Investigation to determine the cause of interstitial pneumonia by the EGFR inhibitors, and the development of that suppression method

EGFR抑制剂引起间质性肺炎的病因调查及其抑制方法的开发

• 批准号: 20791210
• 负责人: ISHIGURO Yukari
• 金额: $ 2.75万
• 依托单位: Yokohama City University
• 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-20791210/
• 关键词: EGFR阻害剤; 間質性肺炎

Acute interstitial pneumonia is one of serious side effects of epidermal growth factor receptor (EGFR) inhibitor, although that cause is still unknown. Here we report that cancer cells treated with EGFR inhibitors induce fibrosis of normal lung cell. Human tangue squamous cell carcinoma (HSC-3) was cultured with EGFR-tyrosine kinase inhibitor (AG1478) or EGFR antibody. IL-6 expression level was elevated by EGFR inhibitors in HSC-3. Those supernatants were used as the conditioned medium. Then, OUS-11, normal human lung fibroblast-like cell line, was cultured with the conditioned medium. We investigated the expression of collagen, which was the marker for fibrosis, to confirm whether fibrosis was induced or not in OUS-11. That result showed that the expression level of collagen in OUS-11 treated with conditioned medium was higher than control cells. These data suggested that acute interstitial pneumonia was induced IL-6 from cancer cells treated with EGFR inhibitors.

急性间质性肺炎是表皮生长因子受体（EGFR）抑制剂的严重副作用之一，但其原因尚不清楚。在这里，我们报道用 EGFR 抑制剂治疗的癌细胞会诱导正常肺细胞纤维化。人舌鳞状细胞癌 (HSC-3) 与 EGFR 酪氨酸激酶抑制剂 (AG1478) 或 EGFR 抗体一起培养。 HSC-3 中 EGFR 抑制剂升高了 IL-6 表达水平。将那些上清液用作条件培养基。然后，用条件培养基培养正常人肺成纤维细胞样细胞系OUS-11。我们研究了作为纤维化标志物的胶原蛋白的表达，以确认 OUS-11 中是否诱导了纤维化。结果表明，经条件培养基处理的OUS-11中胶原蛋白的表达水平高于对照细胞。这些数据表明，急性间质性肺炎是由EGFR抑制剂处理的癌细胞诱导产生IL-6的。

项目成果

Fibrosis of normal lung cells is caused by some particular factors from cancer cells treated with EGFR-TKI.

正常肺细胞的纤维化是由接受 EGFR-TKI 治疗的癌细胞的某些特定因素引起的。

• 发表时间: 2008
• 作者: 石黒由香利;石黒斉;佃守
• 通讯作者: 佃守

頭頸扁平上皮癌において、GefitinibはBRAK/CXCL14の発現を介して抗腫瘍効果を示す

吉非替尼通过头颈鳞状细胞癌中 BRAK/CXCL14 的表达发挥抗肿瘤作用

• 发表时间: 2009
• 作者: 加藤靖正;田口享秀;石黒由香利;佃守
• 通讯作者: 佃守

Involvement of EGFR in the response of squamous cell carcinoma of the head and neck cell lines to gefitinib.

• DOI: 10.3892/or.19.1.65
• 发表时间: 2008
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: T. Taguchi;M. Tsukuda;Yukari Imagawa-Ishiguro;Y. Kato;D. Sano

The role of aPKC lambda in prostate cancer progression

aPKC lambda 在前列腺癌进展中的作用

• 发表时间: 2008
• 作者: Ishiguro H;Akimoto K;Nagashima Y;Kojima Y;Ishiguro Y;Sasaki T;Umemura H;Ohno S;Kubota Y
• 通讯作者: Kubota Y

ケモカインBRAK/CXCL14をマーカー分子とした頭頸部扁平上皮癌への新たな併用療法の試み

以趋化因子BRAK/CXCL14为标记分子的头颈鳞状细胞癌新联合疗法试验

• 发表时间: 2009
• 作者: 小澤重幸;加藤靖正;伊藤慎;小森令賀;椎木直人;槻木恵一;前畑洋次郎;田口亨秀;石黒-今川由香利;佃守;畑隆一郎;久保田英朗
• 通讯作者: 久保田英朗