Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids.

Abstract

Inflammation plays a prominent role in tumor growth. Anti-inflammatory drugs have therefore been proposed as anti-cancer therapeutics. In this study, we determined the anti-angiogenic activity of a single dose of liposomal prednisolone phosphate (PLP-L), by monitoring tumor vascular function and viability over a period of one week. C57BL/6 mice were inoculated subcutaneously with B16F10 melanoma cells. Six animals were PLP-L-treated and six served as control. Tumor tissue and vascular function were probed using MRI before and at three timepoints after treatment. DCE-MRI was used to determine K(trans), v(e), time-to-peak, initial slope and the fraction of non-enhancing pixels, complemented with immunohistochemistry. The apparent diffusion coefficient (ADC), T(2) and tumor size were assessed with MRI as well. PLP-L treatment resulted in smaller tumors and caused a significant drop in K(trans) 48 h post-treatment, which was maintained until one week after drug administration. However, this effect was not sufficient to significantly distinguish treated from non-treated animals. The therapy did not affect tumor tissue viability but did prevent the ADC decrease observed in the control group. No evidence for PLP-L-induced tumor vessel normalization was found on histology. Treatment with PLP-L altered tumor vascular function. This effect did not fully explain the tumor growth inhibition, suggesting a broader spectrum of PLP-L activities.

• Authors: Ewelina Kluza, Marieke Heisen, Sophie Schmid, Daisy W J van der Schaft, Raymond M Schiffelers, Gert Storm, Bart M ter Haar Romeny, Gustav J Strijkers, Klaas Nicolay
• Journal: Angiogenesis (Angiogenesis) Vol. 14 Issue 2 Pg. 143-53 (May 2011) ISSN: 1573-7209 [Electronic] Germany
• PMID: 21225337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Contrast Media
• Glucocorticoids
• Liposomes
• prednisolone phosphate
• Prednisolone

Topics

• Angiogenesis Inhibitors (pharmacology, therapeutic use)
• Animals
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Contrast Media
• Diffusion Magnetic Resonance Imaging
• Glucocorticoids (pharmacology, therapeutic use)
• Liposomes (chemistry)
• Mice
• Mice, Inbred C57BL
• Microscopy, Fluorescence
• Microvessels (drug effects, pathology)
• Neoplasms (blood supply, drug therapy, pathology)
• Prednisolone (analogs & derivatives, pharmacology, therapeutic use)