Tirapazamine is a hypoxic cell cytotoxin in phase II/III trials. To further understand its mechanism of action in vivo, we examined the effect of tirapazamine on tumor energy metabolism and pH. RIF-1 and SCCVII tumors were grown subcutaneously in the flanks of C3H mice. Tumor energy metabolism, expr
Metabolism of tumor regression from angiogenesis inhibition: 31P magnetic resonance spectroscopy
โ Scribed by Fredric A. Hoffer; George A. Taylor; Melissa Spevak; Donald Ingber; Terry Fenton
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 471 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0740-3194
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โฆ Synopsis
P NMR spectroscopy was used to analyze the in vivo metabolism of reticulum cell sarcoma of mice. The ratio of high-to lowenergy phosphates ATPB/(Pi t PME) was measured to reflect the relative metabolic state in the tumor. Of the 34 mice studied, 26 were treated with an antiangiogenesis regimen of heparin and cortisone. Eighty-two percent of the tumors treated eventually decreased in volume (P < 0.01 ). Volumes and spectroscopic information of 20 tumors were analyzed. Although the average untreated volume was similar to the volume after 3 days of treatment, the average ATPB/(Pi + PME) ratio rose from 0.34 k 0.10 to 0.47 * 0.07 (P = 0.02). However, after 6 days of treatment, the volume significantly decreased (P i 0.0001 ) but the ratio did not significantly rise further (P = 0.06). The rise in the high-energy phosphate preceded a significant decrease in volume of the tumors. In addition, the replenishment of the high-energy stores with tumor regression coincided with the histologic findings of a decrease in the number of tumor cells, a decrease of the mitotic index, and a decrease of the number of necrotic cells present with ongoing treatment. Our data suggest that noninvasive methods of assessing early biochemical response of tumor regression may be possible. o 1989 Academic Press. Inc.
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