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https://www.readbyqxmd.com/read/28521475/microrna-1258-an-invasion-and-metastasis-regulator-that-targets-heparanase-in-gastric-cancer
#1
Jinxin Shi, Ping Chen, Jingxu Sun, Yongxi Song, Bin Ma, Peng Gao, Xiaowan Chen, Zhenning Wang
Numerous microRNAs (miRNAs/miRs) are involved in suppressing or promoting the formation of cancer. However, to the best of our knowledge, the role of miRNA-1258 in gastric cancer (GC) has not previously been investigated. Our previous study demonstrated an increased expression of heparanase (HPSE) in GC tissues and HPSE-facilitated invasion and metastasis of GC cells. Consequently, in the present study, the function of miR-1258 in the invasion and metastasis of GC cells was investigated to determine whether miR-1258 is associated with GC through HPSE...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521428/significance-of-heparanase-in-metastatic-lymph-nodes-of-cervical-squamous-cell-cancer
#2
Bin Hu, Qing Wang, Yingying Shi, Shufang Lu, Hongjie Qu, Lu Wang, Jinquan Cui
The aim of this study was to explore the expression of heparanase (HPA) in metastatic lymph nodes (LNs) of cervical cancer and to evaluate HPA as a marker of micro-metastasis of LNs. Immunohistochemistry was performed to detect the expression of HPA in 53 cases with metastasis of LNs (group A) and 49 cases without (group B). Scoring was determined based on the intensity of immunostaining and the size of the staining area. Three points or higher score was considered as positive. Among all cases, the positive rate of HPA was 76...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28505136/gubenyiliu-ii-inhibits-breast-tumor-growth-and-metastasis-associated-with-decreased-heparanase-expression-and-phosphorylation-of-erk-and-akt-pathways
#3
Yi Zhang, Gan-Lin Zhang, Xu Sun, Ke-Xin Cao, Ya-Wen Shang, Mu-Xin Gong, Cong Ma, Nan Nan, Jin-Ping Li, Ming-Wei Yu, Guo-Wang Yang, Xiao-Min Wang
Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII...
May 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28498476/effects-of-unfractionated-heparin-and-rivaroxaban-on-the-expression-of-heparanase-and-fibroblast-growth-factor-2-in-human-osteoblasts
#4
Jingjun Xia, Wei Sheng, Liubao Pei, Ning Li, Zhipeng Zhang, Jialiang Wang, Jianing Zu, Nanxiang Wang, Duanyang Wang
Long-term treatment with anticoagulants may contribute to osteoporosis. Although unfractionated heparin and rivaroxaban have adverse effects on bone microstructure and function in adult rats, the underlying mechanism remains to be elucidated. Heparanase (HPSE) and fibroblast growth factor (FGF)2 are important signals in bone formation and fracture healing. Therefore, the present study was designed to investigate the effects of unfractionated heparin and rivaroxaban on the expression of HPSE and FGF2 in human osteoblasts...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28490587/heparanase-upregulation-contributes-to-porcine-reproductive-and-respiratory-syndrome-virus-release
#5
Chunhe Guo, Zhenbang Zhu, Yang Guo, Xiaoying Wang, Piao Yu, Shuqi Xiao, Yaosheng Chen, Yongchang Cao, Xiaohong Liu
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause substantial economic losses to the pig industry worldwide. Heparan sulfate (HS) is used by PRRSV for initial attachment to target cells. However, the role of HS in the late phase of PRRSV infection and the mechanism of virus release from host cells remain largely unknown. In this study, we showed that PRRSV infection caused a decrease of HS expression and upregulated heparanase, the only known enzyme capable to degrade HS. We subsequently demonstrated that the NF-κB signaling pathway and cathepsin L protease were involved in regulation of PRRSV infection-induced heparanase...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28486399/assessment-of-heparanase-mediated-angiogenesis-using-microvascular-endothelial-cells-identification-of-%C3%AE-carrageenan-derivative-as-a-potent-anti-angiogenic-agent
#6
Nicolas Poupard, Pamela Badarou, Fabienne Fasani, Hugo Groult, Nicolas Bridiau, Frédéric Sannier, Stéphanie Bordenave-Juchereau, Claudine Kieda, Jean-Marie Piot, Catherine Grillon, Ingrid Fruitier-Arnaudin, Thierry Maugard
Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent heparanase inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective heparanase inhibitor with an IC50 of 7...
May 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28453727/endothelial-glycocalyx-breakdown-is-mediated-by-angiopoietin-2
#7
Alexander Lukasz, Carina Hillgruber, Hans Oberleithner, Kristina Kusche-Vihrog, Hermann Pavenstädt, Alexandros Rovas, Bettina Hesse, Tobias Goerge, Philipp Kümpers
Aims: The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal surface of the endothelium, provides a first vasoprotective barrier against vascular leakage and adhesion in sepsis and vessel inflammation. Angiopoietin-2 (Angpt-2), an antagonist of the endothelium-stabilizing receptor Tie2 secreted by endothelial cells, promotes vascular permeability through cellular contraction and junctional disintegration. We hypothesized that Angpt-2 might also mediate the breakdown of the eGC...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28451171/antiangiogenic-platinum-through-glycan-targeting
#8
Erica J Peterson, A Gerard Daniel, Samantha J Katner, Lisa Bohlmann, Chih-Wei Chang, Anna Bezos, Christopher R Parish, Mark von Itzstein, Susan J Berners-Price, Nicholas P Farrell
Heparan sulfate is identified as a ligand receptor for polynuclear platinum anti-cancer agents through sulfate cluster binding. We present a new biological role for platinum and coordination compounds and a new target for metal-based drugs while presenting a new chemotype for heparanase and growth factor inhibition through modulation (metalloshielding) of their interactions. Masking of extracellular (ECM)-resident heparan sulfate (HS) through metalloshielding results in very effective inhibition of physiologically critical HS functions including enzyme (heparanase, HPSE) and protein growth factor recognition...
January 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28446717/gemcitabine-induced-heparanase-promotes-aggressiveness-of-pancreatic-cancer-cells-via-activating-egfr-signaling
#9
Jin-Wen Song, Ying-Xia Tan, Su-Bo Li, Shi-Kun Zhang, Lu-Ming Wan, Shou-Ping Ji, Hong Zhou, Zhi-Hang Zhou, Feng Gong
Pancreatic cancer (PC), characterized by aggressive local invasion and metastasis, is one of the most malignant cancers. Gemcitabine is currently used as the standard drug for the treatment of advanced and metastatic PC, but with limited efficacy. In this study, we demonstrated that gemcitabine increased the expression of heparanase (HPA1), the only known mammalian endoglycosidase capable of cleaving heparan sulfate, both in vitro and in vivo. Furthermore, overexpression of HPA1 in PC cell lines enhanced proliferation and invasion, accompanied with elevated phosphorylation of EGFR...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439967/involvement-of-heparanase-procoagulant-domain-in-bleeding-and-wound-healing
#10
Yonatan Crispel, Shourouk Ghanem, Judith Attias, Inna Kogan, Benjamin Brenner, Yona Nadir
BACKGROUND: Heparanase, known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of factor Xa. Our study demonstrated that peptides derived from TF pathway inhibitor (TFPI)-2 impeded the procoagulant effect of heparanase and attenuated inflammation, tumor growth and vascularization. AIMS: The present study aimed to identify the procoagulant domain in the heparanase molecule and to evaluate its effects in a model of wound healing that involves inflammation and angiogenesis...
April 25, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28401953/overexpression-of-heparanase-enhances-t-lymphocyte-activities-and-intensifies-the-inflammatory-response-in-a-model-of-murine-rheumatoid-arthritis
#11
Andreas Digre, Kailash Singh, Magnus Åbrink, Rogier M Reijmers, Stellan Sandler, Israel Vlodavsky, Jin-Ping Li
Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced animals developed clinical symptoms, i...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28400617/nek2-induces-osteoclast-differentiation-and-bone-destruction-via-heparanase-in-multiple-myeloma
#12
M Hao, R Franqui-Machin, H Xu, J Shaughnessy, B Barlogie, D Roodman, D E Quelle, S Janz, M H Tomasson, R D Sanderson, L Qiu, I Frech, G Tricot, F Zhan
No abstract text is available yet for this article.
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28394941/correction-heparanase-a-potential-new-factor-involved-in-the-renal-epithelial-mesenchymal-transition-emt-induced-by-ischemia-reperfusion-i-r-injury
#13
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0160074.].
2017: PloS One
https://www.readbyqxmd.com/read/28388549/elevated-heparanase-expression-is-associated-with-poor-prognosis-in-breast-cancer-a-study-based-on-systematic-review-and-tcga-data
#14
REVIEW
Xu Sun, Ganlin Zhang, Jiayun Nian, Mingwei Yu, Shijian Chen, Yi Zhang, Guowang Yang, Lin Yang, Peiyu Cheng, Chen Yan, Yunfei Ma, Hui Meng, Xiaomin Wang, Jin-Ping Li
Heparanase promotes tumorigenesis, angiogenesis, and metastasis. Here, we conducted a study based on systematic review and the Cancer Genome Atlas (TCGA) data that examined heparanase expression in clinical samples to determine its prognostic value. According to the meta-analysis and TCGA data, we found that heparanase expression was up-regulated in most breast cancer specimens, and elevated heparanase expression was associated with increased lymph node metastasis, larger tumor size, higher histological grade, and poor survival...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388547/involvement-of-heparanase-in-the-pathogenesis-of-acute-kidney-injury-nephroprotective-effect-of-pg545
#15
Zaid Abassi, Shadi Hamoud, Ahmad Hassan, Iyad Khamaysi, Omri Nativ, Samuel N Heyman, Rabia Shekh Muhammad, Neta Ilan, Preeti Singh, Edward Hammond, Gianluigi Zaza, Antonio Lupo, Maurizio Onisto, Gloria Bellin, Valentina Masola, Israel Vlodavsky, Giovani Gambaro
Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387673/upregulated-expression-of-heparanase-and-heparanase-2-in-the-brains-of-alzheimer-s-disease
#16
Beatriz García, Carla Martín, Olivia García-Suárez, Bárbara Muñiz-Alonso, Helena Ordiales, Santiago Fernández-Menéndez, Jorge Santos-Juanes, Laura Lorente-Gea, Sonia Castañón, Ikerne Vicente-Etxenausia, Kelvin Manuel Piña Batista, Irune Ruiz-Díaz, María Cristina Caballero-Martínez, Jesús Merayo-Lloves, Isabel Guerra-Merino, Luis M Quirós, Iván Fernández-Vega
BACKGROUND: Heparan sulfate proteoglycans (HSPGs) promote amyloid-β peptide and tau fibrillization in Alzheimer's disease (AD) and provide resistance against proteolytic breakdown. Heparanase (HPSE) is the only enzyme that cleaves heparan sulfate (HS). Heparanase 2 (HPSE2) lacks HS-degrading activity, although it is able to interact with HS with high affinity. OBJECTIVE: To analyze HPSE and HPSE2 expressions at different stages of AD. METHODS: RT-PCR was used to analyze transcription levels of both heparanases at different stages of AD, and immunohistochemistry was performed to localize each one in different parts of the brain...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28386074/the-role-of-heparanase-in-the-pathogenesis-of-acute-pancreatitis-a-potential-therapeutic-target
#17
Iyad Khamaysi, Preeti Singh, Susan Nasser, Hoda Awad, Yehuda Chowers, Edmond Sabo, Edward Hammond, Ian Gralnek, Irena Minkov, Alessandro Noseda, Neta Ilan, Israel Vlodavsky, Zaid Abassi
Acute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains of HS sulfate proteoglycans into shorter oligosaccharides, activity that is highly implicated in cellular invasion associated with cancer metastasis and inflammation. Given that AP involves a strong inflammatory aspect, we examined whether heparanase plays a role in AP...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385219/production-of-heparin-and-%C3%AE-carrageenan-anti-heparanase-derivatives-using-a-combination-of-physicochemical-depolymerization-and-glycol-splitting
#18
Nicolas Poupard, Hugo Groult, Justine Bodin, Nicolas Bridiau, Stéphanie Bordenave-Juchereau, Frédéric Sannier, Jean-Marie Piot, Ingrid Fruitier-Arnaudin, Thierry Maugard
Strongly associated with tumor angiogenesis and metastasis, the enzyme heparanase is an endo-β-d-glucuronidase which is overexpressed in the tumor microenvironment. Its inhibition could be one of the most promising anti-angiogenic approaches to date. Although heparin is known as a good heparanase inhibitor, it also possesses major anticoagulant properties that may be incompatible with its use as an anti-angiogenic agent, hence the considerable interest for other sources of sulfated polysaccharides. Recent investigations point to λ-carrageenans, highly sulfated galactans with a tremendous potential that are found in red algae...
June 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28364042/kinetic-based-trapping-by-intervening-sequence-variants-of-the-active-sites-of-protein-disulfide-isomerase-identifies-platelet-protein-substrates
#19
Jack D Stopa, Katherine M Baker, Steven P Grover, Robert Flaumenhaft, Bruce Furie
Thiol isomerases such as protein disulfide isomerase (PDI) direct disulfide rearrangements required for proper folding of nascent proteins synthesized in the endoplasmic reticulum. Identifying PDI substrates is challenging since PDI catalyzes conformational changes that cannot be easily monitored (e.g., compared with proteolytic cleavage or amino acid phosphorylation), PDI has multiple substrates, and it can catalyze either oxidation, reduction, or isomerization of substrates. Kinetic-based substrate trapping wherein the active site motif CGHC is modified to CGHA to stabilize a PDI-substrate intermediate is effective in identifying some substrates...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28359266/identification-of-novel-class-of-triazolo-thiadiazoles-as-potent-inhibitors-of-human-heparanase-and-their-anticancer-activity
#20
C P Baburajeev, Chakrabhavi Dhananjaya Mohan, Shobith Rangappa, Daniel J Mason, Julian E Fuchs, Andreas Bender, Uri Barash, Israel Vlodavsky, Basappa, Kanchugarakoppal S Rangappa
BACKGROUND: Expression and activity of heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains of proteoglycans, is associated with progression and poor prognosis of many cancers which makes it an attractive drug target in cancer therapeutics. METHODS: In the present work, we report the in vitro screening of a library of 150 small molecules with the scaffold bearing quinolones, oxazines, benzoxazines, isoxazoli(di)nes, pyrimidinones, quinolines, benzoxazines, and 4-thiazolidinones, thiadiazolo[3,2-a]pyrimidin-5-one, 1,2,4-triazolo-1,3,4-thiadiazoles, and azaspiranes against the enzymatic activity of human heparanase...
March 31, 2017: BMC Cancer
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