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Systemic urokinase

Emiliano Tognoli, Matte Leoni, Daniele Morelli, Elisa Sottotetti, Antonia Martinetti, Stefano Signoroni, Carlotta Galeone, Gianfranco Gallino
Unrestrained activation of the proteolytic systems in anastomotic tissue during repair has been implicated in the pathogenesis of anastomotic leakage. We hypothesized that this mechanism may promote an up-regulation of the urokinase-type plasminogen activator system and a spillover of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) into blood. In this retrospective analysis patients with anastomotic leakage were compared to a group of matched uncomplicated patients. Anastomotic leakage complicated patients had significantly higher suPAR (p=0...
October 19, 2016: Wound Repair and Regeneration
Dongzhi Yang, Gregory W Severin, Casey A Dougherty, Rachel Lombardi, Daiqin Chen, Marcian E Van Dort, Todd E Barnhart, Brian D Ross, Andrew P Mazar, Hao Hong
Mounting evidence suggests that the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a central role in tumor progression. The goal of this study was to develop an 89Zr-labeled, antibody-based positron emission tomography (PET) tracer for quantitative imaging of the uPA/uPAR system. An anti-uPA monoclonal antibody (ATN-291) was conjugated with a deferoxamine (Df) derivative and subsequently labeled with 89Zr. Flow cytometry, microscopy studies, and competitive binding assays were conducted to validate the binding specificity of Df-ATN-291 against uPA...
October 8, 2016: Oncotarget
Mei-Chi Chang, Hsiao-Hua Chang, Po-Shuan Lin, Yu-An Huang, Chiu-Po Chan, Yi-Ling Tsai, Shen-Yang Lee, Po-Yuan Jeng, Han-Yueh Kuo, Sin-Yuet Yeung, Jiiang-Huei Jeng
Transforming growth factor-β1 (TGF-β1) plays an important role in the pulpal repair and dentinogenesis. Plasminogen activation (PA) system regulates extracellular matrix turnover. In this study, we investigated the effects of TGF-β1 on PA system of dental pulp cells and its signaling pathways. Dental pulp cells were treated with different concentrations of TGF-β1. MTT assay, reverse transcription-polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbant assay (ELISA) were used to detect the effect of TGF-β1 on cell viability, mRNA and protein expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) as well as their secretion...
October 9, 2016: Journal of Tissue Engineering and Regenerative Medicine
Hao Wang, Ting Yang, Diandian Li, Yanqiu Wu, Xue Zhang, Caishuang Pang, Junlong Zhang, Binwu Ying, Tao Wang, Fuqiang Wen
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD. METHODS: Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Yogender Pal Khasa
Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem...
October 3, 2016: Bioengineered
Barna Vasarhelyi, Gergely Toldi, Attila Balog
The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls...
April 2016: EJIFCC
Linda Fredriksson, Daniel A Lawrence, Robert L Medcalf
The plasminogen activation (PA) system is best known for its role in fibrinolysis. However, it has also been shown to regulate many nonfibrinolytic functions in the central nervous system (CNS). In particular, tissue-type plasminogen activator (tPA) is reported to have pleiotropic activities in the CNS, regulating events such as neuronal plasticity, excitotoxicity, and cerebrovascular barrier integrity, whereas urokinase-type plasminogen activator is mainly associated with tissue remodeling and cell migration...
September 27, 2016: Seminars in Thrombosis and Hemostasis
Sung Un Kang, Jae Won Choi, Jae Won Chang, Kang Il Kim, Yeon Soo Kim, Ju Kyeong Park, Yang Eun Kim, Yun Sang Lee, Sang Sik Yang, Chul-Ho Kim
Advances in physics and biology have made it possible to apply non-thermal atmospheric pressure plasma (NTP) in the biomedical field. Although accumulating evidence suggests that NTP has various medicinal effects, such as facilitating skin wound healing on exposed tissue while minimizing undesirable tissue damage, the underlying molecular mechanisms are not fully understood. In this study, NTP generated from N2 optimized wound healing in the scratch wound healing assay. In addition, matrix metalloproteinase (MMP)-9 expression and enzyme activity increased and the urokinase-type plasminogen activator (uPA) system was activated after NTP treatment...
September 27, 2016: Experimental Dermatology
Mateja Prunk, Janko Kos
Proteases are involved in a variety of processes associated with tumor development and progression. Because of their integral role in extracellular matrix and basal lamina degradation they play important roles in cancer cell migration, invasion, angiogenesis and metastasis. They are also involved in cancer cell signaling, the epithelial-mesenchymal transition, the antitumor immune response, cell de-differentiation and cancer stem cell remodeling. Their involvement in pro-tumorigenic processes makes them interesting targets for anticancer therapy...
September 22, 2016: Current Medicinal Chemistry
Koji Sugioka, Hiroshi Mishima, Aya Kodama, Motoki Itahashi, Masahiko Fukuda, Yoshikazu Shimomura
Keratocytes, corneal resident cells in the corneal stroma, exist between collagen lamellae and maintain the corneal stromal structure. When the corneal stroma is damaged, keratocytes are transformed to myofibroblasts to aid corneal wound healing by phagocytizing debris. Keratocytes and extracellular collagen influence each other because keratocytes cultured in a 3D collagen gel undergo morphological changes and keratocytes produce metalloproteases that degrade extracellular collagen. IL-1 and plasminogen are critical mediators for collagen degradation...
November 2016: Cornea
L Chen, L Dong, L She, H Z Zhang, X D Wang, Z C Yan, W Wu, L Yang
It is written to discuss the effect and syndromes of novel YL-1 hollow needle aspiration drainage system to treat chronic subdural hematoma. Collecting clinical data about 697 patients with chronic subdural hematoma in neurosurgery of People' Hospital in North Jiangsu from January 2004 to December 2014, including clinical manifestation, imaging data, operation time, postoperative complications and prognostic factors and so on. 593 patients got cured, 53 patients with recurrence, 19 patients with acute subdural hematoma, 13 patients with poor drainage, 9 case of patients with acute epidural hematoma, puncture failure in 6 cases, 3 cases of pulmonary infection, one got intracranial hemorrhage (brain stem and basal ganglia hemorrhage)...
September 20, 2016: Neurological Sciences
Casey J Holmes, Jennifer K Plichta, Richard L Gamelli, Katherine A Radek
Burn wound healing complications, such as graft failure or infection, are a major source of morbidity and mortality in burn patients. The mechanisms by which local burn injury alters epidermal barrier function in autologous donor skin and surrounding burn margin are largely undefined. We hypothesized that defects in the epidermal cholinergic system may impair epidermal barrier function and innate immune responses. The objective was to identify alterations in the epidermal cholinergic pathway, and their downstream targets, associated with inflammation and cell death...
September 19, 2016: Shock
Georgios Theodorou, Ioannis Politis
The urokinase-plasminogen activator (u-PA), its receptor (u-PAR) and the inhibitors of u-PA (PAI-1 and PAI-2) provide a multi-molecular system in leucocytes that exerts pleiotropic functions influencing the development of inflammatory and immune responses. The objective of the present study was to examine the ability of water soluble extracts (WSE) obtained from traditional Greek yoghurt made from bovine or ovine milk to modulate the expression of u-PA, u-PAR, PAI-1 and PAI-2 in ovine monocytes and neutrophils...
August 2016: Journal of Dairy Research
Aline Van Acker, Els Louagie, Jessica Filtjens, Sylvie Taveirne, Els Van Ammel, Tessa Kerre, Dirk Elewaut, Tom Taghon, Bart Vandekerckhove, Jean Plum, Georges Leclercq
Ly49E is a member of the Ly49 family of NK receptors and is distinct from other members of this family on the basis of its structural properties, expression pattern and ligand recognition. Importantly, Ly49E receptor expression is high on small intestinal and colonic intraepithelial lymphocytes (IELs). Intestinal IELs are regulators of the mucosal immune system and contribute to front-line defense at the mucosal barrier, including anti-tumor immune response. Whereas most Ly49 receptors have MHC class-I ligands, we showed that Ly49E is instead triggered by urokinase plasminogen activator (uPA)...
September 1, 2016: Cancer Immunology, Immunotherapy: CII
Adel Gouri, Aoulia Dekaken, Khalid El Bairi, Arifa Aissaoui, Nihad Laabed, Mohamed Chefrour, Joseph Ciccolini, Gérard Milano, Sadek Benharkat
Shifting from the historical TNM paradigm to the determination of molecular and genetic subtypes of tumors has been a major improvement to better picture cancerous diseases. The sharper the picture is, the better will be the possibility to develop subsequent strategies, thus achieving higher efficacy and prolonged survival eventually. Recent studies suggest that urokinase-type plasminogen activator (uPA), uPA Receptor (uPAR), and plasmino-gen activator inhibitor-1 (PAI-1) may play a critical role in cancer invasion and metastasis...
2016: Biomarker Insights
Song Yi Bae, Hyen Joo Park, Ji-Young Hong, Hye-Jung Lee, Sang Kook Lee
The failure of targeted therapy due to the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is considered a major problem in the treatment of non-small cell lung cancer (NSCLC) patients. SerpinB2, a component of the urokinase plasminogen activator (uPA) system, has been recognized as a biomarker for the progression and metastasis of lung cancer. Nevertheless, the relationship between SerpinB2 and EGFR-TKI resistance has not been elucidated. Here, we report that SerpinB2 is down-regulated in gefitinib-resistant (H292-Gef) cells compared to gefitinib-sensitive (H292) cells...
2016: Scientific Reports
Michaela C Huber, Rebecca Mall, Herbert Braselmann, Annette Feuchtinger, Sara Molatore, Katrin Lindner, Axel Walch, Eva Gross, Manfred Schmitt, Natalie Falkenberg, Michaela Aubele
BACKGROUND: Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets...
2016: BMC Cancer
Fanny Matheis, Markus V Heppt, Saskia A Graf, Peter Düwell, Claudia Kammerbauer, Achim Aigner, Robert Besch, Carola Berking
Significant advancements of mutation-based targeted therapy and immune checkpoint blockade have been achieved in melanoma. Nevertheless, acquired resistance and non-responders to therapy require novel strategies. An innovative approach is presented here that is based on the combination of innate immune system activation and simultaneous targeting of the oncogene urokinase-type plasminogen activator receptor (uPAR). We generated two triphosphate-conjugated siRNAs targeting uPAR (ppp-uPAR) by in vitro transcription...
August 3, 2016: Journal of Investigative Dermatology
Tingting Han, Guangping Zhang, Dong Yan, Hong Yang, Tonghui Ma, Zuguang Ye
Plasminogen activator inhibitor-1 (PAI-1) is a key negative regulator of the fibrinolytic system. Elevated levels of PAI-1 are associated with thrombosis and cardiovascular and metabolic diseases. Inhibition of PAI-1 activity represents a new strategy for antithrombotic and antifibrinolysis therapies. In this study, we systematically investigated the inhibitory effect of shikonin on PAI-1 activity. In the chromogenic substrate-based urokinase (uPA)/PAI-1 assay, we found that shikonin inhibited human PAI-1 activity with IC50 values of 30...
September 2016: Fitoterapia
Frederik Persson, Simone Theilade, Jesper Eugen-Olsen, Peter Rossing, Hans-Henrik Parving
Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin angiotensin system (RAS) single and dual blockade on suPAR levels in patients with type 2 diabetes and albuminuria. We conducted a post-hoc analysis of a randomized controlled crossover trial. Urine and plasma samples were analyzed for suPAR levels...
November 2016: Journal of Diabetes and its Complications
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