Temporal aspects of the action of ASA404 (vadimezan; DMXAA).
Temporal aspects of the action of ASA404 (vadimezan; DMXAA).
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DOI：
10.1517/13543784.2010.529128
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发表时间：
2010-11
影响因子：
6.1
通讯作者：
Siemann DW
中科院分区：
文献类型：
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作者：
Baguley BC;Siemann DW
ASA404 是一种黄酮类肿瘤血管破坏剂 (Tumor-VDA)，目前正处于治疗非小细胞肺癌的临床试验中。其作用不同于肿瘤 VDA 的微管蛋白结合类和抗血管生成剂。在小鼠中，ASA404 会诱导肿瘤组织发生一系列变化，一小时内开始出现血管通透性增加、内皮细胞凋亡增加和血流量减少。随后的作用包括释放血清素、诱导肿瘤坏死因子和其他细胞因子和趋化因子，以及诱导一氧化氮。这一级联事件会对血流、肿瘤缺氧、血管衰竭、炎症反应以及某些肿瘤的完全消退产生持续影响。 ASA404 对抗小鼠肿瘤的作用特征之一是其能够增强放射和多种化疗药物的效果。黄酮类化合物因其对血管内皮功能和先天免疫的双重作用而显得独特。将临床前结果转化为临床结果需要了解双重作用的机制以及 ASA404 活性的物种差异。临床试验表明，ASA404 作为有效药物的未来取决于对其细胞作用的深入了解。
ASA404, a flavonoid tumor-vascular disrupting agent (Tumor-VDA), is in clinical trial for the treatment of non-small cell lung cancer. Its action differs from both that of the tubulin binding class of Tumor-VDAs and antiangiogenic agents. In mice, ASA404 induces a sequence of changes in tumor tissue, starting within one hour with increased vascular permeability, increased endothelial apoptosis and decreased blood flow. Later effects include the release of serotonin, induction of tumor necrosis factor and other cytokines and chemokines, as well as induction of nitric oxide. This cascade of events induces sustained effects on blood flow, tumor hypoxia, vascular failure, inflammatory responses and, in some tumors, complete regression. One feature of the action of ASA404 against murine tumors is its ability to potentiate the effects of radiation and a variety of chemotherapeutic agents. The flavonoid class appears to be unique because of its dual action on vascular endothelial function and innate immunity. The translation of preclinical to clinical results demands an understanding of both the mechanisms underlying the dual effects and the species differences in ASA404 activity. Clinical trials indicate that the future of ASA404 as an effective agent relies on a deep appreciation of its cellular action.
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影响因子：
8.8
作者：
Benhamou, Ygal;Favre, Julie;Tamion, Fabienne
通讯作者：
Tamion, Fabienne
影响因子：
2
作者：
Cuschieri, Joseph;Bulger, Eileen;Maier, Ronald V
通讯作者：
Maier, Ronald V
影响因子：
20.3
作者：
Clauss, M;Sunderkötter, C;Risau, W
通讯作者：
Risau, W
抗血管剂5,6-二甲基苯乙烯-4-乙酸诱导内皮细胞凋亡。
影响因子：
8.8
作者：
Ching, LM;Cao, Z;Kieda, C;Zwain, S;Jameson, MB;Baguley, BC
通讯作者：
Baguley, BC
影响因子：
8.8
作者：
通讯作者：
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