The synergistic action of a VEGF-receptor tyrosine-kinase inhibitor and a sensitizing PDGF-receptor blocker depends upon the stage of vascular maturation

Hlushchuk, Ruslan; Baum, Oliver; Gruber, Guenther; Wood, Jeanette; Djonov, Valentin (2007). The synergistic action of a VEGF-receptor tyrosine-kinase inhibitor and a sensitizing PDGF-receptor blocker depends upon the stage of vascular maturation. Microcirculation, 14(8), pp. 813-25. Malden, Mass.: Wiley-Blackwell 10.1080/10739680701370021

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OBJECTIVE: To investigate the effects of tyrosine-kinase inhibitors of vascular endothelial growth factor (VECF) and platelet-derived growth factor (PDCF)-receptors on non-malignant tissue and whether they depend upon the stage of vascular maturation. MATERIALS AND METHODS: PTK787/ZK222584 and CGP53716 (VEGF- and PDGF-receptor inhibitor respectively), both alone and combined, were applied on chicken chorioallantoic membrane (CAM). RESULTS: On embryonic day of CAM development (E)8, only immature microvessels, which lack coverage of pericytes, are present: whereas the microvessels on E12 have pericytic coverage. This development was reflected in the expression levels of pericytic markers (alpha-smooth muscle actin, PDGF-receptor beta and desmin), which were found by immunoblotting to progressively increase between E8 and E12. Monotherapy with 2 microg of PTK787/ZK222584 induced significant vasodegeneration on E8, but not on E12. Monotherapy with CGP53716 affected only pericytes. When CGP53716 was applied prior to treatment with 2 microg of PTK787/ZK222584, vasodegeneration occurred also on E12. The combined treatment increased the apoptotic rate. as evidenced by the cDNA levels of caspase-9 and the TUNEL-assay. CONCLUSION: Anti-angiogenic treatment strategies for non-neoplastic disorders should aim to interfere with the maturation stage of the target vessels: monotherapy with VEGF-receptor inhibitor for immature vessels, and combined anti-angiogenic treatment for well developed mature vasculature.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy
UniBE Contributor:	Hlushchuk, Ruslan, Baum, Oliver, Djonov, Valentin Georgiev
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1073-9688
ISBN:	17907017
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:55
Last Modified:	05 Dec 2022 14:17
Publisher DOI:	10.1080/10739680701370021
PubMed ID:	17907017
Web of Science ID:	000251366400005
URI:	https://boris.unibe.ch/id/eprint/23523 (FactScience: 42198)