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مواد زیستی
جزئیات رویداد
همایش ، رویداد ، ژورنال
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  • potentiation of anti-angiogenic activity of heparin by blocking the atiii-interacting pentasaccharide unit and increasing net anionic charge

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    • تاریخ ارائه: 1391/01/01
    • تاریخ انتشار در تی پی بین: 1391/01/01
    • تعداد بازدید: 726
    • تعداد پرسش و پاسخ ها: 0
    • شماره تماس دبیرخانه رویداد: -
     heparin, a potent anticoagulant used for the prevention of venous thromboembolism, has been recognized as a tumor angiogenesis inhibitor. its limitation in clinical application for cancer therapy, however, arises from its strong anticoagulant activity, which causes associated adverse effects. in this study, we show the structural correlation of lht7, a previously developed heparin-based angiogenesis inhibitor, with its influence on vegf blockade and its decreased anticoagulant activity. lht7 was characterized as having average seven molecules of sodium taurocholates conjugated to one molecule of low-molecular-weight heparin (lmwh). this study showed that the conjugation of sodium taurocholates selectively blocked interaction with antithrombin iii (atiii) while enhancing the binding with vegf. this resulted in lht7 to have negligible anticoagulant activity but potent anti-angiogenic activity. following up on this finding, we showed that the bidirectional effect of sodium taurocholate conjugation was due to its unique structure, that is, the sterane core hindering the atiii-binding pentasaccharide unit of lmwh with its bulky and rigid structural characteristics while the terminal sulfate group interacts with vegf to produce stronger binding. in addition, we showed that lht7 was localized in the tumor, especially on the endothelial cells. one explanation for this might be that lht7 was delivered to the tumor via platelets.

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