Statins, besides being powerful cholesterol-lowering drugs, also exert potent anti-proliferative activities. However, their anti-cancer efficacy differs among the individual statins. Thus, the aim of this study was to identify the biological pathways affected by individual statins in an in vitro model of human pancreatic cancer. The study was performed on a human pancreatic cancer cell line MiaPaCa-2, exposed to all commercially available statins (12 μM, 24 h exposure). DNA microarray analysis was used to determine changes in the gene expression of treated cells. Intracellular concentrations of individual statins were measured by UPLC (ultra performance liquid chromatography)-HRMS (high resolution mass spectrometer). Large differences in the gene transcription profiles of pancreatic cancer cells exposed to various statins were observed; cerivastatin, pitavastatin, and simvastatin being the most efficient modulators of expression of genes involved namely in the mevalonate pathway, cell cycle regulation, DNA replication, apoptosis and cytoskeleton signaling. Marked differences in the intracellular concentrations of individual statins in pancreatic cancer cells were found (>11 times lower concentration of rosuvastatin compared to lovastatin), which may contribute to inter-individual variability in their anti-cancer effects. In conclusion, individual statins exert different gene expression modulating effects in treated pancreatic cancer cells. These effects may be partially caused by large differences in their bioavailability. We report large differences in gene transcription profiles of pancreatic cancer cells exposed to various statins. These data correlate to some extent with the intracellular concentrations of statins, and may explain the inter-individual variability in the anti-cancer effects of statins.

• MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Pancreatic Neoplasms genetics   metabolism   pathology   MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Gene Expression Profiling MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology   MeSH
• Transcriptome drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cell differentiation depends mainly on specific mRNA expression. To quantify the expression of a particular gene, the normalisation with respect to the expression of a reference gene is carried out. This is based on the assumption that the expression of the reference gene is constant during development, in different cells or tissues or after treatment. Xenopus laevis studies have frequently used eEF-1 alpha, GAPDH, ODC, L8, and H4 as reference genes. The aim of this work was to examine, by real-time RT-PCR, the expression profiles of the above-mentioned five reference genes during early development of X. laevis. It is shown that their expression profiles vary greatly during X. laevis development. The developmental changes of mRNA expression can thus significantly compromise the relative mRNA quantification based on these reference genes, when different developmental stages are to be compared. The normalisation against total RNA is recommended instead.

• MeSH
• Biomarkers analysis   MeSH
• Financing, Organized MeSH
• Gene Expression Profiling MeSH
• Genes, Developmental MeSH
• Xenopus laevis embryology   genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH

MicroRNAs (miRNAs), important regulators of cellular processes, show specific expression signatures in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation, indicating their role in the control of hematopoiesis. Because neonatal blood displays various features of immaturity, we might expect differential miRNA regulation. Herein, we determined miRNA expression profiles of umbilical cord blood (UCB) cell lineages and compared them to those of bone marrow (BM) and peripheral blood (PB) cell counterparts. Further, we determined mRNA expression profiles using whole-genome microarrays. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative targets of miRNAs with potential functions in UCB. We pointed out several differentially expressed miRNAs and associated their expression with the target transcript levels. miR-148a expression was suppressed in HSCs and its level inversely correlated with the previously verified target, DNA methyltransferase 3B, suggesting dependence of de novo DNA methylation in HSCs on miR-148a. Prolonged cell survival of UCB HSCs may be associated with low expression of miR-143 and miR-145 and up-regulation of their downstream targets (high expression of c-MYC and miR-17-92 and following repression of TGFBR2). In HSCs, we monitored significant up-regulation of eight miRNAs, which were previously verified as regulators of HOX genes. Further, miR-146b may be associated with immaturity of neonatal immune system because it is strongly up-regulated in UCB granulocytes and T lymphocytes compared to PB cell counterparts. Comparative analysis revealed 13 miRNAs significantly altered between UCB and BM CD34(+) cells. In UCB CD34(+) cells, we monitored up-regulation of miR-520h, promoting differentiation of HSCs into progenitor cells, and reduction of miR-214, whose expression might support HSC survival. In conclusion, UCB cells show specific miRNA expression patterns, indicating different regulation in these cells.

• MeSH
• Antigens, CD34 metabolism   MeSH
• Cell Lineage genetics   MeSH
• Adult MeSH
• Fetal Blood cytology   metabolism   MeSH
• Hematopoietic Stem Cells metabolism   MeSH
• Blood Cells metabolism   physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• MicroRNAs genetics   metabolism   MeSH
• Infant, Newborn MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Aged MeSH
• Cluster Analysis MeSH
• Gene Expression Profiling MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Validation Study MeSH

Cíl studie: Stanovit endometriální profi ly exprese mesengerové RNA (mRNA) vybraných matrixmetaloproteináz (MMP) a tkáňového inhibitoru metaloproteináz-1 (TIMP-1).Typ studie: Experimentální studie.Název a sídlo pracoviště: Gynekologicko-porodnická klinika, LF UP a FN Olomouc, Česká republika,Gynekologicko-porodnická klinika, Univerzitní nemocnice Lund, Švédsko.Metodika: Studovali jsme MMP-1, -3, -7, -10, -11, -12, -13, -14, -16, -26 a TIMP-1 mRNA ve 39 vzorcíchnormální endometriální tkáně získaných z různých fází menstruálního cyklu. Na základě histologickéhovyšetření byly vzorky klasifi kovány jako časná (n=8), střední (n=6) a pozdní (n=7) proliferace,časná (n=4), střední (n=4) a pozdní (n=8) sekrece a menstruální (n=3) fáze. Hladiny mRNAextrahované ze zmražených tkáňových vzorků byly kvantifi kovány pomocí real time PCR.Výsledky: Celkem byly zjištěny čtyři vzorce exprese MMP mRNA v průběhu menstruačního cyklu.MMP-1, -3, -10, a -12 byly exprimovány převážně v perimenstruálním období, MMP-7 a -11 mělynejvyšší hladiny v proliferační fázi, MMP-13, -14 a -16 byly exprimovány v průběhu celého cyklua MMP-26 měla maximum exprese v periovulatorním období. Hladiny TIMP-1 mRNA zůstávalynezměněny během cyklu.Závěr: Specifi cké profi ly endometriální exprese MMP v průběhu menstruačního cyklu ukazují najejich odlišný biologický význam v průběhu cyklu. MMP-26 vykazuje samostatný vzorec exprese.

Objective: To examine the endometrial expression pattern of messenger RNA (mRNA) for selectedmatrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases-1 (TIMP-1).Design: Experimental study.Setting: Department of Obstetrics and gynecology of the Palacky University Medical School andUniversity Hospital, Olomouc, Czech Republic, Department of Obsterics and Gynecology, UniversityHospital, Luna, Sweden.Methods: We studied MMP-1, -3, -7, -10, -11, -12, -13, -14, -16, -26 and TIMP-1 mRNA in 39 normalendometrial samples obtained across the menstrual cycle. Based on histological examination, allspecimens were classifi ed according to an ideal 28 day menstrual cycle as early (n=8), mid (n=6)and late (n=7) proliferative phase, early (n=4), mid (n=4) and late (n=8) secretory phase and menstrual(n=3) phase. mRNA extracted from frozen tissue samples was quantitated using real timePCR.Results: Four distinct patterns of MMP mRNA expression were detected in cycling endometrium.MMP-1, -3, -10, and -12 were expressed predominantly in perimenstrual period, MMP-7 and -11had highest levels in proliferative phase, MMP-13, -14 and -16 were expressed throughout thecycle and MMP-26 was found to be maximal in periovulatory period. Levels of TIMP-1 mRNAremained unchanged during the cycle.Conclusion: The specifi c endometrial expression profi les of MMPs during menstrual cycle pointto their specifi c biologic roles during the cycle. MMP-26 exhibits a unique expression pattern.

• MeSH
• Endometrium MeSH
• Gene Expression MeSH
• Genetic Techniques MeSH
• Humans MeSH
• Menstrual Cycle MeSH
• RNA, Messenger analysis   MeSH
• In Vitro Techniques MeSH
• Tissue Inhibitor of Metalloproteinase-1 genetics   MeSH
• Check Tag
• Humans MeSH

Adenosine triphosphate-binding cassette proteins constitute a large family of active transporters through extracellular and intracellular membranes. Increased drug efflux based on adenosine triphosphate-binding cassette protein activity is related to the development of cancer cell chemoresistance. Several articles have focused on adenosine triphosphate-binding cassette gene expression profiles (signatures), based on the expression of all 49 human adenosine triphosphate-binding cassette genes, in individual tumor types and reported connections to established clinicopathological features. The aim of this study was to test our theory about the existence of adenosine triphosphate-binding cassette gene expression profiles common to multiple types of tumors, which may modify tumor progression and provide clinically relevant information. Such general adenosine triphosphate-binding cassette profiles could constitute a new attribute of carcinogenesis. Our combined cohort consisted of tissues from 151 cancer patients-breast, colorectal, and pancreatic carcinomas. Standard protocols for RNA isolation and quantitative real-time polymerase chain reaction were followed. Gene expression data from individual tumor types as well as a merged tumor dataset were analyzed by bioinformatics tools. Several general adenosine triphosphate-binding cassette profiles, with differences in gene functions, were established and shown to have significant relations to clinicopathological features such as tumor size, histological grade, or clinical stage. Genes ABCC7, A3, A8, A12, and C8 prevailed among the most upregulated or downregulated ones. In conclusion, the results supported our theory about general adenosine triphosphate-binding cassette gene expression profiles and their importance for cancer on clinical as well as research levels. The presence of ABCC7 (official symbol CFTR) among the genes with key roles in the profiles supports the emerging evidence about its crucial role in various cancers. Graphical abstract.

• MeSH
• ATP-Binding Cassette Transporters biosynthesis   genetics   MeSH
• Carcinogenesis * MeSH
• Colorectal Neoplasms genetics   pathology   MeSH
• Humans MeSH
• Breast Neoplasms genetics   pathology   MeSH
• Pancreatic Neoplasms genetics   pathology   MeSH
• Cystic Fibrosis Transmembrane Conductance Regulator biosynthesis   genetics   MeSH
• Sulfonylurea Receptors biosynthesis   genetics   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Transcriptome genetics   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Methanosarcina barkeri (DSM 800) is a metabolically versatile methanogen and shows distinct metabolic status under different substrate regimes. However, the mechanisms underlying distinct transcriptional profiles under different substrate regimes remain elusive. In this study, based on transcriptional analysis, the growth performances and gene expressions of M. barkeri fed on acetate, H2 + CO2, and methanol, respectively, were investigated. M. barkeri showed higher growth performances under methanol, followed by H2 + CO2 and acetate, which corresponded well with the variations of gene expressions. The α diversity (evenness) of gene expressions was highest under the acetate regime, followed by H2 + CO2 and methanol, and significantly and negatively correlated with growth performances. The gene co-expression analysis showed that "Energy production and conversion," "Coenzyme transport and metabolism," and "Translation, ribosomal structure, and biogenesis" showed deterministic cooperation patterns of intra- and inter-functional classes. However, "Posttranslational modification, protein turnover, chaperones" showed exclusion with other functional classes. The gene expressions and especially the relationships among them potentially drove the shifts of metabolic status under different substrate regimes. Consequently, this study revealed the diversity-related ecological strategies that a high α diversity probably provided more fitness and tolerance under natural environments and oppositely a low α diversity strengthened some specific physiological functions, as well as the co-responses of gene expressions to different substrate regimes.

• MeSH
• RNA, Archaeal genetics   MeSH
• Euryarchaeota genetics   metabolism   MeSH
• Hydrogen-Ion Concentration MeSH
• Culture Media chemistry   MeSH
• Acetic Acid chemistry   MeSH
• Methanol chemistry   MeSH
• Methanosarcina barkeri genetics   metabolism   MeSH
• Carbon Dioxide chemistry   MeSH
• Gene Expression Regulation, Archaeal MeSH
• Sequence Analysis, RNA MeSH
• Substrate Specificity MeSH
• Transcriptome * MeSH
• Hydrogen chemistry   MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Astrocytoma is the most prevalent form of primary brain cancer categorized into four histological grades by the World Health Organization. Investigation into individual grades of astrocytoma by previous studies has provided some insight into dysregulation of regulatory networks associated with increasing astrocytoma grades. However, further understanding of key mechanisms that distinguish different astrocytoma grades is required to facilitate targeted therapies. METHODS: In this study, we utilized a large cohort of publicly available RNA sequencing data from patients with diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), primary glioblastoma (grade IV), secondary glioblastoma (grade IV), recurrent glioblastoma (grade IV), and normal brain samples to identify genetic similarities and differences between these grades using bioinformatics applications. RESULTS: Our analysis revealed a distinct gene expression pattern between grade II astrocytoma and grade IV glioblastoma (GBM). We also identified genes that were exclusively expressed in each of the astrocytoma grades. Furthermore, we identified known and novel genes involved in key pathways in our study. Gene set enrichment analysis revealed a distinct expression pattern of transcriptional regulators in primary GBM. Further investigation into molecular processes showed that the genes involved in cell proliferation and invasion were shared across all subtypes of astrocytoma. Also, the number of genes involved in metastasis, regulation of cell proliferation, and apoptosis increased with tumor grade. CONCLUSIONS: We confirmed existing findings and shed light on some important genes and molecular processes that will improve our understanding of glioma biology.

• MeSH
• Astrocytoma genetics   pathology   MeSH
• Molecular Targeted Therapy trends   MeSH
• Adult MeSH
• Glioblastoma genetics   pathology   MeSH
• Humans MeSH
• Brain pathology   MeSH
• Brain Neoplasms genetics   pathology   MeSH
• Cell Proliferation MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• Sequence Analysis, RNA MeSH
• Signal Transduction MeSH
• Gene Expression Profiling * MeSH
• Neoplasm Grading MeSH
• Transcriptome genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Myeloproliferative neoplasms (MPN), comprising essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are hematological disorders of the myeloid lineage characterized by hyperproliferation of mature blood cells. The prediction of the clinical course and progression remains difficult and new therapeutic modalities are required. We conducted a CD34+ gene expression study to identify signatures and potential biomarkers in the different MPN subtypes with the aim to improve treatment and prevent the transformation from the rather benign chronic state to a more malignant aggressive state. We report here on a systematic gene expression analysis (GEA) of CD34+ peripheral blood or bone marrow cells derived from 30 patients with MPN including all subtypes (ET (n = 6), PV (n = 11), PMF (n = 9), secondary MF (SMF; post-ET-/post-PV-MF; n = 4)) and six healthy donors. GEA revealed a variety of differentially regulated genes in the different MPN subtypes vs. controls, with a higher number in PMF/SMF (200/272 genes) than in ET/PV (132/121). PROGENγ analysis revealed significant induction of TNFα/NF-κB signaling (particularly in SMF) and reduction of estrogen signaling (PMF and SMF). Consistently, inflammatory GO terms were enriched in PMF/SMF, whereas RNA splicing-associated biological processes were downregulated in PMF. Differentially regulated genes that might be utilized as diagnostic/prognostic markers were identified, such as AREG, CYBB, DNTT, TIMD4, VCAM1, and S100 family members (S100A4/8/9/10/12). Additionally, 98 genes (including CLEC1B, CMTM5, CXCL8, DACH1, and RADX) were deregulated solely in SMF and may be used to predict progression from early to late stage MPN.

• MeSH
• Antigens, CD34 genetics   MeSH
• Thrombocythemia, Essential genetics   MeSH
• Humans MeSH
• Myeloproliferative Disorders genetics   MeSH
• Polycythemia Vera genetics   MeSH
• Primary Myelofibrosis genetics   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Transcriptome * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Kolorektální karcinom je jedním z nejčastěji se vyskytujících nádorových onemocnění. Bohužel, významná část pacientů v klinických stádiích II a III umírá do pěti let po radikálním chirurgickém zákroku následkem progrese onemocnění. Racionální přístup k indikaci adjuvantní léčby pro tyto pacienty nabízí molekulární charakterizace jejich rizika napfříč oběma klinickými stádii pomocí technologie DNA čipů. Do studie byly zařazeny bioptické vzorky dvanácti pacientů s histologicky potvrzeným kolorektálním karcinomem (KRK) v klinickém stádiu II a III tvořené minimálnu ze 70% maligními buňkami. Šest pacientů mělo dobrou prognózu s délkou bezpříznakového přežití (DFS) delší než 36 měsíců, Šest mělo špatnou prognózu s DFS kratším než 36 měsíců. Pomocí nízkohustotních oligonukleotidových makročipů společnosti SuperArray určených k relativní kvantifikaci exprese 128 genů potenciálně zapojených do procesu metastazování, byly identifikovány profily genové exprese primárních KRK všech 12 pacientů. Analýzou expresních profilů pomocí t-testu (á = 0,01) a metody SAM jsme identifikovali 10 genů rozdílnu exprimovaných (9 upregulovaných, 1 down-regulovaný) v primárních nádorech pacientů se špatnou prognózou. Naše výsledky nasvědčují, že technologie nízkohustotních oligonukleotidových makročipů je užitečnou pomůckou pro lep- ší pochopení molekulární podstaty progrese nádorového onemocnění a zlepšení predikce metastatického potenciálu primárních nádorů u pacientů s lokoregionálně pokročilým kolorektálním karcinomem.

Colorectal cancer (CRC) is one of the most common malignancies. Unfortunately, a significant proportion of surgically cured patients in the early stage of the disease develop progression and die from the disease. Twelve patients who had histologically confirmed left-sided colon adenocarcinoma with a volume fraction showing at least 70% of malignant tumor cells were included. Only stage II-III patients according to IUCC with no prior chemotherapy or radiotherapy were eligible for the study. Six patients were poor prognosis cases with disease free survival (DFS) lower then 36 month and six were good prognosis cases with DFS>36 month. Relative gene expression levels of 128 genes potentially involved in cancer progression and dissemination were obtained by low-density oligonucleotide microarrays (SuperArray Bioscience Corp., Bethesda, MD) from 12 primary colon cancer samples. Gene expression data analysis based on the SAM and ttest (á = 0, 01) methods identified 10 genes with significantly different expression in primary tumors of patients with poor prognosis. Our preliminary data suggest that oligonucleotide microarray technology should contribute to a better understanding of the progression of colorectal cancer, and facilitate prediction of their metastatic potential.

• MeSH
• DNA Fingerprinting methods   utilization   MeSH
• Gene Expression genetics   MeSH
• Financing, Organized MeSH
• Genetic Markers genetics   immunology   MeSH
• Colorectal Neoplasms diagnosis   etiology   genetics   MeSH
• Medical Oncology methods   trends   MeSH
• Humans MeSH
• Pilot Projects MeSH
• Reverse Transcriptase Polymerase Chain Reaction methods   utilization   MeSH
• Disease-Free Survival MeSH
• Prognosis MeSH
• Oligonucleotide Array Sequence Analysis methods   utilization   MeSH
• Neoplasm Staging methods   utilization   MeSH
• Check Tag
• Humans 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