Gene therapy using FGFR-inhibiting vector against lung squamous cell carcinoma

使用 FGFR 抑制载体对抗肺鳞状细胞癌的基因治疗

• 批准号: 23659666
• 负责人: DATE Horoshi
• 金额: $ 2.33万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659666/
• 关键词: FGFR; ｓｈRNA; アデノウィルス; ベクター; 遺伝子治療; shRNA; ＦＧＦＲ; ｓｈＲＮＡ; sh RNA

We performed an experimental study on the gene therapy using a FGFR-inhibiting vector for a new treatment against lung squamous cell carcinomas. First, we have done a clinical study on the inntratumoral expressions of FGFR family genes. Consequently, we considered that not only FGFR1 but also FGR2 could be target genes for treatments. We produced a FGFR2-inhibiting vector using an adenoviral vector (Ad-shFGFR2). in vitro experiments using the Ad-shFGFR2 were performed against a lung cancer cell line A549, which has high expression levels of FGFR2. The Ad-shFGFR2 effectively knocked down the FGFR2 expression (approximately 85%). However, MTT assays revealed that the Ad-shFRFR2 did not effectively inhibit the growth of tumor cells. Therefore, considering that FGFR2 may not be a simple driver gene, we perform an experimental study using co-transfection with other candidates of driver genes.

我们使用FGFR抑制载体进行了一项针对肺鳞状细胞癌新疗法的基因治疗的实验研究。首先，我们对FGFR家族基因在肿瘤内的表达进行了临床研究。因此，我们认为不仅FGFR1而且FGR2可能是治疗的靶基因。我们用腺病毒载体(Ad-shFGFR2)构建了FGFR2抑制载体。使用Ad-shFGFR2对高表达FGFR2的肺癌细胞株A549进行了体外实验。Ad-shFGFR2有效地下调了FGFR2的表达(约85%)。但通过四甲基偶氮唑盐比色法检测，Ad-shFRFR2对肿瘤细胞的生长没有明显的抑制作用。因此，考虑到FGFR2可能不是一个简单的驱动基因，我们使用与其他候选驱动基因共转染的方法进行了实验研究。

项目成果

FGFR2 gene amplification and overexpression frequently occur in squamous cell carcinomas of the lung

FGFR2基因扩增和过度表达经常发生在肺鳞状细胞癌中

• 发表时间: 2012
• 作者: Kikuchi R;Date H;et al.
• 通讯作者: et al.

The Japan-Multinational Traial Organization. Prognostic factors after complete resection of pN2 non-small cell lung cancer.

日本跨国审判组织。

• 发表时间: 2013
• 期刊: J Thorac Cardiovasc Surg
• 作者: 319.Sonobe M;Date H;Wada H;Okubo K;Hamakawa H;Teramukai S;Matsumura A;Nakagawa T;Sumitomo S;Miyamoto Y;Okumura N;Takeo S;Kawakami K;Aoki M;Kosaka S
• 通讯作者: Kosaka S

肺癌における腫瘍内Wnt 発現とWnt 抑制遺伝子治療

肺癌瘤内 Wnt 表达和 Wnt 抑制基因治疗

• 发表时间: 2011
• 作者: 黄 政龍;劉 大革;中島成泰;横見瀬裕保;小林正嗣;菊地柳太郎;石川将史;堀内真理佳;園部 誠;伊達洋至
• 通讯作者: 伊達洋至

Snail Expression Is Associated With a Poor Prognosis in Malignant Pleural Mesotheliomas

• DOI: 10.1016/j.athoracsur.2013.01.012
• 发表时间: 2013-04-01
• 期刊: ANNALS OF THORACIC SURGERY
• 影响因子: 4.6
• 作者: Kobayashi, Masashi;Huang, Cheng-long;Date, Hiroshi
• 通讯作者: Date, Hiroshi

The intratumoral Wnt2B expression affects tumor progression in malignant pleural mesotheliomas

肿瘤内Wnt2B表达影响恶性胸膜间皮瘤的肿瘤进展

• 发表时间: 2011
• 作者: Kobayashi M;Huang CL;Miayahara R;Sonobe M;Menju T;Kikuchi R;Ishikawa M;Kitamura J;Itoi K;Date H
• 通讯作者: Date H