2002
DOI: 10.1038/sj.bjc.6600368
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Induction of endothelial cell apoptosis by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid

Abstract: 5,6-Dimethylxanthenone-4-acetic acid, synthesised in this laboratory, reduces tumour blood flow, both in mice and in patients on Phase I trial. We used TUNEL (TdT-mediated dUTP nick end labelling) assays to investigate whether apoptosis induction was involved in its antivascular effect. 5,6-Dimethylxanthenone-4-acetic acid induced dose-dependent apoptosis in vitro in HECPP murine endothelial cells in the absence of up-regulation of mRNA for tumour necrosis factor. Selective apoptosis of … Show more

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Cited by 105 publications
(99 citation statements)
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“…DMXAA was previously known for its antivascular properties derived from a direct effect on tumor endothelial cells (79) or an indirect effect on macrophages as result of the induction TNF-α and NO generation by tumor-associated macrophages (TAM) (80,81). DMXAA also induced repolarization of M2-like macrophages to an M1-like phenotype in a mouse model of non-small cell lung carcinoma (NSCLC) (82); a similar activity conferred by treatment with a synthetic CDN was recently shown (83).…”
Section: Sting Pathway Activation In Other Cell Typesmentioning
confidence: 99%
“…DMXAA was previously known for its antivascular properties derived from a direct effect on tumor endothelial cells (79) or an indirect effect on macrophages as result of the induction TNF-α and NO generation by tumor-associated macrophages (TAM) (80,81). DMXAA also induced repolarization of M2-like macrophages to an M1-like phenotype in a mouse model of non-small cell lung carcinoma (NSCLC) (82); a similar activity conferred by treatment with a synthetic CDN was recently shown (83).…”
Section: Sting Pathway Activation In Other Cell Typesmentioning
confidence: 99%
“…The tumour-VDA, ASA404, induces apoptosis of tumour vascular endothelial cells and cytokine production, leading to tumour vascular collapse (Ching et al, 2002;Baguley, 2003;Tozer et al, 2005). In animal models, this culminates in extensive tumour necrosis predominantly within the tumour core (Zwi et al, 1994;Laws et al, 1995;Ching et al, 1999Ching et al, , 2004Joseph et al, 1999).…”
mentioning
confidence: 99%
“…A wide variety of biological responses ranging from cytokine induction to activation of macrophage and natural killer cell activity have also been associated with DMXAA (11). The antitumor and antivascular effects of DMXAA seem mediated through a combination of direct effects of the drug on tumor vascular endothelial cells (12) and indirect effects through the induction of tumor necrosis factor-a (TNF-a; ref. 13), serotonin (14), IFN-inducible protein 10 (15), and nitric oxide (16).…”
mentioning
confidence: 99%