title: Antitumour action of 5,6-dimethylxanthenone-4-acetic acid in rats bearing chemically induced primary mammary tumours.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Private bag 92019, Auckland, New Zealand.
authors.forename: Johnson J
authors.initials: JJ
authors.lastname: Liu
authors.forename: Lai-Ming
authors.initials: LM
authors.lastname: Ching
authors.forename: Michael
authors.initials: M
authors.lastname: Goldthorpe
authors.forename: Rachel
authors.initials: R
authors.lastname: Sutherland
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: James A
authors.initials: JA
authors.lastname: Kirker
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McKeage
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007118:Immunoassay; D020287:In Situ Nick-End Labeling; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008770:Methylnitrosourea; D051381:Rats; D044004:Xanthones / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D016207:Cytokines; D044004:Xanthones; C066668:vadimezan; D008770:Methylnitrosourea