity of perifosine, the Akt signaling pathway inhibitor, to CRC cells using 2D and 3D tumor models. In 3D settings, we employed an innovative strategy for simultaneous detection of spatial drug distribution and biological markers of proliferation/apoptosis using a combination of mass spectrometry imaging and immunohistochemistry. In 3D conditions, low and heterogeneous penetration of perifosine into the inner parts of the spheroids was observed. The depth of penetration depended on the treatment duration but not on the external pH. However, pH alteration in the tumor microenvironment affected the distribution of proliferation- and apoptosis-specific markers in the perifosine-treated spheroid. Accurate co-registration of perifosine distribution and biological response in the same spheroid section revealed dynamic changes in apoptotic and proliferative markers occurring not only in the perifosine-exposed cells, but also in the perifosine-free regions. Cytotoxicity of perifosine to both 2D and 3D cultures decreased in an acidic environment below pH 6.7. External pH affects cytotoxicity of the other Akt inhibitor, MK-2206, in a similar way. Our innovative approach for accurate determination of drug efficiency in 3D tumor tissue revealed that cytotoxicity of Akt inhibitors to CRC cells is strongly dependent on pH of the tumor microenvironment. Therefore, the effect of pH should be considered during the design and pre-clinical/clinical testing of the Akt-targeted cancer therapy., Frontiers in Oncology, 10, ISSN:2234-943X

22. Copper ions regulate cytotoxicity of disulfiram to myeloid leukemia cells.

Author

Navrátilová J, Jungová P, Vanhara P, Preisler J, Kanicky V, and Smarda J

Subjects
Acetylcysteine pharmacology, Cell Count, Cell Death drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Culture Media, Conditioned, Drug Resistance, Neoplasm drug effects, Enzyme Inhibitors pharmacology, Humans, Intracellular Space drug effects, Intracellular Space metabolism, Ions, Copper pharmacology, Disulfiram pharmacology, Leukemia, Myeloid pathology
Abstract

White blood cell (WBC) count is considered a prognostic risk factor in acute myeloid leukemia. As density of leukemic cells increases, the cytotoxic activity of certain anticancer drugs, such as vincristine and doxorubicin, progressively decreases. In this study, we investigated the cell density-dependent induction of apoptosis of human acute myeloid leukemia U937 and ML-1 cells by disulfiram (DSF), the dithiocarbamate drug recently proposed for treatment of human cancers. This effect is dependent on uptake of extracellular copper and its intracellular accumulation. High-density cells cannot uptake and accumulate this metal to a sufficient level that would allow induction of apoptosis due to progressive decrease of its extracellular concentration. Simple addition of copper can resume sensitivity of high-density leukemic cells to DSF and improve efficiency of anti-leukemic therapies using this drug, thus providing benefit to patients with high WBC count.

Published
2009
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