This item still needs to be validated !
Title: Melphalan availability in hypoxia-inducible factor-1alpha+/+ and factor-1alpha-/- tumors is independent of tumor vessel density and correlates with melphalan erythrocyte transport
Authors: Wildiers, Hans ×
Guetens, Gunter
De Boeck, Geert
Landuyt, Willy
Verbeken, Eric
Highley, Martin
de Bruijn, Ernst
Van Oosterom, Allan #
Issue Date: Jun-2002
Series Title: International Journal of Cancer vol:99 issue:4 pages:514-9
Abstract: Many tumors are impervious to anticancer agents. Resistance due to lack of cytotoxic penetration into the tumor is often overlooked but can play a significant role in undermining therapy. Insufficient and irregular vascularization of tumors is a possible barrier to drug delivery, but there are others, e.g., impaired vessel permeability and poor interstitial transport. We evaluated the importance of tumor vessel density in the availability of melphalan to tumors. A nude mouse tumor model with different vascularization due to a single-gene deletion of hypoxia-inducible factor 1alpha (HIF-1alpha(+/+) and HIF-1alpha(-/-) embryonic stem cell-derived tumors) was used. The availability of melphalan to HIF-1alpha(+/+) (n = 20) and HIF-1alpha(-/-) (n = 23) tumors was not significantly different (p = 0.12). Furthermore, in the various subgroup analyses accentuating the difference in vessel density, no significant correlation between vessel density and melphalan availability was found. In the second part of the study, melphalan, was demonstrated to be transported in blood in mice with a distribution of 24% in erythrocytes vs. 76% in plasma. A strong correlation (r = 0.93, p < 0.000001) between melphalan concentrations in plasma and erythrocytes was found, indicating an equilibrium between these 2 compartments. Plasma and erythrocyte concentrations of melphalan are correlated with the tumor availability of melphalan (r = 0.66 and 0.64, respectively, both p < 0.001). These data suggest that tumor vessel density is not an important predictor of the tumor availability of small cytotoxic drugs such as melphalan and indicate the importance of erythrocytes in the transport of melphalan.
ISSN: 0020-7136
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
Translational Cell & Tissue Research
Department of Oncology - miscellaneous
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science