Papers Published

  1. Tsurushima, H. and Yuan, X. and Dillehay, L. E. and Leong, K. W., Radioresponsive tumor necrosis factor-related apoptosisinducing ligand (TRAIL) gene therapy for malignant brain tumors, Cancer Gene Therapy, vol. 14 no. 8 (2007), pp. 706-716 .
    (last updated on 2010/06/11)

    Abstract:
    Patients with malignant gliomas have a very poor prognosis. To explore a novel and more effective approach for the treatment of malignant gliomas, a strategy that combined tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy and radiation treatment (RT) was designed in this study. Plasmid pE4- GFP was constructed by including the radioinducible early growth response gene 1 (Egr-1) promoter, and it yielded the best response with fractionated RT. Plasmid pE4- TRAIL was constructed by including the Egr-1 promoter and evaluated using U251 and U87 glioma cells. In the assay of apoptosis and killing activities, pE4-TRAIL exhibited radioresponse. pE4-TRAIL combined with RT is capable of inducing cell death synergistically. The expression of TRAIL death receptors was evaluated; which may be influenced by RT. Glioma cells with wild- type p53 showed upregulated expression of death receptors, and more synergistic effects on killing activities are expected. pE4-TRAIL was transfected into the subcutaneous U251 glioma cells in nude mice by the in vivo electroporation method. In the mice treated with pE4- TRAIL and RT, apoptotic cells were detected in pathological sections, and a significant difference of tumor volumes was observed when compared with the other groups (P <0.001). Our results indicate that radioresponsive gene therapy may have great potential as a novel therapy because this therapeutic system can be spatially or temporally controlled by exogenous RT and provides specificity and safety.

    Keywords:
    radioresponsive gene therapy trail gene therapy the combination with gene therapy and radiation therapy malignant brain tumors in vivo electroporation ionizing-radiation in-vivo glioma-cells hepatocellular-carcinoma antitumor-activity egr-1 promoter induction receptor electroporation activation