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Pegylated TRAIL retains anti-leukemic cytotoxicity and exhibits improved signal transduction activity with respect to TRAIL
- Source :
- Investigational New Drugs. 30:828-832
- Publication Year :
- 2010
- Publisher :
- Springer Science and Business Media LLC, 2010.
-
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.
- Subjects :
- Time Factors
Recombinant Fusion Proteins
Antineoplastic Agents
Apoptosis
HL-60 Cells
TRAIL
Signal transduction
Polyethylene Glycols
TNF-Related Apoptosis-Inducing Ligand
Cell Movement
Humans
Pharmacology (medical)
Phosphorylation
Cytotoxicity
Mitogen-Activated Protein Kinase 1
Pharmacology
Leukemia
Mitogen-Activated Protein Kinase 3
Dose-Response Relationship, Drug
Caspase 3
Chemistry
Mesenchymal stem cell
Mesenchymal Stem Cells
Pegylation
In vitro
Oncology
Immunology
PEGylation
Cancer research
Tumor necrosis factor alpha
Subjects
Details
- ISSN :
- 15730646 and 01676997
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Investigational New Drugs
- Accession number :
- edsair.doi.dedup.....d89de8e9d9bc3301d08029ce501a98f0