Radiation-Inducible Caspase-8 Gene Therapy for Malignant Brain Tumors

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• 作者：Hideo Tsurushima ; Xuan Yuan ; Larry E. Dillehay ; Kam W. Leong
• 关键词：Radiation-inducible gene therapy ; Caspase-8 gene therapy ; Combined gene and radiation therapy ; Malignant glioma ; In vivo electroporation
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2008
• 期刊代码：136_03603016
• 类别：med
• 出版时间：1 June 2008
• 卷：71
• 期：2
• 页码：517-525
• 文件大小：944 K

摘要

The transfection efficiency of in vivo electroporation in rabbit skeletal muscles was evaluated using pCAccluc+ encoding luciferase. To evaluate the angiogenic effects of bFGF gene in ischemic limb, we constructed a plasmid, pCAcchbFGFcs23, containing human bFGF cDNA fused with the secretory signal sequence of interleukin (IL)-2. Then, 500 μg of pCAcchbFGFcs23 or pCAZ3 (control plasmid) was injected into the ischemic thigh muscles in a rabbit model of hind limb ischemia with in vivo electroporation (bFGF-E⁺ group and LacZ-E⁺ group). Other sets of animals were injected with pCAcchbFGFcs23 (bFGF-E⁻ group) or pCAZ3 (LacZ-E⁻ group) without electroporation. Then 28 days later, calf blood pressure ratio, angiographic score, in vivo blood flow, and capillary density in the ischemic limb were measured.

Results

Gene transfer efficiency increased markedly with the increase in voltage up to 100 V. Regarding angiogenic responses, calf blood pressure ratio, in vivo blood flow, and capillary density only in the bFGF-E⁺ group were significantly higher than those in LacZ-E⁻ group. Angiographic scores in the bFGF-E⁺ and bFGF-E⁻ groups were significantly higher than that in the LacZ-E⁻ group.

Conclusion

These data suggest that in vivo electroporation enhances bFGF gene transfer for the treatment of ischemic limb muscles.