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

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 via...

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Main Authors: Kluza, Ewelina, Heisen, Marieke, Schmid, Sophie, van der Schaft, Daisy W. J., Schiffelers, Raymond M., Storm, Gert, ter Haar Romeny, Bart M., Strijkers, Gustav J., Nicolay, Klaas
Format: Online
Language:English
Published: Springer Netherlands 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102848/
id pubmed-3102848
recordtype oai_dc
spelling pubmed-31028482011-07-14 Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids Kluza, Ewelina Heisen, Marieke Schmid, Sophie van der Schaft, Daisy W. J. Schiffelers, Raymond M. Storm, Gert ter Haar Romeny, Bart M. Strijkers, Gustav J. Nicolay, Klaas Original Paper 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 Ktrans, ve, time-to-peak, initial slope and the fraction of non-enhancing pixels, complemented with immunohistochemistry. The apparent diffusion coefficient (ADC), T2 and tumor size were assessed with MRI as well. PLP-L treatment resulted in smaller tumors and caused a significant drop in Ktrans 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. Springer Netherlands 2011-01-12 2011-05 /pmc/articles/PMC3102848/ /pubmed/21225337 http://dx.doi.org/10.1007/s10456-010-9198-5 Text en © The Author(s) 2011
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kluza, Ewelina
Heisen, Marieke
Schmid, Sophie
van der Schaft, Daisy W. J.
Schiffelers, Raymond M.
Storm, Gert
ter Haar Romeny, Bart M.
Strijkers, Gustav J.
Nicolay, Klaas
spellingShingle Kluza, Ewelina
Heisen, Marieke
Schmid, Sophie
van der Schaft, Daisy W. J.
Schiffelers, Raymond M.
Storm, Gert
ter Haar Romeny, Bart M.
Strijkers, Gustav J.
Nicolay, Klaas
Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids
author_facet Kluza, Ewelina
Heisen, Marieke
Schmid, Sophie
van der Schaft, Daisy W. J.
Schiffelers, Raymond M.
Storm, Gert
ter Haar Romeny, Bart M.
Strijkers, Gustav J.
Nicolay, Klaas
author_sort Kluza, Ewelina
title Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids
title_short Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids
title_full Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids
title_fullStr Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids
title_full_unstemmed Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids
title_sort multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids
description 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 Ktrans, ve, time-to-peak, initial slope and the fraction of non-enhancing pixels, complemented with immunohistochemistry. The apparent diffusion coefficient (ADC), T2 and tumor size were assessed with MRI as well. PLP-L treatment resulted in smaller tumors and caused a significant drop in Ktrans 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.
publisher Springer Netherlands
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102848/
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