{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:50:55Z","timestamp":1761058255196},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T00:00:00Z","timestamp":1112140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2005,8,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To evaluate the tumoricidal activity of tumor necrosis factor (TNF)\u2010related apoptosis\u2010inducing ligand (TRAIL) on disseminated liver metastatic tumors, we constructed a recombinant adeno\u2010associated virus (rAAV) expressing the extracellular domain (95\u2013281aa) of human TRAIL (TRAIL<jats:sub>95\u2013281<\/jats:sub>, and the recombinant virus was designated as rAAV\u2010TRAIL) using the 3\u2010plasmid, helper\u2010virus\u2010free, packaging system. Transduction of mouse lymphoma EL\u20104 cells and Jurkat T cells lead to the expression of TRAIL<jats:sub>95\u2013281<\/jats:sub> protein in both virus\u2010transduced cells and the culture media, along with apoptosis of these cells <jats:italic>in vitro<\/jats:italic>. The therapeutic potential of rAAV\u2010TRAIL was then evaluated in an orthotopic transplanted mouse model mimicking liver cancer metastasis, which was established by injection of EL\u20104 cells into the liver of C57BL\/6 mice <jats:italic>via<\/jats:italic> the hepatic portal veins. Subsequent intraportal vein injection of rAAV\u2010TRAIL, not the control virus, into the liver of these mice resulted in significant suppression of tumor growth and prolonged survival, while normal hepatocyte toxicity is undetectable. Histological and biochemical analysis in tumor tissue and serum confirmed that TRAIL<jats:sub>95\u2013281<\/jats:sub> was stably expressed in relatively high level in hepatocytes and was secreted into the serum in active trimeric form. Futhermore, the mechanism for rAAV\u2010TRAIL to inhibit tumor growth was by inducing apoptosis of the tumor cells metastasizing to the livers. These results strongly suggest that the rAAV\u2010TRAIL\u2010mediated gene delivery could be a promising approach for the treatment of liver metastasis cancer. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20982","type":"journal-article","created":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T19:48:29Z","timestamp":1112212109000},"page":"314-321","source":"Crossref","is-referenced-by-count":32,"title":["Recombinant adeno\u2010associated virus\u2010mediated TRAIL gene therapy suppresses liver metastatic 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