Abstract
To improve the pharmacokinetic profile of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) an N-terminal specific pegylation was performed to generate pegylated TRAIL (PEG-TRAIL). In in vitro experiments, we found that although PEG-TRAIL was slightly less efficient than recombinant TRAIL in promoting leukemic cell apoptosis, it showed an improved ability to promote migration of bone-marrow mesenchymal stem cells and to elicit the ERK1/2 intracellular signal transduction pathway. Overall, these data suggest that TRAIL pegylation retains, or even enhances, the biological activities of TRAIL relevant for its therapeutic applications.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Caspase 3 / metabolism
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Cell Movement / drug effects
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Dose-Response Relationship, Drug
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HL-60 Cells
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Humans
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Leukemia / metabolism*
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Leukemia / pathology
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Mesenchymal Stem Cells / drug effects*
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Mesenchymal Stem Cells / metabolism
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phosphorylation
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Polyethylene Glycols / pharmacology*
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Recombinant Fusion Proteins / pharmacology*
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Signal Transduction / drug effects*
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TNF-Related Apoptosis-Inducing Ligand / pharmacology*
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Time Factors
Substances
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Antineoplastic Agents
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PEGylated tumor necrosis factor-related apoptosis-inducing ligand
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Recombinant Fusion Proteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Polyethylene Glycols
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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CASP3 protein, human
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Caspase 3