Antitumor effect on human gastric cancer and induction of apoptosis by vascular endothelial growth factor neutralizing antibody.
Antitumor effect on human gastric cancer and induction of apoptosis by vascular endothelial growth factor neutralizing antibody.
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DOI：
10.1111/j.1349-7006.1999.tb00817.x
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发表时间：
1999-07
期刊：
影响因子：
--
通讯作者：
Nakamura S
中科院分区：
文献类型：
--
作者：
Kamiya K;Konno H;Tanaka T;Baba M;Matsumoto K;Sakaguchi T;Yukita A;Asano M;Suzuki H;Arai T;Nakamura S
通过抗血管生成治疗诱导细胞凋亡已被认为是一种新的抗癌策略。为了阐明血管内皮生长因子（VEGF），这是一个主要的血管生成介质的抑制所取得的抗肿瘤作用的机制，我们使用了一个原位移植模型的人胃癌细胞系（MT 2）与单克隆VEGF中和抗体（VEGF Ab）处理。组织学检测微血管密度（MVD）和凋亡指数（AI）。VEGF Ab显著抑制移植肿瘤的生长（P= 0.03），并且具有肝转移的小鼠的数量显著减少（P= 0.004）。ER-MP 12抗体免疫组化染色检测MVD，对照组为33.6 ± 8.0，治疗组为21.1 ± 5.4，差异有统计学意义（P < 0.0001）。对照组和治疗组的AI值分别为4.73 ± 1.11和7.26 ± 1.62，差异也非常显著（P < 0.0001）。然而，VEGF mRNA在移植瘤中的表达在对照组和治疗组之间没有显示出显著差异。提示VEGF Ab对人胃癌的抗肿瘤作用是通过诱导轻度缺氧后细胞凋亡而实现的，而对胃癌组织中VEGF mRNA的表达无影响。
Induction of apoptosis by antiangiogenic therapy has been suggested as a new anticancer strategy. To clarify the mechanism of the antitumor effect achieved by inhibition of vascular endothelial growth factor (VEGF), which is a major mediator of angiogenesis, we used an orthotopic transplantation model of human gastric carcinoma line (MT2) treated with a monoclonal VEGF neutralizing antibody (VEGF Ab). We histologically examined the microvessel density (MVD) and the apoptotic index (AI) in this model. Transplanted tumor growth was significantly inhibited by the VEGF Ab (P= 0.03), and there was a significant decrease in the number of mice with liver metastasis (P= 0.004). The MVD detected by immunohistochemical staining with ER‐MP12 antibody was 33.6 ± 8.0 in the control group and 21.1 ± 5.4 in the treated group, and the difference was significant (P < 0.0001). The AI values of the control and treated groups were 4.73 ± 1.11 and 7.26 ± 1.62, respectively, and this difference is also significant (P < 0.0001). However, the expression of VEGF mRNA in transplanted tumors did not show a significant difference between the control and treated groups. These results suggest that the antitumor effect of the VEGF Ab on human gastric carcinoma is exerted by inducing mild hypoxia followed by apoptosis, which does not influence VEGF mRNA expression in the carcinoma.
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影响因子：
2.2
作者：
Ahmed, MH;Konno, H;Baba, S
通讯作者：
Baba, S
影响因子：
--
作者：
Asano, M;Yukita, A;Suzuki, H
通讯作者：
Suzuki, H
影响因子：
64.8
作者：
KIM, KJ;LI, B;FERRARA, N
通讯作者：
FERRARA, N
DOI：
10.1093/jnci/89.2.139
发表时间：
1997-01-15
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Gasparini, G;Toi, M;Tominaga, T
通讯作者：
Tominaga, T
影响因子：
64.5
作者：
LOWE, SW;RULEY, HE;HOUSMAN, DE
通讯作者：
HOUSMAN, DE