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Titolo:
Interleukin 12 gene transfer into skin distant from the tumor site elicitsantimetastatic effects equivalent to local gene transfer
Autore:
Oshikawa, K; Rakhmilevich, AL; Shi, FS; Sondel, PM; Yang, NS; Mahvi, DM;
Indirizzi:
Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53792 USA Univ WisconsinMadison WI USA 53792 omprehens Canc, Madison, WI 53792 USA Univ Wisconsin, Dept Surg, Madison, WI 53792 USA Univ Wisconsin Madison WI USA 53792 sin, Dept Surg, Madison, WI 53792 USA Acad Sinica, Inst Bioagr Sci, Taipei 11529, Taiwan Acad Sinica Taipei Taiwan 11529 a, Inst Bioagr Sci, Taipei 11529, Taiwan
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 2, volume: 12, anno: 2001,
pagine: 149 - 160
SICI:
1043-0342(20010120)12:2<149:I1GTIS>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL STIMULATORY FACTOR; CD4 T-CELLS; MURINE INTERLEUKIN-12; NK CELLS; IN-VIVO; ESTABLISHED TUMORS; ANTITUMOR IMMUNITY; CYTOTOXIC ACTIVITY; INTERFERON-GAMMA; COLON-CARCINOMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Yang, NS Univ Wisconsin, Ctr Comprehens Canc, K4-449, Madison, WI 53792 USA Univ Wisconsin K4-449 Madison WI USA 53792 Madison, WI 53792 USA
Citazione:
K. Oshikawa et al., "Interleukin 12 gene transfer into skin distant from the tumor site elicitsantimetastatic effects equivalent to local gene transfer", HUM GENE TH, 12(2), 2001, pp. 149-160

Abstract

We have reported that particle-mediated interleukin 12 (IL-12) gene transfer into the skin overlying the local tumor inhibits systemic metastases. Tofurther characterize this effect, we compared the antitumor and antimetastatic effects of IL-12 cDNA delivered at the local tumor site versus at a site distant from the primary tumor, in a spontaneous metastasis model of LLC-F5 tumor. Local IL-12 gene delivery into the skin overlying the intradermal tumor (local IL-12 treatment) on days 7, 9, and 11 after tumor implantation resulted in the most suppression of the growth of the primary LLC-F5 tumor, whereas IL-12 gene transfer into the skin distant from the tumor (distant LL-12 treatment) was less effective. In contrast, both local IL-12 and distant IL-12 treatment, followed by tumor excision, inhibited lung metastases to a similar extent, resulting in significantly extended survival of test mice. The results of in vivo studies using depleting anti-asialo GM1 antibody and anti-CD3/anti-CD8 monoclonal antibodies, or neutralizing anti-interferon gamma (IFN-gamma) monoclonal antibody demonstrated that natural killer (NK) cells, CD8(+) T cells, and IFN-gamma contributed to the antimetastatic effects in both treatment groups. Furthermore, the levels of mRNA expression of vascular endothelial growth factor and matrix methalloproteinase 9at the tumor microenvironment were suppressed after both local and distantIL-12 treatment. These results suggest that the current particle-mediated IL-12 gene delivery in the spontaneous LLC-F5 metastasis model can confer antimetastatic activities, irrespective of the gene transfection site, via acombination of several mechanisms involving CD8(+) T cells, NK cells, IFN-gamma, and antiangiogenesis.

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Documento generato il 31/03/20 alle ore 16:32:53