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

抗VEGF中和抗体对癌性胸膜炎的治疗作用

基本信息

批准号：
12671302
负责人：
OHTA Yasuhiko
金额：
$ 2.18万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671302/
关键词：
Lung cancer VEGF Carcinomatosa pleuritis 胸膜播種モデルヌードラット光力学治療 PDT

项目摘要

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.

我们使用两种类型的体内模型系统评估了抗血管内皮生长因子（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细胞接种于肺切除术后壁胸膜的胸膜下间隙或直接接种于胸腔。将携带肿瘤细胞的大鼠随机分为两组：未治疗组和抗VEGF中和抗体治疗组。在治疗组中，从接种后第7天起，以250 μg/周两次（总计1 mg）的剂量给予抗体！在尸检时（肿瘤接种后4周），所有大鼠均出现肉眼可见的胸膜播散伴/不伴恶性积液。在第一个模型系统中，尽管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的原发部位肿瘤血管较少，癌细胞中自分泌运动因子受体表达频率较低。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/转移的发展可能相关。