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DMXAA: an antivascular agent with multiple host responses
Bruce C Baguley1, Lai Ming Ching
1Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand. b.baguley@auckland.ac.nz
International Journal of Radiation Oncology, Biology, Physics
|December 3, 2002
Summary
The antivascular drug DMXAA triggers a cascade of vasoactive events in tumors, involving tumor necrosis factor (TNF) and serotonin. Measuring 5-hydroxyindoleacetic acid in plasma may serve as a marker for DMXAA
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Antivascular agents are crucial in cancer therapy.
- Understanding host responses to these agents is key for optimizing treatment.
- DMXAA (5,6-dimethylxanthenone-4-acetic acid) is an antivascular agent with potential therapeutic applications.
Purpose of the Study:
- To measure host responses to the antivascular agent DMXAA.
- To compare DMXAA's host responses with those of other antivascular agents.
Main Methods:
- Tumor necrosis was induced in murine Colon 38 carcinomas.
- Tumor necrosis factor (TNF) concentrations were measured in plasma and tumor tissue.
- Serotonin and nitric oxide release were quantified using high-performance liquid chromatography.
Main Results:
- DMXAA increased plasma and tumor TNF, nitric oxide, and serotonin release.
- TNF played a significant role in DMXAA's antitumor action and host toxicity.
- DMXAA's antivascular effects involve a cascade of vasoactive events.
Conclusions:
- DMXAA's antivascular action is mediated by a complex cascade involving TNF, serotonin, and nitric oxide.
- Plasma 5-hydroxyindoleacetic acid may be a useful surrogate marker for antivascular effects.
- Optimizing this cascade in cancer patients is a critical challenge for future DMXAA therapy.