Publications by authors named "Petra Pokorná"

10 Publications

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Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma.

Sci Rep 2021 Mar 9;11(1):5496. Epub 2021 Mar 9.

Department of Chemistry and Faculty of AgriSciences, Mendel University in Brno, Zemedelska 1, 613 00, Brno, Czech Republic.

Metallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses.
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http://dx.doi.org/10.1038/s41598-021-84185-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943580PMC
March 2021

Spatial-temporal variability of aerosol sources based on chemical composition and particle number size distributions in an urban settlement influenced by metallurgical industry.

Environ Sci Pollut Res Int 2020 Nov 5;27(31):38631-38643. Epub 2020 Jul 5.

Department of Public Health Sciences, University of Rochester Medical Center, 265 Crittenden Boulevard, Rochester, NY, 14642-0708, USA.

The Moravian-Silesian region of the Czech Republic with its capital city Ostrava is a European air pollution hot spot for airborne particulate matter (PM). Therefore, the spatiotemporal variability assessment of source contributions to aerosol particles is essential for the successful abatement strategies implementation. Positive Matrix Factorization (PMF) was applied to highly-time resolved PM chemical composition (1 h resolution) and particle number size distribution (PNSD, 14 nm - 10 μm) data measured at the suburban (Ostrava-Plesná) and urban (Ostrava-Radvanice) residential receptor sites in parallel during an intensive winter campaign. Diel patterns, meteorological variables, inorganic and organic markers, and associations between the chemical composition factors and PNSD factors were used to identify the pollution sources and their origins (local, urban agglomeration and regional). The source apportionment analysis resolved six and four PM sources in Plesná and Radvanice, respectively. In Plesná, local residential combustion sources (coal and biomass combustion) followed by regional combustion sources (residential heating, metallurgical industry) were the main contributors to PM. In Radvanice, local residential combustion and the metallurgical industry were the most important PM sources. Aitken and accumulation mode particles emitted by local residential combustion sources along with common urban sources (residential heating, industry and traffic) were the main contributors to the particle number concentration (PNC) in Plesná. Additionally, accumulation mode particles from local residential combustion sources and regional pollution dominated the particle volume concentration (PVC). In Radvanice, local industrial sources were the major contributors to PNC and local coal combustion was the main contributor to PVC. The source apportionment results from the complementary datasets elucidated the relevance of highly time-resolved parallel measurements at both receptor sites given the specific meteorological conditions produced by the regional orography. These results are in agreement with our previous studies conducted at this site. Graphical abstract.
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http://dx.doi.org/10.1007/s11356-020-09694-0DOI Listing
November 2020

Assessment of air pollution origin based on year-long parallel measurement of PM and PM at two suburban sites in Prague, Czech Republic.

Sci Total Environ 2019 May 1;664:1107-1116. Epub 2019 Feb 1.

Czech Hydrometeorological Institute, Na Šabatce 17, 143 06 Prague 4, Czech Republic.

From 2nd April 2008 to 28th March 2009, a total 248 daily samples of the PM and PM were collected every sixth day parallel at two suburban sites (Libuš and Suchdol) located at the two opposite sides (south and north, respectively) of Prague, Czech Republic. The PM samples were analyzed for ions by ion chromatography (IC), organic and elemental carbon (OC and EC) by OC/EC analyzer and PM samples also for 56 elements by inductively coupled plasma-mass spectrometry (ICP-MS). The average annual PM and PM was 24.4 ± 13.0 μg m and 26.7 ± 15.1 μg m, respectively, in Prague-Libuš, and 25.1 ± 22.1 μg m and 27.1 ± 23.2 μg m, respectively, in Prague-Suchdol. Since the species forming large part of the aerosol mass were strongly correlated (Spearman's rank correlation coefficient r > 0.80), the variability of PM and PM concentration was mainly driven by the local meteorology or regional and/or long range transport. PM mass closure was calculated based on analytical results with the average percentage of recalculated mass of 77 ± 19% in Prague-Libuš and 86 ± 16% in Prague-Suchdol. The most abundant groups in PM at both sites during the four seasons were OM (Prague-Libuš 34% and Prague-Suchdol 37%) and SIA (Prague-Libuš 30% and Prague-Suchdol 34%). The Positive Matrix Factorization (PMF) was applied to the chemical composition of PM from both sites (124 samples) together to determine its sources. The nine factors were assigned as: mixed factor secondary sulphate and biomass burning, secondary sulphate, traffic, secondary nitrate, road dust, residential heating, aged sea salt, industry and mixed factor road salt along with aged sea salt. According to the polar plots and ventilation index (VI) east/west classification analysis the sources were separated based on origin to four categories local, urban agglomeration, regional and long range transport (LRT). The mixed source secondary sulphate and biomass burning, residential heating and industry were common sources of local origin at both sites. Prague-Suchdol was influenced by traffic related pollution from the urban agglomeration more than Prague-Libuš where the traffic and road dust/salt were of local origin. The regional pollution by secondary sulphates and nitrate was also relevant at both sites along with long range transport of sea salt from North Atlantic Ocean, Norwegian Sea and North Sea. The contribution of the local sources to PM was significant mainly at Prague-Libuš site. However, the sources of regional origin were also important and influence of urban agglomeration pollution to PM is not negligible as well.
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http://dx.doi.org/10.1016/j.scitotenv.2019.01.426DOI Listing
May 2019

The influence of local emissions and regional air pollution transport on a European air pollution hot spot.

Environ Sci Pollut Res Int 2019 Jan 17;26(2):1675-1692. Epub 2018 Nov 17.

Department of Aerosols Chemistry and Physics, Institute of Chemical Process Fundamentals of the Czech Academy of Sciences, v.v.i, Rozvojová 1/135, 165 02, Prague 6 - Suchdol, Czech Republic.

The EU air quality standards have been frequently exceeded in one of the European air pollution hot spots: Ostrava. The aim of this study was to perform an air quality comparison between an urban site (Radvanice), which has a nearby metallurgical complex, and a suburban site (Plesná) to estimate air pollution sources and determine their local and/or regional origins. Twenty-four hour PM and PM (particular matter) concentrations, detailed mass size distributions (MSDs) to distinguish the sources of the fine and coarse PM, and their chemical compositions were investigated in parallel at both sites during the winter of 2014. Positive matrix factorization (PMF) was applied to the PM and PM chemical compositions to investigate their sources. During the measurement campaign, prevailing northeastern-southwestern (NE-SW) wind directions (WDs) were recorded. Higher average PM concentration was measured in Radvanice than in Plesná, whereas PM concentrations were similar at both sites. A source apportionment analysis revealed six and five sources for PM and PM, respectively. In Radvanice, the amount of PM and the most chemical species were similar under SW and NE WD conditions. The dominant sources were industrial (43% for PM and 27% for PM), which were caused by a large metallurgical complex located to the SW, and biomass burning (25% for PM and 36% for PM). In Plesná, the concentrations of PM and all species significantly increased under NE WD conditions. Secondary inorganic aerosols were dominant, with the highest contributions deriving from the NE WD. Therefore, regional pollution transport from the industrial sector in Silesian Province (Poland) was evident. Biomass burning contributed 22% and 24% to PM and PM, respectively. The air quality in Ostrava was influenced by local sources and regional pollution transport. The issue of poor air quality in this region is complex. Therefore, international cooperation from both states (the Czech Republic and Poland) is needed to achieve a reduction in air pollution levels.
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http://dx.doi.org/10.1007/s11356-018-3670-yDOI Listing
January 2019

New comprehensive approach for airborne asbestos characterisation and monitoring.

Environ Sci Pollut Res Int 2018 Oct 30;25(30):30488-30496. Epub 2018 Aug 30.

Institute for Environmental Studies, Faculty of Science, Charles University, Benátská 2, 12801, Prague 2, Czech Republic.

High concentrations of airborne asbestos in the ambient air are still a serious problem of air quality in numerous localities around the world. Since 2002, elevated concentrations of asbestos minerals of unknown origin have been detected in the ambient air of Pilsen, Czech Republic. To determine the asbestos fibre sources in this urban air, a systematic study was conducted. First, 14 bulk dust samples were collected in Pilsen at nine localities, and 6 bulk samples of construction aggregates for gravel production were collected in a quarry in the Pilsen-Litice district. The quarry is the largest quarry in the Pilsen region and the closest quarry to the built-up urban area. X-ray diffraction of the asbestos minerals revealed that monoclinic amphibole (MA, namely actinolite based on subsequent SEM-EDX analysis) in the bulk samples accounted for < 1-33% of the mass and that the highest values were found in the bulk dust samples from the railway platform of the Pilsen main railway station. Simultaneously, 24-h samples of airborne particulate matter (PM) at three localities in Pilsen were collected. Actinolite was identified in 40% of the PM samples. The relationship between the meteorology and presence of actinolite in the 24 PM samples was not proven, probably due to the long sampling integration time. Therefore, highly time-and-size-resolved PM sampling was performed. Second, sampling of size-segregated aerosols and measurements of the wind speed (WS), wind direction (WD), precipitation (P) and hourly PM, PM and PM were conducted in a suburban locality near the quarry in two monthly highly time-resolved periods (30, 60, 120 min). Three/eight PM size fractions were sampled by a Davis Rotating-drum Uniform-size-cut Monitor (3/8DRUM) and analysed for the presences of asbestos fibres by scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM-EDX). Asbestos fibre detection in highly time-resolved PM samples and current WD and WS determination allows the apportionment directionality of asbestos fibre sources. The number of critical actinolite asbestos fibres (length ≥ 5 μm and width < 3 μm, 3:1) increased with the PM/PM and PM/PM ratios, WS > 2 m s and precipitation < 1 mm. Additionally, the number of critical actinolite asbestos fibres was not related to a specific WD. Therefore, we conclude that the sources of airborne critical actinolite asbestos fibres in Pilsen's urban area are omnipresent. Frequent use of construction aggregates and gravel from the metamorphic spilite quarries in the Pilsen region and in many localities around the urban area is a plausible explanation for the omnipresence of the critical actinolite asbestos fibres concentration in Pilsen's ambient air. Mitigation strategies to reduce the concentrations of critical actinolite asbestos fibres must be developed. Continuous monitoring and performing SEM-EDX analysis of highly time-and-size-resolved PM samples, correlated with fast changing WS and WD, seems to be a strong tool for efficiently controlling the mitigation strategies of critical actinolite asbestos fibres.
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http://dx.doi.org/10.1007/s11356-018-2791-7DOI Listing
October 2018

Comparison of PM chemical composition and sources at a rural background site in Central Europe between 1993/1994/1995 and 2009/2010: Effect of legislative regulations and economic transformation on the air quality.

Environ Pollut 2018 Oct 14;241:841-851. Epub 2018 Jun 14.

Department of Aerosol Chemistry and Physics, Institute of Chemical Process Fundamentals of the Czech Academy of Sciences, Rozvojová 1/135, 165 02 Prague 6, Czech Republic.

From December 1993 to January 1995 and from October 2009 to October 2010, a total of 320 and 365 daily samples of the PM were collected at a rural background site (National Atmospheric Observatory Košetice) in Central Europe. The PM samples were analyzed for 29 and 26 elements respectively by Particle-Induced X-ray Emission (PIXE) and water-soluble inorganic ions by Ion Chromatography (IC) in 2009/2010. The Positive Matrix Factorization (PMF) was applied to the chemical composition of PM to determine its sources. The decreasing trends of almost all elements concentrations, especially the metals regulated by the EU Directive (2004/107/EC) are evident. The annual median ratios indicate a decrease in concentrations of the PM elements. The slight increase of K concentrations and Spearman's rank correlation coefficient r 0.09 K/Se points to a rise in residential wood combustion. The S concentrations are nearly comparable (higher mean in 2009/2010, while the annual median ratio is under 1). The five major source types in the mid-1990s were ascribed to brown coal combustion, oil combustion, sea salt and dust - long-range transport, re-suspended dust and black coal combustion. The industrial combustion of brown and/or black coal (r 0.75 Se/As, r 0.57 Ga/Ge and r 0.20 As/Zn) and oil (r 0.72 V/Ni) of the regional origin dominated. In the 1990s, the potential source regions were the border area of Czech Republic, German and Poland (brown coal), the Moravia-Silesia region at the Czech-Polish border (black coal), and Slovakia, Austria, Hungary, and the Balkans (oil). In 2009/2010, the apportioned sources were sulfate, residential heating, nitrate, industry, re-suspended dust, and sea salt and dust - long-range transport. The secondary sulfate from coal combustion and residential biomass burning (r 0.96, K/K) of local origin dominated. The declining trend of the elemental concentrations and change in the source pattern of the regional background PM2.5 in Central Europe between the mid-1990s and 2009/10 reflects the economic transformation and impact of stricter legislation in Central Europe.
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http://dx.doi.org/10.1016/j.envpol.2018.06.015DOI Listing
October 2018

Source apportionment of aerosol particles at a European air pollution hot spot using particle number size distributions and chemical composition.

Environ Pollut 2018 Mar 22;234:145-154. Epub 2017 Nov 22.

Center for Air Resources Engineering and Science, Clarkson University, Potsdam, NY 13699-5708, USA; Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, USA.

Ostrava in the Moravian-Silesian region (Czech Republic) is a European air pollution hot spot for airborne particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), and ultrafine particles (UFPs). Air pollution source apportionment is essential for implementation of successful abatement strategies. UFPs or nanoparticles of diameter <100 nm exhibit the highest deposition efficiency in human lungs. To permit apportionment of PM sources at the hot-spot including nanoparticles, Positive Matrix Factorization (PMF) was applied to highly time resolved particle number size distributions (NSD, 14 nm-10 μm) and PM chemical composition. Diurnal patterns, meteorological variables, gaseous pollutants, organic markers, and associations between the NSD factors and chemical composition factors were used to identify the pollution sources. The PMF on the NSD reveals two factors in the ultrafine size range: industrial UFPs (28%, number mode diameter - NMD 45 nm), industrial/fresh road traffic nanoparticles (26%, NMD 26 nm); three factors in the accumulation size range: urban background (24%, NMD 93 nm), coal burning (14%, volume mode diameter - VMD 0.5 μm), regional pollution (3%, VMD 0.8 μm) and one factor in the coarse size range: industrial coarse particles/road dust (2%, VMD 5 μm). The PMF analysis of PM revealed four factors: SIA/CC/BB (52%), road dust (18%), sinter/steel (16%), iron production (16%). The factors in the ultrafine size range resolved with NSD have a positive correlation with sinter/steel production and iron production factors resolved with chemical composition. Coal combustion factor resolved with NSD has moderate correlation with SIA/CC/BB factor. The organic markers homohopanes correlate with coal combustion and the levoglucosan correlates with urban background. The PMF applications to NSD and chemical composition datasets are complementary. PAHs in PM were found to be associated with coal combustion factor.
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http://dx.doi.org/10.1016/j.envpol.2017.10.097DOI Listing
March 2018

An insight into the complex roles of metallothioneins in malignant diseases with emphasis on (sub)isoforms/isoforms and epigenetics phenomena.

Pharmacol Ther 2018 03 5;183:90-117. Epub 2017 Oct 5.

Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic. Electronic address:

Metallothioneins (MTs) belong to a group of small cysteine-rich proteins that are ubiquitous throughout all kingdoms. The main function of MTs is scavenging of free radicals and detoxification and homeostating of heavy metals. In humans, 16 genes localized on chromosome 16 have been identified to encode four MT isoforms labelled by numbers (MT-1-MT-4). MT-2, MT-3 and MT-4 proteins are encoded by a single gene. MT-1 comprises many (sub)isoforms. The known active MT-1 genes are MT-1A, -1B, -1E, -1F, -1G, -1H, -1M and -1X. The rest of the MT-1 genes (MT-1C, -1D, -1I, -1J and -1L) are pseudogenes. The expression and localization of individual MT (sub)isoforms and pseudogenes vary at intra-cellular level and in individual tissues. Changes in MT expression are associated with the process of carcinogenesis of various types of human malignancies, or with a more aggressive phenotype and therapeutic resistance. Hence, MT (sub)isoform profiling status could be utilized for diagnostics and therapy of tumour diseases. This review aims on a comprehensive summary of methods for analysis of MTs at (sub)isoforms levels, their expression in single tumour diseases and strategies how this knowledge can be utilized in anticancer therapy.
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http://dx.doi.org/10.1016/j.pharmthera.2017.10.004DOI Listing
March 2018

Regorafenib in the Real-Life Clinical Practice: Data from the Czech Registry.

Target Oncol 2017 02;12(1):89-95

Department of Oncology, University Hospital in Motol, Charles University, V Uvalu 84, 150 00, Prague, Czech Republic.

Objective: To describe the use of regorafenib for the treatment of metastatic colorectal cancer (mCRC) in clinical practice in the Czech Republic, and to describe the clinical outcomes of patients in terms of safety and survival.

Patients And Methods: The data of patients treated with regorafenib were extracted from the national CORECT registry. The CORECT registry is a non-interventional post-marketing database, gathering information about patients with CRC and treated with targeted agents. Twenty oncology centres in the Czech Republic contributed to this registry. Collected data included patients' characteristics, disease history, cancer treatments, response to treatments and safety.

Results: A total of 148 patients treated with regorafenib in clinical practice were analysed. At regorafenib initiation, almost all patients were fully active or slightly restricted in physical activity. Regorafenib was not administered as first-line treatment in any patient. Median progression-free survival was 3.5 months and median overall survival was 9.3 months. One-year survival rate was 44.6 %. Four partial responses were observed and 51 stable diseases. Progression was observed in 66 patients (44.6 %). The main reported adverse events were skin toxicity (5.4 %) and fatigue (2.0 %).

Conclusions: Regorafenib is a well-established treatment for pretreated patients with mCRC, however real-life data are scarce. Our results demonstrated slightly better efficacy of regorafenib and better safety profile in patients with mCRC compared to the randomised trials.
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http://dx.doi.org/10.1007/s11523-016-0458-1DOI Listing
February 2017

Bevacizumab with chemotherapy in patients with KRAS wild-type metastatic colorectal cancer: Czech registry data.

Future Oncol 2015 ;11(2):225-32

Department of Oncology, University Hospital Motol, Prague, Czech Republic.

Aim: This retrospective analysis investigated the effectiveness of combination therapy with bevacizumab and chemotherapy in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer.

Patients & Methods: Patients with KRAS wild-type metastatic colorectal cancer in the CORECT registry who initiated treatment with bevacizumab between 2008 and 2012 were enrolled. Overall survival and progression-free survival were the main effectiveness end points.

Results: A total of 981 patients were enrolled. Median progression-free survival was 11.3 months (95% CI: 10.7-11.8) and median overall survival was 28.4 months (95% CI: 26.2-30.6). The most common adverse events were thromboembolic disease (4%) and hypertension (3.5%).

Conclusion: This retrospective analysis shows the effectiveness of bevacizumab with chemotherapy in patients with KRAS wild-type metastatic colorectal cancer.
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http://dx.doi.org/10.2217/fon.14.240DOI Listing
September 2015