scholarly journals Investigating Glioblastoma Response to Hypoxia

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 310 ◽  
Author(s):  
Agathe L. Chédeville ◽  
Anbarasu Lourdusamy ◽  
Ana Rita Monteiro ◽  
Richard Hill ◽  
Patricia A. Madureira
Keyword(s):  
Overall Survival ◽  
Patient Survival ◽  
Functional Protein ◽  
Urokinase Plasminogen Activator Receptor ◽  
Glut 1 ◽  
Hypoxic Induction ◽  
Average Patient ◽  
Plasminogen Activator Receptor ◽  
Pai 1 ◽  
Primary Malignant Brain Tumor

Glioblastoma (GB) is the most common and deadly type of primary malignant brain tumor with an average patient survival of only 15–17 months. GBs typically have hypoxic regions associated with aggressiveness and chemoresistance. Using patient derived GB cells, we characterized how GB responds to hypoxia. We noted a hypoxia-dependent glycolytic switch characterized by the up-regulation of HK2, PFKFB3, PFKFB4, LDHA, PDK1, SLC2A1/GLUT-1, CA9/CAIX, and SLC16A3/MCT-4. Moreover, many proangiogenic genes and proteins, including VEGFA, VEGFC, VEGFD, PGF/PlGF, ADM, ANGPTL4, and SERPINE1/PAI-1 were up-regulated during hypoxia. We detected the hypoxic induction of invasion proteins, including the plasminogen receptor, S100A10, and the urokinase plasminogen activator receptor, uPAR. Furthermore, we observed a hypoxia-dependent up-regulation of the autophagy genes, BNIP-3 and DDIT4 and of the multi-functional protein, NDRG1 associated with GB chemoresistance; and down-regulation of EGR1 and TFRC (Graphical abstract). Analysis of GB patient cohorts’ revealed differential expression of these genes in patient samples (except SLC16A3) compared to non-neoplastic brain tissue. High expression of SLC2A1, LDHA, PDK1, PFKFB4, HK2, VEGFA, SERPINE1, TFRC, and ADM was associated with significantly lower overall survival. Together these data provide important information regarding GB response to hypoxia which could support the development of more effective treatments for GB patients.

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.

Tissue Factor (TF) and Urokinase Plasminogen Activator Receptor (uPAR) and Bleeding Complications in Leukemic Patients

1997 ◽  
Vol 77 (01) ◽  
pp. 062-070 ◽  
Author(s):  
Chary López-Pedrera ◽  
Merce Jardí ◽  
Maria del Mar Malagón ◽  
Julia Inglés-Esteve ◽  
Gabriel Dorado ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Leukemic Cell ◽  
Bleeding Complications ◽  
Urokinase Plasminogen Activator Receptor ◽  
Leukemic Cell Lines ◽  
Number Of Patients ◽  
Blast Cells ◽  
Plasminogen Activator Receptor ◽  
Hemostatic Disorder

SummaryTissue factor (TF) and urokinase receptor (uPAR) are key cellular receptors triggering, respectively, coagulation and fibrinolysis. Bleeding complications among leukemic patients have been related to an abnormal expression of TF by blast cells and/or to an abnormal fibrinolytic response. In this study the expression of TF and uPAR has been assessed in 18 acute non-lymphoblastic and 8 lymphoblastic leukemic blast cells using several methodological approaches. TF mRNA was evaluated by in situ hybridization and TF and uPAR antigen were evaluated immunologically in cell lysates and on the cell surface by flow cytometry. In addition, TF-procoagulant activity was measured in coagulation-based assays. The reliability of these methods was corroborated in six leukemic cell lines of different lineages and states of maturation. Disseminated intravascular coagulation was detected in two M3 leukemia patients whose blast cells expressed high amounts of TF. Hyperfibrinolysis was detected in one M1 and two M2 patients, whose blast cells displayed a high content of uPAR antigen, but no TF. Furthermore, M5 leukemia blast cells expressed both TF and uPAR, although no hemostatic defects or bleeding complications were detected in these patients. Taken together, although a limited number of patients was included in this study, these data suggest that in leukemia patients exhibiting bleeding, either TF or uPAR are expressed by their blast cells. However, the presence of these receptors does not necessarily imply the existence of a hemostatic disorder.

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