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    Anti-metastatic effect of non-anticoagulant low molecular weight heparin versus standard low molecular weight heparin, enoxaparain

    Author
    Mousa, S.A.; Linhardt, Robert J.; Francis, J.L.; Amirkhosravi, A.
    ORCID
    https://orcid.org/0000-0003-2219-5833
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    ANTI-METASTATIC EFFECT OF A NON-ANTICOAGULANT LOW-MOLECULAR-.pdf (771.9Kb)
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    Date Issued
    2006
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    Full Citation
    Anti-metastatic effect of non-anticoagulant low molecular weight heparin versus standard low molecular weight heparin, enoxaparain, S. A. Mousa, R. J. Linhardt, J. L. Francis, A. Amirkhosravi, Thrombosis and Haemostasis, 96, 816-821, 2006.
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    URI
    https://hdl.handle.net/20.500.13015/5169; https://doi.org/10.1160/th06-05-0289
    Abstract
    Low-molecular-weight heparins (LMWH) exhibit potent anticoagulant efficacy via their plasmatic effects on thrombin and factor Xa. These agents are also effective in releasing endothelial tissue factor pathway inhibitor (TFPI), the natural inhibitor of tissue factor, and exhibit significant anti-metastatic effects in experimental animal models. However, the potential for bleeding complications has slowed down the more widespread adoption of LMWH therapy in cancer patients. In this study, the effect of a non-anticoagulant form of LMWH (NA-LMWH) on experimental lung metastasis and tumor cell-induced platelet aggregation in vivo was compared to the LMWH enoxaparin. Using the B16 melanoma mouse model of metastasis, subcutaneous (s.c.) injection of NA-LMWH or enoxaparin (10 mg/kg), three hours before intravenous (i.v.) injection of metastatic melanoma cells, followed by daily doses for 14 days, reduced lung tumor formation by 70% (P < 0.001). I.v. injection of tumor cells resulted in a significant (50-62%, P < 0.01) fall in platelet counts. Pre-injection (i.v.) of enoxaparin completely abolished the tumor cell-induced thrombocytopenia, whereas NA-LMWH had no effect. Four hours after a single s.c. dose, enoxaparin but not NA-LMWH prolonged the clotting time three-fold and delayed the time to clot initiation more than 10-fold as measured by a Sonoclot analyzer and by thromboelastography, respectively. Enoxaparin but not NA-LMWH demonstrated a significant anticoagulant effect in mice. Both NA-LMWH and enoxaparin caused similar TFPI release from endothelial cells in vitro. These data provide evidence to support the potential of NA-LMWH as an anti-metastatic agent without any significant impact on coagulation.;
    Description
    Thrombosis and Haemostasis, 96, 816-821; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Publisher
    Thieme Medical Publishers
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; https://harc.rpi.edu/;
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