Mechanisms of escape from trastuzumab-mediated ADCC in esophageal squamous cell carcinoma.

食管鳞状细胞癌中曲妥珠单抗介导的 ADCC 的逃逸机制。

• 批准号: 20790947
• 负责人: KAWAGUCHI Yoshihiko
• 金额: $ 2.75万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790947/
• 关键词: 食道扁平上皮癌; 抗体療法; trastuzumab; Herceptin; 抗体依存性細胞傷害; Trastuzumab; 抗体依存性細胞障害

We elucidated the mechanisms of escape from trastuzumab-mediated ADCC using esophageal squamous cell carcinoma cell clones. The ADCC assay with purified NK cells showed significantly susceptibility to trastuzumab-mediated ADCC in tumor cell clones. These results indicated that the sensitivity to trastuzumab-mediated ADCC was mainly due to the difference in susceptibility to NK cell-mediated ADCC. Furthermore, the degree of permeabilization induced by PFN and apoptosis induced by the combination of PFN with GrB in tumor cell clones was analyzed. As a result, lower sensitivity for PFN/GrB on tumor clones was related to the reduced trastuzumab-mediated ADCC. In conclusion, lower susceptibility to the perforin-granzyme system is one of the important mechanisms explaining escape from trastuzumab-mediated ADCC.

我们使用食管鳞状细胞癌细胞克隆阐明了逃避曲妥珠单抗介导的ADCC的机制。纯化NK细胞的ADCC试验显示肿瘤细胞克隆对曲妥珠单抗介导的ADCC具有显著敏感性。这些结果表明，对曲妥珠单抗介导的ADCC的敏感性主要是由于对NK细胞介导的ADCC的敏感性差异。此外，分析PFN诱导的透化程度和PFN与GrB组合诱导的肿瘤细胞克隆的凋亡。因此，PFN/GrB对肿瘤克隆的敏感性较低与曲妥珠单抗介导的ADCC降低有关。总之，对穿孔素-颗粒酶系统的敏感性降低是解释曲妥珠单抗介导的ADCC逃逸的重要机制之一。

项目成果

Mechanisms of escape from trastuzumab-mediated ADCC in esophageal squamorscell carcinoma.

食管鳞状细胞癌中曲妥珠单抗介导的 ADCC 的逃逸机制。

• 发表时间: 2009
• 期刊: Anticancer Res. 29
• 作者: Kono K;Mizukami Y;Daigo Y;Takano A;Masuda K;Yoshida K;Tsunoda T;Kawaguchi Y;Nakamura Y;Fujii H;Yoshihiko Kawaguchi
• 通讯作者: Yoshihiko Kawaguchi

Protein-bound polysaccharide K (PSK) partially prevents apoptosis of circulating T cells induced by anti-cancer drug S-1 in patients with gastric cancer

蛋白结合多糖 K (PSK) 部分阻止胃癌患者抗癌药物 S-1 诱导的循环 T 细胞凋亡

• 发表时间: 2008
• 期刊: Oncology 74
• 作者: Mizukami Y;Kono K;Kawaguchi Y;Akaike H;Kamimura K;Sugai H;Fujii H;Yoshiki Mizukami;Koji Kono
• 通讯作者: Koji Kono

Localization Pattern of Foxp3^+ Regulatory T cells is associated with Clinical Behavior in Gastric Cancer

Foxp3^ 调节性 T 细胞的定位模式与胃癌的临床行为相关

• 发表时间: 2008
• 期刊: British Journal of Cancer 98
• 作者: Mizukami Y;Kono K;Kawaguchi Y;Akaike H;Kamimura K;Sugai H;Fujii H;Yoshiki Mizukami;Koji Kono;Yoshiki Mizukami;Yosihki Mizukami
• 通讯作者: Yosihki Mizukami

Downregulation of HLA Class I molecules in the tumour is associated with a poor prognosis in patients with oesophageal squamous cell carcinoma.

• DOI: 10.1038/sj.bjc.6604715
• 发表时间: 2008-11-04
• 期刊: British journal of cancer
• 影响因子: 8.8
• 作者: Mizukami Y;Kono K;Maruyama T;Watanabe M;Kawaguchi Y;Kamimura K;Fujii H
• 通讯作者: Fujii H

Protein-Bound Polysaccharide K Partially Prevents Apoptosis of Circulating T Cells Induced by Anti-Cancer Drug S-1 in Patients with Gastric Cancer

• DOI: 10.1159/000151361
• 发表时间: 2008-08
• 期刊: Oncology
• 影响因子: 3.5
• 作者: K. Kono;Y. Kawaguchi;Y. Mizukami;K. Mimura;H. Sugai;H. Akaike;H. Fujii