Induction of endothelial cell apoptosis by the antivascular agent 5,6-Dimethylxanthenone-4-acetic acid.
Induction of endothelial cell apoptosis by the antivascular agent 5,6-Dimethylxanthenone-4-acetic acid.
复制标题
抗血管剂5,6-二甲基苯乙烯-4-乙酸诱导内皮细胞凋亡。
DOI：
10.1038/sj.bjc.6600368
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发表时间：
2002-06-17
影响因子：
8.8
通讯作者：
Baguley, BC
中科院分区：
文献类型：
--
作者：
Ching, LM;Cao, Z;Kieda, C;Zwain, S;Jameson, MB;Baguley, BC
5，6-二甲基氧杂蒽酮-4-乙酸，在这个实验室合成，减少肿瘤血流量，无论是在小鼠和患者的I期试验。我们使用TUNEL（TdT介导的dUTP缺口末端标记）检测来研究其抗血管作用是否涉及凋亡诱导。在肿瘤坏死因子的mRNA不上调的情况下，5，6-二甲基咕吨酮-4-乙酸在体外诱导HECPP小鼠内皮细胞的剂量依赖性凋亡。在给予5，6-二甲基氧杂蒽酮-4-乙酸（25 mg kg-1）30分钟内，在小鼠Colon 38肿瘤切片中体内检测到内皮细胞的选择性凋亡。TUNEL染色随时间增强，3 h后观察到邻近肿瘤组织坏死。荷瘤小鼠脾白色髓中心血管的凋亡也被检测到，而非肿瘤小鼠则没有。肝组织中未观察到细胞凋亡。无活性类似物8-甲基咕吨酮-4-乙酸未观察到细胞凋亡。在一项I期临床试验中，1名患者在输注5，6-二甲基咕吨酮-4-乙酸（3.1 mg m−2）后3小时和24小时进行乳腺肿瘤活检，肿瘤血管内皮细胞TUNEL染色呈阳性。未观察到肿瘤坏死和肿瘤坏死因子的产生。在另外两名患者（剂量为3.7和4.9 mg m−2）的肿瘤活检中未观察到凋亡染色。我们的结论是，5，6-二甲基吨酮-4-乙酸可以诱导血管内皮细胞凋亡在一些小鼠和人类肿瘤。作用迅速，似乎不依赖于肿瘤坏死因子诱导。英国癌症杂志（2002）86，1937-1942。www.bjcancer.com © 2002英国癌症研究中心
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 endothelial cells was detected in vivo in sections of Colon 38 tumours in mice within 30 min of administration of 5,6-Dimethylxanthenone-4-acetic acid (25 mg kg−1). TUNEL staining intensified with time and after 3 h, necrosis of adjacent tumour tissue was observed. Apoptosis of central vessels in splenic white pulp was also detected in tumour-bearing mice but not in mice without tumours. Apoptosis was not observed in liver tissue. No apoptosis was observed with the inactive analogue 8-methylxanthenone-4-acetic acid. Positive TUNEL staining of tumour vascular endothelium was evident in one patient in a Phase I clinical trial, from a breast tumour biopsy taken 3 and 24 h after infusion of 5,6-Dimethylxanthenone-4-acetic acid (3.1 mg m−2). Tumour necrosis and the production of tumour tumour necrosis factor were not observed. No apoptotic staining was seen in tumour biopsies taken from two other patients (doses of 3.7 and 4.9 mg m−2). We conclude that 5,6-Dimethylxanthenone-4-acetic acid can induce vascular endothelial cell apoptosis in some murine and human tumours. The action is rapid and appears to be independent of tumour necrosis factor induction. British Journal of Cancer (2002) 86, 1937–1942. doi:10.1038/sj.bjc.6600368 www.bjcancer.com © 2002 Cancer Research UK
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通过与 5-羟色胺和生物还原药物联合使用，增强抗血管剂 5,6-二甲基呫吨酮-4-乙酸 (DMXAA) 的抗肿瘤作用。
影响因子：
8.8
作者：
Lash, C J;Li, A E;Rutland, M;Baguley, B C;Zwi, L J;Wilson, W R
通讯作者：
Wilson, W R
影响因子：
2.7
作者：
BIZOUARNE, N;MITTERRAND, M;KIEDA, C
通讯作者：
KIEDA, C
影响因子：
8.4
作者：
Philpott, M;Ching, LM;Baguley, BC
通讯作者：
Baguley, BC
DOI：
10.1084/jem.182.1.155
发表时间：
1995-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Angiolillo AL;Sgadari C;Taub DD;Liao F;Farber JM;Maheshwari S;Kleinman HK;Reaman GH;Tosato G
通讯作者：
Tosato G
影响因子：
3
作者：
MCKEAGE, MJ;KESTELL, P;BAGULEY, BC
通讯作者：
BAGULEY, BC