Antiangiogenic effect of metronomic paclitaxel treatment in prostate cancer and non-tumor tissue in the same animals:: a quantitative study
Antiangiogenic effect of metronomic paclitaxel treatment in prostate cancer and non-tumor tissue in the same animals:: a quantitative study
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DOI：
10.1111/j.1600-0463.2004.apm1120306.x
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发表时间：
2004-03-01
期刊：
影响因子：
2.8
通讯作者：
Norrby, K
中科院分区：
文献类型：
--
作者：
Lennernäs, B;Albertsson, P;Norrby, K
临床前研究表明，耐受性良好的连续或节律化疗可产生显著的抗血管生成作用，因此与常规的高剂量、暂时间隔化疗相比，具有上级抗肿瘤作用。然而，没有直接评估肿瘤中的抗血管生成作用的方法，这严重阻碍了评估推定的抗血管生成化疗或治疗的作用。在试图规避或最大限度地减少这种障碍，我们研究了耐受性良好的节拍紫杉醇治疗的抗血管生成作用，在一个替代的无肿瘤组织，允许真正的定量分析，以及在同基因的At-1前列腺癌在同一只大鼠。这种新的模型允许在两种组织中进行化疗的血管生成调节作用的准确比较。化疗对VEGF-A介导的血管生成（大多数肿瘤的一个特征）的影响通过显微镜形态测量和图像分析在无肿瘤肠系膜中进行定量评估。化疗显著抑制肠系膜中VEGF-A介导的血管生成，其程度密切反映了形态学测量的肿瘤坏死的显著增加和肿瘤生长速率的显著降低。这一发现为定量和系统地研究化疗方式和治疗的抗血管生成作用开辟了一条途径，这些化疗方式和治疗大致反映了它们在At-1肿瘤中的抗血管生成作用。
Well-tolerated continuous or metronomic chemotherapy can exert a marked antiangiogenic and thus superior antitumor effect compared with conventional high-dose, temporarily spaced-out chemotherapy, as shown in preclinical studies. There is, however, no means of directly assessing the antiangiogenic effect in a tumor, a serious impediment to assessing the effects of putative antiangiogenic chemotherapeutics or treatments. In an attempt to circumvent or minimize this impediment we studied the antiangiogenic effect of well-tolerated metronomic paclitaxel therapy in a surrogate tumor-free tissue that allows true quantitative analysis as well as in syngeneic At-1 prostate cancer in the same rat. This novel model allows an accurate comparison of the angiogenesis-modulating effect of chemotherapy in the two tissues to be made. The effect of chemotherapy on VEGF-A-mediated angiogenesis, a characteristic of most tumors, was assessed truly quantitatively by microscopic morphometry and image analysis in the tumor-free mesentery. The chemotherapy significantly suppressed VEGF-A-mediated angiogenesis in the mesentery to an extent that closely mirrored the significant increase in tumor necrosis measured morphometrically and the significant decrease in tumor growth rate. This finding opens an avenue to study quantitatively and systematically the antiangiogenic effect of chemotherapeutic modalities and treatments that approximately mirror their antiangiogenic effect in the At-1 tumor.