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Antitumour action of 5,6-dimethylxanthenone-4-acetic acid in rats bearing chemically induced primary mammary tumours


Liu, JJ and Ching, L and Goldthorpe, M and Sutherland, R and Baguley, BC and Kirker, JA and McKeage, MJ, Antitumour action of 5,6-dimethylxanthenone-4-acetic acid in rats bearing chemically induced primary mammary tumours, Cancer Chemotherapy and Pharmacology, 59, (5) pp. 661-669. ISSN 1432-0843 (2007) [Refereed Article]

Copyright Statement

Copyright 2006 Springer-Verlag

DOI: doi:10.1007/s00280-006-0321-7


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/m2) was given to animals when tumours were measurable. Tumour volume, extent of necrosis and cytokine proWles were measured. Results Compared with the control group, DMXAA treatment signiWcantly delayed tumour doubling time and extended the time from treatment to euthanasia. Four of Wve DMXAA-treated animals showed necrosis involving 3.741.2% 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 TNF, IL-6, VEGF and IL-1 were increased 4 h after DMXAA treatment. Conclusions This study shows for the Wrst time that DMXAA has signiWcant in vivo antitumour activity against non-transplanted autochthonous tumours and in a host species other than the mouse.

Item Details

Item Type:Refereed Article
Keywords:Mammary tumour, DMXAA, rats
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Clinical pharmacology and therapeutics
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Liu, JJ (Dr Johnson Liu)
ID Code:89128
Year Published:2007
Web of Science® Times Cited:20
Deposited By:Pharmacy
Deposited On:2014-02-25
Last Modified:2014-08-04

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