Dynamic bioluminescence and fluorescence imaging of the effects of the antivascular agent Combretastatin-A4P (CA4P) on brain tumor xenografts.
Dynamic bioluminescence and fluorescence imaging of the effects of the antivascular agent Combretastatin-A4P (CA4P) on brain tumor xenografts.
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抗血管剂Combretastatin-A4p（CA4P）对脑肿瘤异种移植物的影响的动态生物发光和荧光成像。
DOI：
10.1016/j.canlet.2014.09.038
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发表时间：
2015-01-28
期刊：
影响因子：
9.7
通讯作者：
Gimi B
中科院分区：
文献类型：
--
作者：
Liu L;Mason RP;Gimi B
CORRETABATINA-4(CA4)是从鸡冠草中分离出来的天然产物，通过与秋水仙素结合部位抑制微管蛋白聚合。一种相应的水溶性前体药物(称为CA4P)已经进行了广泛的临床试验，并通过多种方式在临床前研究中进行了评估。我们之前报道了一种基于动态生物发光成像的新方法来评估肿瘤血管破坏，现在介绍了它在同时评估多个肿瘤方面的应用。本研究利用动态生物发光成像技术评价了CA4P对9L大鼠脑肿瘤皮下移植瘤血管的破坏作用。单剂量CA4P(120 mg/kg，腹腔注射)可引起肿瘤血管的快速、暂时关闭，表现为以荧光素为底物后，表达荧光素酶的9L肿瘤的光发射迅速且可重复地减少。CA4P治疗后肿瘤灌注量呈时间依赖性减少，通过对灌注性标记物Hoechst 33342和肿瘤血管标记物CD31的免疫组织学评估证实。治疗后24小时内血管明显恢复。多个肿瘤表现相似，尽管观察到大小依赖的血管抑制。总之，CA4P导致肿瘤血管快速、暂时关闭，并导致大鼠脑瘤移植瘤血流灌注减少，多肿瘤方法应该会导致更有效的研究，需要更少的动物和更高的一致性。
Combretastatin A-4 (CA4) is a natural product isolated from Combretum caffrum that inhibits tubulin polymerization by binding to the colchicine-binding site. A corresponding water soluble pro-drug (referred to as CA4P), has undergone extensive clinical trials and has been evaluated in pre-clinical studies using multiple modalities. We previously reported a novel assay based on dynamic bioluminescent imaging to assess tumor vascular disruption and now present its application to assessing multiple tumors simultaneously. The current study evaluated the vascular-disrupting activity of CA4P on subcutaneous 9L rat brain tumor xenografts in mice using dynamic bioluminescence imaging. A single dose of CA4P (120 mg/kg, intraperitoneally) induced rapid, temporary tumor vascular shutdown revealed by a rapid and reproducible decrease of light emission from luciferase-expressing 9L tumors following administration of luciferin as a substrate. A time-dependent reduction of tumor perfusion after CA4P treatment was confirmed by immunohistological assessment of the perfusion marker Hoechst 33342 and the tumor vasculature marker CD31. The vasculature showed distinct recovery within 24 hours post therapy. Multiple tumors behaved similarly, although a size dependent vascular inhibition was observed. In conclusion, CA4P caused rapid, temporary tumor vascular shutdown and led to reduction of tumor perfusion in rat brain tumor xenografts and the multiple tumor approach should lead to more efficient studies requiring fewer animals and greater consistency.
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2-Aryl-3-芳酰吲哚盐（OXI8007）的合成类似于Combretastatin A-4，并用作血管破坏剂。
影响因子：
5.1
作者：
Hadimani MB;Macdonough MT;Ghatak A;Strecker TE;Lopez R;Sriram M;Nguyen BL;Hall JJ;Kessler RJ;Shirali AR;Liu L;Garner CM;Pettit GR;Hamel E;Chaplin DJ;Mason RP;Trawick ML;Pinney KG
通讯作者：
Pinney KG
影响因子：
2.9
作者：
Liu L;Su X;Mason RP
通讯作者：
Mason RP
影响因子：
9.7
作者：
Eikesdal, HP;Landuyt, W;Dahl, O
通讯作者：
Dahl, O
DOI：
10.1007/s00259-008-1022-8
发表时间：
2009-05-01
影响因子：
9.1
作者：
Inoue, Yusuke;Kiryu, Shigeru;Ohtomo, Kuni
通讯作者：
Ohtomo, Kuni
影响因子：
6.4
作者：
Karam, Jose A.;Fan, Jinhai;Hsieh, Jer-Tsong
通讯作者：
Hsieh, Jer-Tsong