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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
#1
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/28539608/development-and-validation-of-a-high-throughput-whole-blood-thrombolysis-plate-assay
#2
T Bonnard, L S Law, Z Tennant, C E Hagemeyer
The objective of this work was to develop a high throughput assay for testing in vitro the thrombolytic activity using citrated whole blood samples, and to overcome the limitations of currently available techniques. We successfully developed a method that involves forming halo shaped, tissue factor induced, whole blood clots in 96 well plates, and then precisely measuring the thrombolysis process with a spectrophotometer plate reader. We here describe the implementation of this novel method, which we refer to as halo assay, and its validation with plasmin, urokinase and tissue plasminogen activator at different doses...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533492/anti-tumor-activity-of-anthrax-toxin-variants-that-form-a-functional-translocation-pore-by-intermolecular-complementation
#3
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/28532226/novel-biological-therapies-for-the-treatment-of-diabetic-foot-ulcers
#4
Jennifer Adeghate, Syed Nurulain, Kornélia Tekes, Erzsébet Fehér, Huba Kalász, Ernest Adeghate
The number of people with diabetes mellitus (DM) is estimated to exceed 640 million by the year 2040. Diabetic foot ulcer (DFU) is a debilitating illness that affects more than 2% of DM patients. DFU is caused by DM-induced neural and vascular lesions leading to a reduced sensation and microcirculation. The increase in the prevalence of DFU has prompted researchers to find new therapies for the management of DFU. Areas covered: This review presents the current status of novel biological therapies used in the treatment of DFU...
May 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28529685/computed-tomography-guided-catheter-drainage-with-urokinase-and-ozone-in-management-of-empyema
#5
Bing Li, Chuan Liu, Yang Li, Han-Feng Yang, Yong Du, Chuan Zhang, Hou-Jun Zheng, Xiao-Xue Xu
AIM: To retrospectively compare the outcomes of catheter drainage, urokinase and ozone in management of empyema. METHODS: Retrospective study included 209 patients (111 males and 98 females; age range 19 to 72 years) who were diagnosed with empyema. The patients were divided into 3 groups based on the therapy instituted: catheter drainage only (group I); catheter drainage and urokinase (group II); catheter drainage, urokinase and ozone (group III). Drainage was considered successful if empyema was resolved with closure of cavity, clinical symptoms were resolved, and need for any further surgical procedure was avoided...
April 28, 2017: World Journal of Radiology
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
#6
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/28526008/cleavage-of-the-urokinase-receptor-upar-on-oral-cancer-cells-regulation-by-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-and-potential-effects-on-migration-and-invasion
#7
Synnove Norvoll Magnussen, Elin Hadler-Olsen, Daniela Elena Costea, Eli Berg, Cristiane Cavalcanti Jacobsen, Bente Mortensen, Tuula Salo, Inigo Martinez-Zubiaurre, Jan-Olof Winberg, Lars Uhlin-Hansen, Gunbjorg Svineng
BACKGROUND: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28524122/-a-plasminogen-regulation-system-in-brain-tumors
#8
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/28523190/expression-of-upar-in-urinary-podocytes-of-patients-with-fabry-disease
#9
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Juan Politei, Cristian Costales-Collaguazo, Aníbal Stern, Matías Paulero, Tatiana Rengel, Lara Valiño-Rivas, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Alexis Muryan, Alberto Ortiz, María Dolores Sanchez-Niño, Elsa Zotta
Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-β (n = 21)...
2017: International Journal of Nephrology
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/28506312/pathomimetic-avatars-reveal-divergent-roles-of-microenvironment-in-invasive-transition-of-ductal-carcinoma-in-situ
#11
Mansoureh Sameni, Dora Cavallo-Medved, Omar E Franco, Anita Chalasani, Kyungmin Ji, Neha Aggarwal, Arulselvi Anbalagan, Xuequn Chen, Raymond R Mattingly, Simon W Hayward, Bonnie F Sloane
BACKGROUND: The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC. METHODS: We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression...
May 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28498893/role-of-dhx33-in-c-myc-induced-cancers
#12
Jijun Fu, Yuchu Liu, Xingshun Wang, Baolei Yuan, Yandong Zhang
Oncogene c-Myc is frequently amplified and activated in human cancers. Deregulation of c-Myc protein has been shown to occur in 30% of all human cancers, especially in hematopoietic malignancies. As a transcription factor, c-Myc has been shown to regulate up to 15% of all human genome genes, controlling diverse cellular activities including cell cycle, ribosome biogenesis, protein synthesis, metabolism, apoptosis and angiogenesis. In this report, we provide evidence that the RNA helicase DHX33 is a critical downstream target of c-Myc...
May 11, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28498427/effect-of-macrophages-on-breast-cancer-cell-proliferation-and-on-expression-of-hormone-receptors-upar-and-her-2
#13
Therése Lindsten, Alexander Hedbrant, Anna Ramberg, Jonny Wijkander, Anja Solterbeck, Margareta Eriksson, Dick Delbro, Ann Erlandsson
Malignant tumors, including breast cancers, are frequently infiltrated with innate immune cells and tumor-associated macrophages (TAMs) represent the major inflammatory component in stroma of many tumors. In this study, we examined the immunoreactivity of the macrophage markers CD68 and CD163 as well as the hormone receptors estrogen receptor α (ERα), progesterone receptor (PR), estrogen receptor β1 (ERβ1), human epidermal growth factor receptor 2 (HER-2), matrix metalloproteinase 9 (MMP‑9), urokinase-type plasminogen activator receptor (uPAR) and the proliferations marker Ki67 in 17 breast cancer biopsies...
May 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28495863/soluble-urokinase-plasminogen-activator-receptor-and-outcomes-in-patients-with-diabetes-on-hemodialysis
#14
Christiane Drechsler, Salim S Hayek, Changli Wei, Sanja Sever, Bernd Genser, Vera Krane, Andreas Meinitzer, Winfried März, Christoph Wanner, Jochen Reiser
BACKGROUND AND OBJECTIVES: Soluble urokinase plasminogen activator receptor is a novel biomarker strongly predictive of cardiovascular outcomes implicated in the pathogenesis of kidney disease. Soluble urokinase plasminogen activator receptor levels, however, correlate with declining kidney function. It is unclear whether soluble urokinase plasminogen activator receptor levels remain associated with outcomes in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured plasma soluble urokinase plasminogen activator receptor levels in 1175 patients (mean age =66±8 years old, 54% men) with type 2 diabetes mellitus on hemodialysis participating in the German Diabetes and Dialysis Study followed for a median of 4 years for outcomes including all-cause death, cardiovascular events, and infection-related mortality...
May 11, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28494644/the-alpha-7-nicotinic-acetylcholine-receptor-of-deciduous-dental-pulp-stem-cells-regulates-osteoclastogenesis-during-physiological-root-resorption
#15
Lulu Wang, Zhifei Zhou, Yujiang Chen, Shuai Yuan, Yang Du, Xinke Ju, Lizheng Wu, Xiaojing Wang
The physiological root resorption of deciduous teeth is a normal phenomenon, but the mechanisms underlying this process are still unclear. In this study, deciduous dental pulp stem cells (DDPSCs) and permanent dental pulp stem cells (DPSCs) were derived from deciduous teeth and normal permanent teeth at different stages of resorption. In the middle stage of root resorption, DDPSCs exhibited an increase in the ability to induce osteoclast differentiation. Activation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) by secretory mammalian Ly-6 urokinase-type plasminogen activator receptor-associated protein 1 (SLURP-1) caused a significant increase in the expression levels of NF-κB, RANKL and the ratio of RANKL/OPG...
May 11, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28493442/upa-derived-peptide-%C3%A3-6-is-involved-in-the-suppression-of-lipopolysaccaride-promoted-inflammatory-osteoclastogenesis-and-the-resultant-bone-loss
#16
Yosuke Kanno, Chihiro Maruyama, Ayaka Matsuda, Akira Ishisaki
INTRODUCTION: Chronic inflammatory diseases such as rheumatoid arthritis and periodontitis frequently cause bone destruction. Inflammation-induced bone loss results from the increase of bone-resorbing osteoclasts. Recently, we demonstrated that urokinase type plasminogen activator (uPA) suppressed lipopolysaccaride (LPS)-inflammatory osteoclastogenesis through the adenosine monophosphate-activated protein kinase (AMPK) pathway, whereas its receptor (uPAR) promoted that through the Akt pathway...
May 11, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28491286/unwinding-focal-segmental-glomerulosclerosis
#17
REVIEW
Vasil Peev, Eunsil Hahm, Jochen Reiser
Focal segmental glomerulosclerosis (FSGS) represents the most common primary glomerular disease responsible for the development of end-stage renal disease (ESRD) in the United States (US). The disease progresses from podocyte injury to chronic kidney disease (CKD), ultimately leading to total nephron degeneration. Extensive basic science research has been conducted to unwind the mechanisms of FSGS and, with those insights, understand major contributors of CKD in general. As a result, several putative molecules and pathways have been studied, all implicated in the disease; some serve, in addition, as early biomarkers...
2017: F1000Research
https://www.readbyqxmd.com/read/28483628/acute-early-carotid-stent-thrombosis-a-case-series
#18
Konstantinos G Moulakakis, John Kakisis, Georgios Tsivgoulis, Vasilis Zymvragoudakis, Stavros Spiliopoulos, Andreas Lazaris, Giorgos S Sfyroeras, Spyridon N Mylonas, Spyridon N Vasdekis, George Geroulakos, Elias N Brountzos
PURPOSE: Acute early carotid stent thrombosis (AcuteCST) is a rare complication after carotid artery stenting (CAS). Purpose of this retrospective study was to investigate the incidence, causes and optimal management of AcuteCST. METHODS: Medical records of all patients undergoing CAS between 2008 and 2016 were retrospectively reviewed. Time of thrombosis, grade of stenosis, lesion side, pre and post-procedural anticoagulants, causes, symptoms, treatment, recanalization and outcome were reviewed...
May 5, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28479088/ultrasound-and-intra-clot-microbubbles-enhanced-catheter-directed-thrombolysis-in%C3%A2-vitro-and-in%C3%A2-vivo
#19
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/28473293/moesin-and-merlin-regulate-urokinase-receptor-dependent-endothelial-cell-migration-adhesion-and-angiogenesis
#20
Bernard Degryse, Mishan Britto, Chun Xu Shan, Robert G Wallace, Keith D Rochfort, Philip M Cummins, Gerardene Meade, Ronan P Murphy
The glycosyl-phosphatidyl-inositol (GPI)-anchored urokinase receptor (uPAR) has no intracellular domain, but nevertheless initiates signalling through proximal interactions with other membrane receptors including integrins. The relationships between uPAR and ezrin/radixin/moesin (ERM) proteins, moesin and merlin have never been explored. Moesin and merlin are versatile membrane-actin links and regulators of receptors signalling, respectively. We show that uPAR controls moesin and merlin, which propagate uPAR-initiated signals and modulate integrin functions, thereby regulating uPAR activity...
May 1, 2017: International Journal of Biochemistry & Cell Biology
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