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-alpha activity in serum and mRNA for TNF-alpha 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-alpha induced using 5,6-MeXAA were 100-fold lower than those obtained with LPS, indicating that haemorrhagic necrosis was not directly correlated with TNF-alpha 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-alpha and message for TNF-alpha but was not synergistic for antitumour efficacy. Thus, no correlation is evident between cure rates, duration of growth delay, haemorrhagic necrosis and TNF-alpha induction by 5,6-MeXAA or LPS.
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Authors | L M Ching, W R Joseph, L Zhuang, B C Baguley |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 35
Issue 2
Pg. 153-60
( 1994)
ISSN: 0344-5704 [Print] Germany |
PMID | 7987993
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Endotoxins
- Lipopolysaccharides
- Tumor Necrosis Factor-alpha
- Xanthenes
- Xanthones
- vadimezan
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Colonic Neoplasms
(drug therapy, metabolism)
- Dose-Response Relationship, Drug
- Drug Synergism
- Endotoxins
(pharmacology)
- Lipopolysaccharides
(pharmacology)
- Mice
- Necrosis
- Tumor Necrosis Factor-alpha
(biosynthesis, metabolism)
- Xanthenes
(pharmacology)
- Xanthones
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