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Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126

Current experimental and clinical knowledge supports the optimisation of endothelial cell targeting using a strategy combining anti-EGFR drugs with antivascular agents. The purpose of the present study was to examine the effects of the association of ZD6126, an antivascular microtubule-destabilising...

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Autores principales: Bozec, A, Lassalle, S, Gugenheim, J, Fischel, J-L, Formento, P, Hofman, P, Milano, G
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360508/
https://www.ncbi.nlm.nih.gov/pubmed/16940984
http://dx.doi.org/10.1038/sj.bjc.6603308
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author Bozec, A
Lassalle, S
Gugenheim, J
Fischel, J-L
Formento, P
Hofman, P
Milano, G
author_facet Bozec, A
Lassalle, S
Gugenheim, J
Fischel, J-L
Formento, P
Hofman, P
Milano, G
author_sort Bozec, A
collection PubMed
description Current experimental and clinical knowledge supports the optimisation of endothelial cell targeting using a strategy combining anti-EGFR drugs with antivascular agents. The purpose of the present study was to examine the effects of the association of ZD6126, an antivascular microtubule-destabilising agent, with gefitinib and irradiation on the growth of six head and neck human cancer cell lines xenografted in nude mice and to study predictive and molecular factors responsible for antitumour effects. CAL33- and Hep-2-grafted cell lines were the most sensitive to ZD6126 treatment, with VEGF levels significantly higher (P=0.0336) in these tumour xenografts compared to Detroit 562- and CAL27-grafted cell lines with relatively low VEGF levels that were not sensitive to ZD6126. In contrast, neither IL8 levels nor EGFR expression was linked to the antitumour effects of ZD6126. ZD6126 in combination with gefitinib resulted in a synergistic cytotoxic interaction with greater antitumour effects than gefitinib alone. The synergistic interaction between ZD6126 and gefitinib was corroborated by a significant decrease in CD31 labelling. The present study may serve for future innovative clinical applications, as it suggests that VEGF tumour levels are possible predictors for ZD6126 antitumour efficacy. It also supports the notion of antitumour supra-additivity when combining gefitinib and ZD6126, and identifies neoangiogenesis as the main determinant of this synergistic combination.
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spelling pubmed-23605082009-09-10 Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126 Bozec, A Lassalle, S Gugenheim, J Fischel, J-L Formento, P Hofman, P Milano, G Br J Cancer Translational Therapeutics Current experimental and clinical knowledge supports the optimisation of endothelial cell targeting using a strategy combining anti-EGFR drugs with antivascular agents. The purpose of the present study was to examine the effects of the association of ZD6126, an antivascular microtubule-destabilising agent, with gefitinib and irradiation on the growth of six head and neck human cancer cell lines xenografted in nude mice and to study predictive and molecular factors responsible for antitumour effects. CAL33- and Hep-2-grafted cell lines were the most sensitive to ZD6126 treatment, with VEGF levels significantly higher (P=0.0336) in these tumour xenografts compared to Detroit 562- and CAL27-grafted cell lines with relatively low VEGF levels that were not sensitive to ZD6126. In contrast, neither IL8 levels nor EGFR expression was linked to the antitumour effects of ZD6126. ZD6126 in combination with gefitinib resulted in a synergistic cytotoxic interaction with greater antitumour effects than gefitinib alone. The synergistic interaction between ZD6126 and gefitinib was corroborated by a significant decrease in CD31 labelling. The present study may serve for future innovative clinical applications, as it suggests that VEGF tumour levels are possible predictors for ZD6126 antitumour efficacy. It also supports the notion of antitumour supra-additivity when combining gefitinib and ZD6126, and identifies neoangiogenesis as the main determinant of this synergistic combination. Nature Publishing Group 2006-09-18 2006-08-29 /pmc/articles/PMC2360508/ /pubmed/16940984 http://dx.doi.org/10.1038/sj.bjc.6603308 Text en Copyright © 2006 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 Translational Therapeutics
Bozec, A
Lassalle, S
Gugenheim, J
Fischel, J-L
Formento, P
Hofman, P
Milano, G
Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126
title Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126
title_full Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126
title_fullStr Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126
title_full_unstemmed Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126
title_short Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126
title_sort enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent zd6126
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360508/
https://www.ncbi.nlm.nih.gov/pubmed/16940984
http://dx.doi.org/10.1038/sj.bjc.6603308
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