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Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD...

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Autores principales: Wildiers, H, Guetens, G, De Boeck, G, Verbeken, E, Landuyt, B, Landuyt, W, de Bruijn, E A, van Oosterom, A T
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741115/
https://www.ncbi.nlm.nih.gov/pubmed/12799646
http://dx.doi.org/10.1038/sj.bjc.6601005
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author Wildiers, H
Guetens, G
De Boeck, G
Verbeken, E
Landuyt, B
Landuyt, W
de Bruijn, E A
van Oosterom, A T
author_facet Wildiers, H
Guetens, G
De Boeck, G
Verbeken, E
Landuyt, B
Landuyt, W
de Bruijn, E A
van Oosterom, A T
author_sort Wildiers, H
collection PubMed
description Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD) results in decreased delivery of concomitantly administered classical anticancer drugs. We designed an in vivo study to investigate the relation between VEGF-blocking therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more pronounced with potentially functional large vessels than endothelial cords. Interestingly, a trend to increased intratumoral CPT-11 concentration was observed (P=0.09). In parallel, we measured an increase in tumour perfusion, as estimated by high-performance liquid chromatography determination of intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was at least equally effective with or without pretreatment with A4.6.1. These data suggest that tumour vascular function and tumour uptake of anticancer drugs improve with VEGF-blocking therapy, and indicate the relevance for further investigations.
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spelling pubmed-27411152009-09-10 Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11 Wildiers, H Guetens, G De Boeck, G Verbeken, E Landuyt, B Landuyt, W de Bruijn, E A van Oosterom, A T Br J Cancer Experimental Therapeutics Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD) results in decreased delivery of concomitantly administered classical anticancer drugs. We designed an in vivo study to investigate the relation between VEGF-blocking therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more pronounced with potentially functional large vessels than endothelial cords. Interestingly, a trend to increased intratumoral CPT-11 concentration was observed (P=0.09). In parallel, we measured an increase in tumour perfusion, as estimated by high-performance liquid chromatography determination of intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was at least equally effective with or without pretreatment with A4.6.1. These data suggest that tumour vascular function and tumour uptake of anticancer drugs improve with VEGF-blocking therapy, and indicate the relevance for further investigations. Nature Publishing Group 2003-06-16 2003-06-10 /pmc/articles/PMC2741115/ /pubmed/12799646 http://dx.doi.org/10.1038/sj.bjc.6601005 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Experimental Therapeutics
Wildiers, H
Guetens, G
De Boeck, G
Verbeken, E
Landuyt, B
Landuyt, W
de Bruijn, E A
van Oosterom, A T
Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11
title Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11
title_full Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11
title_fullStr Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11
title_full_unstemmed Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11
title_short Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11
title_sort effect of antivascular endothelial growth factor treatment on the intratumoral uptake of cpt-11
topic Experimental Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741115/
https://www.ncbi.nlm.nih.gov/pubmed/12799646
http://dx.doi.org/10.1038/sj.bjc.6601005
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