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Kusum Vats, Rohit Sharma, Haladhar Dev Sarma, Drishty Satpati, Ashutosh Dash
AIMS: The urokinase plasminogen activator receptors (uPAR) over-expressed on tumor cells and their invasive microenvironment are clinically significant molecular targets for cancer research. uPAR-expressing cancerous lesions can be suitably identified and their progression can be monitored with radiolabeled uPAR targeted imaging probes. Hence this study aimed at preparing and evaluating two 68Ga-labeled AE105 peptide conjugates, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 as uPAR PET-probes...
March 16, 2018: Anti-cancer Agents in Medicinal Chemistry
Gehan Hassan AboEl-Magd, Maaly Mohamed Mabrouk
OBJECTIVE: To evaluate the value of soluble urokinase-type plasminogen activator receptor (suPAR) in the diagnosis of acute exacerbation of COPD (AECOPD) and in monitoring treatment response, analyzing the relationship between suPAR and fibrinogen in AECOPD. AECOPD leads to increased airway inflammation, contributing to an exaggerated release of inflammatory mediators. METHODS: We recruited 45 patients with AECOPD and 20 healthy control subjects. Medical histories were taken, and all subjects underwent clinical examination, chest X-ray, pulmonary function tests, and blood gas analysis...
January 2018: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
Peter Y M Woo, James T F Zhuang, Jason M K Ho, Andrew Seto, Hoi-Tung Wong, Kwong-Yau Chan
Leptomeningeal spread and hydrocephalus are increasingly recognized as late disease complications of glioblastoma with almost a quarter of patients requiring early cerebrospinal fluid shunting. The neurosurgeon is challenged with maintaining shunt patency when tumor disease progression is rapid and adjuvant oncologic therapy has yet to be initiated. We describe our experience in treating a young female with diffuse glioblastoma leptomeningeal spread and communicating hydrocephalus who had several episodes of shunt obstruction due to intraluminal tumor cell-fibrin deposits...
March 13, 2018: Acta Neurochirurgica
Hyun-Kyung Kim, Purevjargal Naidansuren, Seung Woo Lee, Rae-Kwon Kim, Su-Jae Lee, Suk Keun Lee, Yong-Kil Hong, Young Ae Joe
The recombinant kringle domain of urokinase (UK1) has been shown to inhibit angiogenesis and brain tumor growth in vivo . To avoid limitations in application due to mass production of recombinant protein, we attempted to develop a novel peptide inhibitor from UK1 sequence consisting of 83 amino acids that contains α-helices, loops and β-sheets. We dissected UK1 sequence to seven peptides based on structure and amino acid characteristics, and examined the anti-angiogenic activities for the constructed peptides...
February 9, 2018: Oncotarget
She-Fang Huang, Shu-Chen Chu, Yi-Hsien Hsieh, Pei-Ni Chen, Yih-Shou Hsieh
Cancer metastasis is a vital trait in malignancies with complicated early diagnosis and therapeutic management. Therefore, the development of new remedies and the utilization of natural medicines that target metastasis are of great interest and have been studied extensively. Chinese medicinal herbs have various anti-carcinogenesis properties; however, the in vitro effect and mechanism of Viola yedoensis on cancer cell metastasis remains poorly understood. V. yedoensis extracts (VYE) can suppress the invasion of a highly metastatic human lung cancer cell line, A549 cells...
2018: International Journal of Medical Sciences
Arran Hodgkinson, Mark A J Chaplain, Pia Domschke, Dumitru Trucu
Spatio-temporal models have long been used to describe biological systems of cancer, but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrades the extracellular matrix and this way leads to enhanced cancer cell migration...
March 2, 2018: Bulletin of Mathematical Biology
Marzena Staniszewska, Violetta Dziedziejko, Ewa Kwiatkowska, Marta Tkacz, Kamila Puchałowicz, Krzysztof Safranow, Leszek Domanski, Andrzej Pawlik
BACKGROUND: Urokinase-type plasminogen activator receptor (uPAR) is found in a variety of cell types including monocytes, lymphocytes, macrophages, and endothelial cells and plays an important role in fibrinolysis and in the activation and chemotaxis of neutrophils and lymphocytes. In this study, we examined the correlation between uPAR plasma concentration and kidney allograft function. AIMS: This study enrolled 78 Caucasian deceased-donor renal transplant recipients...
March 1, 2018: Irish Journal of Medical Science
Daniel Mandell, Raymond Planinsic, Fernando Melean, Christopher Hughes, Amit D Tevar, Abhinav Humar, Benjamin J Cassidy, Richard Simmons, Andre Dewolf, Tetsuro Sakai
Tissue plasminogen activator (tPA) has been reported to treat intraoperative pulmonary thromboembolism (PTE) during liver transplantation (LT). However, tPA administration is often delayed due to fear of uncontrolled bleeding and storage in a refrigerator outside of operating rooms. Various dosages of tPA were used. We hypothesize that a policy of tPA storage and low dosage use improves patient outcomes. At a transplantation center, a multidisciplinary committee has implemented a tPA policy since April 2014, which includes the following: (1) timely administering of low-dose tPA (0...
February 1, 2018: Seminars in Cardiothoracic and Vascular Anesthesia
Niaz Mahmood, Catalin Mihalcioiu, Shafaat A Rabbani
The plasminogen activator (PA) system is an extracellular proteolytic enzyme system associated with various physiological and pathophysiological processes. A large body of evidence support that among the various components of the PA system, urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2) play a major role in tumor progression and metastasis. The binding of uPA with uPAR is instrumental for the activation of plasminogen to plasmin, which in turn initiates a series of proteolytic cascade to degrade the components of the extracellular matrix, and thereby, cause tumor cell migration from the primary site of origin to a distant secondary organ...
2018: Frontiers in Oncology
Pelin Unalan Ozpercin, Burcu Kok Kendirlioglu, Sule Sozen, Ozge Yuksel, Refik Cihnioğlu, Tevfik Kalelioglu, Nesrin Karamustafalioglu
INTRODUCTION: In recent years, the role of inflammation in the pathogenesis of Bipolar Disorder (BD) has been studied thoroughly. Urokinase-type plasminogen activator receptor (uPAR) is one of the molecules, whose concentration is of predictive value with regards to an ongoing inflammation and tissue regeneration, and it is hypothesized that it may also be altered in Bipolar Disorder. In this study, it is aimed to compare the levels of serum soluble uPAR during the manic, depressive and euthymic states of cases diagnosed with bipolar disorder, with healthy individuals...
February 17, 2018: Psychoneuroendocrinology
Rafaela S Fernandes, Luis G V Fernandes, Andre S de Godoy, Patrícia A Miyasato, Eliana Nakano, Leonardo P Farias, Ana L T O Nascimento, Luciana C C Leite
Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma which have a complex life cycle characterized by an asexual multiplication in the snail intermediate host and a sexual reproduction phase in the mammalian definitive host. The initial steps of the human host infection involve the secretion of proteins contained in the acetabular glands of cercariae that promote parasite adhesion and proteolysis of the skin layers. Herein, we performed a functional analysis of SmVAL18, identified as one of the three SCP/TAPS proteins constituent of cercarial secretions...
February 22, 2018: Molecular and Biochemical Parasitology
Michael Schuliga, Christopher Grainge, Glen Westall, Darryl Knight
Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis...
February 20, 2018: International Journal of Biochemistry & Cell Biology
Min Fang, Xiaolong Mei, Hui Yao, Tao Zhang, Tao Zhang, Na Lu, Yanshi Liu, Wenyue Xu, Chunyou Wan
The present study aimed to determine the anticancer effects of the combination of β-elemene and ligustrazine in vitro as well as in in vivo . Following evaluation using an MTT assay, β-elemene, ligustrazine and the β-elemene-ligustrazine combination treatments all exhibited the capacity to inhibit the growth of OS-732 cells, with inhibitory rates of 43.3, 54.4, and 75.0%, respectively. Using a flow cytometry assay, it was determined that the β-elemene-ligustrazine combination possessed the highest apoptotic rate (30...
March 2018: Oncology Letters
Ngoc T T Nguyen, Florian Röttgerding, Gayatri Devraj, Yi-Pin Lin, Arno Koenigs, Peter Kraiczy
The emerging relapsing fever spirochete Borrelia ( B .) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi -host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B...
2018: Frontiers in Cellular and Infection Microbiology
Wei Wang, Qing Li, Tao Yang, Dongsheng Li, Feng Ding, Hongzhi Sun, Guang Bai
Aquaporin 5 (AQP5) is a water channel protein that is over-expressed in many tumors. Elevated expression of AQP5 is associated with poor prognosis of colorectal cancer. Yet, whether AQP5 plays a role in epithelial-mesenchymal transition (EMT) of colorectal cancer has not been reported until now. Here we aim to investigate the function of AQP5 in the EMT process of colorectal cancer. We transfected HCT116 and SW480 cells with AQP5-specific shRNA and verified the knockdown efficiency through western blotting and real-time PCR...
February 17, 2018: Cytotechnology
Feng Hai, Chen Xueming, Zhang Zhiwen, Li Chenyu, Fang Jie, Zhang Zhe, Lian Lishan, Zhu Renming, Yu Hongzhi, Liu Bin
OBJECTIVE: To evaluate the safety and efficacy of selective catheter-directed thrombolysis in treating acute massive pulmonary thromboembolism (AMPTE). MATERIALS AND METHODS: Twenty-six AMPTE patients were enrolled between March 2010 and March 2013. A Uni*Fuse infusion system was inserted into the main pulmonary artery thrombus. The thrombolytic regimen included an intraoperative bolus injection of 250,000 IU urokinase, followed by continuous thrombolytic infusion of 5,000IU/kg...
February 15, 2018: Annals of Vascular Surgery
Andrew S Gilder, Letizia Natali, Danielle M Van Dyk, Cristina Zalfa, Michael A Banki, Donald P Pizzo, Huawei Wang, Richard L Klemke, Elisabetta Mantuano, Steven L Gonias
PLAUR encodes the urokinase receptor (uPAR), which promotes cell survival, migration, and resistance to targeted cancer therapeutics in glioblastoma cells in culture and in mouse model systems. Herein, we show that patient survival correlates inversely with PLAUR mRNA expression in gliomas of all grades, in glioblastomas, and in the subset of glioblastomas that demonstrate the mesenchymal gene expression signature. PLAUR clusters with genes that define the more aggressive mesenchymal subtype in transcriptome profiles of glioblastoma tissue and glioblastoma cells in neurospheres, which are enriched for multipotent cells with stem cell-like qualities...
February 14, 2018: Scientific Reports
Shengyun Cai, Pei Zhang, Suhe Dong, Li Li, Jianming Cai, Mingjuan Xu
BACKGROUND/AIMS: Ovarian cancer (OC) is the fifth leading cause of cancer-related death in women, and it is difficult to diagnose at an early stage. The purpose of this study was to explore the prognostic biological markers of OC. METHODS: Univariate Cox regression analysis was used to identify genes related to OC prognosis from the Cancer Genome Atlas(TCGA) database. Immunohistochemistry was used to analyse the level of SPINK13 in OC and normal tissues. Cell proliferation, apoptosis and invasion were performed using MTT assay, flow cytometric analysis and Transwell assay, respectively...
February 7, 2018: Cellular Physiology and Biochemistry
Chongqing Huang, Guanfeng Yu, Jingyong Huang
OBJECTIVE: To investigate the clinical effect of endovascular interventional treatment for iliac vein compression syndrome (IVCS). MATERIAL AND METHODS: The data of 68 patients with IVCS, underwent interventional treatment in our hospital, were analyzed retrospectively. Among these patients, 46 were complicated with lower extremity varicose veins. 65 patients underwent stent implantation, while 3 patients underwent simple balloon angioplasty. 14 patients were complicated with post-thrombotic syndrome (PTS) and 11patients with acute deep venous thrombosis (DVT)...
February 8, 2018: Annals of Vascular Surgery
Tobias Kromann-Hansen, Eva Louise Lange, Ida K Lund, Gunilla Høyer-Hansen, Peter A Andreasen, Elizabeth A Komives
The catalytic activity of trypsin-like serine proteases is in many cases regulated by conformational changes initiated by binding of physiological modulators to exosites located distantly from the active site. A trypsin-like serine protease of particular interest is urokinase-type plasminogen activator (uPA), which is involved in extracellular tissue remodeling processes. Herein, we used hydrogen/deuterium exchange mass spectrometry (HDXMS) to study regulation of activity in the catalytic domain of the murine version of uPA (muPA) by two muPA specific monoclonal antibodies...
2018: PloS One
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