scholarly journals Experimental and Clinical Evidence Supports the Use of Urokinase Plasminogen Activation System Components as Clinically Relevant Biomarkers in Gastroesophageal Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4097
Author(s):  
Gary Tincknell ◽  
Ann-Katrin Piper ◽  
Morteza Aghmesheh ◽  
Therese Becker ◽  
Kara Lea Vine ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Clinical Evidence ◽  
Patient Survival ◽  
Plasminogen Activator Inhibitor ◽  
Urokinase Plasminogen Activator ◽  
Urokinase Plasminogen Activator Receptor ◽  
Proteolytic Activation ◽  
Plasminogen Activation System ◽  
Plasminogen Activator System ◽  
Activator Inhibitor Type

Gastric and oesophageal cancers (GOCs) are lethal cancers which metastasise early and recur frequently, even after definitive surgery. The urokinase plasminogen activator system (uPAS) is strongly implicated in the invasion and metastasis of many aggressive tumours including GOCs. Urokinase plasminogen activator (uPA) interaction with its receptor, urokinase plasminogen activator receptor (uPAR), leads to proteolytic activation of plasminogen to plasmin, a broad-spectrum protease which enables tumour cell invasion and dissemination to distant sites. uPA, uPAR and the plasminogen activator inhibitor type 1 (PAI-1) are overexpressed in some GOCs. Accumulating evidence points to a causal role of activated receptor tyrosine kinase pathways enhancing uPAS expression in GOCs. Expression of these components are associated with poorer clinicopathological features and patient survival. Stromal cells, including tumour-associated macrophages and myofibroblasts, also express the key uPAS proteins, supporting the argument of stromal involvement in GOC progression and adverse effect on patient survival. uPAS proteins can be detected on circulating leucocytes, circulating tumour cells and within the serum; all have the potential to be developed into circulating biomarkers of GOC. Herein, we review the experimental and clinical evidence supporting uPAS expression as clinical biomarker in GOC, with the goal of developing targeted therapeutics against the uPAS.

Differential expression of plasminogen activators and their inhibitors in an organotypic skin coculture system

1993 ◽  
Vol 106 (1) ◽  
pp. 45-53 ◽  
Author(s):  
C.S. Chen ◽  
B. Lyons-Giordano ◽  
G.S. Lazarus ◽  
P.J. Jensen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Urokinase Plasminogen Activator ◽  
Basal Cells ◽  
Type Plasminogen Activator ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

Using immunohistochemistry and in situ hybridization, we have characterized the expression and localization of components of the plasminogen activator proteolytic cascade in an organotypic coculture system which consists of a “dermal” portion (human dermal fibroblasts throughout a collagen matrix) and a stratified, well-differentiated epidermal portion. Specifically, the following components were examined: the enzymes urokinase-type plasminogen activator and tissue-type plasminogen activator and their type 1 and type 2 inhibitors. Urokinase plasminogen activator mRNA and antigen were found predominantly in the least differentiated, basal keratinocytes; in some fields there was also faint deposition of antigen beneath the basal cells. The distribution of plasminogen activator inhibitor type 1 was similar to that of urokinase, except that inhibitor type 1 antigen deposition beneath the basal cells appeared more intense and uniform. In contrast to the results with urokinase plasminogen activator and inhibitor type 1, tissue plasminogen activator mRNA and antigen were localized focally in the suprabasal, i.e. more differentiated, keratinocytes. Plasminogen activator inhibitor type 2 mRNA and antigen were detected in most epidermal layers, but were more intense suprabasally and often spared the basal layer. These studies demonstrate that the same type of cell, i.e. the keratinocyte, can express different components of the plasminogen activator cascade depending on its state of differentiation. The change in expression of plasminogen activator cascade components with keratinocyte differentiation suggests distinct epidermal functions for these components, related to cell-matrix interaction and epidermal differentiation.

scholarly journals Thrombo-inflammatory biomarkers to predict sepsis outcome

2021 ◽  
Vol 35 ◽  
pp. 205873842110485
Author(s):  
Alaa Efat ◽  
Sabry Abdallah Shoeib ◽  
Ayman F Arafa ◽  
Ashraf Abdelraof Dawod ◽  
Mohamad A Abd ElHafez ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Urokinase Plasminogen Activator ◽  
Plasminogen Activator Inhibitor 1 ◽  
Urokinase Plasminogen Activator Receptor ◽  
Cutoff Value ◽  
Plasminogen Activator Receptor ◽  
Activator Inhibitor ◽  
Pai 1

Background: Sepsis has been redefined recently as life-threatening organ dysfunction caused by dysregulated host responses to infection and septic shock. Soluble urokinase plasminogen activator receptor (SuPAR) and plasminogen activator inhibitor-1(PAI-1) concentration positively correlate to the activation level of the immune system, and are markers of disease severity and aggressiveness. Objective: The study aimed to identify the blood level of plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase plasminogen activator receptor (SuPAR) in sepsis and its association with mortality. Patient and methods: This is an observational prospective study that enrolled 60 adult patients with sepsis (according to SOFA), admitted to Menoufia and Zagazig university hospitals during the period from December 2019 till October 2020. Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase plasminogen activator receptor (SuPAR) were checked in all participants. Results: SuPAR and PAI.1 were significant independent predictors of hospital mortality. SuPAR showed sensitivity 100%, specificity 95.9%, and accuracy 94% for prediction of early mortality at a cutoff value of 13.4(pg/ml). While, PAI-1 demonstrated sensitivity 100%, specificity 93.9%, and accuracy of 95% at a cutoff value of 122.5 for predicting mortality. Conclusion: PAI-1 and suPAR were significant predictors of hospital mortality among sepsis patients. The sample size was relatively small, which may have decreased the statistical power of the results of the present study. Hence, additional studies with large sample sizes are required for further validation of the present results.

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