The Experts below are selected from a list of 441 Experts worldwide ranked by ideXlab platform
Catherine Grillon - One of the best experts on this subject based on the ideXlab platform.
-
Assessment of Heparanase-Mediated Angiogenesis Using Microvascular Endothelial Cells: Identification of λ-Carrageenan Derivative as a Potent Anti Angiogenic Agent
Marine drugs, 2017Co-Authors: Nicolas Poupard, Pamela Badarou, Fabienne Fasani, Hugo Groult, Nicolas Bridiau, Frédéric Sannier, Stéphanie Bordenave-juchereau, Claudine Kieda, Jean-marie Piot, Catherine GrillonAbstract:Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent Heparanase Inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After Heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective Heparanase Inhibitor with an IC50 of 7.32 ng/mL compared to 10.7 ng/mL for the 16 kDa unfractionated heparin. The fractionated polysaccharides were then tested in a Heparanase-rich medium-based in vitro model, mimicking tumor microenvironment, to determine their effect on microvascular endothelial cells (HSkMEC) angiogenesis. As a preliminary study, we identified that under hypoxic and nutrient poor conditions, MCF-7 cancer cells released much more mature Heparanase in their supernatant than in normal conditions. Then a MatrigelTM assay using HSkMEC cultured under hypoxic conditions in the presence (or not) of this Heparanase-rich supernatant was realized. Adding Heparanase-rich media strongly enhanced angiogenic network formation with a production of twice more pseudo-vessels than with the control. When sulfated polysaccharides were tested in this angiogenesis assay, RD-GS-λ-Carrageenan was identified as a promising anti-angiogenic agent.
Kan Ding - One of the best experts on this subject based on the ideXlab platform.
-
Heparanase enhances nerve growth factor induced pc12 cell neuritogenesis via the p38 mapk pathway
Biochemical Journal, 2011Co-Authors: Hengxiang Cui, Chenghao Shao, Qin Liu, Jianping Fang, Amjad Ali, Kan DingAbstract:Heparanase is involved in the cleavage of the HS (heparan sulfate) chain of HSPGs (HS proteoglycans) and hence participates in remodelling of the ECM (extracellular matrix) and BM (basement membrane). In the present study we have shown that NGF (nerve growth factor) promoted nuclear enrichment of EGR1 (early growth response 1), a transcription factor for Heparanase, and markedly induced Heparanase expression in rat adrenal pheochromocytoma (PC12) cells. K252a, an antagonist of the NGF receptor TrkA (tyrosine kinase receptor A), decreased Heparanase protein expression induced by NGF in PC12 cells. Suramin, a Heparanase Inhibitor, decreased Heparanase in PC12 cells and blocked NGF-induced PC12 neuritogenesis. Stable overexpression of Heparanase activated p38 MAPK (mitogen-activated protein kinase) by phosphorylation and enhanced the neurite outgrowth induced by NGF, whereas knock down of Heparanase impaired this process. However, overexpression of latent pro-Heparanase with a Y156A mutation still led to enhanced NGF-induced neurite outgrowth and increased p38 MAPK phosphorylation. Inhibition of p38 MAPK by SB203580 suppressed the promotion of NGF-induced neuritogenesis by the wild-type and mutant Heparanase. The impaired differentiation by knock down of Heparanase could be restored by transfection of wild-type or mutant Heparanase in PC12 cells. The results of the present study suggest that Heparanase, at least in the non-enzymatic form, may promote NGF-induced neuritogenesis via the p38 MAPK pathway.
Renzo Rossi - One of the best experts on this subject based on the ideXlab platform.
-
efficient and highly regioselective direct c 2 arylation of azoles including free nh imidazole benzimidazole and indole with aryl halides
Tetrahedron, 2007Co-Authors: Fabio Bellina, Silvia Cauteruccio, Chiara Calandri, Renzo RossiAbstract:Abstract The Pd- and Cu-mediated reaction of a large variety of π-electron sufficient heteroarenes, which include free (NH)-imidazoles, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylheterocycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol for the synthesis of 2-arylazoles involving the use of aryl iodides has been found to be suitable for the efficient preparation of three bioactive compounds and a key intermediate in the synthesis of a Heparanase Inhibitor.
-
Efficient and highly regioselective direct C-2 arylation of azoles, including free (NH)-imidazole, -benzimidazole and -indole, with aryl halides
'Elsevier BV', 2007Co-Authors: Fabio Bellina, Silvia Cauteruccio, Chiara Calandri, Renzo RossiAbstract:The Pd- and Cu-mediated reaction of a large variety of pi-electron sufficient heteroarenes, which include free (NH)-imidazoles, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylhetero-cycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol for the synthesis of 2-arylazoles involving the use of aryl iodides has been found to be suitable for the efficient preparation of three bioactive compounds and a key intermediate in the synthesis of a Heparanase Inhibitor. (c) 2007 Elsevier Ltd. All rights reserved
Nicolas Poupard - One of the best experts on this subject based on the ideXlab platform.
-
Assessment of Heparanase-Mediated Angiogenesis Using Microvascular Endothelial Cells: Identification of λ-Carrageenan Derivative as a Potent Anti Angiogenic Agent
Marine drugs, 2017Co-Authors: Nicolas Poupard, Pamela Badarou, Fabienne Fasani, Hugo Groult, Nicolas Bridiau, Frédéric Sannier, Stéphanie Bordenave-juchereau, Claudine Kieda, Jean-marie Piot, Catherine GrillonAbstract:Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent Heparanase Inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After Heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective Heparanase Inhibitor with an IC50 of 7.32 ng/mL compared to 10.7 ng/mL for the 16 kDa unfractionated heparin. The fractionated polysaccharides were then tested in a Heparanase-rich medium-based in vitro model, mimicking tumor microenvironment, to determine their effect on microvascular endothelial cells (HSkMEC) angiogenesis. As a preliminary study, we identified that under hypoxic and nutrient poor conditions, MCF-7 cancer cells released much more mature Heparanase in their supernatant than in normal conditions. Then a MatrigelTM assay using HSkMEC cultured under hypoxic conditions in the presence (or not) of this Heparanase-rich supernatant was realized. Adding Heparanase-rich media strongly enhanced angiogenic network formation with a production of twice more pseudo-vessels than with the control. When sulfated polysaccharides were tested in this angiogenesis assay, RD-GS-λ-Carrageenan was identified as a promising anti-angiogenic agent.
Hengxiang Cui - One of the best experts on this subject based on the ideXlab platform.
-
Heparanase enhances nerve growth factor induced pc12 cell neuritogenesis via the p38 mapk pathway
Biochemical Journal, 2011Co-Authors: Hengxiang Cui, Chenghao Shao, Qin Liu, Jianping Fang, Amjad Ali, Kan DingAbstract:Heparanase is involved in the cleavage of the HS (heparan sulfate) chain of HSPGs (HS proteoglycans) and hence participates in remodelling of the ECM (extracellular matrix) and BM (basement membrane). In the present study we have shown that NGF (nerve growth factor) promoted nuclear enrichment of EGR1 (early growth response 1), a transcription factor for Heparanase, and markedly induced Heparanase expression in rat adrenal pheochromocytoma (PC12) cells. K252a, an antagonist of the NGF receptor TrkA (tyrosine kinase receptor A), decreased Heparanase protein expression induced by NGF in PC12 cells. Suramin, a Heparanase Inhibitor, decreased Heparanase in PC12 cells and blocked NGF-induced PC12 neuritogenesis. Stable overexpression of Heparanase activated p38 MAPK (mitogen-activated protein kinase) by phosphorylation and enhanced the neurite outgrowth induced by NGF, whereas knock down of Heparanase impaired this process. However, overexpression of latent pro-Heparanase with a Y156A mutation still led to enhanced NGF-induced neurite outgrowth and increased p38 MAPK phosphorylation. Inhibition of p38 MAPK by SB203580 suppressed the promotion of NGF-induced neuritogenesis by the wild-type and mutant Heparanase. The impaired differentiation by knock down of Heparanase could be restored by transfection of wild-type or mutant Heparanase in PC12 cells. The results of the present study suggest that Heparanase, at least in the non-enzymatic form, may promote NGF-induced neuritogenesis via the p38 MAPK pathway.