Effect of thalidomide on tumour necrosis factor production and anti-tumour activity induced by 5,6-dimethylxanthenone-4-acetic acid.
Effect of thalidomide on tumour necrosis factor production and anti-tumour activity induced by 5,6-dimethylxanthenone-4-acetic acid.
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DOI：
10.1038/bjc.1995.335
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发表时间：
1995-08
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;Xu ZF;Gummer BH;Palmer BD;Joseph WR;Baguley BC
研究性抗肿瘤药物5，6-二甲基咕吨酮-4-乙酸（5，6-MeXAA）是黄酮乙酸（FAA）的类似物，已计划进行临床评价。与FAA一样，5，6-MeXAA表现出优异的实验抗肿瘤活性，并且是小鼠中细胞因子的有效诱导剂。我们已经研究了药理学抑制肿瘤坏死因子（TNF）的产生对5，6-MeXAA的抗肿瘤活性的影响，利用以前的观察结果，即响应于内毒素的TNF产生在体外被沙利度胺抑制。沙利度胺在8和250 mg kg-1之间的剂量有效地抑制响应于5，6-MeXAA的血清TNF活性，其最佳TNF诱导剂量为55 mg kg-1。当沙利度胺与5，6-MeXAA同时给药或在5，6-MeXAA给药前4小时给药时，可实现抑制。在TNF活性受到抑制的条件下，皮下结肠38肿瘤的出血性坏死程度和治愈比例增加。在沙利度胺（100 mg kg-1）与5，6-MeXAA（30 mg kg-1）联合给药的小鼠中，100%的小鼠肿瘤完全消退，而单独接受5，6-MeXAA的小鼠为67%。这些结果表明，沙利度胺可能有新的应用，并对5，6-MeXAA和相关化合物的作用提出了新的问题。
The investigational anti-tumour agent, 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA), an analogue of flavone acetic acid (FAA), has been scheduled for clinical evaluation. Like FAA, 5,6-MeXAA exhibits excellent experimental anti-tumour activity and is an efficient inducer of cytokines in mice. We have examined the effect of pharmacological suppression of tumour necrosis factor (TNF) production on the anti-tumour activity of 5,6-MeXAA, taking advantage of previous observations that TNF production in response to endotoxin in vitro is inhibited by thalidomide. Thalidomide at doses of between 8 and 250 mg kg-1 efficiently suppressed serum TNF activity in response to 5,6-MeXAA at its optimal TNF inducing dose of 55 mg kg-1. Suppression was achieved when thalidomide was administered at the same time as, or up to 4 h before, 5,6-MeXAA. Under conditions in which TNF activity was suppressed, the degree of tumour haemorrhagic necrosis and the proportion of cures in the subcutaneous Colon 38 tumour were increased. In mice administered thalidomide (100 mg kg-1) together with 5,6-MeXAA (30 mg kg-1), complete tumour regression was obtained in 100% of mice, as compared with 67% in mice receiving 5,6-MeXAA alone. The results suggest a possible new application for thalidomide and pose new questions about the action of 5,6-MeXAA and related compounds.
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影响因子：
8.4
作者：
PRATESI, G;RODOLFO, M;PARMIANI, G
通讯作者：
PARMIANI, G
DOI：
10.1016/0277-5379(86)90162-8
发表时间：
1986-06-01
期刊：
EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY
影响因子：
--
作者：
FINLAY, GJ;WILSON, WR;BAGULEY, BC
通讯作者：
BAGULEY, BC
影响因子：
64.8
作者：
GEARING, AJH;BECKETT, P;WOOLLEY, K
通讯作者：
WOOLLEY, K
DOI：
10.1084/jem.177.6.1675
发表时间：
1993-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Moreira AL;Sampaio EP;Zmuidzinas A;Frindt P;Smith KA;Kaplan G
通讯作者：
Kaplan G
DOI：
10.1016/0277-5379(89)90018-7
发表时间：
1989-02-01
期刊：
EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY
影响因子：
--
作者：
BAGULEY, BC;CALVELEY, SB;SMITH, GP
通讯作者：
SMITH, GP