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https://www.readbyqxmd.com/read/29333095/cinnamomum-cassia-extracts-suppress-human-lung-cancer-cells-invasion-by-reducing-u-pa-mmp-expression-through-the-fak-to-erk-pathways
#1
Hsing-Chen Wu, Chi-Ting Horng, You-Li Lee, Pei-Ni Chen, Chin-Yin Lin, Chen-Yu Liao, Yih-Shou Hsieh, Shu-Chen Chu
Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties. These activities have been attributed to the modulation of several biological processes and are beneficial for possible pharmaceutical applications. However, the potential of C. cassia in retarding lung adenocarcinoma cells metastasis remains ambiguous. We determined whether C. cassia extract (CCE) reduces metastasis of human lung adenocarcinoma cells. The results showed that CCE treatment (up to 60 μg/mL) for 24 h exhibited no cytotoxicity on the A549 and H1299 cell lines but inhibited the motility, invasiveness, and migration of these cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA)...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29328476/effect-of-a-synthetic-inhibitor-of-urokinase-plasminogen-activator-on-the-migration-and-invasion-of-human-cervical-cancer-cells-in-vitro
#2
Xuechun Wang, Zhongqing Jiang, Jian An, Xiaodan Mao, Fen Lin, Pengming Sun
As a notable feature of malignant tumors, invasion and metastasis are important events in the process of tumor progression. Amiloride, a synthetic inhibitor of urokinase plasminogen activator (uPA), is involved in these events. To evaluate the therapeutic value of amiloride in cervical cancer, HeLa cells were used as in vitro cellular models. The migration and invasion abilities of HeLa cells, in addition to the mRNA expression of matriptase, uPA, uPA receptor and 72 kDa type IV collagenase (MMP‑2), were detected using scratch assays, Transwell chamber assays and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29324635/diagnostic-value-of-serum-urokinase-type-plasminogen-activator-receptor-in-children-with-acute-appendicitis
#3
Mustafa Onur Oztan, Aysegul Aksoy Gokmen, Fatma Demet Arslan, Ebru Cakir, Ali Sayan, Elif Abay, Selçuk Kaya, Gokhan Koyluoglu
OBJECTIVES: Acute appendicitis (AA) is the most common surgical emergency in children. The accurate and timely diagnosis of AA in children can be challenging, and delayed diagnosis rates have been reported to range from 5.9% to 27.6%. Although combining clinical history and repeated physical examination with laboratory tests and radiographic imaging modalities help reach the diagnosis, novel biomarkers can support the surgeons' decision as well. The aims of this study were to evaluate a new plasma marker, urokinase-type plasminogen activator receptor (uPAR), to improve diagnostic accuracy in AA patients, and to determine a cutoff value of uPAR, which can safely include/exclude the diagnosis of AA...
January 11, 2018: Pediatric Emergency Care
https://www.readbyqxmd.com/read/29318541/biotin-chasing-assay-to-evaluate-upar-stability-and-cleavage-on-the%C3%A2-surface-of-cells
#4
Vladimir Leksa, Herbert B Schiller, Hannes Stockinger
The plasminogen activation system, i.e., the fibrinolytic system, is one of the major plasma proteolytic pathways. The proteolytic conversion of the zymogen plasminogen to the active serine protease plasmin is on the cell surface catalyzed by the serine protease urokinase-type plasminogen activator (urokinase, uPA). Upon binding to the urokinase receptor (uPAR, CD87), single-chain pro-uPA is processed to double-chain uPA which in turn specifically converts cell-bound plasminogen to plasmin. Plasmin is harnessed in many physiological processes, e...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29313168/clinical-and-prognostic-usefulness-of-soluble-urokinase-plasminogen-activator-receptor-in-hemodialysis-patients
#5
Rafał Nikodem Wlazeł, Iwona Szadkowska, Piotr Bartnicki, Kinga Rośniak-Bąk, Jacek Rysz
PURPOSE: Considering its prognostic usefulness and the relationship with chronic kidney disease, we analyzed the clinical utility of soluble urokinase plasminogen activator receptor (suPAR) in end-stage renal disease patients undergoing hemodialysis treatment. We focused on the association between suPAR levels and clinical outcomes, especially those related to cardiovascular events and mortality as well as the effect of hemodialysis on the protein levels. METHODS: We enrolled 64 patients...
January 8, 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29299133/domain-retention-in-transcription-factor-fusion-genes-and-its-biological-and-clinical-implications-a-pan-cancer-study
#6
Pora Kim, Leomar Y Ballester, Zhongming Zhao
Genomic rearrangements involving transcription factors (TFs) can form fusion proteins resulting in either enhanced, weakened, or even loss of TF activity. Functional domain (FD) retention is a critical factor in the activity of transcription factor fusion genes (TFFGs). A systematic investigation of FD retention in TFFGs and their outcome (e.g. expression changes) in a pan-cancer study has not yet been completed. Here, we examined the FD retention status in 386 TFFGs across 13 major cancer types and identified 83 TFFGs involving 67 TFs that retained FDs...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296974/urokinase-plasminogen-activator-and-receptor-promote-collagen-induced-arthritis-through-expression-in-hematopoietic-cells
#7
Sherry Thornton, Harini Raghu, Carolina Cruz, Malinda D Frederick, Joseph S Palumbo, Eric S Mullins, Kasper Almholt, Pernille A Usher, Matthew J Flick
The plasminogen activation (PA) system has been implicated in driving inflammatory arthritis, but the precise contribution of PA system components to arthritis pathogenesis remains poorly defined. Here, the role of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) in the development and severity of inflammatory joint disease was determined using uPA- and uPAR-deficient mice inbred to the strain DBA/1J, a genetic background highly susceptible to collagen-induced arthritis (CIA). Mice deficient in uPA displayed a near-complete amelioration of macroscopic and histological inflammatory joint disease following CIA challenge...
March 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29282305/antibody-mediated-neutralization-of-upa-proteolytic-function-reduces-disease-progression-in-mouse-arthritis-models
#8
Kasper Almholt, Josephine B Hebsgaard, Anneline Nansen, Christina Andersson, Jesper Pass, Birgitte Rønø, Peter Thygesen, Hermann Pelzer, Mette Loftager, Ida K Lund, Gunilla Høyer-Hansen, Thomas Frisch, Claus H Jensen, Kristian S Otte, Niels H Søe, Else M Bartels, Martin Andersen, Henning Bliddal, Pernille A Usher
Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29280977/flaccidoxide-13-acetate-extracted-from-the-soft-coral-cladiella-kashmani-reduces-human-bladder-cancer-cell-migration-and-invasion-through-reducing-activation-of-the-fak-pi3k-akt-mtor-signaling-pathway
#9
Choo-Aun Neoh, Wen-Tung Wu, Guo-Fong Dai, Jui-Hsin Su, Chih-I Liu, Tzu-Rong Su, Yu-Jen Wu
Metastasis of cancer is the cause of the majority of cancer deaths. Active compound flaccidoxide-13-acetate, isolated from the soft coral Cladiella kashmani, has been found to exhibit anti-tumor activity. In this study, Boyden chamber analysis, Western blotting and gelatin zymography assays indicated that flaccidoxide-13-acetate exerted inhibitory effects on the migration and invasion of RT4 and T24 human bladder cancer cells. The results demonstrated that flaccidoxide-13-acetate, in a concentration-dependent manner, reduced the levels of matrix metalloproteinase-2 (MMP-2), MMP-9, urokinase-type plasminogen activator receptor (uPAR), focal adhesion kinase (FAK), phosphatidylinositide-3 kinases (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, Ras homolog gene family, member A (Rho A), Ras, mitogen-activated protein kinase kinase 7 (MKK7) and mitogen-activated protein kinase kinase kinase 3 (MEKK3), and increased the expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in RT4 and T24 cells...
December 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29278651/ap1-mediates-upa-upar-induced-fut4-expression-and-trophoblast-invasion
#10
Qin Zheng, Yu Yang, Xinyuan Cui, Dandan Zhang, Shuai Liu, Qiu Yan
Placental trophoblast invasion is crucial for embryo implantation and successful pregnancy. Urokinase-type plasminogen activator (uPA)/urokinase-type plasminogen activator receptor (uPAR) are expressed on trophoblasts and involved in trophoblast invasion. The transcription factor activator protein 1 (AP-1) (c-FOS and c-JUN) and fucosyltransferase IV (FUT4) have been found to be involved in trophoblast invasion. However, the relationship of uPA/uPAR, AP1 and FUT4 is unclear in trophoblast invasion. The current study aimed to investigate the role of AP1 in uPA/uPAR-induced FUT4 expression and trophoblast invasion...
December 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29273518/d2a-ala-peptide-derived-from-the-urokinase-receptor-exerts-anti-tumoural-effects-in-vitro-and-in-vivo
#11
Federico Furlan, Gabriele Eden, Marco Archinti, Ralitsa Arnaudova, Giuseppina Andreotti, Valentina Citro, Maria Vittoria Cubellis, Andrea Motta, Bernard Degryse
D2A-Ala is a synthetic peptide that has been created by introducing mutations in the original D2A sequence, 130IQEGEEGRPKDDR142 of human urokinase receptor (uPAR). In vitro, D2A-Ala peptide displays strong anti-tumoural properties inhibiting EGF-induced chemotaxis, invasion and proliferation of a human fibrosarcoma cell line, HT 1080, and a human colorectal adenocarcinoma cell line, HT 29. D2A-Ala exerts its effects by preventing EGF receptor (EGFR) phosphorylation. To test D2A-Ala in vivo, this peptide was PEGylated generating polyethyleneglycol (PEG)-D2A-Ala peptide...
December 19, 2017: Peptides
https://www.readbyqxmd.com/read/29239349/influences-of-ivabradine-treatment-on-serum-levels-of-cardiac-biomarkers-sst2-gdf-15-supar-and-h-fabp-in-patients-with-chronic-heart-failure
#12
Peter Jirak, Dzeneta Fejzic, Vera Paar, Bernhard Wernly, Rudin Pistulli, Ilonka Rohm, Christian Jung, Uta C Hoppe, P Christian Schulze, Michael Lichtenauer, Atilla Yilmaz, Daniel Kretzschmar
Chronic heart failure (CHF) represents a major cause of hospitalization and death. Recent evidence shows that novel biomarkers such as soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) are correlated with inflammatory and ischemic responses in CHF patients. In this study we examined the effects of Ivabradine that inhibited the hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel, also called funny current If), thereby leading to selective heart rate reduction and improved myocardial oxygen supply on the cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in 50 CHF patients at the University Hospital of Jena...
December 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29234445/bioactivity-guided-fractionation-of-the-traditional-chinese-medicine-resina-draconis-reveals-loureirin-b-as-a-pai-1-inhibitor
#13
Yu Jiang, Guangping Zhang, Dong Yan, Hong Yang, Zuguang Ye, Tonghui Ma
Thrombotic diseases have become a global burden due to morbidity, mortality, and disability. Traditional Chinese medicine has been proven effective in removing blood stasis and promoting blood circulation, but the exact mechanisms remain unclear. Plasminogen activator inhibitor-1 (PAI-1) is a natural inhibitor of tissue-type and urokinase-type plasminogen activators. In this study, we screened four fractions of Resina Draconis (a traditional Chinese medicine) extract for PAI-1 inhibitory activity. Bioactivity-guided purification and chromogenic substrate-based assay led to the identification of loureirin B as the major PAI-1 inhibitor, with an IC50 value of 26...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29227032/efficacy-and-safety-of-low-dose-urokinase-for-the-treatment-of-hemodynamically-stable-aecopd-patients-with-acute-pulmonary-thromboembolism
#14
Xiaogang Jing, Guojun Zhang, Beifeng Zhang, Lingling Dai, Xi Wang, Liuqun Jia, Huan Wang, Lin An, Yuanjian Yang, Zhe Cheng
PURPOSE: The aim of this study was to assess the incidence of pulmonary thromboembolism (PTE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD),and to evaluate the efficacy and safety of low-dose urokinase (UK) thrombolysis therapy when treating hemodynamically stable AECOPD patients with acute PTE (AECOPD-PTE). METHODS: A total of 419 AECOPD patients, including 96 AECOPD-PTE, were enrolled. A total of 30 AECOPD-PTE patients were collected retrospectively, and 66 AECOPD-PTE patients were prospectively divided into anticoagulation-only, low-dose UK and standard-dose UK groups...
December 11, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/29226653/a-preliminary-study-of-the-value-of-plasma-microrna-193b-and-soluble-urokinase-type-plasminogen-activator-receptor-in-identifying-patients-with-early-stage-colorectal-cancer-and
#15
K L Liu, J L Luo, J Wu, Y D Wang, H J Fan
BACKGROUND: Early detection and management of colorectal cancer (CRC) and colorectal adenoma (CRA) reduces the mortality and morbidity of CRC, but there is a lack of ideal circulation biomarkers. METHODS: A total of 80 patients with early-stage CRC and CRA and 30 healthy controls were included in this preliminary study. Plasma samples were collected before colonoscopy and prepared for measurement of microRNA193b and soluble uPAR. RESULTS: Plasma level of miR-193b was decreased through the normal-adenoma-carcinoma sequence with no significant difference between patients with CRC and advanced CRA...
November 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29222696/thrombomodulin-favors-leukocyte-microvesicle-fibrinolytic-activity-reduces-netosis-and-prevents-septic-shock-induced-coagulopathy-in-rats
#16
Julie Helms, Raphaël Clere-Jehl, Elsa Bianchini, Pierrick Le Borgne, Mélanie Burban, Fatiha Zobairi, Jean-Luc Diehl, Lelia Grunebaum, Florence Toti, Ferhat Meziani, Delphine Borgel
BACKGROUND: Septic shock-induced disseminated intravascular coagulation is responsible for increased occurrence of multiple organ dysfunction and mortality. Immunothrombosis-induced coagulopathy may contribute to hypercoagulability. We aimed at determining whether recombinant human thrombomodulin (rhTM) could control exaggerated immunothrombosis by studying procoagulant responses, fibrinolysis activity borne by microvesicles (MVs) and NETosis in septic shock. METHODS: In a septic shock model after a cecal ligation and puncture-induced peritonitis (H0), rats were treated with rhTM or a placebo at H18, resuscitated and monitored during 4 h...
December 8, 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/29216889/targeting-the-cross-talk-between-urokinase-receptor-and-formyl-peptide-receptor-type-1-to-prevent-invasion-and-trans-endothelial-migration-of-melanoma-cells
#17
Concetta Ragone, Michele Minopoli, Vincenzo Ingangi, Giovanni Botti, Federica Fratangelo, Antonello Pessi, Maria Patrizia Stoppelli, Paolo Antonio Ascierto, Gennaro Ciliberto, Maria Letizia Motti, Maria Vincenza Carriero
BACKGROUND: Accumulating evidence demonstrates that the Urokinase Receptor (uPAR) regulates tumor cell migration through its assembly in composite regulatory units with transmembrane receptors, and uPAR88-92 is the minimal sequence required to induce cell motility through the Formyl Peptide Receptor type 1 (FPR1). Both uPAR and FPR1 are involved in melanoma tumor progression, suggesting that they may be targeted for therapeutic purposes. In this study, the role of the uPAR-FPR1 cross-talk to sustain melanoma cell ability to invade extracellular matrix and cross endothelial barriers is investigated...
December 8, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29216583/hplc-ms-ms-analysis-of-mesupron-and-its-application-to-a-pharmacokinetic-study-in-rats
#18
Changmin Park, Joong Gyu Ha, Seungmok Choi, Eunyoung Kim, Keumhan Noh, Beom Soo Shin, Wonku Kang
Mesupron, the first-in-class inhibitor of urokinase-type plasminogen activator (uPA) is known to regulate cell proliferation and migration, and is under investigation for the treatment of metastatic breast cancer. In this study, a quantification method was developed for the determination of mesupron in rat plasma using liquid chromatography with a tandem mass spectrometry (LC-MS/MS). After protein precipitation with acetonitrile including itraconazole (internal standard, IS), the analytes were chromatographed on a reversed phased column with a mobile phase of acetonitrile and water (7:3, v/v, including 0...
December 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29202399/urokinase-receptor-derived-peptides-as-potent-inhibitors-of-the-formyl-peptide-receptor-type-1-triggered-cell-migration
#19
Ali Munaim Yousif, Vincenzo Ingangi, Francesco Merlino, Diego Brancaccio, Michele Minopoli, Rosa Bellavita, Ettore Novellino, Maria Vincenza Carriero, Alfonso Carotenuto, Paolo Grieco
The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration. We and others have previously documented that the uPAR(84-95) sequence, interacts with the formyl peptide receptors (FPR)s, henceforth inducing cell migration of several cell lines, including leukocytes, and the synthetic shorter peptide (Ser88-Arg-Ser-Arg-Tyr92, SRSRY) retains chemotactic activity in vitro and in vivo. Recently, we have developed the head-to-tail cyclic analog [SRSRY], a new potent and stable inhibitor of monocyte trafficking...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29195018/dendron-grafted-polylysine-based-dual-modal-nanoprobe-for-ultra-early-diagnosis-of-pancreatic-precancerosis-via-targeting-a-urokinase-type-plasminogen-activator-receptor
#20
Hui Li, Ping Wang, Wenyu Gong, Qi Wang, Jia Zhou, Wei-Hong Zhu, Yingsheng Cheng
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. Early detection of precancerous pancreatic intraepithelial neoplasia (PanIN) tissues is an urgent challenge to improve the PDAC prognosis. Here, a urokinase-type plasminogen activator receptor (uPAR)-targeted magnetic resonance (MR)/near-infrared fluorescence (NIRF) dual-modal nanoprobe dendron-grafted polylysine (DGL)-U11 for ultra-early detection of pancreatic precancerosis is reported. Because of its good biocompatibility and biodegradability, globular architecture, and well-defined reactive groups, the DGL is chosen as the platform to load with a pancreatic tumor-targeting peptide U11, a magnetic resonance contrast agent Gd3+ -diethylene triamine pentaacetic acid, and a near-infrared fluorescent cyanine dye Cy5...
December 1, 2017: Advanced Healthcare Materials
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