Abstract
The expression of specific molecules on the surface of vascular endothelial cells in tumours might be a key to anticancer therapy with angiostatic drugs. A new method to find these molecules on tumour vessels, targeting, is presented here. Some of these tumour-specific molecules have been identified by means of so called phage libraries. They are gene-manipulated phages, where the surface is decorated with randomly generated short peptides. After intravenous injection a few of the peptides, expressed on the surface of the phage, attach to complementary structures on the endothelial cell, as a ligand attaches to its receptor. Through biopsies and immunohistochemistry the phage can be isolated and identified. The part of the DNA of the phage that codes for the peptide-sequence of importance is sequenced. This seeking for such vessel-addresses can in the future be used for diagnostic purposes and also for local tumour-treatment. It is envisioned that cytotoxic drugs can be coupled to peptides on nanoparticles and act locally, in order to minimize toxic systemic side effects.
MeSH terms
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Angiogenesis Inhibitors / therapeutic use*
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Animals
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Antineoplastic Agents / therapeutic use*
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Biomarkers, Tumor / metabolism*
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
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Drug Screening Assays, Antitumor / methods*
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Endothelium, Vascular / metabolism*
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Exenatide
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Glucagon / administration & dosage
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Glucagon / analogs & derivatives*
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Glucagon / antagonists & inhibitors*
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Glucagon / pharmacology
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Glucagon / therapeutic use
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Glucagon-Like Peptide 1
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Glucagon-Like Peptide-1 Receptor
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Humans
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Liraglutide
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Nanostructures
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Neoplasms / blood supply
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Neoplasms / drug therapy*
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Neovascularization, Pathologic / drug therapy
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Peptide Fragments / administration & dosage
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Peptide Fragments / antagonists & inhibitors*
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Peptide Fragments / pharmacology
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Peptide Library
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Peptides / therapeutic use
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Protein Precursors / administration & dosage
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Protein Precursors / antagonists & inhibitors*
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Protein Precursors / pharmacology
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Receptors, Glucagon / antagonists & inhibitors
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Venoms / therapeutic use
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Biomarkers, Tumor
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GLP1R protein, human
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Glucagon-Like Peptide-1 Receptor
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Peptide Fragments
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Peptide Library
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Peptides
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Protein Precursors
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Receptors, Glucagon
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Venoms
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Liraglutide
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Glucagon-Like Peptide 1
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Glucagon
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Exenatide
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DP IV-related protease, human
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases