Lambin P, Landuyt W
LEO, KULeuven, Research Building U. Z. Gasthuisberg, Herestraat 49-B-3000 Leuven.
Verh K Acad Geneeskd Belg. 2003;65(1):29-46.
Our preclinical in vivo investigations were aimed to evaluate the potential of selectively targeting the tumour vasculature as an additional anti-cancer strategy. Using a clinical angiography method and the tumour growth delay assay, the efficacy of the vascular targeting compound combretastatin A-4 phosphate was demonstrated in rat rhabdomyosarcomas: specifically, an inverse efficacy as compared to radio- or chemotherapy was measured when comparing small and large tumours. The combination of this vascular targeting compound with ionising radiation indicated, depending on the timing and the sequence, a potential benefit. Within the limits of our experiments, no significant increase in tumour growth delay was measured when TNP-470 anti-angiogenesis was given after the combretastatin A-4 phosphate treatment. The use of the vascular targeting agent did advance the in vivo application of a non-apathogenic anaerobe Clostridium transfer system of therapeutic proteins. A strong improvement of the selective expression of cytosine deaminase in the tumour microenvironment was observed, even with very small tumours. In summary, the present preclinical results demonstrate several advantages from the introduction of vascular targeting next to classical and novel anti-cancer therapies.
我们的临床前体内研究旨在评估将选择性靶向肿瘤血管作为一种额外的抗癌策略的潜力。使用临床血管造影方法和肿瘤生长延迟试验,在大鼠横纹肌肉瘤中证明了血管靶向化合物磷酸康普瑞汀A - 4的疗效:具体而言,在比较小肿瘤和大肿瘤时,与放疗或化疗相比,测量到了相反的疗效。这种血管靶向化合物与电离辐射的联合使用,根据时间和顺序的不同,显示出潜在的益处。在我们的实验范围内,在磷酸康普瑞汀A - 4治疗后给予TNP - 470抗血管生成药物时,未测量到肿瘤生长延迟有显著增加。血管靶向剂的使用确实推动了治疗性蛋白质的非致病性厌氧菌梭菌转移系统在体内的应用。即使对于非常小的肿瘤,也观察到肿瘤微环境中胞嘧啶脱氨酶的选择性表达有显著改善。总之,目前的临床前结果表明,在经典和新型抗癌疗法之外引入血管靶向具有几个优点。