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Urokinase

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https://www.readbyqxmd.com/read/28926296/randomised-controlled-trial-of-urokinase-versus-placebo-for-non-draining-malignant-pleural-effusion
#1
Eleanor K Mishra, Amelia O Clive, Genevieve H Wills, Helen E Davies, Andrew E Stanton, Mohamed Al-Aloul, Alan Hart-Thomas, Justin Pepperell, Matthew Evison, Tarek Saba, Richard Neil Harrison, Anur Guhan, Matthew E Callister, Ramamurthy Sathyamurthy, Sunita Rehal, John P Corcoran, Robert Hallifax, Ioannis Psallidas, Nicky Russell, Rachel Shaw, Melissa Dobson, John M Wrightson, Alex West, Y C Gary Lee, Andrew J Nunn, Robert F Miller, Nick A Maskell, Najib M Rahman
RATIONALE: Patients with malignant pleural effusion (MPE) experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. OBJECTIVES: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with non-draining malignant effusion. METHODS: Prospective double blind randomised trial; patients with non-draining effusion were randomly allocated 1:1 to intrapleural urokinase (100,000 IU three doses 12 hourly) or matched placebo...
September 19, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28925023/fibrinolysis-from-blood-to-the-brain
#2
Robert L Medcalf
We all know about classical fibrinolysis, how plasminogen activation by either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) promotes fibrin breakdown, and how this process was harnessed for the therapeutic removal of blood clots. While this is still perfectly true and still applicable to thromboembolic conditions today, another dimension to this system came to light over two decades ago that implicated the plasminogen activating system in a context far removed from the dissolution of blood clots...
September 19, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28924605/pai-1-is-a-critical-regulator-of-fgf23-homeostasis
#3
Mesut Eren, Aaron T Place, Paul M Thomas, Panagiotis Flevaris, Toshio Miyata, Douglas E Vaughan
Elevated levels of fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, are associated with a number of pathologic conditions including chronic kidney disease, cardiac hypertrophy, and congestive heart failure. Currently, there are no specific treatments available to lower plasma FGF23 levels. We have recently reported that genetic plasminogen activator inhibitor-1 (PAI-1) deficiency provided a significant reduction in circulating FGF23 levels while simultaneously prolonging the life span of Klotho-deficient mice...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28922551/lectin-bs-i-inhibits-cell-migration-and-invasion-via-akt-gsk-3%C3%AE-%C3%AE-catenin-pathway-in-hepatocellular-carcinoma
#4
Qiang Jian, Zhao Yang, Jian Shu, Xiawei Liu, Jing Zhang, Zheng Li
Hepatocellular carcinoma (HCC) is most common malignant cancer worldwide; however, the mortality rate of HCC remains high due to the invasion and metastasis of HCC. Thus, exploring novel treatments to prevent the invasion of HCC is needed for improving clinical outcome of this fatal disease. In this study, we identified lectin from Bandeiraea simplicifolia seeds (BS-I) binds to metastasis-associated HCC cell surface glycans by a lectin microarray and inhibits HCC cell migration and invasion through downregulating the matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9) and urokinase-type plasminogen activator (uPA) production...
September 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28919683/serum-levels-of-urokinase-type-plasminogen-activator-in-healthy-dogs-and-oncologic-canine-patients
#5
Sofia C Ramos, Augusto J de Matos, João Niza Ribeiro, Liliana R Leite-Martins, Rui R F Ferreira, Inês Viegas, Andreia A Santos
AIM: Urokinase plasminogen activator (uPA) has been scarcely studied in veterinary oncology. The aim of this study was to determine the uPA serum concentrations in healthy and oncologic canine patients and to investigate its potential value as a tumor biomarker. MATERIALS AND METHODS: Serum uPA concentrations of healthy and oncologic canine patients were measured by enzyme-linked immunosorbent assay. Their relationships with the dogs' health status and tumor characteristics were analyzed through ANOVA and independent t-test...
August 2017: Veterinary World
https://www.readbyqxmd.com/read/28915654/daurinol-blocks-breast-and-lung-cancer-metastasis-and-development-by-inhibition-of-focal-adhesion-kinase-fak
#6
Jong Kyu Woo, Hyun Jin Jung, Ji-Youn Park, Ju-Hee Kang, Byung Il Lee, DongYun Shin, Chu Won Nho, Soo-Young Cho, Je Kyung Seong, Seung Hyun Oh
FAK overexpression has been reported in diverse primary and metastatic tumor tissues, supporting its pro-tumorigenic and pro-metastatic roles. Therefore, we have developed a neo-treatment strategy using daurinol to effectively treat cancer metastasis. Daurinol blocked cancer cell migration and invasion in vitro and exhibited anti-metastatic activity in an experimental metastasis model of breast and lung cancer. Daurinol selectively inhibited phosphorylation of FAK at Tyr925, Tyr576/577, and Tyr397 sites in a dose- and time-dependent manner...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915633/selection-of-optimal-molecular-targets-for-tumor-specific-imaging-in-pancreatic-ductal-adenocarcinoma
#7
Willemieke S Tummers, Arantza Farina-Sarasqueta, Martin C Boonstra, Hendrica A Prevoo, Cornelis F Sier, Jan S Mieog, Johannes Morreau, Casper H van Eijck, Peter J Kuppen, Cornelis J van de Velde, Bert A Bonsing, Alexander L Vahrmeijer, Rutger-Jan Swijnenburg
Discrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this discrimination and to help select and stratify patients for resection. We evaluated various biomarkers for the specific identification of PDAC and associated lymph node metastases. Using immunohistochemistry (IHC), expression levels and patterns were investigated of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), Cathepsin E (Cath E), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-MET), thymocyte differentiation antigen 1 (Thy1), and urokinase-type plasminogen activator receptor (uPAR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28910958/-therapeutic-effect-of-angiojet-mechanical-thrombus-aspiration-system-combined-with-catheter-directed-thrombolysis-on-acute-deep-vein-thrombosis
#8
Y J Mao, C L Li, F R Lei, Y Q Zhang, A M Qian, H F Sang, X Q Li
Objective: To analyze the curative effect of AngioJet mechanical thrombus aspiration combined with catheter directed thrombolysis (CDT) on acute lower extremity deep vein thrombosis (LEDVT). Methods: The clinical data of 20 cases of acute LEDVT treated by AngioJet combined with CDT were analyzed. The inferior vena cava filter was implanted preoperatively, and then the thrombolysis was performed by using AngioJet. The thrombolytic catheter was placed for CDT treatment, and the thrombolysis was evaluated by review angiography...
September 12, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28904936/evaluation-of-urokinase-plasminogen-activator-receptor-soluble-urokinase-plasminogen-activator-receptor-and-%C3%AE-1-integrin-in-patients-with-hodgkin-s-lymphoma
#9
Shirin Kouhpayeh, Alireza Andalib, Marjan Gharagozloo, Mohammad Hossein Sanei, Nafiseh Esmaeil, Mohammad Reza Maracy
BACKGROUND: The objective of this study is to indicate the role of urokinase plasminogen activator receptor (uPAR), soluble uPAR (suPAR), and β1 integrin in tumor growth and invasion of lymph nodes from Hodgkin's lymphoma (HL) patients. MATERIALS AND METHODS: In this study, 25 lymph nodes from HL patients were analyzed for the expression of β1 integrin and uPAR on mononuclear cells using two-color flow cytometry and immunohistochemical analysis. Moreover, the levels of suPAR in the serum samples of HL patients were measured and compared with 32 healthy controls...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28890326/taurolidine-based-catheter-lock-regimen-significantly-reduces-overall-costs-infection-and-dysfunction-rates-of-tunneled-hemodialysis-catheters
#10
Wolfgang Winnicki, Harald Herkner, Matthias Lorenz, Ammon Handisurya, Željko Kikić, Bernhard Bielesz, Benjamin Schairer, Thomas Reiter, Farsad Eskandary, Gere Sunder-Plassmann, Guerkan Sengoelge
Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week...
September 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28886956/sepsis-biomarkers-reprofiling-to-predict-stroke-associated-infections
#11
Alejandro Bustamante, Teresa García-Berrocoso, Anna Penalba, Dolors Giralt, Alba Simats, Marian Muchada, Elena Zapata, Marta Rubiera, Joan Montaner
We aimed to evaluate the usefulness of sepsis biomarkers to predict stroke-associated infections. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), mid-regional pro-adrenomedullin (MR-proADM), presepsin (sCD14), and soluble urokinase-type plasminogen activator receptor (suPAR), were explored in 125 blood samples collected at different time-points. At baseline, MR-proADM was an independent predictor of infection [>0.94pg/mL, OR=3.63 (1.16-11.33), p=0.026], as well as suPAR at 24h [>2185...
August 26, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28882040/visualizing-breast-cancer-cell-proliferation-and-invasion-for-assessing-drug-efficacy-with-a-fluorescent-nanoprobe
#12
Mingming Luan, Longhai Yu, Yanhua Li, Wei Pan, Xiaonan Gao, Xiuyan Wan, Na Li, Bo Tang
Hard-to-treat cancers are closely relative of uncontrolled cell proliferation, invasion and metastasis. Assessing proliferation and invasion properties of tumor cells both in vitro and in vivo is especially important for acquiring reliable information for cancer pathogenesis, drug screening and therapeutic effect evaluation. Herein, we developed a multicolor fluorescent nanoprobe for simultaneously monitoring breast cancer cells' proliferation marker Ki-67 and invasion marker urokinase plasminogen activator (uPA)...
September 8, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28877230/decision-impact-and-feasibility-of-different-asco-recommended-biomarkers-in-early-breast-cancer-prospective-comparison-of-molecular-marker-endopredict-and-protein-marker-upa-pai-1
#13
Johannes Ettl, Evelyn Klein, Alexander Hapfelmeier, Kirsten Grosse Lackmann, Stefan Paepke, Christoph Petry, Katja Specht, Laura Wolff, Heinz Höfler, Marion Kiechle
BACKGROUND: Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA) and plaminogen activator inhibitor-1 (PAI-1) have been the first biomarkers in hormone receptor (HR) positive breast cancer to reach highest level of evidence. The EndoPredict test (EPclin) combines gene expression information with nodal status and tumor size. The aim of this prospective study was to compare uPA/PAI-1 and EPclin as prognostic biomarkers with regard to feasibility, risk stratification and impact on adjuvant therapy recommendation...
2017: PloS One
https://www.readbyqxmd.com/read/28873129/association-of-serum-soluble-urokinase-receptor-levels-with-progression-of-kidney-disease-in-children
#14
Franz Schaefer, Howard Trachtman, Elke Wühl, Marietta Kirchner, Salim S Hayek, Ali Anarat, Ali Duzova, Sevgi Mir, Dusan Paripovic, Alev Yilmaz, Francesca Lugani, Klaus Arbeiter, Mieczyslaw Litwin, Jun Oh, Maria Chiara Matteucci, Jutta Gellermann, Simone Wygoda, Augustina Jankauskiene, Günter Klaus, Jiri Dusek, Sara Testa, Aleksandra Zurowska, Alberto Caldas Afonso, Melissa Tracy, Changli Wei, Sanja Sever, William Smoyer, Jochen Reiser
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...
September 5, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28871079/sirt6-deficiency-exacerbates-podocyte-injury-and-proteinuria-through-targeting-notch-signaling
#15
Min Liu, Kaili Liang, Junhui Zhen, Meng Zhou, Xiaojie Wang, Ziying Wang, Xinbing Wei, Yan Zhang, Yu Sun, Zhuanli Zhou, Hua Su, Chun Zhang, Ningjun Li, Chengjiang Gao, Jun Peng, Fan Yi
Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28867754/sushi-repeat-containing-protein-x-linked-2-promotes-angiogenesis-through-the-urokinase-type-plasminogen-activator-receptor-dependent-integrin-%C3%AE-v%C3%AE-3-focal-adhesion-kinase-pathways
#16
Kuiliang Liu, Jianghao Fan, Jing Wu
Sushi repeat-containing protein X-linked 2 (SRPX2) is a newly identified chondroitin sulfate proteoglycan that is markedly elevated in multiple solid tumors. It is also suggested that SRPX2 is associated with angiogenesis. A conditioned medium of SRPX2 overexpressing colorectal cancer (CRC) cells and SRPX2 recombinant protein was used to evaluate the effect of secretory SRPX2 on the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) and the involved molecular mechanisms. It was revealed that the activity of SRPX2 is dependent on the urokinase-type plasminogen activator receptor and cooperation of the integrin αvβ3 co-receptor...
2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28860148/targeting-plasminogen-activator-inhibitor-1-in-tetracycline-induced-pleural-injury-in-rabbits
#17
Galina Florova, Ali O Azghani, Sophia Karandashova, Chris Schaefer, Serge V Yarovoi, Paul J Declerck, Douglas B Cines, Steven Idell, Andrey A Komissarov
Elevated active plasminogen activator inhibitor 1 (PAI-1) has an adverse effect on the outcomes of intrapleural fibrinolytic therapy (IPFT) in tetracycline-induced pleural injury in rabbits. In order to enhance IPFT with prourokinase (scuPA), two mechanistically distinct approaches to targeting PAI-1 were tested: slowing its reaction with urokinase (uPA) and mAb-mediated PAI-1 inactivation. Removing positively charged residues at the "PAI-1 docking site" ((179)RHRGGS(184)→(179)AAAAAA(184)) of uPA results in a 60-fold decrease in the rate of inhibition by PAI-1...
August 31, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28854261/gemcitabine-treatment-induces-endoplasmic-reticular-er-stress-and-subsequently-upregulates-urokinase-plasminogen-activator-upa-to-block-mitochondrial-dependent-apoptosis-in-panc-1-cancer-stem-like-cells-cscs
#18
Li Wang, Yi Zhang, Weiguo Wang, Yunjie Zhu, Yang Chen, Bole Tian
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown. METHODS: We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs...
2017: PloS One
https://www.readbyqxmd.com/read/28841839/urokinase-type-plasminogen-activator-receptor-upar-tissue-factor-tf-and-epidermal-growth-factor-receptor-egfr-tumor-expression-patterns-and-prognostic-value-in-oral-cancer
#19
Anders Christensen, Katalin Kiss, Giedrius Lelkaitis, Karina Juhl, Morten Persson, Birgitte Wittenborg Charabi, Jann Mortensen, Julie Lyng Forman, Anne Lyngholm Sørensen, David Hebbelstrup Jensen, Andreas Kjaer, Christian von Buchwald
BACKGROUND: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC...
August 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28839232/urokinase-type-plasminogen-activator-receptor-upar-expression-enhances-invasion-and-metastasis-in-ras-mutated-tumors
#20
Concetta Di Mauro, Ada Pesapane, Luigi Formisano, Roberta Rosa, Valentina D'Amato, Paola Ciciola, Alberto Servetto, Roberta Marciano, Roberta Clara Orsini, Francesca Monteleone, Nicola Zambrano, Gabriella Fontanini, Adele Servadio, Giuseppe Pignataro, Lucia Grumetto, Antonio Lavecchia, Dario Bruzzese, Antonino Iaccarino, Giancarlo Troncone, Bianca Maria Veneziani, Nunzia Montuori, Sabino De Placido, Roberto Bianco
The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell membrane receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. Its expression is increased in many human cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), and correlates with a poor prognosis and early invasion and metastasis. uPAR is able to control, through a cross-talk with tyrosine kinase receptors, the shift between tumor dormancy and proliferation, that usually precedes metastasis formation...
August 24, 2017: Scientific Reports
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