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Heparanase

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https://www.readbyqxmd.com/read/28811133/arylamidonaphtalene-sulfonate-compounds-as-a-novel-class-of-heparanase-inhibitors
#1
Riccardo Rondanin, Sara Fochi, Riccardo Baruchello, Tatiana Bernardi, Paola Oliva, Floriana Semeraro, Daniele Simoni, Giuseppe Giannini
The search for antimetastatic agents for cancer therapy may involve the ability of new compounds to maintain the tissue extracellular matrix integrity. Among known factors, heparanase, an endoglucuronidase responsible for heparan sulfate cleavage, is a promising target whose inhibition could represent a strong obstacle for metastatic cancerous mechanisms. The antimetastatic activity of some suramin derivatives reported in literature suggests a possible involvement of the heparanase enzyme. To confirm such hypothesis, we have investigated FCE27266, a molecule known for its antiangiogenic and antimetastatic properties...
August 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28810553/evaluation-of-the-c-domain-of-heparanase-during-age-induced-macrophage-inflammatory-response
#2
Qiaojing Qin, Guang Xu, Weiwei Qi, Mei Guo, Zhaoxia Wang, Wangjie Xu, Zhongdong Qiao, Yong Gu, Jianying Niu
Diabetic vasculopathy is intensified by macrophage inflammation caused by advanced glycation end products (AGEs). Heparanase (HPA) is a unique endoglycosidase, which cleaves heparan sulfate proteoglycans (HSPGs) including syndecan-1 (Syn-1) to further stimulate macrophage cell migration and inflammation. The present study was planned to evaluated the role of C-domain (if any) of HPA in AGE inflammatory response in macrophages. Cell viability was assessed using MTT assay, migration assay, ELISA for tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, mRNA expression by RT-PCR and heparan degrading enzyme assay for HPA activity...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28805269/cloning-and-bacterial-expression-systems-for-recombinant-human-heparanase-production-substrate-specificity-investigation-by-docking-of-a-putative-heparanase-substrate
#3
Angela Pennacchio, Alessandro Capo, Simonetta Caira, Annabella Tramice, Antonio Varriale, Maria Staiano, Sabato D'Auria
Human heparanase (HPSE) is an enzyme that degrades the extracellular matrix. It is implicated in a multiplicity of physiological and pathological processes encouraging angiogenesis and tumor metastasis. The protein is a heterodimer composed from a subunit of 8 kDa and a subunit of 50 kDa. The two protein subunits are non-covalently associated. The cloning and expression of the two protein subunits in Escherichia coli, and their subsequent purification to homogeneity under native conditions result in the production of an active heparanase enzyme...
August 14, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28794202/circhipk3-sponges-mir-558-to-suppress-heparanase-expression-in-bladder-cancer-cells
#4
Yawei Li, Fuxin Zheng, Xingyuan Xiao, Fei Xie, Dan Tao, Chao Huang, Dong Liu, Miao Wang, Liang Wang, Fuqing Zeng, Guosong Jiang
Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA-seq and identify 6,154 distinct circRNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circRNAs are significantly dysregulated in human bladder cancer tissues. We further show that circHIPK3, also named bladder cancer-related circular RNA-2 (BCRC-2), is significantly down-regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively...
August 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28766595/design-synthesis-and-evaluation-of-heparan-sulfate-mimicking-glycopolymers-for-inhibiting-heparanase-activity
#5
Ravi S Loka, Fei Yu, Eric T Sletten, Hien M Nguyen
Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers. Upon evaluation, a glycopolymer with 12 repeating units was determined to be the most potent inhibitor and to have tight-binding characteristics...
August 2, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28761422/heparan-sulfate-proteoglycans-and-heparanases-in-alzheimer-s-disease-current-outlook-and-potential-therapeutic-targets
#6
Laura Lorente-Gea, Beatriz García, Carla Martín, Luis M Quirós, Iván Fernández-Vega
No abstract text is available yet for this article.
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28743882/hyperoside-pre-treatment-prevents-glomerular-basement-membrane-damage-in-diabetic-nephropathy-by-inhibiting-podocyte-heparanase-expression
#7
Xiaofei An, Lin Zhang, Yanggang Yuan, Bin Wang, Qiuming Yao, Ling Li, Jisheng Zhang, Ming He, Jinan Zhang
Glomerular basement membrane (GBM) damage plays a pivotal role in pathogenesis of albuminuria in diabetic nephropathy (DN). Heparan sulfate (HS) degradation induced by podocyte heparanase is the major cause of GBM thickening and abnormal perm-selectivity. In the present study, we aimed to examine the prophylactic effect of hyperoside on proteinuria development and GBM damage in DN mouse model and the cultured mouse podocytes. Pre-treatment with hyperoside (30 mg/kg/d) for four weeks could significantly decrease albuminuria, prevent GBM damage and oxidative stress in diabetes mellitus (DM) mice...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726915/oleuropein-represses-the-radiation-resistance-of-ovarian-cancer-by-inhibiting-hypoxia-and-microrna-299-targetted-heparanase-expression
#8
Yubai Xing, Dawei Cui, Shun Wang, Pingping Wang, Xiaojing Xing, Hui Li
Radiotherapy in ovarian cancer frequently invokes resistance; this severely compromises its therapeutic effect and results in poor clinical prognosis. How to overcome the acquired resistance and re-sensitize tumors to radiation is the central question in this clinical setting. Cancer cell survival was evaluated using a clonogenic assay. The microRNA expression profile was analyzed using a microarray. Transcript expression was determined using real time PCR. The expression of protein was determined by immunoblotting...
August 1, 2017: Food & Function
https://www.readbyqxmd.com/read/28721300/extracellular-matrix-alterations-in-the-peyronie-s-disease
#9
Marcelo Silva Watanabe, Thérèse Rachel Theodoro, Natália Lima Coelho, Aline Mendes, Monica Luzia Pereira Leonel, Ana Maria Mader, Helena Bonciani Nader, Sidney Glina, Maria Aparecida Silva Pinhal
Peyronie's disease is characterized by fibrous plaque formation of the tunica albuginea, causing penile deformity and fertility problems. The aim of the present study was to investigate alterations in the extracellular matrix in Peyronie's disease. The study used tissues collected by surgical procedure from individuals that presented a well-established disease, while control samples were obtained by biopsies of fresh cadavers. Immunohistochemistry analysis followed by digital quantification was performed to evaluate TGF-β, heparanases and metalloproteinases (MMPs)...
July 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28720149/heparanase-promotes-neuroinflammatory-response-during-subarachnoid-hemorrhage-in-rats
#10
Benjarat Changyaleket, Zhao Zhong Chong, Randal O Dull, Danop Nanegrungsunk, Haoliang Xu
BACKGROUND: Heparanase, a mammalian endo-β-D-glucoronidase that specifically degrades heparan sulfate, has been implicated in inflammation and ischemic stroke. However, the role of heparanase in neuroinflammatory response in subarachnoid hemorrhage (SAH) has not yet been investigated. This study was designed to examine the association between heparanase expression and neuroinflammation during subarachnoid hemorrhage. METHODS: Rats were subjected to SAH by endovascular perforation, and the expression of heparanase was determined by Western blot analysis and immunofluorescence in the ipsilateral brain cortex at 24 h post-SAH...
July 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28716813/inhibition-of-heparanase-in-pediatric-brain-tumor-cells-attenuates-their-proliferation-invasive-capacity-and-in-vivo-tumor-growth
#11
Argyris Spyrou, Soumi Kundu, Lulu Haseeb, Di Yu, Tommie Olofsson, Keith Dredge, Edward Hammond, Uri Barash, Israel Vlodavsky, Karin Forsberg-Nilsson
Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM...
August 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28710312/aspirin-inhibits-cancer-metastasis-and-angiogenesis-via-targeting-heparanase
#12
Xiao-Yang Dai, Juan Yan, Xuhong Fu, Qiuming Pan, Danni Sun, Yuan Xu, Jiang Wang, Litong Nie, Lin-Jiang Tong, Aijun Shen, Mingyue Zheng, Min Huang, Minjia Tan, Hong Liu, Xun Huang, Jian Ding, Meiyu Geng
<br />Recent epidemiological and clinical studies have suggested the benefit of aspirin for cancer patients, which inspired increasing efforts to demonstrate the anti-cancer ability of aspirin and reveal the molecular mechanisms behind. Nevertheless, the anti-cancer activity and related mechanisms of aspirin remain largely unknown. This study aimed to confirm this observation, and more importantly, to investigate the potential target contributed to the anti-cancer of aspirin.<br /><br />Experimental Design:<br /><span style="font-size: 11px;">A homogeneous time resolved fluorescence (HTRF) assay was used to examine the impact of aspirin on heparanase...
July 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28706419/intestinal-anti-inflammatory-activity-of-ground-cherry-physalis-angulata-l-standardized-co2-phytopharmaceutical-preparation
#13
Luiz Domingues Almeida Junior, Ana Elisa Valencise Quaglio, Celso Acácio Rodrigues de Almeida Costa, Luiz Claudio Di Stasi
AIM: To investigate the effects of Ground Cherry (Physalis angulata L.) standardized supercritical CO2 extract in trinitrobenzenesulphonic acid (TNBS) model of rat intestinal inflammation. METHODS: The animals were divided into groups that received vehicle or P. angulata extract (PACO2) orally at the doses 25, 50 and 100 mg/kg daily by 5 d before TNBS damage. Protective effects of PACO2 were assessed by macroscopic analysis, biochemical determinations of the levels of myeloperoxidase (MPO), alkaline phosphatase (ALP), glutathione and cytokines (such as INF-γ, IL-1β, IL-6, IL-10 and TNF-α), gene expression evaluation (including Hsp70, heparanase, NF-κB, mitogen-activated protein kinases (Mapk) 1, 3, 6 and 9, and the mucins genes Muc 1, 2, 3 and 4) and histopathological studies using optical, and electronic (transmission and scanning) microscopy...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28700944/viral-activation-of-heparanase-drives-pathogenesis-of-herpes-simplex-virus-1
#14
Alex M Agelidis, Satvik R Hadigal, Dinesh Jaishankar, Deepak Shukla
Herpes simplex virus-1 (HSV-1) causes lifelong recurrent pathologies without a cure. How infection by HSV-1 triggers disease processes, especially in the immune-privileged avascular human cornea, remains a major unresolved puzzle. It has been speculated that a cornea-resident molecule must tip the balance in favor of pro-inflammatory and pro-angiogenic conditions observed with herpetic, as well as non-herpetic, ailments of the cornea. Here, we demonstrate that heparanase (HPSE), a host enzyme, is the molecular trigger for multiple pathologies associated with HSV-1 infection...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28659919/the-%C3%AE-d-endoglucuronidase-heparanase-is-a-danger-molecule-that-drives-systemic-inflammation-and-correlates-with-clinical-course-after-open-and-endovascular-thoracoabdominal-aortic-aneurysm-repair-lessons-learnt-from-mice-and-men
#15
Lukas Martin, Alexander Gombert, Jianmin Chen, Julia Liebens, Julia Verleger, Johannes Kalder, Gernot Marx, Michael Jacobs, Christoph Thiemermann, Tobias Schuerholz
Thoracoabdominal aortic aneurysm (TAAA) is a highly lethal disorder requiring open or endovascular TAAA repair, both of which are rare, but extensive and complex surgical procedures associated with a significant systemic inflammatory response and high post-operative morbidity and mortality. Heparanase is a β-d-endoglucuronidase that remodels the endothelial glycocalyx by degrading heparan sulfate in many diseases/conditions associated with systemic inflammation including sepsis, trauma, and major surgery. We hypothesized that (a) perioperative serum levels of heparanase and heparan sulfate are associated with the clinical course after open or endovascular TAAA repair and (b) induce a systemic inflammatory response and renal injury/dysfunction in mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28627391/low-molecular-weight-fucoidan-and-its-fractions-inhibit-renal-epithelial-mesenchymal-transition-induced-by-tgf-%C3%AE-1-or-fgf-2
#16
Xinpeng Li, Xiaohong Li, Quanbin Zhang, Tingting Zhao
We investigated the renal protective effects of low molecular weight fucoidan (LMWF) and its two fractions (F0.5 and F1.0), which were extracted from Laminaria japonica, on the epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) in HK-2 human renal proximal tubular cells. Cell morphology and EMT markers (fibronectin and alpha-smooth muscle actin) demonstrated that cells treated with TGF-β1 or FGF-2 developed EMT to a significant extent...
June 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28581485/activity-based-probes-for-functional-interrogation-of-retaining-%C3%AE-glucuronidases
#17
Liang Wu, Jianbing Jiang, Yi Jin, Wouter W Kallemeijn, Chi-Lin Kuo, Marta Artola, Wei Dai, Cas van Elk, Marco van Eijk, Gijsbert A van der Marel, Jeroen D C Codée, Bogdan I Florea, Johannes M F G Aerts, Herman S Overkleeft, Gideon J Davies
Humans express at least two distinct β-glucuronidase enzymes that are involved in disease: exo-acting β-glucuronidase (GUSB), whose deficiency gives rise to mucopolysaccharidosis type VII, and endo-acting heparanase (HPSE), whose overexpression is implicated in inflammation and cancers. The medical importance of these enzymes necessitates reliable methods to assay their activities in tissues. Herein, we present a set of β-glucuronidase-specific activity-based probes (ABPs) that allow rapid and quantitative visualization of GUSB and HPSE in biological samples, providing a powerful tool for dissecting their activities in normal and disease states...
June 5, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28581441/nk-cell-heparanase-controls-tumor-invasion-and-immune-surveillance
#18
Eva M Putz, Alyce J Mayfosh, Kevin Kos, Deborah S Barkauskas, Kyohei Nakamura, Liam Town, Katharine J Goodall, Dean Y Yee, Ivan Kh Poon, Nikola Baschuk, Fernando Souza-Fonseca-Guimaraes, Mark D Hulett, Mark J Smyth
NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA)...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28571915/3d-spheroids-what-can-they-tell-us-about-pancreatic-ductal-adenocarcinoma-cell-phenotype
#19
Nicoletta Gagliano, Chiarella Sforza, Michele Sommariva, Alessandra Menon, Vincenzo Conte, Patrizia Sartori, Patrizia Procacci
We aimed at analyzing the effect of the 3D-arrangement on the expression of some genes and proteins which play a key role in pancreatic adenocarcinoma (PDAC) progression in HPAF-II, HPAC and PL45 PDAC cells cultured in either 2D-monolayers or 3D-spheroids. Cytokeratins 7, 8, 18, 19 were differently expressed in 3D-spheroids compared to 2D-monolayers. Syndecan 1 was upregulated in HPAF-II and PL45 3D-spheroids, and downregulated in HPAC. Heparanase mRNA levels were almost unchanged in HPAF-II, and increased in HPAC and PL45 3D-spheroids...
August 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28571003/bptf-inhibits-nk-cell-activity-and-the-abundance-of-natural-cytotoxicity-receptor-co-ligands
#20
Kimberly Mayes, Zeinab Elsayed, Aiman Alhazmi, Michael Waters, Suehyb G Alkhatib, Mark Roberts, Carolyn Song, Kristen Peterson, Vivian Chan, Nikhil Ailaney, Pumoli Malapati, Tana Blevins, Berislav LisniÄ, Catherine I Dumur, Joseph W Landry
Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in the tumor microenvironment (TME). In culture, BPTF suppresses direct natural cytotoxicity receptor (NCR) mediated NK cell cytolytic activity to mouse and human cancer cell lines, demonstrating conserved functions. Blocking mouse NCR1 in vivo rescues BPTF KD tumor weights, demonstrating its importance for the control of tumor growth...
May 12, 2017: Oncotarget
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