Abstract
A previous publication (Leith et al., 1992) showed that administration of basic fibroblast growth factor (FGF-2, 0.25 mg kg-1, q.i.d. x 7) to mice bearing xenografted DLD-2 human colon cancers would increase treated tumour growth rates as compared to control neoplasms. Additionally, at the end of the 7 day treatment period, clonogenic excision assays showed that the percentage of hypoxic cells in tumours from mice receiving FGF-2 administration was significantly decreased as compared to control neoplasms (from about 42 to about 19%). The present study was undertaken to better define the kinetics of changes in hypoxic percentages as a function of tumour volume and FGF-2 treatment. In sham-injected control tumours, the hypoxic percentage increased from about 14% at day 15 postimplantation, (i.e. when sham- or FGF-2 injections were begun) to about 42% by day 22, and to about 75% at 29 days postimplantation (respective average volumes 220, 910, and 2810 mm3). In contrast, the hypoxic percentages in mice treated with FGF-2 remained at the levels seen in control mice on day 15, not only throughout the 7 day FGF-2 treatment schedule, but for at least 1 week after the cessation of growth factor administration. The hypoxic percentage was 16% on day 29 postimplantation, even though average tumour volumes were about 4325 mm3. These data show that the effect of FGF-2 administration on tumour growth rate and hypoxic percentages in xenografted DLD-2 neoplasms is rapid, and continues for some period of time even after administration is ended. Studies of tumour perfusion with injected 86RbCl at equivalent tumour volumes of about 1800 mm3 indicated that the percentage of cardiac output to FGF-2 treated tumours was 33% greater than in sham-injected control neoplasms.
Highlights
We recently reported in this journal that administration of basic fibroblast growth factor (FGF-2; q.i.d. x 7; 0.25 mg kg-') caused a significant increase in the growth rates of xenografted DLD-2 human colon cancers, and concomitantly decreased the percentage of hypoxia within these neoplasms (Leith et al, 1992)
In the Figure, we have indicated by the dashed line what might have been observed if the hypoxic percentage in the tumours of the FGF-2 treated mice immediately began to increase at a rate similar to that seen in the control mice at the end of treatment
FGF-2 administration prevents the steady increase in the percentage of hypoxia seen in DLD-2 control neoplasms of increasing size
Summary
We recently reported in this journal that administration of basic fibroblast growth factor (FGF-2; q.i.d. x 7; 0.25 mg kg-') caused a significant increase in the growth rates of xenografted DLD-2 human colon cancers, and concomitantly decreased the percentage of hypoxia within these neoplasms (Leith et al, 1992). Hypoxia levels were determined 1 day after the end of a 7 day period of FGF-2 administration, at a time when the volumes of control (given sham-injections with Hank's balanced salt solution) or FGF2 treated tumours had increased from 211 mm to 992 and 1751 mm respectively. The FGF-2 treated tumours were about 1.8 times the volume of controls at the time of assay, the percentage of hypoxia within these neoplasm was 19.1% (13.5-26.9; 95% confidence limits) whereas the percentage in control neoplasms was 42.2% (34.2-52.1). Increases in tumour volume can be uncoupled from changes in hypoxia by FGF-2 administration. In these studies the effects of the nonequivalent tumour volumes on interpretation of steady-state levels of hypoxia as a function of volume were not explicitly studied
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