Migration Stimulating Factor (MSF) is a 70 kDa truncated isoform of fibronectin (FN); its mRNA is generated from the FN gene by an unusual two-stage processing. Unlike full-length FN, MSF is not a matrix molecule but a soluble protein which displays cytokine-like activities not displayed by any other FN isoform due to steric hindrance. There are two isoforms of MSF; these are referred to as MSF+aa and MSF-aa, while the term MSF is used to include both.MSF was first identified as a motogen secreted by foetal and cancer-associated fibroblasts in tissue culture. It is also produced by sprouting (angiogenic) endothelial cells, tumour cells and activated macrophages. Keratinocytes and resting endothelial cells secrete inhibitors of MSF that have been identified as NGAL and IGFBP-7, respectively. MSF+aa and MSF-aa show distinct functionality in that only MSF+aa is inhibited by NGAL.MSF is present in 70-80% of all tumours examined, expressed by the tumour cells as well as by fibroblasts, endothelial cells and macrophages in the tumour microenvironment (TME). High MSF expression is associated with tumour progression and poor prognosis in all tumours examined, including breast carcinomas, non-small cell lung cancer (NSCLC), salivary gland tumours (SGT) and oral squamous cell carcinomas (OSCC). Epithelial and stromal MSF carry independent prognostic value. MSF is also expressed systemically in cancer patients, being detected in serum and produced by fibroblast from distal uninvolved skin. MSF-aa is the main isoform associated with cancer, whereas MSF+aa may be expressed by both normal and malignant tissues.The expression of MSF is not invariant; it may be switched on and off in a reversible manner, which requires precise interactions between soluble factors present in the TME and the extracellular matrix in contact with the cells. MSF expression in fibroblasts may be switched on by a transient exposure to several molecules, including TGFβ1 and MSF itself, indicating an auto-inductive capacity.Acting by both paracrine and autocrine mechanisms, MSF stimulates cell migration/invasion, induces angiogenesis and cell differentiation and alters the matrix and cellular composition of the TME. MSF is also a survival factor for sprouting endothelial cells. IGD tri- and tetra-peptides mimic the motogenic and angiogenic activities of MSF, with both molecules inhibiting AKT activity and requiring αvβ3 functionality. MSF is active at unprecedently low concentrations in a manner which is target cell specific. Thus, different bioactive motifs and extracellular matrix requirements apply to fibroblasts, endothelial cells and tumour cells. Unlike other motogenic and angiogenic factors, MSF does not affect cell proliferation but it stimulates tumour growth through its angiogenic effect and downstream mechanisms.The epithelial-stromal pattern of expression and range of bioactivities displayed puts MSF in the unique position of potentially promoting tumour progression from both the "seed" and the "soil" perspectives.

• Klíčová slova
• Angiogenesis, Cancer-associated fibroblasts (CAF), Cell migration, Fibronectin isoforms, IGD peptides, IGFBP-7, Macrophages, Migration Stimulating Factor (MSF), NGAL, Oncofoetal protein, Prognostic factor, Sprouting (angiogenic) endothelial cells, TGFβ1, Tumour cells, Tumour microenvironment (TME),
• MeSH
• cytokiny MeSH
• endoteliální buňky MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory plic * MeSH
• nemalobuněčný karcinom plic * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny MeSH

OBJECTIVES: To compare peri-partal parameters between two groups of pregnant women - with and without gestational diabetes mellitus (GDM), to correlate degree of glucose abnormality with incidence of peri-partal morbidity and, finally, to analyse the potential effect of comorbidities (i.e. obesity, hypertension, thyreopathy, polycystic ovary syndrome, trombophylia, anemia, allergy, smoking) on pregnancy outcomes. DESIGN: Epidemiological observational "case-control" study. SETTING: Department of Obstetric and Gynaecology, Faculty Hospital Brno; Department of Internal Medicine, Diabetes Centre, Faculty Hospital Brno; Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno. METHODS: The study comprised 432 pregnant women (364 with GDM diagnosis, 68 healthy controls) followed during a period 2011-2013. GDM was diagnosed by oral glucose tolerance test in 24-28th week of gestation (by fasting plasma glucose >5,6 mmol/l or >8,8 mmol/l in 60th min or >7,8 mmol/l in 120th min post-75g glucose load). Following peri-partal parameters were studied: ultrasonographic examination before delivery, a date of delivery, length of childbirth, induction, perinatal complications, post-delivery complications, section, abnormity in pH, base excess, Apgar score, birth weight. RESULTS: Subjects with GDM had significantly increased rate of labour induction compared to healthy controls (P = 0.0035, chi-square test). Subgroup of GDM women classified as having a higher risk for adverse perinatal outcomes by a definition of Czech Obstetric and Gynaecology Society had significantly more labour inductions, more sections and instrumental deliveries. New-borns of those mothers had significantly more common worse perinatal outcomes (Apgar score and macrosomia). CONCLUSION: Based on our data risk stratification of GDM subjects according to Czech Obstetric and Gynaecology Society appears relevant and justified.

• Klíčová slova
• gestational diabetes mellitus, impaired glucose tolerance perinatal morbidity., pregnancy,
• MeSH
• alergie epidemiologie   MeSH
• anemie epidemiologie   MeSH
• Apgar skóre MeSH
• císařský řez statistika a číselné údaje   MeSH
• dospělí MeSH
• gestační diabetes epidemiologie   metabolismus   MeSH
• glukózový toleranční test MeSH
• hypertenze epidemiologie   MeSH
• indukovaný porod statistika a číselné údaje   MeSH
• komorbidita MeSH
• komplikace těhotenství epidemiologie   MeSH
• kouření epidemiologie   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• nemoci štítné žlázy epidemiologie   MeSH
• novorozenec MeSH
• obezita epidemiologie   MeSH
• porodní děj MeSH
• porodní hmotnost * MeSH
• pozornost MeSH
• studie případů a kontrol MeSH
• syndrom polycystických ovarií epidemiologie   MeSH
• těhotenství MeSH
• trombofilie epidemiologie   MeSH
• vedení porodu MeSH
• výsledek těhotenství epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• krevní glukóza MeSH

Evidence has recently indicated that the MRAS and HNF1A genetic polymorphisms are associated with coronary artery disease. The MRAS and HNF1A genes are located on chromosomes 3q and 12q within the regions where associations with diabetes and diabetic nephropathy occur. We thus performed genetic and functional analyses of these two genes to evaluate their impacts on diabetes and diabetic nephropathy. MRAS and HNF1A genetic polymorphisms were genotyped in 1399 Czech subjects including non-diabetic controls (339), type 1 (243) and type 2 (817) diabetic patients with and without diabetic nephropathy using TaqMan allelic discrimination. Gene expression levels in the kidneys of diabetic Goto-Kakizaki and Wistar rats were detected with real-time RT-PCR. Despite no significance in genetic analysis of diabetic subjects, SNP rs2259816 in the HNF1A gene tended to associate with diabetic nephropathy in type 1 diabetic patients. The hnf1a gene expression was significantly decreased in kidney tissues of Goto-Kakizaki rats compared to Wistar and insulin-treated Goto-Kakizaki rats. There was neither significant association in the MRAS genetic polymorphism with diabetic nephropathy nor variation of mras gene expression in the kidneys of Goto-Kakizaki and Wistar rats. Data from the present study have not proved any significant association of the MRAS and HNF1A genetic polymorphisms with diabetes and diabetic nephropathy in a cohort of Czech population. However, the functional analysis and the trend in genetic analysis suggest that the HNF1A gene may have primary genetic impact on the development of diabetic nephropathy.

• MeSH
• diabetes mellitus genetika   MeSH
• diabetické nefropatie genetika   MeSH
• dospělí MeSH
• genotyp MeSH
• hepatocytární jaderný faktor 1-alfa genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• krysa rodu Rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• Ras proteiny genetika   MeSH
• senioři MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu Rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-alfa MeSH
• MRAS protein, human MeSH Prohlížeč
• Ras proteiny MeSH

The prevailing aerobic glycolysis (so called Warburg effect) in cancer cells is according to current understanding the consequence of reprogramming of cellular metabolism during the process of malignant transformation. Metabolic regulation is inseparable component of cell proliferation machinery and has a tight link with activities of oncogenes and suppressor genes. The purpose of metabolic reprogramming of cancer (but also normal intensively proliferating cells) is to incorporate greater fraction of glucose metabolites into newly synthesised macromolecules. Apart from that, aerobic glycolysis confers several other selective advantages to cancer cells. Epidemiological data indicate that type 2 diabetes mellitus is associated with increased incidence of several types of cancer and that cancer mortality can be influenced by certain types of anti-diabetic treatment, however future research is needed to explain whether this relationship might be causal. Deeper knowledge about metabolic properties of rapidly proliferating cells can be exploited for further improvement of anti-cancer, immunosuppressive or anti-inflammatory therapies.

• MeSH
• diabetes mellitus 2. typu komplikace   metabolismus   patofyziologie   MeSH
• glykolýza MeSH
• lidé MeSH
• nádory etiologie   metabolismus   patofyziologie   MeSH
• onkogeny fyziologie   MeSH
• proliferace buněk MeSH
• rizikové faktory MeSH
• signální transdukce MeSH
• tumor supresorové geny fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• celogenomová asociační studie MeSH
• diabetes mellitus 2. typu diagnóza   genetika   MeSH
• genetická predispozice k nemoci MeSH
• genotyp * MeSH
• lidé MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH

The Receptor for Advanced Glycation End-products (RAGE) belongs to the family of pattern-recognition receptors and is significantly involved in the molecular mechanisms mediating pro-inflammatory action of hyperglycemia in diabetes. The aim of the current study was to elucidate the possible functional impact of the genetic variability in the AGER gene constituting previously identified risk haplotype for diabetic nephropathy (-429C/-374T/2184G) by testing the haplotype-specific effect on the AGER gene transcriptional activity IN VITRO. Promotor and intron 8 constructs carrying respective substitutions were amplified and cloned into pGL3-Basic reporter vector and subsequently used for transfection of HEK293 cells. Following 48hrs incubation in either normo- (5 mM/L) or hyperglycemic (25 mM/L) culture medium luciferase activity was measured to assess transcriptional efficiency. Risk haplotype was associated with the highest transcriptional activity in hyperglycemia and greatest relative increase of activity between normo- and hyperglycemia conditions (approx. 3-times). We conclude that ascertained functional differences in the regulatory regions of the AGER gene might have significant consequences for the development of hyperglycemia-related pathology in diabetics.

• MeSH
• alely MeSH
• analýza rozptylu MeSH
• buněčné linie MeSH
• diabetické nefropatie genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genotyp MeSH
• haplotypy genetika   MeSH
• kultivované buňky MeSH
• lidé MeSH
• promotorové oblasti (genetika) genetika   MeSH
• receptor pro konečné produkty pokročilé glykace MeSH
• receptory imunologické genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptor pro konečné produkty pokročilé glykace MeSH
• receptory imunologické MeSH

The aim of the study was to investigate relationship between activity of superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor alpha (TNFalpha) and between Ala-9Val polymorphism in the gene encoding MnSOD (SOD2) and the initial stage and prognosis of the head and neck squamous cell carcinoma (HNSCC). Prospective study cohort comprised 88 patients who underwent surgical treatment for the diagnosis of HNSCC (53 patients were diagnosed with locoregional metastatic spread (N+) at the time of diagnosis). After the initial surgery subjects were followed for the subsequent period of 26 months during which 14 manifested relapse. Genotypes were detected by the PCR-based methodology. Activity of p-SOD, ery-SOD and TNFalpha were determined by ELISA, and the concentration of MDA by high performance liquid chromatography. Genotype and allele frequencies of the Ala-9Val differed neither between groups defined according to the stage of primary disease (TNM), nor between relapse vs. remission groups after the follow-up (p>0.05). Activity of p-SOD was significantly higher in T3/4 stage compared to T1/2 (p=0.01) and was also higher in N+ compared to N0 patients (p=0.002). Carriers of the Ala/Ala genotype had higher p-SOD activity (p=0.04). There was no significant difference in DFI between SOD2 genotype groups (p>0.05), however, the Ala/Ala group exhibited the shortest median DFI. In conclusion, our results suggest that increased p-SOD at the time of the initial treatment for HNSCC is connected with greater extent and nodal metastatic spread of the initial disease and with an earlier relapse of the disease. Progression of the disease might be further modified by the presence of Ala/Ala genotype of the SOD2. Activity of p-SOD could thus offer diagnostic as well as prognostic value.

• MeSH
• dospělí MeSH
• erytrocyty enzymologie   MeSH
• genotyp MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru enzymologie   genetika   patologie   MeSH
• lymfatické metastázy patologie   MeSH
• malondialdehyd metabolismus   MeSH
• míra přežití MeSH
• nádory hlavy a krku enzymologie   genetika   patologie   MeSH
• oxidační stres MeSH
• polymorfismus genetický MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom enzymologie   genetika   sekundární   MeSH
• staging nádorů MeSH
• superoxiddismutasa krev   genetika   metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• malondialdehyd MeSH
• superoxiddismutasa MeSH
• superoxide dismutase 2 MeSH Prohlížeč

AIMS/HYPOTHESIS: In the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits: single- and multi-locus analyses. MATERIALS AND METHODS: The study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCR-based methodology (PCR only, PCR plus RFLP, or allele-specific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis. RESULTS: After correction for multiple comparisons, only one SNP, in the gene encoding the receptor of advanced glycation end products, AGER 2184A/G (gene symbol formerly known as RAGE) showed a significant association with DN (p = 0.0006) in single-locus analysis. In multi-locus analysis, six SNPs exhibited a significant association with DN: four SNPs on chromosome 6p (AGER 2184A/G, LTA 252A/G, EDN1 8002G/A and AGER -429T/C) and two SNPs on chromosome 7q (NOS3 774C/T and NOS3 E298D), omnibus p = 0.033. Haplotype analysis revealed significant differences between DN and control groups in haplotype frequencies on chromosome 6 (p = 0.0002); however, there were no significant difference in the frequencies of the NOS3 haplotypes on chromosome 7. Logistic regression analysis identified SNPs AGER 2184A/G and NOS3 774C/T, together with diabetes duration and HbA1c, as significant predictors of DN. Testing for interactions between SNPs on chromosomes 6 and 7 did not provide significant evidence for epistatic interaction. CONCLUSIONS/INTERPRETATION: Using the set-association approach we identified significant associations of several SNPs on chromosomes 6 and 7 with DN. The single- and multi-locus analyses represent complementary methods.

• MeSH
• Bayesova věta MeSH
• diabetické nefropatie epidemiologie   genetika   MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 6 * MeSH
• lidské chromozomy, pár 7 * MeSH
• mapování chromozomů MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický MeSH
• referenční hodnoty MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Iron is an essential element to all living organisms. It is a component of many proteins with important functions in physiological processes such as oxygen transport, respiration, DNA synthesis, cell cycle regulation and many others. Free iron is highly reactive and its excess can lead to tissue and organ damage. Intestinal absorption of iron is precisely regulated because there is no excretory mechanism for excessive iron. Improved methodology led to the identification of many genes and proteins involved in the iron metabolism and to the understanding of basic processes of iron intake, transport and storage. However, some aspects remain still unclear--primarily the regulation of iron intake according to the body's requirements. Disorders of iron metabolism, both the deficiency and the overload belong to relatively common diseases. Growing understanding of the physiology of the iron metabolism is rapidly reflected in diagnostics, preventive screening and therapy of the iron disorders.

• MeSH
• lidé MeSH
• poruchy metabolismu železa * MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• železo MeSH

Late diabetic complications due to vascular and extravascular impairments develop as a consequence of chronic diabetes mellitus. Extent of affection reflects disease duration and therapeutic compensation; however, other modulating factors are involved. Due to growing incidence and permanent shift to younger age diabetes represents serious health problem. T2DM develops in consequence of "dysadaptation" of human genome to rapidly changing environment and life style. Primary prevention of diabetes is rather limited at present, secondary prevention or minimalization of late consequences is practically achievable. Full understanding of pathogenesis and identification of high-risk diabetic subjects will help to upgrade therapeutical options and improve patient's prognosis. This review devoted to late diabetic complications will summarize recent findings about proximal hyperglycaemia-induced alterations leading to common pathogenic action - inhibition of glycolysis on the level of GAPDH due to increased ratio NADH/NAD+, generation of superoxide and intracellular accumulation of dicarbonyls. Activated expression of series of genes leads to tissue remodelation responsible for organ manifestation. Subsequent article will deal with putative genetic susceptibility to their development.

• MeSH
• diabetes mellitus metabolismus   MeSH
• glukosa metabolismus   MeSH
• hyperglykemie komplikace   metabolismus   MeSH
• komplikace diabetu metabolismus   prevence a kontrola   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• glukosa MeSH