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Systemic urokinase

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https://www.readbyqxmd.com/read/28632880/the-urokinase-receptor-derived-peptide-uparant-recovers-dysfunctional-electroretinogram-and-blood-retinal-barrier-leakage-in-a-rat-model-of-diabetes
#1
Maurizio Cammalleri, Filippo Locri, Stefania Marsili, Massimo Dal Monte, Claudio Pisano, Angelo Mancinelli, Liliana Lista, Dario Rusciano, Mario De Rosa, Vincenzo Pavone, Paola Bagnoli
Purpose: The activation of the urokinase-type plasminogen activator and its receptor system is associated with retinal diseases. Among peptide inhibitors of this system, UPARANT acts by preventing the onset of pathologic signs of neovascular ocular diseases. We investigated whether systemic UPARANT may act in a therapeutic regimen by suppressing the retinal damage that characterizes diabetic retinopathy using a rat model of streptozotocin-induced diabetes. Methods: In healthy rats, plasma, eye, and retina concentrations of UPARANT were evaluated by mass spectrometry...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28627240/quercetin-has-antimetastatic-effects-on-gastric-cancer-cells-via-the-interruption-of-upa-upar-function-by-modulating-nf-%C3%AE%C2%BAb-pkc-%C3%AE-erk1-2-and-ampk%C3%AE
#2
Hai Li, Chen Chen
Gastric cancer (GC) is a malignancy with few effective treatment options after metastasis occurs. Quercetin (Qu) intake has been associated with reduced incidence and slow development of GC, probably due to its anti-proliferative and apoptotic effects, but it is unclear whether Qu can inhibit the metastatic activity. The urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system plays an important role in cancer metastasis. In this study, we measured both uPA activity and uPAR expression in GC and pericarcinous tissues, and we investigated the correlation between uPAR expression and the migratory and invasive activities of various GC cell lines...
March 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28623638/urokinase-containing-locking-solution-in-the-prevention-of-dialysis-catheter-dysfunction-a-double-blind-randomized-controlled-trial
#3
Florence Bonkain, Freya Van Hulle, Peter Janssens, Concetta Catalano, Mandelina Allamani, Jean-Claude Stolear, Dominique Vandervelde, Mark Libertalis, Serge Treille, Marie M Couttenye, Annemie Dhondt, Wim Van Biesen, Jean François Fils, Christian Tielemans, Karl M Wissing
INTRODUCTION: The prophylactic use of recombinant tissue plasminogen activator once weekly reduces the incidence rate of tunneled cuffed catheter (TCC) malfunction and bacteremia as compared to the exclusive use of heparin as locking solution. Restricting the use of prophylactic thrombolytic agents to patients with a history of thrombotic TCC malfunction could be more cost effective. We conduct a multicenter, double-blind, randomized controlled trial and test the hypothesis that weekly use of urokinase lock will reduce the incidence of thrombotic malfunction by 50% in prevalent hemodialysis patients with a history of thrombotic malfunction...
June 14, 2017: Journal of Vascular Access
https://www.readbyqxmd.com/read/28595175/untreated-psoriasis-impairs-male-fertility-a-case-control-study
#4
Giacomo Caldarola, Domenico Milardi, Giuseppe Grande, Andrea Quercia, Silvia Baroni, Renato Morelli, Riccardo Marana, Alfredo Pontecorvi, Clara De Simone, Ketty Peris
BACKGROUND: Recent evidence indicates that a systemic state of inflammation may impair fertility, but data about psoriatic males are scarce. OBJECTIVES: The aim of this study was to assess gonadal function in psoriatic males implementing our knowledge about fertility in these subjects. METHODS: Male psoriatic patients, aged between 18 and 55 years, and a group of healthy subjects matched for age, BMI and geographic origin were enrolled. All subjects underwent a complete physical and andrological examination, standard semen analysis, complete microbiological analysis and ultrasound evaluation of sexual glands...
June 9, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28560690/extrarenal-determinants-of-kidney-filter-function
#5
REVIEW
Eunsil Hahm, Vasil Peev, Jochen Reiser
The kidney is an organ involved in cross talk with many human organs. The link between the immune system and the kidney has been studied in some detail, although data precisely elucidating their interaction are sparse, in particular with regard to the function of the kidney filter apparatus. Current research suggests that an understanding of the impairment of this cross talk between the bone marrow, as a fundament of the immune system and the kidney will provide meaningful insights into the pathophysiological mechanisms of impaired kidney filter function...
July 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28545187/enterolactone-suppresses-proliferation-migration-and-metastasis-of-mda-mb-231-breast-cancer-cells-through-inhibition-of-upa-induced-plasmin-activation-and-mmps-mediated-ecm-remodeling
#6
Aniket V Mali, Asavari A Joshi, Mahabaleshwar V Hegde, Shivajirao S Kadam
Background: To enhance their own survival, tumor cells can manipulate their microenvironment through remodeling of the extra cellular matrix (ECM). The urokinase-type plasminogen activator (uPA) system catalyzes plasmin production which further mediates activation of matrix metalloproteinases (MMPs) and plays an important role in breast cancer invasion and metastasis through ECM remodeling. This provides a potential target for therapeutic intervention of breast cancer treatment. Enterolactone (EL) is derived from dietary flax lignans in the human body and is known to have anti-breast cancer activity...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28533492/anti-tumor-activity-of-anthrax-toxin-variants-that-form-a-functional-translocation-pore-by-intermolecular-complementation
#7
Shihui Liu, Qian Ma, Rasem Fattah, Thomas H Bugge, Stephen H Leppla
Anthrax lethal toxin is a typical A-B type protein toxin secreted by Bacillus anthracis. Lethal factor (LF) is the catalytic A-subunit, a metalloprotease having MEKs as targets. LF relies on the cell-binding B-subunit, protective antigen (PA), to gain entry into the cytosol of target cells. PA binds to cell surface toxin receptors and is activated by furin protease to form an LF-binding-competent oligomer-PA pre-pore, which converts to a functional protein-conductive pore in the acidic endocytic vesicles, allowing translocation of LF into the cytosol...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529645/tumor-penetrating-theranostic-nanoparticles-for-enhancement-of-targeted-and-image-guided-drug-delivery-into-peritoneal-tumors-following-intraperitoneal-delivery
#8
Ning Gao, Erica N Bozeman, Weiping Qian, Liya Wang, Hongyu Chen, Malgorzata Lipowska, Charles A Staley, Y Andrew Wang, Hui Mao, Lily Yang
The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery...
2017: Theranostics
https://www.readbyqxmd.com/read/28524122/-a-plasminogen-regulation-system-in-brain-tumors
#9
O I Kit, E M Frantsiyants, L S Kozlova, E E Rostorguev, I V Balyazin-Parfenov, Yu A Pogorelova
INTRODUCTION: Tumor progression and neovascularization during malignant processes are believed to be associated with plasminogen activators and the PAI-1 inhibitor, but their role and interactions in various types of brain tumors have been studied insufficiently. AIM: To conduct a comparative study of plasminogen regulation in optic nerve sheath meningiomas, glioblastomas, and brain metastases of breast cancer, as well as in perifocal tissues surrounding the tumors...
2017: Zhurnal Voprosy Neĭrokhirurgii Imeni N. N. Burdenko
https://www.readbyqxmd.com/read/28520219/plasminogen-activator-inhibitor-type-1-as-a-regulator-of-fibrosis
#10
Reyhaneh Rabieian, Maryam Boshtam, Mahshid Zareei, Shirin Kouhpayeh, Aria Masoudifar, Hamed Mirzaei
Fibrosis is known as a frequent and irreversible pathological condition which is associated with organ failure. Tissue fibrosis is a central process in a variety of chronic progressive diseases such as diabetes, hypertension, and persistent inflammation. This state could contribute to chronic injury and the initiation of tissue repair. Fibrotic disorders represent abnormal wound healing with defective matrix turnover and clearance that lead to excessive accumulation of extracellular matrix components. A variety of identified growth factors, cytokines, and persistently activated myofibroblasts have critical roles in the pathogenesis of fibrosis...
May 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28479088/ultrasound-and-intra-clot-microbubbles-enhanced-catheter-directed-thrombolysis-in%C3%A2-vitro-and-in%C3%A2-vivo
#11
Shunji Gao, Qiong Zhu, MengJiao Guo, Yuan Gao, Xiaoxiao Dong, Zhong Chen, Zheng Liu, Feng Xie
Insufficient penetration of microbubbles (MBs) into the vessel-obstructing thrombi significantly reduces the effectiveness of ultrasound thrombolysis (UT). The widely performed catheter-directed therapy (CDT) makes it possible to increase the local concentration of MBs in the clot. In an occluded vessel with a bypass, treatment of fresh human whole blood clots with CDT-based UT (intra-clot injection of MBs and urokinase, with ultrasound exposure) resulted in a significantly higher percentage of weight loss (35...
May 4, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28469403/effects-of-acute-exercise-on-circulating-soluble-form-of-the-urokinase-receptor-in-patients-with-major-depressive-disorder
#12
Anna Gustafsson, Filip Ventorp, Anita Gm Wisén, Lars Ohlsson, Lennart Ljunggren, Åsa Westrin
Inflammation has been proposed to play a role in the generation of depressive symptoms. Previously, we demonstrated that patients with major depressive disorder (MDD) have increased plasma levels of the soluble form of the urokinase receptor (suPAR), a marker for low-grade inflammation. The aim of this study was to test the hypothesis that acute exercise would induce inflammatory response characterized by increased suPAR and elucidate whether patients with MDD display altered levels of suPAR in response to acute exercise...
2017: Biomarker Insights
https://www.readbyqxmd.com/read/28458650/plasma-soluble-urokinase-type-plasminogen-activator-receptor-is-not-associated-with-neurological-outcome-in-patients-with-aneurysmal-subarachnoid-hemorrhage
#13
Heikki Kiiski, Ville Jalkanen, Marika Ala-Peijari, Mari Hämäläinen, Eeva Moilanen, Jukka Peltola, Jyrki Tenhunen
OBJECT: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of death or long-term disability. Despite advances in neurocritical care, there is still only a very limited ability to monitor the development of secondary brain injury or to predict neurological outcome after aSAH. Soluble urokinase-type plasminogen activator receptor (suPAR) has shown potential as a prognostic and as an inflammatory biomarker in a wide range of critical illnesses since it displays an association with overall immune system activation...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28442916/expression-and-activity-of-the-urokinase-plasminogen-activator-system-in-canine-primary-brain-tumors
#14
John H Rossmeisl, Kelli Hall-Manning, John L Robertson, Jamie N King, Rafael V Davalos, Waldemar Debinski, Subbiah Elankumaran
BACKGROUND: The expression of the urokinase plasminogen activator receptor (uPAR), a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA), have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28429105/increased-expression-of-upa-upar-and-pai-1-in-psoriatic-skin-and-in-basal-cell-carcinomas
#15
K A Rubina, V Yu Sysoeva, E I Zagorujko, Z I Tsokolaeva, M I Kurdina, Ye V Parfyonova, V A Tkachuk
There is substantial evidence implicating the urokinase system in tissue remodeling during neo-vascularization, inflammation, tumor invasion, and metastasis. Regulated degradation of the extracellular matrix at the leading edge of migrating cells, mediated by uPA and uPAR, is required for tissue remodeling, invasiveness, and angiogenesis. Psoriasis and basal cell carcinoma (BCC) are the most common skin diseases. Pathogenesis of both of them is associated with keratinocyte hyperproliferation, inflammatory cell migration, and angiogenesis-processes in which the plasminogen system (uPA, uPAR, tPA, and PAI-1) plays a crucial role...
April 20, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28416743/the-urokinase-plasminogen-activation-system-in-gastroesophageal-cancer-a-systematic-review-and-meta-analysis
#16
Daniel Brungs, Julia Chen, Morteza Aghmesheh, Kara L Vine, Therese M Becker, Martin G Carolan, Marie Ranson
BACKGROUND: The urokinase plasminogen activation (uPA) system is a crucial pathway for tumour invasion and establishment of metastasis. Although there is good evidence that uPA system expression is a clinically relevant biomarker in some solid tumours, its role in gastroesophageal cancer is uncertain. RESULTS: We identified 22 studies encompassing 1966 patients which fulfilled the inclusion criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high risk clinicopathological features...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405670/a-long-acting-pai-1-inhibitor-reduce-thrombus-formation
#17
Shuangzhou Peng, Guangpu Xue, Lihu Gong, Chao Fang, Jingfei Chen, Cai Yuan, Zhuo Chen, Lishan Yao, Bruce Furie, Mingdong Huang
Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activators (t/uPA) and plays an important role in the fibrinolytic system. Inhibition of PAI-1 activity prevents thrombosis and accelerates fibrinolysis, indicating that PAI-1 inhibitors may be used as effective antithrombotic agents. We previously designed a PAI-1 inhibitor (PAItrap) which is a variant of inactivated urokinase protease domain. In the present study, we tried to fuse PAItrap with human serum albumin (HSA) to develop a long-acting PAI-1 inhibitor...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28385810/regulation-of-p53-mediated-changes-in-the-upa-fibrinolytic-system-and-in-lung-injury-by-loss-of-surfactant-protein-c-expression-in-alveolar-epithelial-cells
#18
Bijesh Puthusseri, Amarnath Marudamuthu, Nivedita Tiwari, Jian Fu, Steven Idell, Sreerama Shetty
Pulmonary surfactant protein C (SP-C) expression by type II alveolar epithelial cells (AECs) is markedly reduced in diverse types of lung injuries and is often associated with AEC apoptosis. It is unclear whether loss of SP-C contributes to the increased p53 and urokinase-type plasminogen activator (uPA) system cross-talk and apoptosis of AECs. Therefore, we inhibited SP-C expression in human and murine AECs using lentivirus vector expressing shRNA and tested p53 and downstream changes in the uPA-fibrinolytic system...
June 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28364860/regulatory-effects-of-estetrol-on-the-endothelial-plasminogen-pathway-and-endothelial-cell-migration
#19
Maria Magdalena Montt-Guevara, Giulia Palla, Stefania Spina, Guja Bernacchi, Elena Cecchi, Adrian Esteban Campelo, Jorge Eduardo Shortrede, Alessio Canu, Tommaso Simoncini
BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate...
May 2017: Maturitas
https://www.readbyqxmd.com/read/28340565/u-par-expression-in-cancer-associated-fibroblast-new-acquisitions-in-multiple-myeloma-progression
#20
S Ciavarella, A Laurenzana, S De Summa, B Pilato, A Chillà, R Lacalamita, C Minoia, F Margheri, A Iacobazzi, A Rana, F Merchionne, G Fibbi, M Del Rosso, A Guarini, S Tommasi, S Serratì
BACKGROUND: Multiple Myeloma (MM) is a B-cell malignancy in which clonal plasma cells progressively expand within the bone marrow (BM) as effect of complex interactions with extracellular matrix and a number of microenvironmental cells. Among these, cancer-associated fibroblasts (CAF) mediate crucial reciprocal signals with MM cells and are associated to aggressive disease and poor prognosis. A large body of evidence emphasizes the role of the urokinase plasminogen activator (u-PA) and its receptor u-PAR in potentiating the invasion capacity of tumor plasma cells, but little is known about their role in the biology of MM CAF...
March 24, 2017: BMC Cancer
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