Development of vector specific to diffuse-type gastric cancer cells for peritoneal metastasis control

开发用于控制腹膜转移的弥漫型胃癌细胞特异性载体

• 批准号: 23501322
• 负责人: SASAKI Hiroki
• 金额: $ 3.24万
• 依托单位: National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-23501322/
• 关键词: 遺伝子治療; びまん型胃がん; 胃がん; 癌

We investigated the promoter activity of the GSDMB gene, which was identified to be expressed preferentially in diffuse-type gastric cancers (GCs). This promoter was found to act weakly in human mesothelial cell line MeT-5A but strongly in 5 of 6 diffuse-type GC cell lines. We next constructed the GSDMB promoter-driven HSVtk-lentivirus vector. This vector showed no cytotoxicity in MeT-5A cells, whereas 70% of diffuse-type GC-derived 60As6 cells were killed by Ganciclovir (GCV) treatment. We then established a peritoneal-metastasis control mouse model using 60As6 cells. By GCV treatment only once a week for 30 days after i.p. of 106 60As6 cells, we evaluated in vivo effects of this vector. The survival rate of GCV-treated mice showed 67%, but that of control mice showed 33%.

我们研究了GSDMB基因的启动子活性，发现GSDMB基因在弥漫型胃癌(GC)中优先表达。该启动子在人间皮细胞系MET-5A中有微弱的作用，而在6个弥漫型GC细胞系中有5个有较强的作用。接下来，我们构建了GSDMB启动子驱动的HSVtk慢病毒载体。该载体对MET-5A细胞无细胞毒性，而70%的弥漫型GC来源的60As6细胞可被更昔洛韦(GCV)杀死。然后，我们用60As6细胞建立了腹膜转移对照小鼠模型。每周1次，共30天。在106个60As6细胞中，我们评价了该载体的体内效应。GCV组小鼠存活率为67%，而对照组小鼠存活率为33%。

项目成果

Mesenchymal Stem Cells Provide an Advantageous Tumor Microenvironment for the Restoration of Cancer Stem Cells

• DOI: 10.1159/000337296
• 发表时间: 2012-01-01
• 期刊: PATHOBIOLOGY
• 影响因子: 5
• 作者: Nishimura, Kanako;Semba, Shuho;Yokozaki, Hiroshi
• 通讯作者: Yokozaki, Hiroshi

びまん性胃癌で特異的に発現するプロテアーゼの探索

寻找在弥漫性胃癌中特异性表达的蛋白酶

• 发表时间: 2012
• 作者: 藤田剛;青柳一彦;柳原五吉;佐々木博己;今野弘之
• 通讯作者: 今野弘之

腹膜播種におけるびまん性胃癌幹細胞に対するTGF-beta の二元的機能

TGF-β对弥漫性胃癌干细胞腹膜播散的双重作用

• 发表时间: 2012
• 作者: 藤田剛;高橋陵宇;千脇史子;柳原五吉;青柳一彦;坂本裕美;深川剛生;片井均;落谷孝広;今野弘之;吉田輝彦;佐々木博己
• 通讯作者: 佐々木博己

Multi-marker based RT-PCR for peritoneal cytology of gastric cancverMulti-marker based RT-PCR for peritoneal cytology of gastric cancver

基于多标记的 RT-PCR 用于胃癌腹膜细胞学检查基于多标记的 RT-PCR 用于胃癌腹膜细胞学检查

• 发表时间: 2011
• 作者: Mori K;Sato Y;Kitayama J;Kaizaki S;Ishigami H;Yamaguchi H;Shimizu N;Nomura S;Wada I;Yokota H;Kageyama Y;Sasaki H;Uozaki M;Fukayama M;Yatomi Y;Takai D;Seto M
• 通讯作者: Seto M

Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

• DOI: 10.3892/ijo.2014.2387
• 发表时间: 2014-06-01
• 期刊: INTERNATIONAL JOURNAL OF ONCOLOGY
• 影响因子: 5.2
• 作者: Tanabe, Shihori;Aoyagi, Kazuhiko;Sasaki, Hiroki
• 通讯作者: Sasaki, Hiroki