The efficiency of cisplatin (CDDP) is significantly hindered by the development of resistance during the treatment course. To gain a detailed understanding of the molecular mechanisms underlying the development of cisplatin resistance, we comparatively analyzed established a CDDP-resistant neuroblastoma cell line (UKF-NB-4CDDP) and its susceptible parental cells (UKF-NB-4). We verified increased chemoresistance of UKF-NB-4CDDP cells by analyzing the viability, induction of apoptosis and clonal efficiency. To shed more light on this phenomenon, we employed custom cDNA microarray (containing 2234 probes) to perform parallel transcriptomic profiling of RNA and identified that 139 genes were significantly up-regulated due to CDDP chemoresistance. The analyses of molecular pathways indicated that the top up-regulation scoring functions were response to stress, abiotic stimulus, regulation of metabolic process, apoptotic processes, regulation of cell proliferation, DNA repair or regulation of catalytic activity, which was also evidenced by analysis of molecular functions revealing up-regulation of genes encoding several proteins with a wide-spectrum of enzymatic activities. Functional analysis using lysosomotropic agents chloroquine and bafilomycin A1 validated their potential to re-sensitize UKF-NB-4CDDP cells to CDDP. Taken together, the identification of alterations in specific genes and pathways that contribute to CDDP chemoresistance may potentially lead to a renewed interest in the development of novel rational therapeutics and prognostic biomarkers for the management of CDDP-resistant neuroblastoma.

• Klíčová slova
• chemoresistance, cisplatin, lysosomes, microarray, neuroblastoma, transport,
• MeSH
• buněčné klony MeSH
• chemorezistence účinky léků   genetika   MeSH
• chlorochin farmakologie   MeSH
• cisplatina farmakologie   terapeutické užití   MeSH
• genová ontologie MeSH
• genové regulační sítě účinky léků   MeSH
• lidé MeSH
• lyzozomy účinky léků   metabolismus   MeSH
• makrolidy farmakologie   MeSH
• nádorové buněčné linie MeSH
• neuroblastom farmakoterapie   genetika   patologie   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• transkriptom účinky léků   genetika   MeSH
• tvar buňky účinky léků   MeSH
• upregulace účinky léků   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bafilomycin A1 MeSH Prohlížeč
• chlorochin MeSH
• cisplatina MeSH
• makrolidy MeSH

We focused on the biomechanical and morphological characteristics of prostate cancer cells and their changes resulting from the effect of docetaxel, cisplatin, and long-term zinc supplementation. Cell population surviving the treatment was characterized as follows: cell stiffness was assessed by atomic force microscopy, cell motility and invasion capacity were determined by colony forming assay, wound healing assay, coherence-controlled holographic microscopy, and real-time cell analysis. Cells of metastatic origin exhibited lower height than cells derived from the primary tumour. Cell dry mass and CAV1 gene expression followed similar trends as cell stiffness. Docetaxel- and cisplatin-surviving cells had higher stiffness, and decreased motility and invasive potential as compared to non-treated cells. This effect was not observed in zinc(II)-treated cells. We presume that cell stiffness changes may represent an important overlooked effect of cisplatin-based anti-cancer drugs. Atomic force microscopy and confocal microscopy data images used in our study are available for download in the Zenodo repository ( https://zenodo.org/ , Digital Object Identifiers:10.5281/zenodo.1494935).

• MeSH
• aktiny metabolismus   MeSH
• buněčný převod mechanických signálů * MeSH
• cisplatina farmakologie   MeSH
• hojení ran MeSH
• invazivní růst nádoru MeSH
• lidé MeSH
• nádorové buňky kultivované MeSH
• nádory prostaty farmakoterapie   patologie   MeSH
• proliferace buněk * MeSH
• protinádorové látky farmakologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktiny MeSH
• cisplatina MeSH
• protinádorové látky MeSH

Zinc ions are essential cofactors of a wide range of enzymes, transcription factors, and other regulatory proteins. Moreover, zinc is also involved in cellular signaling and enzymes inhibition. Zinc dysregulation, deficiency, over-supply, and imbalance in zinc ion transporters regulation are connected with various diseases including cancer. A zinc ion pool is maintained by two types of proteins: (i) zinc-binding proteins, which act as a buffer and intracellular donors of zinc and (ii) zinc transporters responsible for zinc fluxes into/from cells and organelles. The decreased serum zinc ion levels have been identified in patients suffering from various cancer diseases, including head and neck tumors and breast, prostate, liver, and lung cancer. On the contrary, increased zinc ion levels have been found in breast cancer and other malignant tissues. Zinc metalloproteomes of a majority of tumors including brain ones are still not yet fully understood. Current knowledge show that zinc ion levels and detection of certain zinc-containing proteins may be utilized for diagnostic and prognostic purposes. In addition, these proteins can also be promising therapeutic targets. The aim of the present work is an overview of the importance of zinc ions, zinc transporters, and zinc-containing proteins in brain tumors, which are, after leukemia, the second most common type of childhood cancer and the second leading cause of death in children after accidents.

• Klíčová slova
• Cancer, Childhood brain tumors, Metallothioneins, Zinc metalloenzymes, Zinc transporters,
• MeSH
• biologické modely MeSH
• cílená molekulární terapie MeSH
• dítě MeSH
• lidé MeSH
• nádorové proteiny metabolismus   MeSH
• nádory mozku diagnóza   metabolismus   MeSH
• zinek metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• nádorové proteiny MeSH
• zinek MeSH

Increasing urbanization and industrialization lead to the release of metals into the biosphere, which has become a serious issue for public health. In this paper, the direct electrochemical reduction of zinc ions is studied using electrochemically reduced graphene oxide (ERGO) modified glassy carbon electrode (GCE). The graphene oxide (GO) was fabricated using modified Hummers method and was electrochemically reduced on the surface of GCE by performing cyclic voltammograms from 0 to -1.5 V. The modification was optimized and properties of electrodes were determined using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The determination of Zn(II) was performed using differential pulse voltammetry technique, platinum wire as a counter electrode, and Ag/AgCl/3 M KCl reference electrode. Compared to the bare GCE the modified GCE/ERGO shows three times better electrocatalytic activity towards zinc ions, with an increase of reduction current along with a negative shift of reduction potential. Using GCE/ERGO detection limit 5 ng·mL-1 was obtained.

• Klíčová slova
• carbon, cyclic voltammetry, electrochemical impedance spectroscopy, electrochemistry, graphene oxide, heavy metal detection, reduced graphene oxide,
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVES: Current studies give us inconsistent results regarding the association of neoplasms and zinc(II) serum and tissues concentrations. The results of to-date studies using meta-analysis are summarized in this paper. METHODS: Web of Science (Science citation index expanded), PubMed (Medline), Embase and CENTRAL were searched. Articles were reviewed by two evaluators; quality was assessed by Newcastle-Ottawa scale; meta-analysis was performed including meta-regression and publication bias analysis. RESULTS: Analysis was performed on 114 case control, cohort and cross-sectional studies of 22737 participants. Decreased serum zinc level was found in patients with lung (effect size = -1.04), head and neck (effect size = -1.43), breast (effect size = -0.93), liver (effect size = -2.29), stomach (effect size = -1.59), and prostate (effect size = -1.36) cancers; elevation was not proven in any tumor. More specific zinc patterns are evident at tissue level, showing increase in breast cancer tissue (effect size = 1.80) and decrease in prostatic (effect size = -3.90), liver (effect size = -8.26), lung (effect size = -3.12), and thyroid cancer (effect size = -2.84). The rest of the included tumors brought ambiguous results, both in serum and tissue zinc levels across the studies. The association between zinc level and stage or grade of tumor has not been revealed by meta-regression. CONCLUSION: This study provides evidence on cancer-specific tissue zinc level alteration. Although serum zinc decrease was associated with most tumors mentioned herein, further--prospective--studies are needed.

• MeSH
• epitel patologie   MeSH
• lidé MeSH
• nádory krev   patologie   MeSH
• statistické modely MeSH
• zinek krev   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Názvy látek
• zinek MeSH

Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82-17.03) and ovarian tumors (OR 7.83; 1.09-56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03-0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08-2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03-2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47-2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.

• MeSH
• databáze bibliografické MeSH
• imunohistochemie MeSH
• lidé MeSH
• metalothionein metabolismus   MeSH
• metastázy nádorů MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory hlavy a krku diagnóza   metabolismus   patologie   MeSH
• nádory jater diagnóza   metabolismus   patologie   MeSH
• nádory vaječníků diagnóza   metabolismus   patologie   MeSH
• odds ratio MeSH
• prognóza MeSH
• studie případů a kontrol MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Názvy látek
• metalothionein MeSH
• nádorové biomarkery MeSH

Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanisms participating on the protection of a cell against free radicals. In this review, our attention is paid to metallothioneins (MTs) as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses. The mechanism of the reaction of metallothioneins with oxidants and electrophilic compounds is discussed. Numerous reports indicate that MT protects cells from exposure to oxidants and electrophiles, which react readily with sulfhydryl groups. Moreover, MT plays a key role in regulation of zinc levels and distribution in the intracellular space. The connections between zinc, MT and cancer are highlighted.

• Publikační typ
• časopisecké články MeSH