• MeSH
• Central Nervous System MeSH
• Gene Expression MeSH
• Publication type
• Periodical MeSH

• Conspectus
• Obecná genetika. Obecná cytogenetika. Evoluce
• NML Fields
• genetika, lékařská genetika
• biologie

Cíl práce: Zhodnotit přítomnost exprese genů PAX5 a Shb ve tkáni povrchových uroteliálních karcinomů močového měchýře, posoudit její korelaci s patologií genu p53 a uvážit prognostický význam jednotlivých faktorů. Pacienti a metodika: Do studie bylo zahrnuto 61 pacientů s histologicky prokázaným povrchovým uroteliálním karcinomem močového měchýře. Exprese mRNA genů PAX5 a Shb ve tkáni nádoru byla detekována pomocí reverzní polymerázové řetězové reakce (RT-PCR) a výsledek byl vyjádřen semikvantitativně. Přítomnost mutací p53 byla zachycena pomocí SSCP (single strand conformation polymorphism) a potvrzena sekvenováním. K imunohistochemickému vyšetření p53 byla použita protilátka DO1, k vyjádření výsledku bylo použito semikvantitativní hodnocení pomocí HSCORE (HS). Kontrolní skupinu pro posouzení PAX5 a Shb exprese tvořilo 8 mužů, u kterých byl vzorek urotelu odebrán během operace pro benigní hyperplazií prostaty. Výsledky: Přítomnost exprese PAX5 a Shb byla prokázána u 50, respektive 52 pacientů s uroteliálním nádorem, ale u žádného z kontrolní skupiny. Mutace p53 byla zachycena u jediného pacienta s tumorem pTaG2 a byla lokalizována v exonu 5 (delece prolinu 128). Jaderná imunoreaktivita p53 byla přítomna u většiny pacientů, při použití prahové hodnoty HS 200 mělo 56,9 % nemocných pozitivní nález. Kvantita imunohistochemické pozitivity p53 nekorelovala s kvantitou exprese PAX5. Při použití prahových hodnot HS 200 pro p53 a 0,2 pro PAX5 mělo z 8 progredujících pacientů 7 nadprahovou hodnotu HS a 4 nadprahovou hodnotu PAX5. Závěr: Exprese genu PAX5 je častým nálezem u povrchových uroteliálních karcinomů močového měchýře.

The objective of the work: To evaluate the presence of the PAX5 and Shb genes expression in the tissue of superficial urotelial urinary bladder cancers, to judge its correlation with the p53 gene pathology and to consider the prognostic value of individual factors. Patients and Method: 61 patients with histologically proven superficial urotelial bladder cancer were included into the study. The mRNA expression of PAX5 and Shb genes in the cancer tissue was detected by the reverse polymerase chain reaction (RT- PCR) and the result was expressed semiquantitatively. The presence of p53 mutations was recorded by SSCP (single strand conformation polymorphism) and confirmed by sequening. The immunohistological examination of p53 was made by using DO1 antibody and the result was expressed using semiquantitative evaluation by HSCORE (HS). 8 men created the control group for PAX5 and Shb expression evaluation. Their urotel sample was withdrawn during the operation of benign prostate hyperplasia. Results: The presence of PAX5 and Shb expression was proven in 50, let us say in 52 patients with urotelial cancer, but it was not proven in anybody of the control group. p53 mutation was recorded in one patient with pTaG2 tumour and it was localised in 5 exon (proline 128 deletion). Nuclear immunoreactivity of p53 was present in the majority of patients, 56,9% of patients had positive finding using the threshold value HS 200. The quantity of p53 immunohistochemical positivity did not correlate with the quantity of PAX5 expression. Using the threshold values of HS 200 for p53 and 0,2 for PAX5 the 7 of 8 progressing patients had supra-threshold HS value and 4 of them had supra-threshold PAX5 value. Conclusion: The PAX5 gene expression is an often finding in superficial urotelial urinary bladder cancers.

• MeSH
• Research Support as Topic MeSH
• Genes, p53 genetics   MeSH
• Humans MeSH
• Mutation genetics   MeSH
• Urinary Bladder Neoplasms diagnosis   genetics   MeSH
• Gene Expression Profiling methods   utilization   MeSH
• Check Tag
• Humans 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
• Infant MeSH
• Humans MeSH
• MicroRNAs genetics   metabolism   MeSH
• Biomarkers, Tumor genetics   MeSH
• Neuroblastoma genetics   MeSH
• Prognosis MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Gene Expression Profiling MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Pattern-recognition receptors (PRRs) recognize pathogen-associated molecular patterns and play an important role in triggering innate immune responses. PRRs distribution and function is well documented in mice and humans, but studies in pigs are scarce. Salmonella enterica serovar Typhimurium is common pathogen found in pigs and was used as a model for interaction with PRRs. This study investigated expression of PRRs in porcine leukocyte subpopulations at the mRNA level. Eight subpopulations of leukocytes comprising NK cells, Th, Tc, double positive T cells and γδ T cells, B cells, monocytes and neutrophils were sorted, and the expression of 12 PRRs was measured, including selected Toll-like receptors and their co-receptors, NOD-like receptor NOD2, RP-105, CD14, and dectin. The highest expression rates of most PRRs were observed in monocytes and neutrophils. The B cells expressed high levels of TLR1, TLR6, TLR9, TLR10, and RP-105. Only monocytes and γδ T cells were found to respond to Salmonella enterica serovar Typhimurium infection by intensification of PRRs expression. In Th and B cells, PRRs mRNA down-regulation was detected after infection.

• MeSH
• Down-Regulation MeSH
• Leukocytes metabolism   microbiology   MeSH
• RNA, Messenger genetics   MeSH
• Neutrophils metabolism   MeSH
• Swine MeSH
• Immunity, Innate MeSH
• Receptors, Pattern Recognition genetics   metabolism   MeSH
• Gene Expression Regulation immunology   MeSH
• Salmonella typhimurium physiology   MeSH
• Salmonella Infections, Animal immunology   MeSH
• Serogroup MeSH
• T-Lymphocytes metabolism   MeSH
• Toll-Like Receptors genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: The blood flukes of genus Schistosoma are the causative agent of schistosomiasis, a parasitic disease that infects more than 200 million people worldwide. Proteases of schistosomes are involved in critical steps of host-parasite interactions and are promising therapeutic targets. We recently identified and characterized a group of S1 family Schistosoma mansoni serine proteases, including SmSP1 to SmSP5. Expression levels of some SmSPs in S. mansoni are low, and by standard genome sequencing technologies they are marginally detectable at the method threshold levels. Here, we report their spatial gene expression patterns in adult S. mansoni by the high-sensitivity localization assay. METHODOLOGY: Highly sensitive fluorescence in situ RNA hybridization (FISH) was modified and used for the localization of mRNAs encoding individual SmSP proteases (including low-expressed SmSPs) in tissues of adult worms. High sensitivity was obtained due to specifically prepared tissue and probes in combination with the employment of a signal amplification approach. The assay method was validated by detecting the expression patterns of a set of relevant reference genes including SmCB1, SmPOP, SmTSP-2, and Sm29 with localization formerly determined by other techniques. RESULTS: FISH analysis revealed interesting expression patterns of SmSPs distributed in multiple tissues of S. mansoni adults. The expression patterns of individual SmSPs were distinct but in part overlapping and were consistent with existing transcriptome sequencing data. The exception were genes with significantly low expression, which were also localized in tissues where they had not previously been detected by RNA sequencing methods. In general, SmSPs were found in various tissues including reproductive organs, parenchymal cells, esophagus, and the tegumental surface. CONCLUSIONS: The FISH-based assay provided spatial information about the expression of five SmSPs in adult S. mansoni females and males. This highly sensitive method allowed visualization of low-abundantly expressed genes that are below the detection limits of standard in situ hybridization or by RNA sequencing. Thus, this technical approach turned out to be suitable for sensitive localization studies and may also be applicable for other trematodes. The results suggest that SmSPs may play roles in diverse processes of the parasite. Certain SmSPs expressed at the surface may be involved in host-parasite interactions.

• MeSH
• Gene Expression * MeSH
• In Situ Hybridization, Fluorescence methods   standards   MeSH
• Helminth Proteins genetics   MeSH
• RNA metabolism   MeSH
• Schistosoma mansoni enzymology   genetics   MeSH
• Serine Proteases genetics   MeSH
• Gene Expression Profiling MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first-degree relatives or healthy controls. Our aim was to establish whether a distinct type of 'prodiabetogenic' gene expression pattern in the group of relatives of patients with T1D could be identified. Whole-genome expression profile of nine patients with T1D, their ten first-degree relatives and ten healthy controls was analysed using the human high-density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody-negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL-1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative's gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.

• MeSH
• Molecular Sequence Annotation MeSH
• Autoimmunity MeSH
• Autoantibodies biosynthesis   genetics   MeSH
• Antigens, CD genetics   immunology   MeSH
• Genome-Wide Association Study MeSH
• Diabetes Mellitus, Type 1 genetics   immunology   pathology   MeSH
• Child MeSH
• Adult MeSH
• Immunity, Humoral MeSH
• Interleukin-1 genetics   immunology   MeSH
• Infant MeSH
• Leukocytes, Mononuclear immunology   metabolism   pathology   MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Primary Cell Culture MeSH
• Immunity, Innate MeSH
• Receptors, CCR3 genetics   immunology   MeSH
• Gene Expression Regulation immunology   MeSH
• Family MeSH
• Signal Transduction MeSH
• Gene Expression Profiling MeSH
• Case-Control Studies MeSH
• Toll-Like Receptors genetics   immunology   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Identification of coordinately regulated genes according to the level of their expression during the time course of a process allows for discovering functional relationships among genes involved in the process. RESULTS: We present a single class classification method for the identification of genes of similar function from a gene expression time series. It is based on a parallel genetic algorithm which is a supervised computer learning method exploiting prior knowledge of gene function to identify unknown genes of similar function from expression data. The algorithm was tested with a set of randomly generated patterns; the results were compared with seven other classification algorithms including support vector machines. The algorithm avoids several problems associated with unsupervised clustering methods, and it shows better performance then the other algorithms. The algorithm was applied to the identification of secondary metabolite gene clusters of the antibiotic-producing eubacterium Streptomyces coelicolor. The algorithm also identified pathways associated with transport of the secondary metabolites out of the cell. We used the method for the prediction of the functional role of particular ORFs based on the expression data. CONCLUSION: Through analysis of a time series of gene expression, the algorithm identifies pathways which are directly or indirectly associated with genes of interest, and which are active during the time course of the experiment.

• MeSH
• Algorithms MeSH
• Chromosomes, Bacterial genetics   MeSH
• Financing, Organized MeSH
• Computer Simulation MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Gene Expression Profiling MeSH
• Streptomyces coelicolor genetics   classification   metabolism   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.

• Keywords
• miR-7113-3p, miR-6721-5p,
• MeSH
• Squamous Cell Carcinoma of Head and Neck * diagnostic imaging   genetics   MeSH
• Real-Time Polymerase Chain Reaction methods   MeSH
• Humans MeSH
• MAP Kinase Kinase 1 genetics   MeSH
• Biomarkers, Tumor analysis   MeSH
• Gene Expression Profiling classification   methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Study MeSH

When patterns are set during embryogenesis, it is expected that they are straightly established rather than subsequently modified. The patterning of the three mouse molars is, however, far from straight, likely as a result of mouse evolutionary history. The first-formed tooth signaling centers, called MS and R2, disappear before driving tooth formation and are thought to be vestiges of the premolars found in mouse ancestors. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report that broad activation of Edar expression precedes its spatial restriction to tooth signaling centers. This reveals a hidden two-step patterning process for tooth signaling centers, which was modeled with a single activator-inhibitor pair subject to reaction-diffusion (RD). The study of Edar expression also unveiled successive phases of signaling center formation, erasing, recovering, and fusion. Our model, in which R2 signaling center is not intrinsically defective but erased by the broad activation preceding M1 signaling center formation, predicted the surprising rescue of R2 in Edar mutant mice, where activation is reduced. The importance of this R2-M1 interaction was confirmed by ex vivo cultures showing that R2 is capable of forming a tooth. Finally, by introducing chemotaxis as a secondary process to RD, we recapitulated in silico different conditions in which R2 and M1 centers fuse or not. In conclusion, pattern formation in the mouse molar field relies on basic mechanisms whose dynamics produce embryonic patterns that are plastic objects rather than fixed end points.

• MeSH
• Models, Biological * MeSH
• Chemotaxis MeSH
• Epithelium embryology   metabolism   MeSH
• Mice, Mutant Strains MeSH
• Mice MeSH
• Edar Receptor genetics   metabolism   MeSH
• Body Patterning * MeSH
• Signal Transduction * MeSH
• Hair embryology   MeSH
• Gene Expression Regulation, Developmental MeSH
• Tooth Germ embryology   metabolism   MeSH
• Tooth embryology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Molecular Diagnostic Techniques MeSH
• Neoplasms * diagnosis   genetics   MeSH
• Gene Expression Profiling MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• molekulární biologie, molekulární medicína
• onkologie
• NML Publication type
• kolektivní monografie