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  • Title: Antitumour action of 5,6-dimethylxanthenone-4-acetic acid in rats bearing chemically induced primary mammary tumours.
    Author: Liu JJ, Ching LM, Goldthorpe M, Sutherland R, Baguley BC, Kirker JA, McKeage MJ.
    Journal: Cancer Chemother Pharmacol; 2007 Apr; 59(5):661-9. PubMed ID: 16944150.
    Abstract:
    PURPOSE: To evaluate the antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a vascular disrupting agent currently under phase II clinical trials in combination with cancer chemotherapy, in rats bearing chemically induced primary mammary tumours. METHODS: Tumours were induced in female Wistar rats by injection of N-nitroso-N-methylurea at 100 mg/kg subcutaneously. A clinically relevant single dose of DMXAA (1,800 mg/m(2)) was given to animals when tumours were measurable. Tumour volume, extent of necrosis and cytokine profiles were measured. RESULTS: Compared with the control group, DMXAA treatment significantly delayed tumour doubling time and extended the time from treatment to euthanasia. Four of five DMXAA-treated animals showed necrosis involving 3.7-41.2% of the area of the tumour section at 24 h compared with none of four control animals (P < 0.028, Chi-square test). Intratumoural levels of TNFalpha, IL-6, VEGF and IL-1alpha were increased 4 h after DMXAA treatment. CONCLUSIONS: This study shows for the first time that DMXAA has significant in vivo antitumour activity against non-transplanted autochthonous tumours and in a host species other than the mouse.
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