PURPOSE: To investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). METHODS: Immunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers. RESULTS: uPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4%), 1271 (40.7%), and 1311 (42%) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics. CONCLUSION: Overexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.

• Klíčová slova
• Biochemical recurrence, Prostate cancer, Radical prostatectomy, Urokinase-type plasminogen activator,
• MeSH
• aktivátor plazminogenu urokinázového typu biosyntéza   fyziologie   MeSH
• inhibitor aktivátoru plazminogenu 1 biosyntéza   fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru epidemiologie   etiologie   MeSH
• nádorové biomarkery biosyntéza   fyziologie   MeSH
• nádory prostaty epidemiologie   etiologie   metabolismus   chirurgie   MeSH
• prognóza MeSH
• prostatektomie * MeSH
• receptory urokinázového aktivátoru plazminogenu biosyntéza   fyziologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• inhibitor aktivátoru plazminogenu 1 MeSH
• nádorové biomarkery MeSH
• PLAUR protein, human MeSH Prohlížeč
• receptory urokinázového aktivátoru plazminogenu MeSH
• SERPINE1 protein, human MeSH Prohlížeč

AIMS: Coronary artery bypass grafting (CABG) is linked to the induction of the blood coagulation/fibrinolysis cascade, which is an integral component of inflammation induced by cardiac surgery. We followed the modulation of urokinase plasminogen activator receptor uPAR (CD87) separately for monocytes and granulocytes in blood of cardiac surgery patients. METHODS: Expression of uPAR, analyzed as Median Fluorescence Intensity (MFI), on blood monocytes and granulocytes was determined by flow cytometry. Changes in uPAR expression in patients undergoing CABG using standard cardiopulmonary bypass ("on-pump") were compared to the changes in uPAR expression in patients undergoing CABG using mini-invasive cardiopulmonary bypass ("mini on-pump"). RESULTS: In "on-pump" patients, the median of uPAR expression on granulocytes before surgery was 18.1 (InterQuartile Range (IQR): 15.6-20.4). uPAR expression was significantly decreased after surgery (p<0.001), on the first postoperative day (p<0.001), and on the third postoperative day (p<0.05). In "mini on-pump" patients, the median of uPAR expression on granulocytes before surgery was 15.2 (IRQ: 13.8-19.4). The significantly decreased uPAR expression was found only at the end of surgery (p<0.05). The similar pattern of uPAR expression was also found for monocytes. The preoperative level in "on-pump" patients was 23.3 (IRQ: 18.9-30.2). There was significantly decreased uPAR expression at the end of surgery (p<0.01) and at the first postoperative day (p<0.05). In "mini on-pump" patients, the preoperative uPAR expression was 16.9 (IQR: 14.5-20.2). Expression of uPAR was significantly decreased only after surgery (p<0.05). When comparing "onpump" patients to "mini on-pump" patients, no significant differences in the expression of uPAR were found. CONCLUSION: uPAR expression on granulocytes and monocytes is significantly modulated by cardiac surgery.

• MeSH
• granulocyty imunologie   MeSH
• koronární bypass * MeSH
• lidé středního věku MeSH
• lidé MeSH
• monocyty imunologie   MeSH
• receptory urokinázového aktivátoru plazminogenu imunologie   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
• Názvy látek
• receptory urokinázového aktivátoru plazminogenu MeSH

IMPORTANCE: Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults. OBJECTIVE: To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016. EXPOSURES: Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy. MAIN OUTCOMES AND MEASURES: The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2. RESULTS: Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m2. The 5-year end point-free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007). CONCLUSIONS AND RELEVANCE: Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.

• MeSH
• biologické markery krev   MeSH
• chronická renální insuficience krev   diagnóza   terapie   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• náhrada funkce ledvin MeSH
• následné studie MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• receptory urokinázového aktivátoru plazminogenu krev   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH
• receptory urokinázového aktivátoru plazminogenu MeSH

PURPOSE: Urokinase-plasminogen activator (uPA), its receptor (uPAR), and the plasmin-activator inhibitor type 1 (PAI-1) have been associated with oncologic outcomes in various malignancies and could help identify bladder cancer (BC) patients treated with radical cystectomy (RC) who are likely to benefit from intensification of therapy to prevent disease progression. Our aim was to assess the value of uPA, uPAR, and PAI-1 for prognosticating survival outcomes of patients treated with RC for BC. MATERIALS AND METHODS: Tumor specimens from 272 consecutive patients treated with RC for advanced BC were assessed with immunohistochemical staining for uPA, uPAR, and PAI-1. Overexpression was assessed by pathological image analysis. Kaplan-Meier estimates and multivariable Cox-regression were used to analyze survival. Harrell's C-index was used to assess for clinical impact of the uPA system. RESULTS: uPA, uPAR, and PAI-1 were overexpressed in 48.2%, 51.1%, and 52.2% of patients, respectively. uPA overexpression was associated with lymphovascular invasion (P = 0.034) and nodal status (P = 0.013); PAI-1 overexpression was associated with primary muscle-invasive BC (P = 0.015) and lymphovascular invasion (P = 0.024). uPA, uPAR, and the number of overexpressed markers were all 3 significantly associated with shorter overall recurrence-free-, distant recurrence-free-, and cancer-specific survival. In multivariable analyses, uPA overexpression remained associated with shorter recurrence-free survival (hazard ratio [HR] = 1.79; P = 0.036) in the entire cohort, in patients without lymph node metastasis (HR = 1.98; P = 0.018) and those with nonorgan-confined disease (HR = 1.98; P = 0.022). uPAR overexpression was associated with shorter recurrence-free survival in patients without lymph node metastasis (HR = 2.01; P = 0.021) and those with organ-confined disease (HR = 4.11; P = 0.037). CONCLUSION: Members of the uPA system are associated with features of biologically aggressive BC and oncologic outcomes. However, their value beyond currently available information remains limited.

• Klíčová slova
• Bladder cancer, PAI-1, Radical cystectomy, uPA, uPAR,
• MeSH
• aktivátor plazminogenu urokinázového typu analýza   fyziologie   MeSH
• cystektomie * metody   MeSH
• inhibitor aktivátoru plazminogenu 1 analýza   fyziologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory močového měchýře chemie   mortalita   chirurgie   MeSH
• prognóza MeSH
• receptory urokinázového aktivátoru plazminogenu analýza   fyziologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• inhibitor aktivátoru plazminogenu 1 MeSH
• PLAUR protein, human MeSH Prohlížeč
• receptory urokinázového aktivátoru plazminogenu MeSH

The authors present an account on possible aimed thrombolytic treatment of occlusion of the retinal artery by urokinase. Aimed thrombolysis can be performed at ophthalmological departments with an available radiodiagnostic department, which performs angiographies of carotid arteries. The authors discuss the necessary dose of 200,000 to 300,000 i.u. of urokinase. One-hour infusion with an initial booster dose is best. Early administration of the preparation is considered most important by the authors. The authors present the case-history of a 34-year-old patient with complete occlusion of the central retinal artery with haemodynamically severe aortal stenosis with a congenital background. Urokinase was administered six hours after occlusion of the artery. Gradually reperfusion of the retina occurred and improvement of the visual acuity from 0.01 to 0.17 with a residual relative wedge-shaped loss of the visual field and paleness of the disc of the optic nerve.

• MeSH
• aktivátor plazminogenu urokinázového typu terapeutické užití   MeSH
• dospělí MeSH
• lidé MeSH
• okluze retinální arterie farmakoterapie   MeSH
• trombolytická terapie * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH

Fibrinolysis is process, which leads to the degradation of fibrin to fibrin monomers. Fibrinolysis helps to regulate hemostasis and prevents the creation of inappropriately large thrombus, which could reduce blood flow to the bloodstream. The main enzyme involved in fibrinolysis is plasmin. Tissue plasminogen activator (tPA) and urokinase (uPA) are agents converting plasminogen into active plasmin, together with urokinase receptor (uPAR) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) form plasminogen activator system (PAS) which is among others also part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumours. In contrast to tPA that is fundamental in fibrinolysis, uPA plays an essential role in tissue degradation as part of physiological and pathological processes. uPAR is a GPI (glycosylphosphatidylinositol)-anchored protein. The binding of uPA to uPAR results in activation of protein tyrosine kinase, protein kinase C and MAP kinase. At the same time, direct signalling pathway via Jak/STAT cascade utilising signalling transduction of Scr-like protein tyrosine kinase have also been described. uPAR expression is regulated by many growth factors, e.g. EGF, FGF-2 and HGF. It seems that individual PAS factors are involved in the process of rendering malignant tumors invasive. To what degree this influence is essential to specific malignancies, should be answered by further research. In the article the authors present a summary of findings about the interaction of fibrinolysis and tumor process, especially on the effects of urokinase and other activators and their inhibitors in metastasis of malignant tumors. The text contains information on the factors theirs introduction into practice is still the subject of numerous discussions, but in the future, individual PAS factors could play an important role in planning treatment strategies and also could become targets of targeted therapy.

• MeSH
• aktivátor plazminogenu urokinázového typu antagonisté a inhibitory   fyziologie   MeSH
• aktivátory plazminogenu fyziologie   MeSH
• invazivní růst nádoru patofyziologie   MeSH
• lidé MeSH
• metastázy nádorů patofyziologie   MeSH
• tkáňový aktivátor plazminogenu fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• aktivátory plazminogenu MeSH
• tkáňový aktivátor plazminogenu MeSH

Repeated irradiation of the rabbit eye with UV rays of 312 nm wavelength (UVB) evoked the appearance of active plasminogen activator of urokinase type (u-PA) in the anterior eye segment. Using histochemistry, active u-PA appeared first in the corneal epithelium followed by the corneal endothelium, inflammatory cells in the corneal stroma and the lens epithelium. With a semiquantitative fluorescent method active u-PA was also found in the tear fluid and aqueous humour. UV rays of 365 nm wavelength (UVA) under the same conditions did not cause the appearance of active u-PA in the anterior eye segment.

• MeSH
• aktivátor plazminogenu urokinázového typu analýza   účinky záření   MeSH
• histocytochemie MeSH
• komorová voda enzymologie   účinky záření   MeSH
• králíci MeSH
• molekulární sekvence - údaje MeSH
• přední segment oční enzymologie   účinky záření   MeSH
• sekvence aminokyselin MeSH
• slzy enzymologie   účinky záření   MeSH
• ultrafialové záření MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH

Background/Objectives: This retrospective study analyzed soluble urokinase plasminogen activator receptor (suPAR) plasma levels alongside routine inflammatory markers, including the neutrophil-to-lymphocyte count ratio, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and D-dimers in COVID-19 patients hospitalized during the Omicron wave of the pandemic. Methods: We measured plasma suPAR levels using a suPARnostic® Quick Triage kit. We divided COVID-19 patients into two groups based on the severity of SARS-CoV-2 infection according to the National Institutes of Health (NIH) criteria. The logistic regression analysis tested the predictive value of the biomarkers. Results: We evaluated 160 consecutive COVID-19 patients hospitalized between January and August 2022. The cohort exhibited a high incidence of comorbidities, with an in-hospital mortality rate of 5.6%. Upon admission, the median suPAR plasma levels were not significantly different between patients with mild COVID-19 (n = 110) and those with moderate/severe disease (n = 50), with 7.25 ng/mL and 7.55 ng/mL, respectively. We observed significant differences (p < 0.01) between the groups for CRP and IL-6 levels that were higher in moderate/severe disease than in mild infection. Additionally, suPAR plasma levels were above the normal range (0-2.00 ng/mL) in all patients, with a significant positive correlation identified between suPAR levels and serum IL-6, PCT, and creatinine levels. Conclusions: These findings indicate that COVID-19 during the Omicron wave is strongly associated with elevated suPAR levels; however, these levels do not directly correlate with the severity of SARS-CoV-2 infection.

• Klíčová slova
• C-reactive protein, COVID-19, interleukin-6, procalcitonin, urokinase-type plasminogen activator receptor,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The treatment of choice for central venous access device (CVAD) occlusion is intracatheter thrombolysis, which has been reported to reestablish patency in up to 80% of cases. However, these salient results have only been achieved in highly selected CVAD subgroups such as nontunneled devices in adult patients, devices with recent occlusion, and in partially occluded devices through which fluid can still be infused (withdrawal occlusions). Less is known about the success of intracatheter thrombolysis in the broader range of CVAD malfunction encountered in clinical practice, especially in those devices that are totally occluded. OBJECTIVE: This multiple-center, open-label study was performed to test the hypothesis that a new recombinant urokinase (r-UK, urokinase alfa) is safe and effective in reestablishing patency in a large unselected cohort of occluded CVADs. METHODS: Pediatric and adult patients with any type of CVAD occlusion of any duration were treated with 5000 IU/mL intracatheter r-UK. Lumen patency was assessed after 5, 15, and 30 mins; a second dose of r-UK was instilled if the catheter remained occluded after 30 mins. RESULTS: A total of 903 r-UK instillations were performed in 878 patients (age range, 16 days to 96 yrs). Overall, instillation of r-UK successfully restored total catheter patency (all treated lumens) to 75% of CVADs (681 of 902). Patency was restored to at least one occluded lumen in 79% of devices (712 of 902). Patency was restored equally in catheters with total occlusion (76%) as in catheters with only withdrawal occlusion (75%). The median +/- sd time to patency was 15 +/- 20.8 mins (range, 5-203 mins). CONCLUSION: The use of a new r-UK, 5000 IU/mL, is safe and effective for the restoration of patency to occluded CVADs.

• MeSH
• aktivátor plazminogenu urokinázového typu terapeutické užití   MeSH
• aktivátory plazminogenu terapeutické užití   MeSH
• algoritmy MeSH
• dítě MeSH
• dospělí MeSH
• katetrizace centrálních vén škodlivé účinky   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• selhání zařízení MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• trombolytická terapie metody   MeSH
• trombóza farmakoterapie   etiologie   MeSH
• výsledek terapie MeSH
• zaváděcí katétry škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• aktivátory plazminogenu MeSH

• MeSH
• aktivátor plazminogenu urokinázového typu aplikace a dávkování   MeSH
• dospělí MeSH
• endopeptidasy aplikace a dávkování   MeSH
• injekce MeSH
• krvácení farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• oční nemoci farmakoterapie   MeSH
• senioři MeSH
• sklivec * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• aktivátor plazminogenu urokinázového typu MeSH
• endopeptidasy MeSH