2012 Fiscal Year Final Research Report
Non-invasive assessment for therapeutic response to gene therapy using redox imaging and MALDI-TOF mass-spectrometry
| Project/Area Number |
22659111
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied pharmacology
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| Research Institution | Kyushu University |
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Principal Investigator |
NAKANO Kenji 九州大学, 先端融合医療レドックスナビ研究拠点, 教授 (00315061)
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| Co-Investigator(Kenkyū-buntansha) |
HYOUDOU Fuminori 九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (10380693)
FUJIMURA Yoshinori 九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (20390304)
MIURA Daisuke 九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (40532627)
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| Co-Investigator(Renkei-kenkyūsha) |
UTSUMI Hideo 九州大学, 先端融合医療レドックスナビ研究拠点, 特任教授 (20101694)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 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 |
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| Research Abstract |
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.
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[Remarks] 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
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