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Titolo:
COMBINATION THERAPY WITH INTERLEUKIN-2 AND WILD-TYPE P53 EXPRESSED BYADENOVIRAL VECTORS POTENTIATES TUMOR-REGRESSION IN A MURINE MODEL OF BREAST-CANCER
Autore:
PUTZER BM; BRAMSON JL; ADDISON CL; HITT M; SIEGEL PM; MULLER WJ; GRAHAM FL;
Indirizzi:
MCMASTER UNIV,DEPT BIOL & PATHOL,1280 MAIN ST W HAMILTON ON L8S 4K1 CANADA MCMASTER UNIV,DEPT BIOL HAMILTON ON L8S 4K1 CANADA MCMASTER UNIV,DEPT PATHOL HAMILTON ON L8S 4K1 CANADA
Titolo Testata:
Human gene therapy
fascicolo: 5, volume: 9, anno: 1998,
pagine: 707 - 718
SICI:
1043-0342(1998)9:5<707:CTWIAW>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VIVO; GENE-THERAPY; ANTITUMOR IMMUNITY; RECOMBINANT ADENOVIRUS; MEDIATED TRANSFER; MAMMARY-TUMORS; LUNG-CANCER; CELLS; APOPTOSIS; INDUCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
B.M. Putzer et al., "COMBINATION THERAPY WITH INTERLEUKIN-2 AND WILD-TYPE P53 EXPRESSED BYADENOVIRAL VECTORS POTENTIATES TUMOR-REGRESSION IN A MURINE MODEL OF BREAST-CANCER", Human gene therapy, 9(5), 1998, pp. 707-718

Abstract

Although cytokine gene transfer for cancer treatment can stimulate immune recognition and tumor regression in animal models, there is stilla need for improvements to these strategies, In this study, we examined the efficacy of a combination gene therapy using adenovirus (Ad) 5 vectors expressing human interleukin-2 and the wild-type (wt) human p53 gene under control of the human cytomegalovirus immediate early promoter (AdIL-2 and Adp53wt, respectively), Infected murine cell lines and primary mouse tumor cells secreted high levels of IL-2 and over expressed the p53 protein for at least 9 days, After infection of cells with Adp53wt, DNA synthesis was significantly inhibited and apoptosis was induced within 3-5 days, Both vectors were tested in a transgenic mouse mammary adenocarcinoma model for antitumor response, Following a single intratumoral injection of mice bearing PyMT induced tumors, the combination of Adp53wt (1 x 10(9) pfu) plus a relatively low dose of AdIL-2 (1.5 x 10(8) pfu) caused regressions in 65% of the treated tumors without toxicity, Fifty percent of the treated mice remained tumor free and were immune to rechallenge with fresh tumor cells, In contrast, injection of either vector alone at this does resulted in only a delay in tumor growth, Only mice co-injected with Adp53wt and AdIL-2 showed specific antitumor cytolytic T lymphocyte (CTL) activity, indicating that the immune response involved in tumor regression was promoted by the combination therapy, These results suggest that cancer treatmentstrategies involving combined delivery of immunomodulatory and antiproliferative genes may be highly effective.

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Documento generato il 02/07/20 alle ore 20:42:00