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Interaction between endotoxin and the antitumour agent 5,6-dimethylxanthenone-4-acetic acid in the induction of tumour necrosis factor and haemorrhagic necrosis of colon 38 tumours

  • Original Article
  • Lipopolysaccharide, Antitumour Activity, Cytokine, Synergism
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Abstract

The investigational antitumour agent 5,6-dimethyl-xanthenone-4-acetic acid (5,6-MeXAA) induced dosedependent 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 singificant 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.

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Authors and Affiliations

  1. Camcer Resrach Laboratory, Aucrkland University School of Medicine, Private Bag 92019, Auchland, New Zealand

    Lai-Ming Ching, Wayne R. Joseph, Li Zhuang & Bruce C. Baguley

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  1. Lai-Ming Ching
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  2. Wayne R. Joseph
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  3. Li Zhuang
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  4. Bruce C. Baguley
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Ching, LM., Joseph, W.R., Zhuang, L. et al. Interaction between endotoxin and the antitumour agent 5,6-dimethylxanthenone-4-acetic acid in the induction of tumour necrosis factor and haemorrhagic necrosis of colon 38 tumours. Cancer Chemother. Pharmacol. 35, 153–160 (1994). https://doi.org/10.1007/BF00686639

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  • DOI: https://doi.org/10.1007/BF00686639

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