Non-invasive assessment for therapeutic response to gene therapy using redox imaging and MALDI-TOF mass-spectrometry

使用氧化还原成像和 MALDI-TOF 质谱法对基因治疗的治疗反应进行非侵入性评估

• 批准号: 22659111
• 负责人: NAKANO Kenji
• 金额: $ 2.06万
• 依托单位: Kyushu University
• 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 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659111/
• 关键词: 非侵襲的治療応答性アッセイ; レドックスイメージング; メタボリック・プロフ ァイリング; 遺伝子治療; 非侵襲的治療応答アッセイ; メタボリック・プロファイリング; 核酸治療; レドックスイメージ; OMRI

The purpose of this study is to develop the non-invasive assays to evaluate therapeuticresponse to gene therapy, as the indexes of redox state assessed by Overhauser MRI(OMRI) and metabolic profiling analyzed by MALDI-TOF mass-spectrometry. The ratio of radical disappearance curve analyzed by OMRI was increased for the TNF-αgene therapy compared with the control in subcutaneous tumor model. However, there was no significant difference between two groups in peritoneal dissemination, wherethe heterogeneity of tumor and normal tissues was present, suggesting the gating technology of redox imaging restricting tumor area may be necessary to improve the assay. In a separate experiment, the microanalysis of metabolites in endothelial cells post-transfection of redox-related transcription factor: YB-1-targeting siRNA using MALDI-TOF mass-spectrometry revealed the reduction of NAD and the increase of Histidine and Aspartate in cells with YB-1-siRNA. These results suggest that the improvement of visualizing (gating) ability of OMRI for tumor area could potentiate the redox imaging-based non-invasive assay to estimate the response to gene therapy.

本研究的目的是建立一种非侵入性的评价基因治疗反应的方法，通过Overhauser MRI（OMRI）评价氧化还原状态和MALDI-TOF质谱分析代谢谱。OMRI分析显示，与对照组相比，TNF-α基因治疗组皮下肿瘤模型的放射性消失曲线比率增加。但在肿瘤与正常组织异质性的腹膜播散方面，两组间无显著差异，提示限制肿瘤面积的氧化还原显像门控技术可能是改善检测的必要手段。在另一项实验中，使用MALDI-TOF质谱法对转染氧化还原相关转录因子：YB-1靶向siRNA后的内皮细胞中的代谢物进行微量分析，结果显示在YB-1-siRNA细胞中NAD减少，组氨酸和天冬氨酸增加。这些结果表明，OMRI对肿瘤区域的可视化（门控）能力的提高可以增强基于氧化还原成像的非侵入性检测来估计对基因治疗的反应。

项目成果

腫瘍血管を標的とする非ウイルス型デリバリーシステムを用いたmiRNA治療：治療抵抗性の腹膜播種・膵癌に対する新たな治療戦略.

使用非病毒递送系统靶向肿瘤血管的 miRNA 疗法：针对难治性腹膜播散和胰腺癌的新治疗策略。

• 发表时间: 2012
• 作者: Setoyama D;Fujimura Y;Miura D;Fuminori Hyodo;中野 賢二
• 通讯作者: 中野 賢二

Metabolome early response to hydrogen peroxide-induced oxidative stress in mammalian cell

哺乳动物细胞中代谢组对过氧化氢诱导的氧化应激的早期反应

• 发表时间: 2012
• 作者: Setoyama D;Fujimura Y;and Miura D
• 通讯作者: and Miura D

Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor.

• DOI: 10.1016/j.virol.2011.02.014
• 发表时间: 2011-04-25
• 期刊: Virology
• 影响因子: 3.7
• 作者: Nakano K;Kobayashi M;Nakamura K;Nakanishi T;Asano R;Kumagai I;Tahara H;Kuwano M;Cohen JB;Glorioso JC
• 通讯作者: Glorioso JC

Dual blockade of phosphatidylinositol 3′-kinase and mitogen-activated protein kinase pathways overcomes paclitaxel-resistance in colorectal cancer

• DOI: 10.1016/j.canlet.2011.02.042
• 发表时间: 2011-07-28
• 期刊: CANCER LETTERS
• 影响因子: 9.7
• 作者: Xu, Rui;Nakano, Kenji;Katano, Mitsuo
• 通讯作者: Katano, Mitsuo

Control of Mammalian Cells by LC-MS-based Metabolomics. 59thASMS Conference on Mass Spectrometry and Allied Topics (June 5-9, 2011, Colorado Convention Centre, Denver, Colorado)8. Fujimura Y, Miura D, Hyodo F, Yasukawa K, Tachibana H, Utsumi H, Wariishi H

通过基于 LC-MS 的代谢组学控制哺乳动物细胞。