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Titolo:
Adenovirus-interleukin-12-mediated tumor regression in a murine hepatocellular carcinoma model is not dependent on CD1-restricted natural killer T cells
Autore:
Andrews, KJ; Ribas, A; Butterfield, LH; Vollmer, CM; Eilber, FC; Dissette, VB; Nelson, SD; Shintaku, P; Mekhoubad, S; Nakayama, T; Taniguchi, M; Glaspy, JA; McBride, WH; Economou, JS;
Indirizzi:
Univ Calif Los Angeles, Ctr Hlth Sci, Div Surg Oncol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Div Hematol Oncol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Div Pathol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Div Expt Radiat Oncol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Chiba Univ, Sch Med, Ctr Biomed Sci, Div Mol Immunol, Chiba 260, Japan Chiba Univ Chiba Japan 260 Biomed Sci, Div Mol Immunol, Chiba 260, Japan
Titolo Testata:
CANCER RESEARCH
fascicolo: 22, volume: 60, anno: 2000,
pagine: 6457 - 6464
SICI:
0008-5472(20001115)60:22<6457:ATRIAM>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOVIRUS EXPRESSING INTERLEUKIN-12; INTERFERON-INDUCIBLE PROTEIN-10; ANTIGEN-PRESENTING FUNCTION; ANGIOGENESIS IN-VIVO; V(ALPHA)14 NKT CELLS; BREAST-CANCER MODEL; MOUSE CD1; INTRATUMORAL INJECTION; ANTITUMOR EFFICACY; GENE-THERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Economou, JS Univ Calif Los Angeles, Ctr Hlth Sci, Div Surg Oncol, Room 54-140,10833 LeConte Ave, Los Angeles, CA 90095 USA Univ Calif Los Angeles Room 54-140,10833 Le Conte Ave Los Angeles CA USA 90095
Citazione:
K.J. Andrews et al., "Adenovirus-interleukin-12-mediated tumor regression in a murine hepatocellular carcinoma model is not dependent on CD1-restricted natural killer T cells", CANCER RES, 60(22), 2000, pp. 6457-6464

Abstract

The cytokine interleukin-12 (IL-12) has shown potent antitumor activity inseveral tumor models. Recently, natural killer (NR)T cells have been proposed to mediate the antitumor effects of IL-12, In this study, the antitumorresponse of IL-12 was investigated in a gene therapeutic model against s.c. growing mouse hepatocellular carcinomas using an adenoviral vector expressing murine IL-12 (AdVmIL-12), An adenoviral-based system was chosen because of the ability of adenoviruses to transduce dividing and nondividing cells and because of their high transduction efficiencies. Our goals were to examine the efficacy of AdVmIL-12 in a hepatocellular carcinoma model and to investigate the mechanism of the AdVmIL-12-mediated antitumor response withspecific interest in the role of NK T cells. Our studies demonstrate that intratumoral AdVmIL-12mediated regression of s.c. hepatocellular tumors is associated with rapid antitumor responses. AdVmIL-12 treatment was associated with an immune cellular infiltrate consisting of CD4 and CD8 T lymphocytes, macrophages, NK cells, and NK T cells. Antibody ablation of CD4 and CD8T cells and use of NK cell-defective beige mice failed to abrogate the response to AdVmIL-12, Studies in T-cell- and B-cell-deficient severe combinedimmunodeficient and recombinase activating gene-2-deficient mice and T-cell-, B-cell-, and NK cell-defective severe combined immunadeficient/beige mice also failed to abrogate this response. AdVmIL-12 retained potent antitumor activity in mice with specific genetic defects in immune cellular cytotoxicity (perforin knockout mice) and costimulation (CD28 knockout mice). Useof mice with specific NK T cell deficiencies, V(alpha)14 T-cell receptor and CD1 knockout mice, also failed to abrogate the response to AdVmIL-12, Histological and immunohistochemical studies of AdVmIL-12-treated tumors showed extensive inhibition of neovascularization and a marked decrease in factor VIII-stained endothelial cells. Our studies indicate that the antitumor response of AdVmIL-12 is independent of direct cytotoxic cellular immunity (specifically, the function of NK T cells) and suggest that the initial mechanisms of AdVmIL-12-mediated tumor regression involve inhibition of angiogenesis.

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Documento generato il 27/11/20 alle ore 22:24:58