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- W2334696060 abstract "Background: Targeting the Vascular Endothelial Growth Factor (VEGF) and Estrogen Receptor (ER) signaling pathways concomitantly may provide enhanced therapeutic benefit in ER positive breast cancer. We have previously shown the VEGFR tyrosine kinase inhibitor, PTK787/ZK222584 (PTK/ZK) is a competitive aromatase inhibitor in vitro (Banerjee et al Cancer Res 2009 69: 4716-4723). Here we investigated whether (1) PTK/ZK shows both anti-angiogenic and aromatase inhibitory properties in in vivo models of ER positive breast cancer and (2) the combination of PTK/ZK and letrozole (LET) is superior to letrozole alone.Methods: Human breast cancer cell lines were engineered to express aromatase. Both MCF7 AROM1 (ER+HER2-) and BT474 AROM3 (ER+, HER2+) cells were grown as subcutaneous xenografts with androstenedione support in ovariectomized, nude mice. Mice bearing MCF7 AROM1 or BT474 AROM3 tumors were randomised to receive daily, by oral gavage, concentrations of vehicle, PTK/ZK (25, 50, or 100mg/kg), letrozole (1 mg/kg) or PTK/ZK (50mg/kg) in combination with letrozole (1 mg/kg) for 28 days. Mice were injected with FITC-lectin prior to sacrifice at weekly intervals. Tumor sections were stained for Ki67, apoptosis (TUNEL), CD31 and PgR. Mice bearing BT474 AROM3 xenografts were also treated twice daily with either vehicle or 50 mg/kg PTK/ZK for 3 days and uteri were then weighed and TFF1 and mRNA expression determined.Results: In MCF7 AROM1 xenografts, the daily growth rate was significantly reduced in all treatment groups compared to vehicle (p 50%) after 1 week with all treatments (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5139." @default.
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- W2334696060 date "2009-12-15" @default.
- W2334696060 modified "2023-09-24" @default.
- W2334696060 title "Biological Evidence for Dual Antiangiogenic – Antiaromatase Activity of the VEGF-R Inhibitor PTK787/ZK222584." @default.
- W2334696060 doi "https://doi.org/10.1158/0008-5472.sabcs-09-5139" @default.
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