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Assessment of Hypoxia-Responsive Elements for Hypoxia-Targeting Imaging and Therapy
https://repo.qst.go.jp/records/69531
https://repo.qst.go.jp/records/695318e9bce6c-041d-43d7-acd5-69a0eefe0122
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-10-23 | |||||
| タイトル | ||||||
| タイトル | Assessment of Hypoxia-Responsive Elements for Hypoxia-Targeting Imaging and Therapy | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Inubushi, Masayuki
× Inubushi, Masayuki× Hata, Hironobu× Murai, Tomoyoshi× Kitagawa, Yoshimasa× et.al× 犬伏 正幸 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Purpose: It is of great importance to establish in-vivo imaging methods of hypoxic cells and tissues, and to develop specific treatment strategies for them combined with novel therapies such as radioimmunotherapy and gene therapy in oncology and cardiovascular medicine. As the first step in this study we designed a series of hypoxia-responsive transcription factors, and assessed their activities to induce gene expression in response to hypoxia. Methods: We synthesized a series of transcription factors containing multiple copies (n=2, 4, 6, 8, 10, 12) of hypoxia responsive elements (HRE) derived from the human vascular endodermis proliferation factor (hVEGF), and inserted them into the multi-cloning site of pGL4.26 vectors (Promega), which have a minimum promoter and the luciferase reporter gene, orthodromically (pGL4-nHRE+ [n=2,4,6,8,10,12]) or antidromically (pGL4-nHRE- [n=2,4,6,8,10,12]). The HCT-116 human colon cancer cell line was transiently transfected with these constructs, and was cultured under hypoxic conditions induced by deferoxamine methylate (20, 40, 80, 160, 320 mug/ml) or with 1% oxygen levels (for 6, 12, 18 or 24 hours). The constructs were analyzed for the ability to induce the luciferase gene expression by chemiluminescent assays as normalized to normoxic controls. Results: We confirmed that our synthesized transcription factors containing multiple copies of HREs responded to hypoxia depending on the level of hypoxic stress. Not only the constructs with orthodromical HREs but also those with antidromical HREs showed the hypoxic response, which reached at maximum about 75 times and 35 times higher than normaxic controls, respectively. The induction levels increased gradually according to the number of HRE copies, but reached to a plateau when the copy number is more than 8 in both series of constructs. Conclusions: Our synthesized hypoxia-responsive transcription factor will be valuable to construct vectors which can induce two genes bidirectionally at the same time. We are now generating these vectors with combinations of bioluminescent and radionuclide reporter genes for multimodality hypoxia imaging, a reporter gene and a therapeutic gene for monitoring hypoxia-targeting gene therapy, and two different therapeutic genes expecting for the synergetic effects in hypoxic lesions. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Annual Congress of the European Association of Nuclear Medicine 2008 | |||||
| 発表年月日 | ||||||
| 日付 | 2008-10-15 | |||||
| 日付タイプ | Issued | |||||
