The therapeutic effect of anti-VEGF neutralizing antibody against carcinomatosa pleuritis

我们利用两种体内模型系统评估了抗血管内皮细胞生长因子（VEGF）中和抗体对胸膜播散和胸腔积液形成的抑制作用。将PC-14细胞接种于(1)肺切除术后胸膜壁下间隙或(2)直接接种于胸腔。将携带肿瘤细胞的大鼠随机分为未治疗组和抗vegf中和抗体治疗组。治疗组自首次接种后第7天起，以250 /μg的剂量给药，每周2次（总1mg）。在尸检时（肿瘤接种4周后），所有大鼠均出现胸膜散布，伴/不伴恶性积液。在第一个模型系统中，尽管各组间原发性胸膜下肿瘤的平均体积无显著差异，但治疗组的播散程度受到抑制。免疫组化检查显示，治疗组原发部位肿瘤血管减少，肿瘤细胞中自分泌运动因子受体表达频率降低。在第二个模型中，对胸膜播散的抑制作用尚不清楚。这些结果表明，在血液/淋巴途径和癌细胞运动的背景下，VEGF与胸膜播散/转移的发展可能存在关联。

We assessed the inhibitory effect of anti-vascular eridothelial growth factor (VEGF) neutralizing antibody on the formation of pleural dissemination and pleural effusion using two types of in-vivo model systems. Immune-deficient rats were inoculated with PC-14 cells into (1) a subpieurai space of the parietal pleura after pneumonectomy or (2) into the thoracic cavity directly The rats bearing tumor cells were randomly separated into two groups : non-treatment and treatment with anti-VEGF neutralizing antibody groups. In the treatment group, the antibody was administered at a dose of 250 /μg twice weekly (total 1 mg) from the 7th day after the tiimor inoculation! At the time of the autopsy (4 weeks after the tumor inoculation), all rats developed gross pleural dissemination with/without malignant effusions. In the first model system, despite no significant difference in the mean volume of the primary subpleurai tumors between the groups, the degree of dissemination was suppressed in the treatment group. The immunohistochemical examination showed less tumor vasculature and less frequency of the autocrine motility factor receptor expression in cancer cells at the primary site of the treatment group. In the second model, the inhibitory effect on pleural dissemination was not clear. These results demonstrated the possible association of VEGF with the development of pleural dissemination/metastasis in the context of blood/lymphatic routes and cancer cell motility.