BACKGROUND: Cytokines were shown both to enhance tumour growth and formation of metastases and to inhibit proliferation of tumour cells. TNF alpha may mediate apoptosis and necrosis of cancer cells, the exact role of IL-2 remains to be elucidated. Plasma levels of TNF alpha and TNF and IL-2 soluble receptors (sTNF-R, sIL-2R) should thus be in some relation to the biological characteristics of the breast cancer. METHODS AND RESULTS: Plasma levels of TNF alpha, sTNF-R I and II and sIL-2R were measured in 31 women with different stages of breast cancer both before the institution of the therapy and after 3 months of the treatment. Plasma levels of both types of sTNF-Rs were higher in patients with breast cancer than in controls (sTNF-R I-2166.6 +/- 568.9 VS. 1121.3 +/- 260.6 pg/ml, p < 0.001, sTNF-R II-3792.8 +/- 958.9 vs. 1996.2 +/- 404.3 pg/ml, p < 0.001) with no significant difference between clinical stages. Plasma levels of both sTNF-R (0.871, p < 0.001) and sIL-2R tightly correlated one with each other. Plasma levels of TNF alpha decreased after treatment (from 3.92 +/- 1.86 to 3.40 +/- 1.15 pg/ml, p < 0.001), but plasma levels of sTNF-Rs and sIL-2R were not influenced by the treatment. CONCLUSIONS: Plasma levels of soluble TNF receptors may thus serve as a non-specific marker of the untreated breast cancer. Their relation to other biologic characteristics of this tumour is not clear. It remains also to be clarified if the long-term treatment leads to the normalization of sTNF-Rs plasma levels.

• MeSH
• dospělí MeSH
• karcinom krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu krev   terapie   MeSH
• receptory interleukinu-2 krev   MeSH
• receptory TNF krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• TNF-alfa analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• receptory interleukinu-2 MeSH
• receptory TNF MeSH
• TNF-alfa MeSH

A comparison of effectiveness of TNF antagonists adalimumab, infliximab and etanercept in the treatment of rheumatoid arthritis (RA) was made, which was derived from studies provided abroad based on routine clinical practice. The calculation of cost-effectiveness of each TNF antagonist for Czech Republic was made on the basis of Dutch DREAM registry of patients with RA (Kiewit et al, 2008). The prices of therapy of all three TNF antagonists are similar in the first year of treatment of patients with average weight, in the second year the price of infliximab is lower, but only in the case of patients where the doses do not reach 4 amp. of infliximab. Clinical effectiveness was evaluated in DAS28 and HAQ units. Cost-effectiveness of all TNF antagonists was similar, when 2 amp. of infliximab per dose phycician considered sufficient, but when patients were given higher doses of infliximab the trend to lower cost-effectiveness of infliximab compared to adalimumab and etanercept was observed.

• MeSH
• adalimumab MeSH
• analýza nákladů a výnosů MeSH
• antirevmatika ekonomika   terapeutické užití   MeSH
• etanercept MeSH
• humanizované monoklonální protilátky MeSH
• imunoglobulin G ekonomika   terapeutické užití   MeSH
• infliximab MeSH
• lidé MeSH
• monoklonální protilátky ekonomika   terapeutické užití   MeSH
• receptory TNF terapeutické užití   MeSH
• revmatoidní artritida farmakoterapie   ekonomika   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• adalimumab MeSH
• antirevmatika MeSH
• etanercept MeSH
• humanizované monoklonální protilátky MeSH
• imunoglobulin G MeSH
• infliximab MeSH
• monoklonální protilátky MeSH
• receptory TNF MeSH
• TNF-alfa MeSH

BACKGROUND: TNF-alpha, IGF-I and leptin are agents which influence insulin resistance, they play probably a part in the pathogenesis of diabetic nephropathy and influence mutually their production. The objective of the submitted investigation was to assess whether there exist relations between their concentrations in the plasma of diabetic patients. METHODS AND RESULTS: The authors examined 37 patients aged 18-67 years from a diabetic clinic, 10 with normal albuminuria and normal renal function, 12 with microalbuminuria and 15 with macroalbuminuria and/or reduced renal function. TNF alpha, IGF-I and leptin were assessed in plasma, using commercial kits, by the ELISA method. IgF-I in plasma correlated inversely with glycated haemoglobin (r = -0.20, p < 0.05). In women a correlation was found between IGF-I and TNF-alpha concentrations (r = 0.65, p < 0.01). No other mutual correlations were found between concentrations of the investigated substances and between cytokine concentrations and serum creatinine, glycated haemoglobin, the blood glucose level and body mass index. CONCLUSIONS: IGF-I plasma levels correlate inversely with glycated haemoglobin and in women with the TNF-alpha level. No other correlations were found between IGF-I. TNF-alpha and leptin plasma levels. The levels do not correlate with age, renal function and compensation of diabetes.

• MeSH
• diabetes mellitus krev   MeSH
• dospělí MeSH
• insulinu podobný růstový faktor I analýza   MeSH
• inzulinová rezistence MeSH
• leptin analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• TNF-alfa analýza   MeSH
• tuková tkáň MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• insulinu podobný růstový faktor I MeSH
• leptin MeSH
• TNF-alfa MeSH

OBJECTIVE: To determine serum levels of TNF-alpha (tumor necrosis factor alpha) as a prediction of endometriosis. DESIGN: Prospective clinical case control study. SETTING: Department of Obstetrics and Gynaecology and Department of Pathology, Jessenius Faculty Hospital, Kollarova 2, Martin, Slovakia. METHODS: The serum TNF-alpha was determined in women who underwent laparoscopy or laparotomy due to pelvic pain, infertility, dysmenorea or pelvic tumor. Endometriosis was confirmed histologically and classified by rAFS. RESULTS: On the basis of entering criteria 65 women were enrolled in this study. In 61 cases serum level of TNF-alpha was evaluated. The average serum level of TNF-alpha in the endometriotic group was 73.847 pg/ml (n=30) and without endometriosis was 21.089 pg/ml (n=31). We have found a significant statistical difference between the above mentioned groups in the medium levels of TNF-alpha (p<0.0001). We did not find statistical significance between TNF-alpha levels and in the group of women with endometriosis in relation to the stage of the disease (I.-II., III.-IV., adenomyosis). At a cut-off level of TNF-alpha 30 pg/ml there was a 63.33% sensitivity, 77.42% specificity, a positive prediction value 73.07%, and 68.57% of negative predictive value. CONCLUSION: TNF-alpha serum levels are good diagnostic markers of endometriosis in the spectrum of noninvasive methods.

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• endometrióza krev   diagnóza   MeSH
• lidé MeSH
• senzitivita a specificita MeSH
• TNF-alfa analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• TNF-alfa MeSH

INTRODUCTION: Inflammation is a very important part of innate immunity and is regulated in many steps. One such regulating step is the cytokine network, where tumor necrosis factor α (TNF-α) plays one of the most important roles. METHODS: A PubMed and Web of Science databases search was performed for studies providing evidences on the role of TNF-α in inflammation, apoptosis, and cancer. RESULTS AND CONCLUSION: This review concisely summarizes the role of this pro-inflammatory cytokine during inflammation. It is focused mainly on TNF-α intracellular signaling and its influence on the typical inflammatory features in the organism. Being one of the most important pro-inflammatory cytokines, TNF-α participates in vasodilatation and edema formation, and leukocyte adhesion to epithelium through expression of adhesion molecules; it regulates blood coagulation, contributes to oxidative stress in sites of inflammation, and indirectly induces fever. The connection between TNF-α and cancer is mentioned as well.

• MeSH
• lidé MeSH
• receptory TNF imunologie   MeSH
• TNF-alfa imunologie   MeSH
• zánět imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• receptory TNF MeSH
• TNF-alfa MeSH

BACKGROUND AND AIMS: Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA]. METHODS: Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab. RESULTS: We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test. CONCLUSIONS: Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.

• Klíčová slova
• Crohn’s disease, IBD, anti-TNF, children, metabolomics, microbiome,
• MeSH
• Bacteria MeSH
• Crohnova nemoc * patologie   MeSH
• dítě MeSH
• infliximab farmakologie   terapeutické užití   MeSH
• inhibitory TNF farmakologie   terapeutické užití   MeSH
• lidé MeSH
• metabolom MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• infliximab MeSH
• inhibitory TNF MeSH

OBJECTIVES: Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis. METHODS: Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as ≥1 swollen joint at baseline (=TNFi start). RESULTS: Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis. CONCLUSION: This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy.

• Klíčová slova
• MTX, SSZ, TNF inhibitors, ankylosing, epidemiology, spondylitis,
• MeSH
• antirevmatika * terapeutické užití   MeSH
• axiální spondyloartritida * MeSH
• inhibitory TNF terapeutické užití   MeSH
• lidé MeSH
• spondylartritida * farmakoterapie   MeSH
• TNF-alfa MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antirevmatika * MeSH
• inhibitory TNF MeSH
• TNF-alfa MeSH

Crohn's disease (CD) and ulcerative colitis (UC) are two forms of inflammatory bowel disease (IBD), where the role of gut but not skin dysbiosis is well recognized. Inhibitors of TNF have been successful in IBD treatment, but up to a quarter of patients suffer from unpredictable skin adverse events (SkAE). For this purpose, we analyzed temporal dynamics of skin microbiota and serum markers of inflammation and epithelial barrier integrity during anti-TNF therapy and SkAE manifestation in IBD patients. We observed that the skin microbiota signature of IBD patients differs markedly from healthy subjects. In particular, the skin microbiota of CD patients differs significantly from that of UC patients and healthy subjects, mainly in the retroauricular crease. In addition, we showed that anti-TNF-related SkAE are associated with specific shifts in skin microbiota profile and with a decrease in serum levels of L-FABP and I-FABP in IBD patients. For the first time, we showed that shifts in microbial composition in IBD patients are not limited to the gut and that skin microbiota and serum markers of the epithelium barrier may be suitable markers of SkAE during anti-TNF therapy.

• Klíčová slova
• 16S RNA sequencing, IBD, TNF-alpha antagonist, serum biomarker, skin adverse events, skin microbiota,
• MeSH
• biologické markery MeSH
• Crohnova nemoc * MeSH
• idiopatické střevní záněty * farmakoterapie   MeSH
• inhibitory TNF MeSH
• lidé MeSH
• mikrobiota * MeSH
• ulcerózní kolitida * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• inhibitory TNF MeSH

We compared the response of normal (FHC) and cancer (HT-29) human colon epithelial cells to the important apoptotic inducers TNF-alpha, anti-Fas antibody and TNF-related apoptosis inducing ligand (TRAIL). The two cell lines did not respond to TNF-alpha (15 ng/ml), expressed a limited sensitivity to anti-Fas antibody (200 ng/ml) and a different response to TRAIL (100 ng/ml). We studied apoptosis with regard to the changes at the receptor level (DR, DcR and FLIP) and at the level of mitochondria (Bid protein cleavage, Apo2.7 protein expression and caspase-9 activation). Two different approaches were used to sensitize the cells to TRAIL-induced apoptosis: inhibition of protein synthesis (cycloheximide, CHX) and inhibition of the pro-survival MEK/ERK pathway (U0126). While the two cell lines were markedly sensitized to all three TNF family members by CHX, a different degree of response (especially for TRAIL) was obtained when inhibition of the MEK/ERK pathway was achieved. TRAIL-induced apoptosis was significantly enhanced by U0126 co-treatment in the HT-29 cells, but not in the FHC cells. The most significant differences between the HT-29 and FHC cells co-treated with TRAIL and U0126 were demonstrated with regard to the involvement of the mitochondrial apoptotic pathway, suggesting its importance in the regulation of cell sensitivity to the TRAIL-induced apoptosis.

• MeSH
• apoptóza MeSH
• buněčné linie MeSH
• epitelové buňky účinky léků   metabolismus   MeSH
• karcinom metabolismus   patologie   MeSH
• kaspasy metabolismus   MeSH
• lidé MeSH
• mitochondriální proteiny metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory tračníku metabolismus   patologie   MeSH
• proliferace buněk účinky léků   MeSH
• protein TRAIL farmakologie   MeSH
• protilátky farmakologie   MeSH
• protoonkogenní proteiny c-bcl-2 metabolismus   MeSH
• TNF decoy receptory metabolismus   MeSH
• TNF-alfa farmakologie   MeSH
• TRAIL receptory metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CH-11 anti-fas antibody, human MeSH Prohlížeč
• kaspasy MeSH
• mitochondriální proteiny MeSH
• protein TRAIL MeSH
• protilátky MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• TNF decoy receptory MeSH
• TNF-alfa MeSH
• TNFRSF10D protein, human MeSH Prohlížeč
• TRAIL receptory MeSH

OBJECTIVES: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. RESULTS: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.

• Klíčová slova
• DAPSA28, PsA, drug retention, first TNF-inhibitor, predictors, real-world evidence,
• MeSH
• imunoterapie MeSH
• inhibitory TNF terapeutické užití   MeSH
• lidé MeSH
• psoriatická artritida * farmakoterapie   MeSH
• registrace MeSH
• únava MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory TNF MeSH