ISSN:
1432-0843
Keywords:
Key words Lipopolysaccharide
;
Antitumour activity
;
Cytokine
;
Synergism
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The investigational antitumour agent 5,6-dimethyl-xanthenone-4-acetic acid (5,6-MeXAA) induced dose-dependent haemorrhagic necrosis of colon 38 tumours to a similar extent to that induced using bacterial lipopolysaccharide (LPS). TNF-α activity in serum and mRNA for TNF-α in splenocytes were induced over a broad range of LPS doses, whereas with 5,6-MeXAA, induction occurred only at concentrations approaching the maximum tolerated dose. At concentrations that provided similar degrees of haemorrhagic necrosis, the levels of serum TNF-α induced using 5,6-MeXAA were 100-fold lower than those obtained with LPS, indicating that haemorrhagic necrosis was not directly correlated with TNF-α levels. There was also no correlation between the degree of tumour necrosis and the duration of growth delay. Treatment with LPS did not induce a significant delay in growth, despite extensive tumour haemorrhagic necrosis, whereas with 5,6-MeXAA, treatments that improved the cure rate did not necessarily give longer growth delays. Therapy using a combination of sub-optimal doses of both compounds was synergistic for the induction of serum TNF-α and message for TNF-α but was not synergistic for antitumour efficacy. Thus, no correlation is evident between cure rates, duration of growth delay, haemorrhagic necrosis and TNF-α induction by 5,6-MeXAA or LPS.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00686639
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