Background: The hippocampus, entorhinal cortex (EC), and basal forebrain (BF) are among the earliest regions affected by Alzheimer's disease (AD) pathology. They play an essential role in spatial pattern separation, a process critical for accurate discrimination between similar locations. Objective: We examined differences in spatial pattern separation performance between older adults with amnestic mild cognitive impairment (aMCI) with AD versus those with non-Alzheimer's pathologic change (non-AD) and interrelations between volumes of the hippocampal, EC subregions and BF nuclei projecting to these subregions (medial septal nuclei and vertical limb of the diagonal band of Broca - Ch1-2 nuclei) with respect to performance. Methods: Hundred and eighteen older adults were recruited from the Czech Brain Aging Study. Participants with AD aMCI (n = 37), non-AD aMCI (n = 26), mild AD dementia (n = 26), and cognitively normal older adults (CN; n = 29) underwent spatial pattern separation testing, cognitive assessment and brain magnetic resonance imaging. Results: The AD aMCI group had less accurate spatial pattern separation performance than the non-AD aMCI (p = 0.039) and CN (p < 0.001) groups. The AD aMCI and non-AD groups did not differ in other cognitive tests. Decreased BF Ch1-2 volume was indirectly associated with worse performance through reduced hippocampal tail volume and reduced posteromedial EC and hippocampal tail or body volumes operating in serial. Conclusion: The study demonstrates that spatial pattern separation testing differentiates AD biomarker positive and negative older adults with aMCI and provides evidence that BF Ch1-2 nuclei influence spatial pattern separation through the posteromedial EC and the posterior hippocampus.

• Publikační typ
• časopisecké články MeSH

Cílem studie bylo zjistit expresi galektinu-3 (gal3), cytokeratinu 19 (CK19), neural cell adhesion molecule (NCAM) a E-cadherinu (Ecad) v nádorech štítné žlázy s folikulárními rysy, se zřetelem na jejich využití v diferenciální diagnostice. Soubor tvořilo 139 případů – 87 folikulárních adenomů (FA), 26 folikulárních karcinomů (FC) a 26 případů folikulární varianty papilárního karcinomu (FVPC). Gal3 byl exprimován v 29/87 (33%) FA, v 13/26 (50%) FC a v 24/26 (92%) FVPC. CK19 byl ex- primován v 11/87 (13%) FA, v 4/26 (15%) FC a v 17/26 (65%) FVPC. Exprese NCAM byla zastižena v 60/87 (69%) FA, v 20/26 (77%) FC a v 7/26 (27%) FVPC. Ecad byl exprimován v 81/87 (93%) FA, v 22/26 (85%) FC a v 17/26 (65%) FVPC. Senzitivita a specificita pro diagnózu maligního nádoru byly u gal3 0,70 a 0,85, u CK19 0,48 a 0,97, u NCAM 0,28 a 0,47 a u Ecad 0,48 a 0,20. V expresi všech markerů byl nalezen signifikantní rozdíl (p < 0,05) mezi FVPC versus FA a FC, naopak signifikantní rozdíl me- zi FA a FC prokázán nebyl. Detekci gal3 a CK19 je možné doporučit jako pomocné kritérium v di- ferenciální diagnostice FVPC versus FA a FC.

The aim of the study was to evaluate the expression of galectin-3 (gal3), cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin (Ecad) in thyroid gland tumors with follicular growth pattern with particular focus on their use in differential diagnosis. A series of 139 cases – 87 follicular adenomas (FAs), 26 follicular carcinomas (FCs), and 26 cases of the follicular variant of papillary carcinoma (FVPC) was studied. Expression of gal3 was found in 29/87 (33%) of FAs, in 13/26 (50%) of FCs, and in 24/26 (92%) of FVPCs. Expression of CK19 was found in 11/87 (13%) of FAs, in 4/26 (15%) of FCs, and in 17/26 (65%) of FVPCs. Expression of NCAM was found in 60/87 (69%) of FAs, in 20/26 (77%) of FCs, and in 7/26 (27%) FVPCs. Expression of Ecad was found in 81/87 (93%) of FAs, in 22/26 (85%) of FCs, and in 17/26 (65%) of FVPCs. The sensitivity and specificity of gal3 for malignancy were 0.70 and 0.85, of CK19 0.48 and 0.98, of NCAM 0.28 and 0.47, and of Ecad 0.48 and 0.20, respectively. A significant difference (p < 0.05) in expression of all studied markers between FVPC versus FA and FC was found, in contrast to FA and FC. Therefore, the use of gal3 and CK19 in differential diagnosis of FVPC versus FA and FC can be recommended.

• MeSH
• diferenciální diagnóza MeSH
• folikulární adenokarcinom imunologie   patologie   MeSH
• folikulární papilární karcinom imunologie   patologie   MeSH
• galektiny MeSH
• imunohistochemie metody   statistika a číselné údaje   využití   MeSH
• kadheriny MeSH
• keratiny MeSH
• lidé MeSH
• molekula buněčné adheze nervové L1 MeSH
• nádorové biomarkery MeSH
• nádory štítné žlázy etiologie   patologie   MeSH
• testy funkce štítné žlázy MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

• Publikační typ
• abstrakt z konference MeSH

Clinical behavior of neuroblastoma (NBL) is remarkably heterogeneous, as it ranges from spontaneous regression to aggressive clinical phenotype and death. There is increasing body of evidence demonstrating that microRNAs could be considered the potential biomarkers for clinical applications in NBL. In this report, we focus on molecular characterization of high-risk as well as low-risk and intermediate-risk NBL cases in the context of the microRNA expression profile that is specific for the given risk category of the disease. We investigated a total of 30 NBL patients, out of whom there were 19 patients with low- to intermediate-risk and 11 with high-risk NBLs as defined by the Clinical Oncology Group. We determined the expression profiles of 754 microRNAs (miRNAs), whereas the miRNA expression levels were normalized to RNU44, mean expression levels were calculated, and data were analyzed by use of the microarray biostatistical approaches. We identified the signature of 38 miRNAs differentially expressed between these groups of NBL patients (P < 0.05): 17 miRNAs were upregulated and 21 miRNAs were downregulated in the tumors of high-risk NBL patients. We confirm some of the previous observations and we report several new microRNAs associated with aggressive NBL, both being relevant subjects for further translational validation and functional studies.

• MeSH
• kojenec MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• nádorové biomarkery genetika   MeSH
• neuroblastom genetika   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

For a comprehensive overview of the genetic alterations of neuroblastoma, their association and clinical significance, we conducted a whole-genome DNA copy number analysis. PATIENTS AND METHODS: A series of 493 neuroblastoma (NB) samples was investigated by array-based comparative genomic hybridization in two consecutive steps (224, then 269 patients). RESULTS: Genomic analysis identified several types of profiles. Tumors presenting exclusively whole-chromosome copy number variations were associated with excellent survival. No disease-related death was observed in this group. In contrast, tumors with any type of segmental chromosome alterations characterized patients with a high risk of relapse. Patients with both numerical and segmental abnormalities clearly shared the higher risk of relapse of segmental-only patients. In a multivariate analysis, taking into account the genomic profile, but also previously described individual genetic and clinical markers with prognostic significance, the presence of segmental alterations with (HR, 7.3; 95% CI, 3.7 to 14.5; P < .001) or without MYCN amplification (HR, 4.5; 95% CI, 2.4 to 8.4; P < .001) was the strongest predictor of relapse; the other significant variables were age older than 18 months (HR, 1.8; 95% CI, 1.2 to 2.8; P = .004) and stage 4 (HR, 1.8; 95% CI, 1.2 to 2.7; P = .005). Finally, within tumors showing segmental alterations, stage 4, age, MYCN amplification, 1p and 11q deletions, and 1q gain were independent predictors of decreased overall survival. CONCLUSION: The analysis of the overall genomic pattern, which probably unravels particular genomic instability mechanisms rather than the analysis of individual markers, is essential to predict relapse in NB patients. It adds critical prognostic information to conventional markers and should be included in future treatment stratification.

• MeSH
• amplifikace genu MeSH
• analýza přežití MeSH
• DNA nádorová genetika   MeSH
• financování organizované MeSH
• geny myc MeSH
• kojenec MeSH
• lidé MeSH
• multivariační analýza MeSH
• nádorové biomarkery MeSH
• následné studie MeSH
• nestabilita genomu MeSH
• neuroblastom genetika   patologie   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• Publikační typ
• multicentrická studie MeSH
• srovnávací studie MeSH

• MeSH
• CD8-pozitivní T-lymfocyty cytologie   imunologie   MeSH
• cytotoxické T-lymfocyty * MeSH
• exprese genu MeSH
• HIV infekce imunologie   MeSH
• HIV * imunologie   patogenita   MeSH
• inhibitory kontrolních bodů * analýza   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• poměr CD4 a CD8 lymfocytů MeSH
• průtoková cytometrie MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium. METHODS: A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test. RESULTS: We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls. CONCLUSIONS: We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status. IMPACT: The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis.

• MeSH
• cirkulující mikroRNA * MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádory hlavy a krku * diagnóza   genetika   MeSH
• průřezové studie MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Východiska: Dlaždicobuněčný karcinom ústní dutiny (oral squamous cell carcinoma – OSCC) je jedným z nejběžnějších nádorů ze skupin dlaždicobuněčných karcinomů hlavy a krku. Zvyšující se výskyt karcinomů ústní dutiny a jejich zjištění v pokročilých stadiích je celosvětovým zdravotním problémem. Stále více údajů svědčí o tom, že při růstu a progresi zhoubných nádorů hrají důležitou roli microRNA (miRNAs), zatímco o významu miR-7113-3p and miR-6721-5p v OSCC nejsou k dispozici žádné informace. Tento článek pojednává o zkoumání exprese MAP2K1, miR-7113-3p a miR-6721-5p pro možné biologické funkce při rozvoji dlaždicobuněčného karcinomu ústní dutiny. Materiál a metody: Pomocí kvantitativní polymerázové řetězové reakce v reálném čase jsme stanovili expresi mRNA u MAP2K1, miR-7113-3p a miR-6721-5p v čerstvě zmražených tkáních OSCC a v čerstvě zmražených přilehlých normálních tkáních 30 pacientů a zkoumali jsme jejich vztah ke klinickým parametrům. Výsledky: Exprese MAP2K1 v nádorové tkáni byla oproti normálním tkáním významně vyšší, zatímco exprese miR-7113-3p a miR-6721-5p byla významně nižší. Také byla pozorována statistická korelace p = 0,04 mezi zvýšenou expresí MAP2K1 a perineurální invazí. Navíc jsme zaznamenali, že mezi down-regulací miR-7113-3p a zvýšenou expresí MAP2K1 je pozitivní korelace (p = 0,0218) a mezi down-regulací miR-6721-5p a zvýšenou expresí MAP2K1 je negativní korelace (p = 0,7771). Závěr: Z těchto nálezů vyplývá, že u pacientů s OSCC mohou miR-7113-3p a miR-6721-5p sloužit jako prospektivní biomarkery, které by v budoucnu mohly být využívány k detekci OSCC v časném stadiu. Zvýšená exprese MAP2K1 je spojena s rozvojem OSCC a perineurální invazí.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the head and neck squamous cell cancer group. The increasing frequency of oral carcinomas and their late-stage appearance is a major worldwide health concern. MicroRNAs (miRNAs) appear to play an important role in cancer growth and progression, according to growing data, whereas no information is available regarding miR-7113-3p and miR-6721-5p involvement in OSCC. In this article, the expression of MAP2K1, miR-7113-3p, and miR-6721-5p was examined for possible biological functions in the advancement of oral squamous cell carcinoma. Material and methods: We used quantitative real-time PCR (to examine the mRNA expression of MAP2K1, miR-7113-3p, and miR-6721-5p in fresh frozen OSCC tissues and adjacent normal fresh frozen tissues from 30 patients, and we investigated their relationship with clinical parameters. Results: MAP2K1 expression was found to be dramatically increased in tumor tissues than in normal tissues, whereas miR7113-3p and miR-6721-5p expression was significantly decreased. Furthermore, a statistical correlation of P = 0.04 was also observed between increased MAP2K1 expression and perineural invasion. Additionally, we noted that the downregulation of miR-7113-3p appears to correlate positively with overexpression of MAP2K1 (P = 0.0218), and a negative correlation was observed between downregulation of miR-6721-5p and overexpression of MAP2K1 (P = 0.7771). Conclusion: Based on these findings, miR-7113-3p and miR-6721-5p might be prospective biomarkers for OSCC patients, and could be utilized to detect OSCC at an early stage for future diagnosis. MAP2K1 overexpression has been linked to the development of OSCC and perineural invasion.

• Klíčová slova
• miR-7113-3p, miR-6721-5p,
• MeSH
• dlaždicobuněčné karcinomy hlavy a krku * diagnostické zobrazování   genetika   MeSH
• kvantitativní polymerázová řetězová reakce metody   MeSH
• lidé MeSH
• MAP kinasa-kinasa 1 genetika   MeSH
• nádorové biomarkery analýza   MeSH
• stanovení celkové genové exprese klasifikace   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• klinická studie MeSH

• MeSH
• adenoidně cystický karcinom patologie   MeSH
• dějiny 16. století MeSH
• diferenciální diagnóza MeSH
• imunohistochemie MeSH
• karcinoid metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   ultrastruktura   MeSH
• nádorové biomarkery analýza   MeSH
• nádory kožních adnex patologie   MeSH
• nádory mazových žláz metabolismus   patologie   ultrastruktura   MeSH
• sebaceózní adenokarcinom metabolismus   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transmisní elektronová mikroskopie MeSH
• Check Tag
• dějiny 16. století MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

BACKGROUND: Prostate cancer (PCa) is a heterogeneous malignancy with high variability in clinical course. Insufficient stratification according to the aggressiveness at the time of diagnosis causes unnecessary or delayed treatment. Current stratification systems are not effective enough because they are based on clinical, surgical or biochemical parameters, but do not take into account molecular factors driving PCa cancerogenesis. MicroRNAs (miRNAs) are important players in molecular pathogenesis of PCa and could serve as valuable biomarkers for the assessment of disease aggressiveness and its prognosis. METHODS: In the study, in total, 280 PCa patients were enrolled. The miRNA expression profiles were analyzed in FFPE PCa tissue using the miRCURY LNA miRNA PCR System. The expression levels of candidate miRNAs were further verified by two-level validation using the RT-qPCR method and evaluated in relation to PCa stratification reflecting the disease aggressiveness. RESULTS: MiRNA profiling revealed 172 miRNAs dysregulated between aggressive (ISUP 3-5) and indolent PCa (ISUP 1) (p < 0.05). In the training and validation cohort, miR-15b-5p and miR-106b-5p were confirmed to be significantly upregulated in tissue of aggressive PCa when their level was associated with disease aggressiveness. Furthermore, we established a prognostic score combining the level of miR-15b-5p and miR-106b-5p with serum PSA level, which discriminated indolent PCa from an aggressive form with even higher analytical parameters (AUC being 0.9338 in the training set and 0.8014 in the validation set, respectively). The score was also associated with 5-year biochemical progression-free survival (bPFS) of PCa patients. CONCLUSIONS: We identified a miRNA expression pattern associated with disease aggressiveness in prostate cancer patients. These miRNAs may be of biological interest as the focus can be also set on their specific role within the molecular pathology and the molecular mechanism that underlies the aggressivity of prostate cancer.

• MeSH
• lidé MeSH
• mikro RNA * metabolismus   MeSH
• nádorové biomarkery genetika   MeSH
• nádory prostaty * patologie   MeSH
• polymerázová řetězová reakce MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH