Development of'BioKnife', a uPA-targeted oncolytic Sendai virus to treat intractable malignancies.
开发“BioKnife”,一种针对 uPA 的溶瘤仙台病毒,用于治疗难治性恶性肿瘤。
基本信息
- 批准号:22659246
- 负责人:
- 金额:$ 2.07万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Challenging Exploratory Research
- 财政年份:2010
- 资助国家:日本
- 起止时间:2010 至 2011
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Malignant pleural mesothelioma(MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor(uPAR). We here examined the potential of our new and powerful recombinant Sendai virus(rSeV), which shows uPAR-specific cell-to-cell fusion activity(rSeV/dMFct14(uPA2), named“BioKnife"), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro ; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I(RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/NK-κB axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting.
恶性胸膜间皮瘤(MPM)是非常难治的,很容易蔓延整个胸膜腔的表面,这些细胞已被证明表达尿激酶型纤溶酶原激活物受体(uPAR)。我们在这里研究了我们的新的和强大的重组仙台病毒(rSeV),它显示uPAR特异性细胞间融合活性(rSeV/dMFct 14(uPA 2),命名为“BioKnife”),在两个独立的原位异种移植模型的人肿瘤细胞杀伤的潜力。使用BioKnife的多细胞治疗导致了这些模型的有效拯救,与肿瘤特异性融合和凋亡相关。在体外的MSTO-211 H和H226细胞中也观察到这种作用;然而,我们证实后者表达uPAR而不表达uPA。有趣的是,BioKnife感染强烈促进了H226细胞释放uPA,而使用吡咯烷二硫代氨基甲酸酯或表达C-末端缺失的维甲酸诱导基因I(RIG-IC)显性负性抑制剂的BioKnife完全消除了这种作用,表明BioKnife依赖性的uPA表达由RIG-I/NK-κB轴介导,检测RNA病毒基因组复制。因此,这些结果表明,通过BioKnife的肿瘤细胞杀伤机制可能具有治疗临床环境中以频繁uPAR表达为特征的MPM患者的显著潜力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines.
- DOI:10.3164/jcbn.10-24
- 发表时间:2010-07
- 期刊:
- 影响因子:2.4
- 作者:Itoh S;Taketomi A;Harimoto N;Tsujita E;Rikimaru T;Shirabe K;Shimada M;Maehara Y
- 通讯作者:Maehara Y
Sclerosed hemangioma of the liver: possible diagnostic value of diffusion-weighted magnetic resonance imaging
- DOI:10.1007/s11604-009-0407-3
- 发表时间:2010-04-01
- 期刊:
- 影响因子:2.1
- 作者:Hida, Tomoyuki;Nishie, Akihiro;Honda, Hiroshi
- 通讯作者:Honda, Hiroshi
Dietary fiber, source foods and colorectal cancer risk: the Fukuoka Colorectal Cancer Study
- DOI:10.3109/00365521.2010.492528
- 发表时间:2010-10-01
- 期刊:
- 影响因子:1.9
- 作者:Uchida, Kazuhiro;Kono, Suminori;Terasaka, Reiji
- 通讯作者:Terasaka, Reiji
ウイルスおよび宿主りゲノム解析による肝移植後再発C型肝炎に対する治療戦略
基于病毒和宿主基因组分析的肝移植术后丙型肝炎复发治疗策略
- DOI:
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:武冨紹信;他
- 通讯作者:他
Improved Results of a Surgical Resection for the Recurrence of Hepatocellular Carcinoma After Living Donor Liver Transplantation
- DOI:10.1245/s10434-010-0999-y
- 发表时间:2010-09-01
- 期刊:
- 影响因子:3.7
- 作者:Taketomi, Akinobu;Fukuhara, Takasuke;Maehara, Yoshihko
- 通讯作者:Maehara, Yoshihko
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MAEHARA Yoshihiko其他文献
MAEHARA Yoshihiko的其他文献
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{{ truncateString('MAEHARA Yoshihiko', 18)}}的其他基金
Development of the the innovative treatment and the proposal of the Self-niche hypothesis in refractory cancer
难治性癌症创新治疗的发展和自我利基假说的提出
- 批准号:
16K15620 - 财政年份:2016
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Pre-clinical application of an innovative therapy, "BioKnife", to malignant pleural mesothelioma
创新疗法“生物刀”治疗恶性胸膜间皮瘤的临床前应用
- 批准号:
24249071 - 财政年份:2012
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
New cancer treatment focusing on genetic instability of the cancer stem cell
新的癌症治疗重点关注癌症干细胞的遗传不稳定性
- 批准号:
24659614 - 财政年份:2012
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
A novel treatment strategy for digestive system cancer against angiogenic signal in tumor stroma using nanosize particle.
使用纳米粒子对抗肿瘤基质中血管生成信号的消化系统癌症的新治疗策略。
- 批准号:
21249072 - 财政年份:2009
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Defective eNOS signaling is mediated by Rho-kinase activation in rats with secondary biliary cirrhosis
继发性胆汁性肝硬化大鼠中 Rho 激酶激活介导缺陷性 eNOS 信号传导
- 批准号:
19390352 - 财政年份:2007
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Combined interleukin-12 and Dendritic cell neoadjuvant immunotherapy for hepatocellular carcinoma in immunosuppressed mice
白介素 12 和树突状细胞联合新辅助免疫疗法治疗免疫抑制小鼠的肝细胞癌
- 批准号:
17390372 - 财政年份:2005
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Detection and clinical application of circulating cancer cells, using highy pricise cancer cell determination system
循环癌细胞的检测及临床应用,采用高性价比的癌细胞测定系统
- 批准号:
13470241 - 财政年份:2001
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
New strategy for cancer therapy using Hi-resolution microsatellite instability analysis and Real-time quantitative reverse transcriptase polymerase reaction
利用高分辨率微卫星不稳定性分析和实时定量逆转录酶聚合酶反应的癌症治疗新策略
- 批准号:
12557101 - 财政年份:2000
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Genetic alteration, angiogenesis and stromal proliferation related to the development and metastasis of gastric cancer
与胃癌发生和转移相关的基因改变、血管生成和基质增殖
- 批准号:
09470269 - 财政年份:1997
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Chemosensitivity test based on the intracellular level of free calcium
基于细胞内游离钙水平的化学敏感性试验
- 批准号:
03670590 - 财政年份:1991
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
相似海外基金
Pre-clinical application of an innovative therapy, "BioKnife", to malignant pleural mesothelioma
创新疗法“生物刀”治疗恶性胸膜间皮瘤的临床前应用
- 批准号:
24249071 - 财政年份:2012
- 资助金额:
$ 2.07万 - 项目类别:
Grant-in-Aid for Scientific Research (A)