Sinonasal carcinomas are head and neck tumours arising from the nasal cavity and paranasal sinuses characterized by unfavourable outcome, difficult treatment, diagnosis and prognosis. MicroRNAs are key molecules in the regulation of development and progression of cancer and their expression profiles could be used as prognostic biomarkers, to predict the patients' survival and response to treatment. In this study, we used quantitative real‑time PCR with TaqMan® Advanced miRNA Assays to investigate the relative expression values of selected micro- RNAs in a unique set of formalin-fixed paraffin-embedded tissue samples obtained from 46 patients with sinonasal squamous cell carcinoma. Our results showed statistically significant up-regulation of three mature microRNAs: miR-9-5p (fold change: 6.80), miR-9-3p (fold change: 3.07) and let-7d (fold change: 3.93) in sinonasal carcinoma patients. Kaplan-Meier survival analysis and logrank test identified association between higher expression of miR-9-5p and longer survival of the patients (P = 0.0264). Lower expression of let-7d was detected in the patients with impaired survival, and higher expression of miR-137 was linked to shorter survival of the patients. We also identified several correlations between expression of the studied microRNAs and recorded clinicopathological data. Higher expression of miR-137 and lower expression of let-7d correlated with local recurrence (P = 0.045 and P = 0.025); lower expression of miR-9-5p and higher expression of miR-155-5p correlated with regional recurrence (P = 0.045 and P = 0.036). Higher expression of miR-9-3p correlated with occupational risk (P = 0.031), presence of vascular invasion (P = 0.013) and perineural invasion (P = 0.031). Higher expression of miR-155-5p was present in the samples originating from maxillary sinus (P = 0.011), cN1-3 classified tumours (P = 0.009) and G2-3 classified tumours (P = 0.017). In conclusion, our study supports the hypothesis of future prospect to use expression of miRNAs as prognostic biomarkers of squamous cell sinonasal carcinoma. In particular, miR-9-5p and miR-9-3p seem to be important members of the sinonasal cancer pathogenesis.
- MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory sinu maxillaris genetika patologie MeSH
- prognóza MeSH
- regresní analýza MeSH
- regulace genové exprese u nádorů * MeSH
- spinocelulární karcinom genetika patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA MeSH
- nádorové biomarkery MeSH
Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism for inactivation of tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. The aim of this study was to investigate promoter methylation of specific genes in samples of sinonasal carcinoma by comparison with normal sinonasal tissue. To search for epigenetic events we used methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to compare the methylation status of 64 tissue samples of sinonasal carcinomas with 19 control samples. We also compared the human papilloma virus (HPV) status with DNA methylation. Using a 20% cut-off for methylation, we observed significantly higher methylation in RASSF1, CDH13, ESR1 and TP73 genes in the sinonasal cancer group compared with the control group. HPV positivity was found in 15/64 (23.4 %) of all samples in the carcinoma group and in no sample in the control group. No correlation was found between DNA methylation and HPV status. In conclusion, our study showed that there are significant differences in promoter methylation in the RASSF1, ESR 1, TP73 and CDH13 genes between sinonasal carcinoma and normal sinonasal tissue, suggesting the importance of epigenetic changes in these genes in carcinogenesis of the sinonasal area. These findings could be used as prognostic factors and may have implications for future individualised therapies based on epigenetic changes.
- MeSH
- aktivace enzymů MeSH
- dlaždicobuněčné karcinomy hlavy a krku MeSH
- DNA-(cytosin-5-)methyltransferasa genetika metabolismus MeSH
- DNA-(cytosin-5)-methyltransferasa 1 MeSH
- epigenomika MeSH
- kadheriny genetika metabolismus MeSH
- lidé MeSH
- metylace DNA * MeSH
- nádory hlavy a krku diagnóza genetika patofyziologie virologie MeSH
- Papillomaviridae izolace a purifikace MeSH
- prognóza MeSH
- promotorové oblasti (genetika) genetika MeSH
- spinocelulární karcinom diagnóza genetika patofyziologie virologie MeSH
- tumor supresorové geny * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA-(cytosin-5-)methyltransferasa MeSH
- DNA-(cytosin-5)-methyltransferasa 1 MeSH
- H-cadherin MeSH Prohlížeč
- kadheriny MeSH
To determine whether PHEMA [poly(2-hydroxyethylmethacrylate)] is suitable for portal vein embolization in patients scheduled to right hepatectomy and whether it is as effective as the currently used agent (a histoacryl/lipiodol mixture). Two groups of nine patients each scheduled for extended right hepatectomy for primary or secondary hepatic tumor, had right portal vein embolization in an effort to induce future liver remnant (FLR) hypertrophy. One group had embolization with PHEMA, the other one with the histoacryl/lipiodol mixture. In all patients, embolization was performed using the right retrograde transhepatic access. Embolization was technically successful in all 18 patients, with no complication related to the embolization agent. Eight patients of either group developed FLR hypertrophy allowing extended right hepatectomy. Likewise, one patient in each group had recanalization of a portal vein branch. Histology showed that both embolization agents reach the periphery of portal vein branches, with PHEMA penetrating somewhat deeper into the periphery. PHEMA has been shown to be an agent suitable for embolization in the portal venous system comparable with existing embolization agent (histoacryl/lipiodol mixture).
- MeSH
- enbukrylát farmakologie terapeutické užití MeSH
- ethjodizovaný olej farmakologie terapeutické užití MeSH
- hepatektomie metody MeSH
- játra účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- polyhydroxyethylmethakrylát farmakologie terapeutické užití MeSH
- senioři MeSH
- terapeutická embolizace metody MeSH
- vena portae účinky léků MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- enbukrylát MeSH
- ethjodizovaný olej MeSH
- polyhydroxyethylmethakrylát MeSH
Hyperlipidemia treatment based on niacin requires gastrointestinal administration of relatively high doses. The recommended dietary allowance of niacin as vitamin B3 is 14 to 16 mg daily in adults, while the doses of niacin used in the treatment of hyperlipidemia are generally in the range of 1 to 3 g. Administration of such large doses requires a high concentration of the active compound in the tablet and proper control of the drug release. In this study, a hydrogel matrix based on poly(2-hydroxyethyl methacrylate) and polyvinylpyrrolidone was investigated as delivery vehicle for controlled NA release into the gastrointestinal environment. The prepared hydrogel matrices varied in used monomer and crosslinker types and concentrations. The content of NA in tablets was between 65-80 %. The release profiles of NA from tablets were examined under three different pH values (1, 4.5 and 6.8) over the time period of 30 h. The effects of the monomer ratio, the crosslinking of the polymer network, and the solubility of niacin during drug release under various pH are discussed. The results showed that the release time period can be achieved in a relatively wide range of time and can be adjusted according to the medical requirements.
- MeSH
- gastrointestinální trakt * MeSH
- hydrogely MeSH
- hyperlipidemie farmakoterapie MeSH
- hypolipidemika aplikace a dávkování terapeutické užití MeSH
- lékové transportní systémy MeSH
- léky s prodlouženým účinkem MeSH
- methakryláty MeSH
- niacin aplikace a dávkování terapeutické užití MeSH
- nosiče léků MeSH
- povidon MeSH
- reagencia zkříženě vázaná MeSH
- rozpustnost MeSH
- tablety MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hydrogely MeSH
- hydroxyethyl methacrylate MeSH Prohlížeč
- hypolipidemika MeSH
- léky s prodlouženým účinkem MeSH
- methakryláty MeSH
- niacin MeSH
- nosiče léků MeSH
- povidon MeSH
- reagencia zkříženě vázaná MeSH
- tablety MeSH
3D microscopy and image analysis provide reliable measurements of length, branching, density, tortuosity and orientation of tubular structures in biological samples. We present a survey of methods for analysis of large samples by measurement of local differences in geometrical characteristics. The methods are demonstrated on the structure of the capillary bed in a rat brain.
- MeSH
- arteriae cerebrales cytologie MeSH
- fluorescenční mikroskopie metody MeSH
- interpretace obrazu počítačem metody MeSH
- kapiláry cytologie MeSH
- konfokální mikroskopie metody MeSH
- krysa rodu Rattus MeSH
- vylepšení obrazu metody MeSH
- zobrazování trojrozměrné metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
INTRODUCTION: The aim of our study was to compare keratometry and central corneal thickness measurements obtained with three different ophthalmic devices and to decide if they can be used interchangeably in clinical practice. METHODS: 43 healthy persons were included in the study (29 women and 14 men, average age 25 ± 3.5 years). Central corneal thickness (CCT) was measured with the Scheimpflug HR imaging system (Pentacam), Allegro BioGraph and with ultrasound pachymetry (RXP OcuScan). Keratometry in two main meridians of the cornea (K1, K2) was measured with Pentacam, Allegro BioGraph and automated keratometry. RESULTS: The mean difference in K1-readings was 0.01 ± 0.31 D for BioGraph vs. automated keratometry, 0.06 ± 0.23 D for BioGraph vs. Pentacam and 0.05 ± 0.34 D for automated keratometry and Pentacam. The mean difference in K2-readings was 0.29 ± 0.45 D for BioGraph vs. automated keratometry, 0.11 ± 0.28 D for BioGraph vs. Pentacam and 0.19 ± 0.44 D for automated keratometry and Pentacam. The interdevice differences were in all cases statistically significant (p < 0.05). The mean difference in CCT was 4.57 ± 7.84 μm for BioGraph vs. ultrasound, 4.33 ± 7.55 μm for BioGraph vs. Pentacam and 8.90 ± 7.49 μm for ultrasound vs. Pentacam. The interdevice differences in CCT were also statistically significant (p < 0.05). CONCLUSION: Our results suggest that the measurements of keratometry and CCT may differ significantly between the tested machines and therefore should not be used interchangeably in clinical practice.
- MeSH
- dospělí MeSH
- fotografování MeSH
- interferometrie MeSH
- lidé MeSH
- pachymetrie rohovky metody MeSH
- rohovka diagnostické zobrazování MeSH
- rohovková topografie MeSH
- ultrasonografie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Crohns disease is a complex chronic inflammatory disease of the gastrointestinal tract with multifactorial pathogenesis. Over the recent years, there has been rather a sharp increase in the incidence of Crohn's disease and, even though this disease had been known for some time, the cause remains unknown. Studies exploring genetic basis of Crohn's disease have provided new knowledge of the pathogenesis of this disease, suggesting that this may be associated with a failure of mechanisms behind symbiosis of gut microflora and intestinal mucosal immune system. Crohn's disease seems to be caused by inadequate immune response to intestinal flora in genetically predisposed individuals. Crohn's disease has been linked to a number of genes. Many of them are related to the modulation of non-specific immune response, defects of which are considered to be key in Crohn's disease pathogenesis. The aim of this review paper is to summarize the new knowledge on the pathogenesis of Crohn's disease at the level of polymorphisms of the NOD2, ATG16L1 genes and the IL23-Th17-lymfocytes signalling pathway genes and to consider further research directions in this disease.
- MeSH
- Crohnova nemoc etiologie genetika patofyziologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
Human CMV infects between 50-85% of healthy individuals and can cause live-threatening infections in immunocompromised patients. Therefore, peptide vaccination is being developed as a promising immunotherapeutic approach for treatment of patients at risk of CMV disease. The enzymatically inactive toxoid of Bordetella adenylate cyclase (CyaA-AC(-)) was shown to be an efficient tool for delivery of peptide epitopes and stimulation of Ag-specific T-cell immune responses. We investigated here the capacity of two CyaA-AC(-) constructs to deliver epitopes derived from the CMV phosphoprotein pp65 for activation of human T cells in vitro. Expansion of γ-IFN-secreting CMV-specific CD8(+) T cells, as well as increase of total IFN-γ and TNF-α production by PBMCs from CMV-seropositive donors were observed after in vitro stimulation with CyaA-AC(-) constructs carrying CMV epitopes, whereas limited activation of immune response occurred with free peptides. The activation of immune response was confirmed by expansion of CMV-specific T-cell clones and anti-CMV cytotoxic effect of stimulated PBMCs. These data open the way to clinical evaluation of CyaA-AC(-) constructs as tools for detection and expansion of CMV-specific T-cell immune responses for diagnostic and immunotherapeutic applications against CMV-associated diseases.
- MeSH
- adenylátcyklasy genetika imunologie MeSH
- aktivace lymfocytů MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- Cytomegalovirus imunologie MeSH
- epitopy T-lymfocytární imunologie MeSH
- fosfoproteiny imunologie MeSH
- lidé MeSH
- peptidové fragmenty genetika imunologie MeSH
- proteiny virové matrix imunologie MeSH
- sekvence aminokyselin MeSH
- vakcíny proti cytomegalovirové infekci genetika imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenylátcyklasy MeSH
- cytomegalovirus matrix protein 65kDa MeSH Prohlížeč
- epitopy T-lymfocytární MeSH
- fosfoproteiny MeSH
- peptidové fragmenty MeSH
- proteiny virové matrix MeSH
- vakcíny proti cytomegalovirové infekci MeSH
Multiple sclerosis (MS) is characterized by autoimmune attack leading to demyelination of the white matter in the central nervous system with devastating clinical consequences. Several immune-mediated destruction mechanisms were previously proposed including different T-cell subsets but complex view on immune system function in patients with MS is missing. In the present study, T-lymphocyte populations and pro-inflammatory as well as suppressive cytokine profiles were evaluated in detail in previously untreated patients with relapsing-remitting MS (RRMS). CD4(+) and CD8(+) naïve, central memory (Tcm), effector memory (Tem), terminal effector memory (Ttem), CD4(+) regulatory T-cells (Treg) and CD8(+) T-suppressor cells (Ts) were analysed using flow cytometry, and levels of ten plasma cytokines were determined using fluorescent bead-based immunoassay. We evaluated two groups of RRMS with minor (n=33) and major (n=25) clinical impairment and compared them with healthy controls (n=40) in order to detect any correlation between severity of MS clinical symptoms and immune disturbances. Significant differences were noted in CD4(+)CD45RA(+)CCR7(+) naïve T-cells, CD4(+)CD45RO(+)CCR7(-) and CD8(+)CD45RO(+)CCR7(-) Tem cells, while no differences were recognized in Tcm, Ttem, Treg and Ts cells in RRMS patients. Nine out of ten studied cytokines were disturbed in plasma samples of patients with RRMS. In conclusion, we demonstrate complex immune dysbalances in untreated MS patients.
- MeSH
- cytokiny krev MeSH
- dospělí MeSH
- imunofenotypizace metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- počet lymfocytů metody statistika a číselné údaje MeSH
- relabující-remitující roztroušená skleróza diagnóza imunologie metabolismus patofyziologie MeSH
- stupeň závažnosti nemoci MeSH
- T-lymfocyty fyziologie MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
Ozone depletion leads to an increase in UV rays of solar radiation reaching the surface of the Earth which is harmful to biological systems. Of the eye, the cornea is directly open to increased amount of UV rays of which mainly UVB rays are capable to induce reactive oxygen species damaging the cells. Previous studies showed that the irradiation of the cornea with UVB rays leads to morphological as well as metabolic disturbances of the cornea. Also, corneal hydration and corneal light absorption are increased after UVB rays. These changes were observed after five days of repeated irradiation of the cornea with UVB rays. The aim of the present paper was to examine how early the changes of corneal hydration and light absorption occur after UVB irradiation. The rabbit corneas were irradiated with UVB rays for one, two, three or four days. Corneal light absorption was examined spectrophotometrically and corneal hydration measured by pachymeter (as corneal thickness). Results show that changes of corneal hydration and light absorption appear early after UVB irradiation and increase along with the number of irradiations. In conclusion, irradiation of the rabbit cornea with UVB rays leads to harmful changes of its optical properties.
- MeSH
- absorpce MeSH
- časové faktory MeSH
- experimentální radiační poranění etiologie metabolismus patologie MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- rohovka metabolismus patologie účinky záření MeSH
- spektrofotometrie * MeSH
- světlo MeSH
- tělesná voda metabolismus MeSH
- ultrafialové záření škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
