Show simple item record

dc.contributor.authorHasan, J.*
dc.contributor.authorShnyder, Steven D.*
dc.contributor.authorClamp, A.R.*
dc.contributor.authorMcGown, A.T.*
dc.contributor.authorBicknell, R.*
dc.contributor.authorPresta, M.*
dc.contributor.authorBibby, Michael C.*
dc.contributor.authorDouble, John A.*
dc.contributor.authorCraig, S.*
dc.contributor.authorLeeming, D.*
dc.contributor.authorStevenson, K.*
dc.contributor.authorGallagher, J.T.*
dc.contributor.authorJayson, G.C.*
dc.date.accessioned2009-07-21T13:34:02Z
dc.date.available2009-07-21T13:34:02Z
dc.date.issued2005
dc.identifier.citationHasan J, Shnyder SD and Clamp AR, et al (2005) Heparin octasaccharides inhibit angiogenesis in vivo. Clinical Cancer Research. 11(22): 8172-8179.en
dc.identifier.urihttp://hdl.handle.net/10454/3089
dc.descriptionNoen
dc.description.abstractBackground: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. Experimental Design: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. Results: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing 16 saccharide residues were investigated. Conclusions: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin.en
dc.language.isoenen
dc.relation.isreferencedbyhttp://clincancerres.aacrjournals.org/cgi/reprint/11/22/8172en
dc.subjectGlycosaminoglycan; In vivo; Neovascularization; Angiogenesis; Inhibitor; Anticoagulant; Heparinen
dc.titleHeparin octasaccharides inhibit angiogenesis in vivo.en
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen


This item appears in the following Collection(s)

Show simple item record