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抑制载体进行了针对肺鳞状细胞癌的新疗法，对基因治疗进行了实验研究。首先，我们已经对FGFR家族基因的inntratumoral表达进行了临床研究。因此，我们认为不仅FGFR1，而且FGR2也可能是治疗的靶基因。我们使用腺病毒载体（AD-SHFGFR2）产生了FGFR2抑制载体。使用AD-SHFGFR2的体外实验是针对具有高表达水平的FGFR2的肺癌细胞系A549进行的。 AD-SHFGFR2有效地击倒了FGFR2表达（约85％）。但是，MTT分析表明，AD-SHFRF2并未有效抑制肿瘤细胞的生长。因此，考虑到FGFR2可能不是一个简单的驱动基因，我们使用与驱动器基因的其他候选者共转染进行了一项实验研究。

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