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The antitumor efficacy of IL-24 mediated by E1A and E1B triple regulated oncolytic adenovirus Xiao LL; Wu YM; Qian J; Tan Y; Xie GL; Zhang KJ; Wang YG; Jia XY; Liu XYCancer Biol Ther 2010[Aug]; 10 (3): 242-50BACKGROUND: IL-24 (interleukin-24) is a promising, multi-functional anti-cancer agent able to selectively induce tumor cell apoptosis while sparing normal cells. Additionally, IL-24 can enhance the immune response to tumors and suppress tumor angiogenesis. In this study, we introduced IL-24 into the oncolytic adenovirus, Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24. in which E1A was engineered to target Rb (retinoblastoma) deficient or dysfunctional tumors. The survivin promoter (sp), was used to drive expression of IL-24, thereby allowing it to target most tumors. Finally, the 55 KDa gene of E1B was also deleted, thereby preventing replication in normal cells. RESULTS: Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24 showed enhanced antitumor effects over the E1, singly regulated oncolytic adenovirus, ONYX-015, in in vitro experiments. Furthermore, Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24 could effectively inhibit the progression of NCI-H460 lung carcinoma xenografts in nude mice. METHODS: The antitumor effect of Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24 was assessed by MTT assay and crystal violet staining in a panel of tumor cells. Cell staining and western blotting for caspase activation were used to assess apoptosis. We assessed the antitumor effects of Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24 in a xenograft model. CONCLUSION: This is the first study to use an E1A and E1B triple regulated oncolytic adenovirus vector carrying IL-24 to treat large tumors. We attained efficient antitumor effects both in vitro and in vivo, which provides an experimental foundation for clinical cancer therapy.|Adenovirus E1A Proteins/*genetics/metabolism[MESH]|Adenovirus E1B Proteins/*genetics/metabolism[MESH]|Animals[MESH]|Apoptosis/genetics[MESH]|Cell Line, Tumor[MESH]|Genetic Therapy/*methods[MESH]|Genetic Vectors/genetics[MESH]|HeLa Cells[MESH]|Humans[MESH]|Interleukins/biosynthesis/*genetics[MESH]|Mice[MESH]|Mice, Nude[MESH]|Neoplasms/genetics/*therapy[MESH]|Oncolytic Virotherapy/*methods[MESH]|Oncolytic Viruses/*genetics/metabolism[MESH]|Xenograft Model Antitumor Assays[MESH] |
