Noninvasive assessment of regulable transferred-p53 gene expression and evaluation of therapeutic response with FDG–PET in tumor model
| Autor: | Takako Furukawa, Chizuru Sogawa, Tsuneo Saga, Hitomi Sudo, Michiko Koshikawa-Yano, Mitsuru Koizumi, Aya Sugyo, Winn Aung, Atsushi B. Tsuji, Sumitaka Hasegawa |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Transgene
Genetic enhancement Genetic Vectors Biology Mice Fluorodeoxyglucose F18 In vivo Cell Line Tumor Neoplasms Gene expression Genetics medicine Animals Humans Molecular Biology Gene Cells Cultured Reporter gene medicine.diagnostic_test Cellular Assay Genetic Therapy Molecular biology Luminescent Proteins Positron emission tomography Positron-Emission Tomography Cancer research Molecular Medicine Radiopharmaceuticals Tumor Suppressor Protein p53 |
| Zdroj: | Gene Therapy. 17:1142-1151 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/gt.2010.70 |
| Popis: | The use of tumor-suppressor gene p53 as an anticancer therapeutic has been vigorously investigated. However, progress has met with limited success to date. Some major drawbacks are the difficulty in achieving controllable and efficient gene transfer as well as in analyzing the transferred gene expression in real time and the treatment response in a timely manner. Thus, development of novel gene transfer vector with a regulative gene expression system coupled with the reporter gene, by which transgene can be monitored simultaneously, is critical. Moreover, noninvasive imaging-based assessment of the therapeutic response to exogenous wild-type p53 gene transfer is crucial for refining treatment protocols. In this study, as a simple preclinical model, we constructed a doxycycline-regulated bidirectional vector harboring a reporter gene encoding red fluorescence protein and p53. Then, we determined the controllable and simultaneously coordinated expression of both proteins and the p53-mediated anticancer effects in vitro and in vivo. Next, we observed that cells or tumors with induced p53 overexpression exhibited decreased uptake of [(14)C]FDG in cellular assay and [(18)F]FDG in positron emission tomography (PET) imaging. Thus, by coupling with bidirectional vector, controllable p53 transfer was achieved and the capability of fluoro-2-deoxy-D-glucose (FDG)-PET to assess the therapeutic response to p53 gene therapy was evidently confirmed, which may have an impact on the improvement of p53 gene therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|