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https://www.readbyqxmd.com/read/28215163/targeting-heparan-sulfate-proteoglycans-and-their-modifying-enzymes-to-enhance-anticancer-chemotherapy-efficacy-and-overcome-drug-resistance
#1
Cinzia Lanzi, Nadia Zaffaroni, Giuliana Cassinelli
Targeting heparan sulfate proteoglycans (HSPGs) and enzymes involved in heparan sulfate (HS) chain editing is emerging as a new anticancer strategy. The involvement of HSPGs in tumor cell signaling, inflammation, angiogenesis and metastasis indicates that agents able to inhibit aberrant HSPG functions can potentially act as multitarget drugs affecting both tumor cell growth and the supportive boost provided by the microenvironment. Moreover, accumulating evidence supports that an altered expression or function of HSPGs, or of the complex enzyme system regulating their activities, can also depress the tumor response to anticancer treatments in several tumor types...
February 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28209511/heparanase-1-induced-shedding-of-heparan-sulfate-from-syndecan-1-in-hepatocarcinoma-cell-facilitates-lymphatic-endothelial-cell-proliferation-via-vegf-c-erk-pathway
#2
Shengjin Yu, Huiming Lv, He Zhang, Yu Jiang, Yu Hong, Rongjun Xia, Qifang Zhang, Weiwei Ju, Lili Jiang, Geng Ou, Jinhui Zhang, Shujing Wang, Jianing Zhang
Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that HPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface...
February 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28206697/heparanase-1-involvement-in-prostate-physiopathology
#3
REVIEW
Guilherme O Barbosa, Nilva K Cervigne, Hernandes F Carvalho, Taize M Augusto
The prostate is a compound exocrine gland of the male reproductive tract universally present in mammals. It is highly responsive to androgen and can be committed by a variety of pathological complications as prostatitis, benign and malignant proliferative changes, which may be intensified by aging. Prostate intensively turnover its extracellular matrix (ECM) either at homeostasis or disease which includes a dynamically change of glycosaminoglycan composition during the life of an individual. Among the different enzymes playing a role in such changes, Heparanase-1 is responsible for cleaving heparan sulfate (HS) at a limited number of sites, clearly involved in tissue remodeling...
February 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28173134/non-reducing-end-labeling-of-heparan-sulfate-via-click-chemistry-and-a-high-throughput-elisa-assay-for-heparanase
#4
Zhengliang L Wu, Xinyi Huang, Cheryl M Ethen, Timothy Tatge, Marta Pasek, Joseph Zaia
No abstract text is available yet for this article.
February 6, 2017: Glycobiology
https://www.readbyqxmd.com/read/28170292/heparanase-mediates-intestinal-inflammation-and-injury-in-a-mouse-model-of-sepsis
#5
Song Chen, Ying He, Ziwei Hu, Siyu Lu, Xiaohan Yin, Xiaochun Ma, Chuanzhu Lv, Guiyun Jin
Heparanase, a heparan sulfate (HS)-specific endoglycosidase, plays an important role in inflammation and mediates acute pulmonary and renal injuries during sepsis. To explore its role in septic intestinal injury, a non-anticoagulant heparanase inhibitor, N-desulfated/re- N-acetylated heparin (NAH), was administrated to a mouse sepsis model induced by cecal ligation and puncture (CLP). Immunohistochemical staining revealed massive shedding of HS from the intestinal mucosal surfaces after CLP, and effective inhibition of heparanase by NAH was confirmed by markedly reduced HS shedding...
January 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28167639/therapeutic-restoration-of-endothelial-glycocalyx-in-sepsis
#6
Jong Wook Song, Joseph A Zullo, Dionysios Liveris, Matthew Dragovich, X Frank Zhang, Michael S Goligorsky
Endothelial glycocalyx (EG) is disintegrated during sepsis. We showed (Am J Pathol, 2016) that this occurs very early in the course of sepsis and its prevention improves survival of mice with sepsis. Here, we sought to investigate the possibility to pharmacologically accelerate the restoration of disintegrated EG in sepsis. We used a soilage injection model to induce polymicrobial sepsis in C57/BL6 mice and measured total body EG. En face aortic preparations were used for staining for markers of EG and atomic force microscopy (AFM) was used to measure EG in vitro...
February 6, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28163306/heparanase-roles-in-cell-survival-extracellular-matrix-remodelling-and-the-development-of-kidney-disease
#7
REVIEW
Ton J Rabelink, Bernard M van den Berg, Marjolein Garsen, Ganqi Wang, Michael Elkin, Johan van der Vlag
Heparanase has regulatory roles in various processes, including cell communication, gene transcription and autophagy. In addition, it is the only known mammalian endoglycosidase that is capable of degrading heparan sulfate (HS). HS chains are important constituents and organizers of the extracellular matrix (ECM), and have a key role in maintaining the integrity and function of the glomerular filtration barrier. In addition, HS chains regulate the activity of numerous bioactive molecules, such as cytokines and growth factors, at the cell surface and in the ECM...
February 6, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28150826/amplified-impedimetric-aptasensor-combining-target-induced-dna-hydrogel-formation-with-ph-stimulated-signal-amplification-for-the-heparanase-assay
#8
Zhe-Han Yang, Ying Zhuo, Ruo Yuan, Ya-Qin Chai
Herein, a novel electrochemical impedimetric biosensor for the heparanase (HPA) assay was developed based on target protein-induced DNA hydrogel formation, followed by pH-stimulation of the hydrogel density to increase the signal amplification. The method involved the synthesis of two different copolymer chains, consisting of two cooperatively functioning cross-linking elements, where one element was associated with the HPA-response and the other one with the pH-response. Initially, single-strand DNA as a capture probe was modified on the electrode surface...
February 2, 2017: Nanoscale
https://www.readbyqxmd.com/read/28147305/the-heparanase-inhibitor-pg545-attenuates-colon-cancer-initiation-and-growth-associating-with-increased-p21-expression
#9
Preeti Singh, Alexandra Blatt, Sari Feld, Yaniv Zohar, Esraa Saadi, Liza Barki-Harrington, Edward Hammond, Neta Ilan, Israel Vlodavsky, Yehuda Chowers, Elizabeth Half
Heparanase activity is highly implicated in cellular invasion and tumor metastasis, a consequence of cleavage of heparan sulfate and remodeling of the extracellular matrix underlying epithelial and endothelial cells. Heparanase expression is rare in normal epithelia, but is often induced in tumors, associated with increased tumor metastasis and poor prognosis. In addition, heparanase induction promotes tumor growth, but the molecular mechanism that underlines tumor expansion by heparanase is still incompletely understood...
January 29, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28128060/proteoglycans-and-diabetes
#10
Linda Hiebert
BACKGROUND: Most proteoglycans are heterogeneous molecules composed of a protein core with glycosaminoglycans (GAGs) attached. GAGs are highly negatively charged molecules that readily bind to enzymes, growth factors, cytokines etc. and as such have many functions. The role played by proteoglycans in diabetes has only recently been investigated. METHODS: The importance of proteoglycans and the effects of diabetes on proteoglycans are discussed. Possible strategies for reducing diabetic complications associated with preventing proteoglycan destruction are examined...
January 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28121356/mechanisms-of-ogt2115-inhibition-of-invasion-and-migration-in-kb-oral-cancer-cells
#11
S Shen, J-X Tang
OBJECTIVE: The purpose of this study was to investigate the effect of the heparanase inhibitor OGT2115 on the tumorigenic properties of KB oral cancer cells. MATERIALS AND METHODS: We treated KB cells with different concentrations of OGT2115. Then proliferation, invasion, and migration were detected using different assays. Cell cycle was explored using flow cytometry. RESULTS: We found that the treatment inhibited proliferation, invasion, and migration in a dose-dependent manner...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28103268/direct-observation-of-enhanced-nitric-oxide-in-a-murine-model-of-diabetic-nephropathy
#12
Margien G S Boels, Ernst E H van Faassen, M Cristina Avramut, Johan van der Vlag, Bernard M van den Berg, Ton J Rabelink
Uncoupling of nitric oxide synthase (NOS) secondary to redox signaling is a central mechanism in endothelial and macrophage activation. To date studies on the production of nitric oxide (NO) during the development of diabetic complications show paradoxical results. We previously showed that recoupling eNOS by increasing the eNOS cofactor tetrahydrobiopterin (BH4) could restore endothelial function and prevent kidney injury in experimental kidney transplantation. Here, we employed a diabetic mouse model to investigate the effects of diabetes on renal tissue NO bioavailability...
2017: PloS One
https://www.readbyqxmd.com/read/28081450/heparanase-driven-inflammation-from-the-ages-stimulated-macrophages-changes-the-functions-of-glomerular-endothelial-cells
#13
Guang Xu, Qiaojing Qin, Min Yang, Zhongdong Qiao, Yong Gu, Jianying Niu
AIMS: Amounts of macrophages were infiltrated in glomeruli in diabetic nephropathy. Heparanase has been thought to be closely related to proteinuria. Our aims were to determine the effect of heparanase on the inflammation in AGEs-stimulated macrophages and its role on the functions of glomerular endothelial cells (GEnCs). METHODS: The expression of inflammation cytokines in macrophages were assayed by q-RT PCR, western, and ELISA. Then western was used to measure the expression of RAGE and key proteins in NF-κB pathway in macrophages...
December 30, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28075546/matrix-pathobiology-central-roles-for-proteoglycans-and-heparanase-in-health-and-disease
#14
Nikos K Karamanos
This thematic minireview series highlights new concepts in matrix pathobiology. The reviews in this series cover the roles of the two matrix proteoglycans, decorin and biglycan, in inflammation and autophagy, the various functions of syndecans in cancer development and prognosis and the recently discovered mechanisms underlying the multiple roles of heparanase in cancer progression, inflammation, and autophagy.
January 2017: FEBS Journal
https://www.readbyqxmd.com/read/28064160/specific-heparanase-inhibition-reverses-glucose-induced-mesothelial-to-mesenchymal-transition
#15
Valentina Masola, Simona Granata, Gloria Bellin, Giovanni Gambaro, Maurizio Onisto, Carlo Rugiu, Antonio Lupo, Gianluigi Zaza
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells induced by high glucose (HG) levels is a major biological mechanism leading to myofibroblast accumulation in the omentum of patients on peritoneal dialysis (PD). Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate chains, is involved in the EMT of several cell lines, and may have a major role in this pro-fibrotic process potentially responsible for the failure of dialysis. Its specific inhibition may therefore plausibly minimize this pathological condition...
January 7, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28038446/heparanase-augments-insulin-receptor-signaling-in-breast-carcinoma
#16
Rachel Goldberg, Amir Sonnenblick, Esther Hermano, Tamar Hamburger, Amichay Meirovitz, Tamar Peretz, Michael Elkin
Recently, growing interest in the potential link between metabolic disorders (i.e., diabetes, obesity, metabolic syndrome) and breast cancer has mounted, including studies which indicate that diabetic/hyperinsulinemic women have a significantly higher risk of bearing breast tumors that are more aggressive and associated with higher death rates. Insulin signaling is regarded as a major contributor to this phenomenon; much less is known about the role of heparan sulfate-degrading enzyme heparanase in the link between metabolic disorders and cancer...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025251/non-reducing-end-labeling-of-heparan-sulfate-via-click-chemistry-and-a-high-throughput-elisa-assay-for-heparanase
#17
Zhengliang L Wu, Xinyi Huang, Cheryl Ethen, Timothy Tatge, Marta Pasek, Joseph Zaia
Heparan sulfate (HS) is a linear polysaccharide found in the extracellular matrix (ECM) and on the cell membrane. It plays numerous roles in cellular events, including cell growth, migration and differentiation through binding to various growth factors, cytokines and other ECM proteins. Heparanase (HPSE) is an endoglycosidase that cleaves HS in the ECM and cell membrane. By degrading HS, HPSE not only alters the integrity of the ECM but also releases growth factors and angiogenic factors bound to HS chains, therefore, changes various cellular activities, including cell mobility that is critical for cancer metastasis...
December 26, 2016: Glycobiology
https://www.readbyqxmd.com/read/27999107/heparanase-overexpression-induces-glucagon-resistance-and-protects-animals-from-chemically-induced-diabetes
#18
Dahai Zhang, Fulong Wang, Nathaniel Lal, Amy Pei-Ling Chiu, Andrea Wan, Jocelyn Jia, Denise Bierende, Stephane Flibotte, Sunita Sinha, Ali Asadi, Xiaoke Hu, Farnaz Taghizadeh, Thomas Pulinilkunnil, Corey Nislow, Israel Vlodavsky, James D Johnson, Timothy J Kieffer, Bahira Hussein, Brian Rodrigues
Heparanase, a protein with enzymatic and nonenzymatic properties, contributes toward disease progression and prevention. In the current study, a fortuitous observation in transgenic mice globally overexpressing heparanase (hep-tg) was the discovery of improved glucose homeostasis. We examined the mechanisms that contribute toward this improved glucose metabolism. Heparanase overexpression was associated with enhanced glucose-stimulated insulin secretion and hyperglucagonemia, in addition to changes in islet composition and structure...
January 2017: Diabetes
https://www.readbyqxmd.com/read/27992393/manipulating-the-extracellular-matrix-an-animal-model-of-the-bladder-pain-syndrome
#19
Ifeoma Offiah, Athanasios Didangelos, Barry A OʼReilly, Stephen B McMahon
Bladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively...
January 2017: Pain
https://www.readbyqxmd.com/read/27979811/high-glucose-facilitated-endothelial-heparanase-transfer-to-the-cardiomyocyte-modifies-its-cell-death-signature
#20
Fulong Wang, Jocelyn Jia, Nathaniel Lal, Dahai Zhang, Amy Pei-Ling Chiu, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
AIMS: The secretion of enzymatically active heparanase (Hep(A)) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (Hep(L)) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of Hep(L) from the endothelial cell (EC), Hep(L) uptake and function can protect the cardiomyocyte by modifying its cell death signature. METHODS AND RESULTS: HG promoted both Hep(L) and Hep(A) secretion from microvascular (rat heart micro vessel endothelial cells, RHMEC) and macrovascular (rat aortic endothelial cells, RAOEC) EC...
December 2016: Cardiovascular Research
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