Suppression of serum tumour necrosis factor-alpha by thalidomide does not lead to reversal of tumour vascular collapse and anti-tumour activity of 5,6-dimethylxanthenone-4-acetic acid - PubMed (original) (raw)

. 1998 Nov-Dec;18(6A):4409-13.

Affiliations

PMID: 9891501

Suppression of serum tumour necrosis factor-alpha by thalidomide does not lead to reversal of tumour vascular collapse and anti-tumour activity of 5,6-dimethylxanthenone-4-acetic acid

W L Browne et al. Anticancer Res. 1998 Nov-Dec.

Abstract

The antitumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), developed in this laboratory as a potent analogue of flavone acetic acid (FAA), has a novel antitumour action involving both immune and vascular components. DMXAA induces the synthesis of tumour necrossi factor-alpha (TNF) and it has been hypothesised that this mediates its selective reduction of tumour blood flow and consequent induction of tumour necrosis. Unexpectedly, the drug thalidomide, while reducing the serum TNF response to DMXAA, potentiates its antitumour effect. We have investigated this in the MDAH-MCa-4 mammary carcinoma model, comparing it to previous data with the Colon 38 adenocarcinoma. We have related DMXAA-induced blood flow changes in the MCa-4 tumour to tumour growth delay, serum TNF and extractable TNF from tumour tissue. We have also compared the effect of thalidomide (387 mumol/kg) on DMXAA (80 mumol/kg) with that of a monoclonal anti-TNF antibody (50 micrograms/mouse). We find that tumour blood flow reduction is strongly correlated with tumour growth delay. Coadministration of anti-TNF antibody abolishes serum TNF levels and slightly reduces the antitumour effects of DMXAA. While tumour growth delay is not correlated with serum induced TNF levels, it is related to tumour TNF levels. We conclude that while the data are consistent with TNF being the principal mediator of the action of DMXAA, serum TNF levels do not reflect the antitumour response.

PubMed Disclaimer

Cited by

The influence of the combined treatment with Vadimezan (ASA404) and taxol on the growth of U251 glioblastoma xenografts.
Milanović D, Braun F, Weber W, Grosu AL, Behe M, Niedermann G. Milanović D, et al. BMC Cancer. 2012 Jun 13;12:242. doi: 10.1186/1471-2407-12-242. BMC Cancer. 2012. PMID: 22695475 Free PMC article.
Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.
Marrero A, Becker T, Sunar U, Morgan J, Bellnier D. Marrero A, et al. Photochem Photobiol. 2011 Jul-Aug;87(4):910-9. doi: 10.1111/j.1751-1097.2011.00943.x. Epub 2011 Jun 13. Photochem Photobiol. 2011. PMID: 21575001 Free PMC article.
5,6-dimethylxanthenone-4-acetic acid (DMXAA): a new biological response modifier for cancer therapy.
Zhou S, Kestell P, Baguley BC, Paxton JW. Zhou S, et al. Invest New Drugs. 2002 Aug;20(3):281-95. doi: 10.1023/a:1016215015530. Invest New Drugs. 2002. PMID: 12201491 Review.
The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice.
Zhao L, Ching LM, Kestell P, Baguley BC. Zhao L, et al. Br J Cancer. 2002 Aug 12;87(4):465-70. doi: 10.1038/sj.bjc.6600479. Br J Cancer. 2002. PMID: 12177785 Free PMC article.
Induction of endothelial cell apoptosis by the antivascular agent 5,6-Dimethylxanthenone-4-acetic acid.
Ching LM, Cao Z, Kieda C, Zwain S, Jameson MB, Baguley BC. Ching LM, et al. Br J Cancer. 2002 Jun 17;86(12):1937-42. doi: 10.1038/sj.bjc.6600368. Br J Cancer. 2002. PMID: 12085190 Free PMC article. Clinical Trial.

Suppression of serum tumour necrosis factor-alpha by thalidomide does not lead to reversal of tumour vascular collapse and anti-tumour activity of 5,6-dimethylxanthenone-4-acetic acid - PubMed (original) (raw)