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2007 | 54 | 2 |

Tytuł artykułu

pVAX1 plasmid vector-mediated gene transfer of soluble TRAIL suppresses human hepatocellular carcinoma growth in nude mice

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
The extracellular domain of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may function as a soluble cytokine to selectively kill various cancer cells without toxicity to most normal cells. We used a high-biosafety plasmid pVAX1 as a vector and constructed a recombinant plasmid expressing the extracellular domain (95-281 aa) of human TRAIL fused with signal peptides of human IgGγ, designated as pVAX-sT. Transduction of human BEL7402 liver cancer cells with pVAX-sT led to high levels of sTRAIL protein in the cell culture media and induced apoptosis. The therapeutic potential of pVAX-sT was then evaluated in the BEL7402 transplanted naked mouse model. Subsequent intratumoral administration of naked pVAX-sT resulted in the expression of soluble TRAIL in the sera and the tumor site, as well as effective suppression of tumor growth, with no toxicity to liver. In conclusion, the successful inhibition of liver cancer growth and the absence of detectable toxicity suggest that pVAX-sT could be useful in the gene therapy of liver cancer.

Wydawca

-

Rocznik

Tom

54

Numer

2

Opis fizyczny

p.307-313,fig.,ref.

Twórcy

autor
  • Medical School of Shandong University, Jinan, China
autor
autor
autor
autor

Bibliografia

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  • Spierings DC, de Vries EG, Vellenga E, van den Heuvel FA, Koornstra JJ, Wesseling J, Hollema H, de Jong S (2004) Tissue distribution of the death ligand TRAIL and its receptors. J Histochem Cytochem 52: 821–831.
  • Huang X, Lin T, Gu J, Zhang L, Roth JA, Liu J, Fang B (2003) Cell to cell contact required for bystander effect of the TNF-related apoptosis-inducing ligand (TRAIL) gene. Int J Oncol 22: 1241–1245.
  • Ichikawa K, Liu W, Zhao L, Wang Z, Liu D, Ohtsuka T, Zhang H, Mountz JD, Koopman WJ, Kimberly RP, Zhou T (2001) Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 7: 954–960.
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  • Jo M, Kim TH, Seol DW, Esplen JE, Dorko K, Billiar TR, Strom SC (2000) Apoptosis induced in normal human hepatocytes by tumor necrosis factor related apoptosisinducing ligand. Nat Med 6: 564–567.
  • Kagawa S, He C, Gu J, Koch P, Rha SJ, Roth JA, Curley SA, Stephens LC, Fang B (2001) Antitumor activity and bystander effects of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene. Cancer Res 61: 3330–3338.
  • Kelley SK, Harris LA, Xie D, Deforge L, Totpal K, Bussiere J, Fox JA (2001) Preclinical studies to predict the disposition of TRAIL in humans: Characterization of in vivo efficacy, pharmacokinetics and safety. J Pharmacol Exp Ther 299: 31–38.
  • Kim JM, Jeong JG, Ho SH, HahnW, Park EJ, Kim S, Yu SS, Lee YW, Kim S (2003) Protection against collageninduced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist. Gene Ther 10: 1543–1550.
  • Lawrence D, Shahrokh Z, Marsters S, Achilles K, Shih D, Mounho B, Hillan K, Totpal K, DeForge L, Schow P, Hooley J, Sherwood S (2001) Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Nat Med 7: 383–385.
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  • Shen YL, Xia XX, Zhang Y, Liu JW, Wei DZ, Yang SL (2003) Refolding and purification of Apo2l/TRAIL produced as inclusion bodies in high-cell-density cultures of recombinant Escherichia coli. Biotechnol Lett 25: 2097–2101.
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Typ dokumentu

Bibliografia

Identyfikatory

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bwmeta1.element.agro-article-e7b38503-71c0-4a24-9f07-069a415b5ebe
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