Antiangiogenic and anticancer effect of an orally active low molecular weight heparin conjugates and its application to lung cancer chemoprevention

Kim, Jiyoung; Al-Hilal, Taslim A.; Chung, Soo Kyo; Kim, Sang Yoon; Ryu, Gyu Ha; Son, Woo Chan; Byun, Youngro

doi:10.1016/j.jconrel.2014.12.015

Cited by 40 publications

(26 citation statements)

References 34 publications

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“…This effect was consistent with many other previously reported studies[14, 32]. Although the effects of heparin on HMVEC-L proliferation were marginal, it should be considered in the context of VEGF stimulation.…”

Section: Discussionsupporting

confidence: 93%

Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy

et al. 2018

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Children with hypoplastic lung diseases, such as congenital diaphragmatic hernia, can require life support via extracorporeal membrane oxygenation and systemic anticoagulation, usually in the form of heparin. The role of heparin in angiogenesis and organ growth is inconclusive, with conflicting data reported in the literature. This study aimed to investigate the effects of heparin on lung growth in a model of compensatory lung growth (CLG). Compared to the absence of heparin, treatment with heparin decreased the vascular endothelial growth factor (VEGF)-mediated activation of VEGFR2 and mitogenic effect on human lung microvascular endothelial cells in vitro. Compared to non-heparinized controls, heparinized mice demonstrated impaired pulmonary mechanics, decreased respiratory volumes and flows, and reduced activity levels after left pneumonectomy. They also had lower lung volume, pulmonary septal surface area and alveolar density on morphometric analyses. Lungs of heparinized mice displayed decreased phosphorylation of VEGFR2 compared to the control group, with consequential downstream reduction in markers of cellular proliferation and survival. The use of bivalirudin, an alternative anticoagulant that does not interact with VEGF, preserved lung growth and pulmonary mechanics. These results demonstrated that heparin impairs CLG by reducing VEGFR2 activation. These findings raise concern for the clinical use of heparin in the setting of organ growth or regeneration.

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Section: Discussionsupporting

confidence: 93%

Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy

et al. 2018

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“…Therefore, Hep and HS are promising biomolecules for the development of anticancer therapeutics because they play a significant role in the growth factor (GF)‐driven signalling processes involved in tumour onset and the progression of different human cancer cell types (Knelson et al, ). Consequently, modified LMW Hep was introduced as an orally active anti‐cancer drug for prevention of lung cancer (Kim et al, ; Lee et al, ). By contrast, CS has been proven to be a potential anticancer therapeutic agent because of its anti‐angiogenic effects during tumour progression, by the inhibition of monocyte migration through vascular endothelial cell monolayers (Liu et al, ).…”

Section: Survey On Medical Application Of Native Glycosaminoglycansmentioning

confidence: 99%

Medical application of glycosaminoglycans: a review

Köwitsch

Zhou

Groth

2017

J Tissue Eng Regen Med

183

145

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The characteristic molecular composition of the different glycosaminoglycans (GAGs) is related to their role as structural components and regulators of a multitude of functions of proteins, cells and tissues in the human body. Therefore, it is not surprising that GAGs are widely used as coating materials for implants, components of 3D-constructs such as tissue engineering scaffolds and hydrogels, but also as diagnostic devices such as biosensors and in controlled release applications. Beside a physisorption or encapsulation of GAGs, these applications often require their chemical modification to allow a stable covalent attachment on surfaces or cross-linking reactions with other molecules. Then, the preservation of the functionality of GAGs under maintenance of their biocompatibility is a challenging task and must be addressed in accordance with the designated field of application. Here, we will give a brief overview on structure and biological functions of GAGs, different methods of their activation and immobilization, the recent progress in GAG-related biomaterials development, as well as some examples of their application in the field of tissue engineering and regenerative medicine.

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“…PVAX is designed to incorporate VA and H 2 O 2 ‐responsive peroxalate ester linkages covalently in its backbone, which is able to reduce the generation of ROS and exert anti‐inflammatory capability after release of degraded product, VA . Hep‐DOCA is synthesized to reduce the side effects of bleeding caused by heparin and the co‐assembly of Hep‐DOCA with PVAX form nanoparticles with improved anti‐inflammatory capability . PVAX and released VA remove the excessive ROS and Hep‐DOCA resist thrombus formation (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Inflammation‐Associated Thrombosis with ROS‐Responsive Heparin‐DOCA/PVAX Nanoparticles

Xiang

Wang

et al. 2019

Macromolecular Bioscience

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Inflammation‐associated thrombosis is a non‐negligible source of mortalities and morbidities worldwide. To manipulate inflammation‐associated coagulation, nanoparticles that contain anti‐inflammatory polymer (copolyoxalate containing vanillyl alcohol, PVAX) and anti‐thrombotic heparin derivative deoxycholic acid (Hep‐DOCA) are prepared. The strategy takes advantage of the reducted side effects of heparin through heparin conjugation, achievement of long‐term anti‐inflammation by inflammation‐trigged release of anti‐inflammatory agents, and formation of PVAX/heparin‐DOCA nanoparticles by co‐self‐assembly. It is demonstrated that the Hep‐DOCA conjugate and PVAX are synthesized successfully; PVAX and Hep‐DOCA nanodrugs (HDP) are obtained by co‐assembly; the HDP nanoparticles effectively reduce the inflammation and coagulation without inducing lethal bleeding both in vivo and in vitro. The method provided here is versatile and effective, which paves new way to develop nanodrugs to treat inflammation‐associated thrombosis safely.

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Antiangiogenic and anticancer effect of an orally active low molecular weight heparin conjugates and its application to lung cancer chemoprevention

Cited by 40 publications

References 34 publications

Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy

Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy

Medical application of glycosaminoglycans: a review

Inhibition of Inflammation‐Associated Thrombosis with ROS‐Responsive Heparin‐DOCA/PVAX Nanoparticles

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