Targeting [alpha]^sub V^-integrins decreased metastasis and increased survival in a nude rat breast cancer brain metastasis model
Brain metastases commonly occur in patients with breast, lung and melanoma systemic cancers. The anti-α^sub V^ integrin monoclonal antibody intetumumab binds cell surface proteins important for adhesion, invasion and angiogenesis in the metastatic cascade. The objective of this study was to investig...
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Veröffentlicht in: | Journal of neuro-oncology 2012-10, Vol.110 (1), p.27 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Brain metastases commonly occur in patients with breast, lung and melanoma systemic cancers. The anti-α^sub V^ integrin monoclonal antibody intetumumab binds cell surface proteins important for adhesion, invasion and angiogenesis in the metastatic cascade. The objective of this study was to investigate the anti-metastatic effect of intetumumab in a hematogenous breast cancer brain metastasis model. Female nude rats received intra-carotid infusion of human brain-seeking metastatic breast cancer cells (231BR-HER2) and were randomly assigned into four groups: (1) control; (2) intetumumab mixed with cells in vitro 5 min before infusion without further treatment; (3) intetumumab intravenously 4 h before and weekly after cell infusion; (4) intetumumab intravenously weekly starting 7 days after cell infusion. Brain metastases were detected by magnetic resonance imaging (MRI) and immunohistochemistry. Comparisons were made using the Kruskal-Wallis test and Dunnett's test. Survival times were estimated using Kaplan-Meier analysis. All control rats with brain tissue available for histology (9 of 11 rats) developed multiple brain metastases (median = 14). Intetumumab treatment either in vitro prior to cell infusion or intravenous before or after cell infusion prevented metastasis formation on MRI and decreased the number of metastases on histology (median = 2, p = 0.0055), including 30 % of animals without detectable tumors at the end of the study. The overall survival was improved by intetumumab compared to controls (median 77+ vs. 52 days, p = 0.0277). Our results suggest that breast cancer patients at risk of metastases might benefit from early intetumumab treatment.[PUBLICATION ABSTRACT] |
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ISSN: | 0167-594X 1573-7373 |
DOI: | 10.1007/s11060-012-0942-0 |