Should tumor VEGF expression influence decisions on combining low-dose chemotherapy with antiangiogenic therapy? Preclinical modeling in ovarian cancer.

Détails

ID Serval
serval:BIB_356727F485FE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Should tumor VEGF expression influence decisions on combining low-dose chemotherapy with antiangiogenic therapy? Preclinical modeling in ovarian cancer.
Périodique
Journal of Translational Medicine
Auteur(s)
Holtz D.O., Krafty R.T., Mohamed-Hadley A., Zhang L., Alagkiozidis I., Leiby B., Guo W., Gimotty P.A., Coukos G.
ISSN
1479-5876 (Electronic)
ISSN-L
1479-5876
Statut éditorial
Publié
Date de publication
2008
Volume
6
Pages
2
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.Publication Status: epublish
Résumé
Because of its low toxicity, low-dose (LD) chemotherapy is ideally suited for combination with antiangiogenic drugs. We investigated the impact of tumor vascular endothelial growth factor A (VEGF-A) expression on the efficacy of LD paclitaxel chemotherapy and its interactions with the tyrosine kinase inhibitor SU5416 in the ID8 and ID8-Vegf models of ovarian cancer. Functional linear models using weighted penalized least squares were utilized to identify interactions between Vegf, LD paclitaxel and antiangiogenic therapy. LD paclitaxel yielded additive effects with antiangiogenic therapy against tumors with low Vegf expression, while it exhibited antagonism to antiangiogenic therapy in tumors with high Vegf expression. This is the first preclinical study that models interactions of LD paclitaxel chemotherapy with antiangiogenic therapy and tumor VEGF expression and offers important lessons for the rational design of clinical trials.
Mots-clé
Angiogenesis Inhibitors/therapeutic use, Animals, Antineoplastic Agents/therapeutic use, Dose-Response Relationship, Drug, Female, Humans, Indoles/therapeutic use, Maximum Tolerated Dose, Mice, Mice, Inbred C57BL, Microcirculation/drug effects, Ovarian Neoplasms/blood supply, Ovarian Neoplasms/drug therapy, Paclitaxel/therapeutic use, Pyrroles/therapeutic use, Recombinant Proteins/therapeutic use, Vascular Endothelial Growth Factor A/genetics, Vascular Endothelial Growth Factor A/physiology
Pubmed
Open Access
Oui
Création de la notice
14/10/2014 12:43
Dernière modification de la notice
20/08/2019 14:22
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