The urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 are thought to play an important part in gastric cancer (GC) invasion and metastasis. Little is known about the behavior and prognostic impact of the receptor for UPA (UPAR). The aims of the present study were: (1) to measure UPAR, UPA and PAI-1 levels in GC and in non-malignant tissue distant from the tumor (NORM); (2) to evaluate their relationship with histomorphological parameters; and (3) to determine their prognostic value. UPAR, UPA and PAI-1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery. The GC was also examined in terms of the presence (n = 10) or absence (n = 10) of metastasis, differentiation (five differentiated, 15 undifferentiated) and histotype. Survival was analysed using life table analysis. UPAR, UPA and PAI-1 were significantly higher in GC vs NORM, in the presence of metastasis (UPAR, UPA) and in undifferentiated GC (UPAR, PAI-1). UPAR significantly correlated with UPA and PAI-1. Low levels of UPAR (P = 0.04), UPA (P = 0.007) and PAI-1 (P = 0.02) were associated with a better survival. Our results demonstrate a sharp increase in UPAR in GC and suggest a prognostic role for it. The concomitant activation of UPAR, UPA and PAI-1 in GC confirm the important role of the plasminogen activator system in the process of invasion and metastasis.
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http://dx.doi.org/10.1023/a:1018454305889 | DOI Listing |
Mol Ther
January 2025
Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, New South Wales, Australia. Electronic address:
Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in COPD is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1, uPAR) that induced collagen and airway remodeling.
View Article and Find Full Text PDFChem Commun (Camb)
January 2025
Center for Metareceptome Research, Graduate School of Pharmaceutical Sciences, Chung-Ang University, 84 Heukseok-ro, Dongjak, Seoul 06974, Republic of Korea.
A class of (thio)chromenone derivatives has been identified as suitable ligands for uPAR, a glycoprotein with a prognostic value in a large number of human cancers. The (thio)chromenone agents actively inhibited the binding of uPAR to uPA with a binding affinity of 18.6 nM, reducing cell migration in the wound healing assay by up to 40% without apparent cell motility.
View Article and Find Full Text PDFInt J Dent Hyg
November 2024
Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK.
Introduction: The plasminogen activating (PA) system has a multitude of functions such as wound healing, proteolytic activity, collagen degradation and cell growth, and the role of the urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) system has been studied in many disease states. The aim of this study was to investigate salivary concentrations of uPA, uPAR and uPA activity in patients with periodontitis to identify biomarkers and novel pathogenic relationships.
Methods: Saliva samples were obtained from 169 participants, comprising patients with periodontitis (n = 103) and periodontally healthy volunteers (n = 66) and analysed for uPA and uPAR with a multiplex protein assay using proximity extension analysis in a subset of samples, followed by validation with ELISA.
Int Immunopharmacol
January 2025
Department of Medical Biotechnology, Fasa University of Medical Sciences, Fasa, Iran; Zarrin Avaye Kowsar Salamat (ZAX Company), Fasa, Iran. Electronic address:
Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis.
View Article and Find Full Text PDFiScience
November 2024
Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Male SARS-CoV-2-infected patients have higher hospitalization rates, ICU admissions, and mortality compared to females, yet with unclear underlying mechanisms. We investigated the influence of biological sex on COVID-19 severity and patient outcomes. We profiled 41 circulating host response markers and identified differentially regulated proteins based on disease severity using covariates, such as sex, age, BMI, diabetes, and corticosteroid administration.
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