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Reduction of tumor blood flow by flavone acetic acid: a possible component of therapy
M C Bibby1, J A Double, P M Loadman
1United Kingdom, Clinical Oncology Unit, University of Bradford, United Kingdom.
Abstract:
Flavone acetic acid (FAA) is active against normally refractory murine sc tumors. Clinical studies are disappointing despite achievement of plasma profiles associated with the antitumor murine activity in man. To clarify the mechanism of action, we have followed histologic changes, tumor blood volume, and drug concentrations in a well-differentiated, slow-growing cystic adenocarcinoma in mice. FAA causes massive tumor necrosis beginning 2 hours after treatment. Tumor plasma volumes are reduced by 2 hours after treatment and tumor blood vessels are shutdown, which suggests that tumor vasculature plays a role in the dramatic response of sc tumors in pure-strain male NMRI mice.
Insights
Flavone acetic acid (FAA) effectively combats murine tumors by causing rapid necrosis and reducing tumor blood volume. This suggests that targeting tumor vasculature is key to FAA
Area of Science:
- Oncology
- Cancer Research
- Pharmacology
Background:
- Flavone acetic acid (FAA) shows promise against refractory murine tumors.
- Clinical trials yielded disappointing results despite achieving effective plasma concentrations.
- The precise mechanism of FAA's antitumor activity requires further investigation.
Purpose of the Study:
- To elucidate the mechanism of action of Flavone acetic acid (FAA) in a murine cancer model.
- To investigate the effects of FAA on tumor histology, blood volume, and drug concentration.
Main Methods:
- Histologic examination of tumor tissue after FAA treatment.
- Measurement of tumor blood volume.
- Quantification of drug concentrations within the tumor.
Main Results:
- FAA induced massive tumor necrosis within 2 hours of administration.
- Significant reduction in tumor plasma volume was observed by 2 hours post-treatment.
- Tumor blood vessels showed evidence of shutdown following FAA treatment.
Conclusions:
- FAA's antitumor effect in murine models is associated with rapid tumor necrosis.
- Tumor vasculature plays a critical role in the response to FAA treatment.
- Understanding FAA's vascular effects may improve its clinical application.