Corpus ID: 21872611

Increased plasma serotonin following treatment with flavone-8-acetic acid, 5,6-dimethylxanthenone-4-acetic acid, vinblastine, and colchicine: relation to vascular effects.

  title={Increased plasma serotonin following treatment with flavone-8-acetic acid, 5,6-dimethylxanthenone-4-acetic acid, vinblastine, and colchicine: relation to vascular effects.},
  author={B. Baguley and L. Zhuang and P. Kestell},
  journal={Oncology research},
  volume={9 2},
A number of antitumor agents are known to cause selective reduction in tumor blood flow, leading in some cases to tumor necrosis and growth delay. These agents include flavone acetic acid (FAA), an antitumor agent with high experimental but no clinical antitumor activity, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a highly active analogue of FAA, endotoxin, vinblastine, and colchicine. We find here that plasma concentrations of serotonin (5-hydroxytryptamine) and its metabolite 5… Expand
Measurement of plasma 5-hydroxyindoleacetic acid as a possible clinical surrogate marker for the action of antivascular agents.
Measurement of changes in plasma 5HIAA provides a new approach to the monitoring of therapies with an antivascular effect and is sensitive to dietary sources of 5HT, which should be minimised. Expand
5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA): a New Biological Response Modifier for Cancer Therapy
Co-administration of DMXAA with other drugs has been shown to result in enhanced anti-tumour activity andalterations in pharmacokinetics, asreported for the combination of DMxAA withmelphalan, thalidomide, cyproheptadine, and the bioreductive agent tirapazamine, inmouse models. Expand
Determination of two major metabolites of the novel anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid in hepatic microsomal incubations by high-performance liquid chromatography with fluorescence detection
High-performance liquid chromatographic methods have been developed and validated for the glucuronidated and oxidative metabolites of the novel anti-tumour agent 5,6-dimethylxanthenone-4-acetic acidExpand
The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice
The results suggest an important role for tumour necrosis factor in mediating both the host toxicity and antitumour activity of 5,6-dimethylxanthenone-4-acetic acid, but also suggest that tumour Necrosis factor can be replaced by other vasoactive factors in its antitumours action, an observation of relevance to current clinical studies. Expand
Rat tumor response to the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid as measured by dynamic contrast-enhanced magnetic resonance imaging, plasma 5-hydroxyindoleacetic acid levels, and tumor necrosis.
Concerns are raised about the utility of established DCE-MRI biomarkers to assess tumor response to DMXAA, because of the absence of any reduction in K(trans) or IAUGC following treatment with 200 mg/kg, despite a significant increase in 5-HIAA. Expand
Transport of the investigational anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid and its acyl glucuronide by human intestinal Caco-2 cells.
Data indicate that the transport of DMXAA across Caco-2 monolayers was through a passive process, whereas the transportofDMXAA-G was mediated by MRP1/2. Expand
Enhancement of the anti-tumour effects of the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by combination with 5-hydroxytryptamine and bioreductive drugs.
It is demonstrated that 5-HT and/or bioreductive drugs can improve the therapeutic activity of DMXAA in mice, and that with SN 23816 both approaches can be used together to provide considerably enhanced anti-tumour activity. Expand
Identification and reactivity of the major metabolite (ß-1-glucuronide) of the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in humans
The data suggest that the major metabolite in patients’ urine is DMXAA β-1- glucuronide, which may undergo hydrolysis, molecular rearrangement and covalent binding to plasma protein, and may have important implications for the pharmacokinetics, pharmacodynamics and toxicity of DM XAA. Expand
Plasma disposition, metabolism and excretion of the experimental antitumour agent 5,6-dimethylxanthenone-4-acetic acid in the mouse, rat and rabbit
Examination of rat and mouse urine by HPLC revealed the presence of two metabolites, which were characterized by mass spectrometry and nuclear magnetic resonance to be the acyl glucuronide of DMXAA and 6-(hydroxymethyl)-5-methylxanthenone-4-acetic acid, indicating both mice and rats metaboliseDMXAA by similar pathways. Expand
Species differences in the metabolism of the antitumour agent 5,6-dimethylxanthenone-4-acetic acid in vitro : implications for prediction of metabolic interactions in vivo
The results indicate that animal models may have a limited role in the extrapolation to patients of drug interactions with agents such as DMXAA that have immunomodulating activity that may vary widely between species. Expand