INTRODUCTION: Periostin is a matricellular protein. Elevated serum concentrations of periostin have been reported in patients with various cardiovascular diseases, including heart failure. Patients with end-stage renal disease have a substantially increased risk for cardiovascular diseases. However, there is a lack of clinical studies to clarify the prognostic significance of systemic periostin on all-cause mortality in patients with end-stage renal disease on hemodialysis. METHODS: 313 stable end-stage renal disease patients were recruited and followed for 5 years concerning all-cause mortality. At baseline, we collected blood samples and clinical data. Serum periostin concentrations were measured using a certified ELISA. RESULTS: The optimal cut-off value for serum periostin regarding all-cause mortality, calculated through receiver operating characteristic analysis, was 777.5 pmol/L. Kaplan-Meier survival analysis using this cut-off value demonstrated that higher periostin concentrations are linked to higher all-cause mortality (log-rank test: p = 0.002). Subgroup analysis revealed that serum periostin concentrations only affected all-cause mortality in male but not in female patients (p = 0.002 in male patients and p = 0.474 in female patients). Multivariate Cox regression analyses, adjusted for confounding factors, likewise showed that elevated serum periostin concentrations were positively associated with all-cause mortality in male (p = 0.028) but not in female patients on hemodialysis (p = 0.313). CONCLUSION: Baseline serum periostin is an independent risk factor for all-cause mortality in male patients with chronic renal disease on hemodialysis.

• MeSH
• biologické markery krev   MeSH
• chronické selhání ledvin * terapie   mortalita   krev   komplikace   MeSH
• dialýza ledvin * MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekuly buněčné adheze * krev   MeSH
• periostin MeSH
• příčina smrti trendy   MeSH
• prognóza MeSH
• rizikové faktory MeSH
• ROC křivka MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Acute myeloid leukemia (AML) cells are highly resistant to chemotherapeutic drugs. Cytokines and adhesion molecules may contribute to this resistance and affect treatment outcome. The aim of this study was to evaluate the independence and additional prognostic information of baseline serum levels of selected cytokines and soluble adhesion molecules, included in analyses with standard prognostic indicators. METHODS: We used biochip array technology to measure levels of selected cytokines and soluble adhesion molecules in serum samples of 80 newly diagnosed AML patients. The markers of tumour microenvironment were analysed against high risk karyotype, hyperleucocytosis, higher age, lactic dehydrogenase levels and presence of FLT3-ITD and NPM-1 mutation. RESULTS: All evaluated analytes were independent of standard prognostic indicators. Fifteen were associated with overall and eight with progression-free survival in univariate analysis. After correction for multiple testing, we identified soluble interleukin-2 receptor-α as an independent indicator of overall survival. Further, the soluble type I TNF-α receptor was close to statistical significance for both overall and progression-free survival. CONCLUSIONS: Baseline levels of soluble interleukin-2 receptor-α predict overall survival in newly diagnosed AML. The TNF-α type I soluble receptor is a candidate prognostic marker in AML and is worth of further investigation.

• MeSH
• akutní myeloidní leukemie krev   genetika   mortalita   MeSH
• cytokiny krev   MeSH
• doba přežití bez progrese choroby MeSH
• interleukin-2 krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekuly buněčné adheze krev   MeSH
• mutace genetika   MeSH
• nádorové mikroprostředí fyziologie   MeSH
• prognóza MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Introduction: The prognosis of multiple myeloma is still unfavorable due to inherent characteristics of the disease and the often-delayed diagnosis due to widespread and unspecific symptoms such as back pain and fatigue. Therefore, a simple diagnostic blood test would be helpful to speed up the diagnostic procedure in such patients (pts.). Here, we evaluated the diagnostic value of plasma levels of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in the peripheral blood and bone marrow of pts. with plasma cell disorders and in healthy controls. Materials and Methods: Immunoreactive CEACAM6 was determined in the peripheral blood and bone marrow (n = 95/100) of pts. with monoclonal gammopathy of unknown significance (MGUS: 28/37), newly diagnosed multiple myeloma (NDMM: 42/40), and relapsed/refractory multiple myeloma (RRMM: 25/23) by sandwich ELISA. Results: Median CEACAM6 levels in the peripheral blood of pts. with plasma cell disorders were significantly higher than those of healthy controls (healthy controls: 15.2 pg/ml (12.1-17.1); MGUS: 19.0 pg/ml (16.4-22.5); NDMM: 18.0 pg/ml (13.4-21.2); and RRMM: 18.9 pg/ml (15.2-21.5); p < 0.001). Plasma levels of CEACAM6 discriminated healthy subjects from MGUS/NDMM pts. (AUC = 0.71, 95% CI: 0.6-0.8); i.e., a CEACAM6 level > 17.3 pg/ml has an 82% (95% CI: 70-90) predictive probability for the identification of MGUS or NDMM. Moreover, CEACAM6 levels in the bone marrow were significantly higher in RRMM pts. than in NDMM pts. (p = 0.04), suggesting a role of this molecule in disease progression. Conclusion: CEACAM6 plasma levels can noninvasively identify pts. with a plasma cell disorder and should be evaluated prospectively as a potential diagnostic marker. Moreover, due to high CEACAM6 levels in the bone marrow in RRMM pts., this adhesion molecule might be a therapeutic target in multiple myeloma pts.

• MeSH
• CD antigeny krev   metabolismus   MeSH
• GPI-vázané proteiny krev   metabolismus   MeSH
• kostní dřeň metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom krev   MeSH
• molekuly buněčné adheze krev   metabolismus   MeSH
• nádorové biomarkery krev   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: In phase 2 trials, lebrikizumab, an anti-interleukin-13 monoclonal antibody, reduced exacerbation rates and improved FEV1 in patients with uncontrolled asthma, particularly in those with high concentrations of type 2 biomarkers (eg, periostin or blood eosinophils). We undertook replicate phase 3 studies to assess the efficacy and safety of lebrikizumab in patients with uncontrolled asthma despite inhaled corticosteroids and at least one second controller medication. METHODS: Adult patients with uncontrolled asthma, pre-bronchodilator FEV1 40-80% predicted, and stable background therapy were randomly assigned (1:1:1) with an interactive voice-web-based response system to receive lebrikizumab 37·5 mg or 125 mg, or placebo subcutaneously, once every 4 weeks. Randomisation was stratified by screening serum periostin concentration, history of asthma exacerbations within the last 12 months, baseline asthma medications, and country. The primary efficacy endpoint was the rate of asthma exacerbations over 52 weeks in biomarker-high patients (periostin ≥50 ng/mL or blood eosinophils ≥300 cells per μL), analysed with a Poisson regression model corrected for overdispersion with Pearson χ2 that included terms for treatment group, number of asthma exacerbations within the 12 months before study entry, baseline asthma medications, geographic region, screening periostin concentration, and blood eosinophil counts as covariates. Both trials are registered at ClinicalTrials.gov, LAVOLTA I, number NCT01867125, and LAVOLTA II, number NCT01868061. FINDINGS: 1081 patients were treated in LAVOLTA I and 1067 patients in LAVOLTA II. Over 52 weeks, lebrikizumab reduced exacerbation rates in biomarker-high patients in the 37·5 mg dose group (rate ratio [RR] 0·49 [95% CI 0·34-0·69], p<0·0001) and in the 125 mg dose group (RR 0·70 [0·51-0·95], p=0·0232) versus placebo in LAVOLTA I. Exacerbation rates were also reduced in biomarker-high patients in both dose groups versus placebo in LAVOLTA II (37·5 mg: RR 0·74 [95% CI 0·54-1·01], p=0·0609; 125 mg: RR 0·74 [0·54-1·02], p=0·0626). Pooling both studies, the proportion of patients who experienced treatment-emergent adverse events (79% [1125 of 1432 patients] for both lebrikizumab doses vs 80% [576 of 716 patients] for placebo), serious adverse events (8% [115 patients] for both lebrikizumab doses vs 9% [65 patients] for placebo), and adverse events leading to study drug discontinuation (3% [49 patients] for both lebrikizumab doses vs 4% [31 patients] for placebo) were similar between lebrikizumab and placebo. The following serious adverse events were reported in the placebo-controlled period: one event of aplastic anaemia and five serious adverse events related to raised concentrations of eosinophils in patients treated with lebrikizumab and one event of eosinophilic pneumonia in the placebo group. INTERPRETATION: Lebrikizumab did not consistently show significant reduction in asthma exacerbations in biomarker-high patients. However, it blocked interleukin-13 as evidenced by the effect on interleukin-13-related pharmacodynamic biomarkers, and clinically relevant changes could not be ruled out. FUNDING: F Hoffmann-La Roche.

• MeSH
• antiastmatika aplikace a dávkování   MeSH
• biologické markery krev   MeSH
• bronchiální astma krev   farmakoterapie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• eozinofily účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekuly buněčné adheze krev   MeSH
• monoklonální protilátky aplikace a dávkování   MeSH
• počet leukocytů MeSH
• progrese nemoci MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

AIM: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients with newly diagnosed acute myeloid leukemia (AML) using biochip array technology. We searched for links between baseline levels and age, hyperleukocytosis, secondary origin of AML, resistance to induction therapy with cytarabine and daunorubicin and standard risk stratification according to cytogenetics and molecular genetics. METHODS: We evaluated the sera of 51 consecutive patients. Serum samples were analyzed by biochip based immunoassays on the Evidence Investigator analyzer. T-tests were used for statistical analysis. RESULTS: We found that higher age is associated with lower levels of interleukin (IL)-12. Patients with secondary disease were older, had higher levels of EGF and IL-7, and lower levels of E-selectin, IL-12 and IL-13. In hyperleukocytosis, the levels of IL-1β, IL-2, TNF-α, VCAM-1, ICAM-1, -E-selectin and L-selectin were increased, whereas levels of IFN-γ and MCP-1 were decreased. In patients who failed to achieve complete remission after induction therapy, we found lower E-selectin and P-selectin levels. High risk patients had lower levels of IFN-γ. CONCLUSION: Some leukemic cell subpopulations have the ability to produce cytokines that modulate the microenvironment by inducing inflammation. This causes endothelial cells to be activated and overexpress adhesion molecules. Hyperleukocytosis and secondary origin of the disease are the major factors influencing the cytokine and adhesion molecule profile in newly diagnosed AML patients.

• MeSH
• akutní myeloidní leukemie krev   farmakoterapie   genetika   patologie   MeSH
• chemorezistence MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekuly buněčné adheze krev   MeSH
• mutace MeSH
• senioři MeSH
• translokace genetická MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIM: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients with newly diagnosed acute myeloid leukemia (AML) and in healthy subjects using biochip array technology. METHODS: A total of 15 AML patients and 15 healthy subjects (blood donors) were studied. Serum samples were analyzed by biochip based immunoassays on the Evidence Investigator analyzer. This approach allows multi-analytical determination from a single sample. T-tests were used for statistical analysis. RESULTS: In newly diagnosed AML patients, we found significant increase (p < 0.01) in serum VCAM-1, ICAM-1, E-selectin, L-selectin, and significant increase (p < 0.05) in serum IL-6, IL-8. No significant differences were found in the levels of other evaluated cytokines and adhesion molecules. CONCLUSION: Our results indicate that serum levels of specific cytokines and adhesion molecules (VCAM-1, ICAM-1, E-selectin, L-selectin, IL-6, IL-8) are significantly altered in patients with newly diagnosed AML, showing activity of the disease. Whether these alterations could serve as a prognostic marker for AML is not known. Further studies will be needed to define the potential role of these and additional markers in the risk stratification of AML.

• MeSH
• akutní myeloidní leukemie krev   genetika   patologie   MeSH
• cévní buněčněadhezivní molekula-1 krev   MeSH
• čipová analýza proteinů metody   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• E-selektin krev   MeSH
• interleukin-6 krev   MeSH
• interleukin-8 krev   MeSH
• L-selektin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezibuněčná adhezivní molekula-1 krev   MeSH
• molekuly buněčné adheze krev   MeSH
• nádorové biomarkery krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Diabetes mellitus is associated with increased inflammatory response, which may contribute to atherosclerosis progression. Experimental results demonstrated anti-inflammatory activity of glitazones; their effect on leukocyte adhesion molecules has not been studied to date. We therefore studied the effect of rosiglitazone treatment on leukocyte surface expression of adhesion molecules in patients with type 2 diabetes mellitus and compared our results with findings in healthy subjects. 33 subjects with type 2 diabetes and 32 healthy controls were included; patients were examined at baseline and after 5 months of rosiglitazone treatment (4 mg/d). Leukocyte expression of adhesion molecules LFA-1, CD18 and ICAM-1 was quantified using flow cytometry; in addition, CD14 (lipopolysaccharide receptor) expression was analyzed as a marker of nonspecific immunity. The expression of examined molecules at baseline was higher in patients compared to controls. Despite only mild decrease in blood glucose, rosiglitazone treatment induced substantial decrease of CD18 and CD14 expression and borderline decrease of LFA-1 and ICAM-1 expression (on monocytes only). We thus observed improvement in the expression of leukocyte inflammatory markers after rosiglitazone treatment. This effect is supposed to be mediated by direct effect of rosiglitazone on PPAR-gamma receptors on leukocytes.

• MeSH
• antigeny CD14 krev   MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu krev   farmakoterapie   imunologie   MeSH
• down regulace MeSH
• hypoglykemika terapeutické užití   MeSH
• krevní glukóza účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• molekuly buněčné adheze krev   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• thiazolidindiony terapeutické užití   MeSH
• výsledek terapie 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

Advanced glycation end-products (AGEs) are key players in pathogenesis of long-term vascular diabetes complications. Several enzymes such as fructosamine 3-kinase (FN3K) and glyoxalase I (GLO I) are crucial in preventing glycation processes. The aim of our study was to evaluate an association of FN3K (rs1056534, rs3848403) and GLO1 rs4746 polymorphisms with parameters of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in 595 diabetic and non-diabetic subjects. Genotypic and allelic frequencies of mentioned polymorphisms did not differ between subgroups. In diabetic patients significant differences were observed in sRAGE concentrations according to their rs1056534 and rs3848403 genotype. While GG and CG genotypes of rs1056534 with mutated G allele were associated with significant decrease of sRAGE (GG: 1055+/-458 and CG: 983+/-363 vs. CC: 1796+/-987 ng/l, p<0.0001), in rs3848403 polymorphism TT genotype with mutated T allele was related with significant sRAGE increase (TT: 1365+/-852 vs. CT: 1016+/-401 and CC: 1087+/-508 ng/l, p=0.05). Significant differences in adhesion molecules were observed in genotype subgroups of GLO1 rs4746 polymorphism. In conclusion, this is the first study describing significant relationship of FN3K (rs1056534) and (rs3848403) polymorphisms with concentration of sRAGE in patients with diabetes.

• MeSH
• biologické markery krev   MeSH
• diabetes mellitus 1. typu krev   diagnóza   enzymologie   genetika   MeSH
• diabetes mellitus 2. typu krev   diagnóza   enzymologie   genetika   MeSH
• dospělí MeSH
• fenotyp MeSH
• fosfotransferasy s alkoholovou skupinou jako akceptorem genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• laktoylglutathionlyasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• molekuly buněčné adheze krev   MeSH
• polymorfismus genetický * MeSH
• receptory imunologické krev   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients treated for acute myeloid leukemia (AML) using biochip array technology. This approach allows multi-analytical determination from a single sample. METHODS: A total of 15 AML patients were studied. Blood samples were taken at the diagnosis (active leukemia) and at circa 6 months after completion of last chemotherapy (durable complete remission in all patients). RESULTS: Comparing cytokine and adhesion molecule levels in active leukemia and in durable complete remission, we found significant increase (P<0.01) in serum interleukin-7 (IL-7), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and significant decrease (P<0.01) in serum E-selectin. DISCUSSION: Our results indicate that serum levels of specific cytokines and adhesion molecules (IL-7, EGF, VEGF, E-selectin) are significantly altered in patients treated for AML, reflecting activity of the disease. Further investigation is needed to establish if the changes observed in the levels of these molecules could be used as a prognostic indicator of AML.

• MeSH
• akutní myeloidní leukemie krev   farmakoterapie   MeSH
• čipová analýza proteinů MeSH
• cytokiny krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekuly buněčné adheze krev   MeSH
• pilotní projekty MeSH
• vaskulární endoteliální růstový faktor A MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIM: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients with acute lymphoblastic leukemia (ALL) and in healthy subjects using biochip array technology. This approach allows multi-analytical determination from a single sample. METHODS: A total of 15 ALL patients and 15 healthy subjects (blood donors) were studied. Serum samples were analyzed by biochip based immunoassays on the Evidence Investigator analyzer. T-tests were used for statistical analysis. RESULTS: Comparing cytokine and adhesion molecule levels in ALL patients and in healthy subject, we found significant increase in serum VCAM-1 (p < 0.000001), ICAM-1 (p < 0.0001), L-selectin (p < 0.0001), IL-8 (p < 0.001), MCP-1 (p < 0.01), and significant decrease (p < 0.01) in serum IL-3 and IL-4. CONCLUSION: Our results indicate that serum levels of specific cytokines and adhesion molecules (VCAM-1, ICAM-1, L-selectin, IL-8, IL-3, IL-4, MCP-1) are significantly altered in patients with newly diagnosed ALL, reflecting acti-vity of the disease. Further investigation is needed to establish if these alterations could be used as a prognostic indicator for ALL.

• MeSH
• akutní lymfatická leukemie krev   MeSH
• čipová analýza proteinů metody   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• molekuly buněčné adheze krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH