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Titolo:
Combination surgery and nonviral interleukin 2 gene therapy for head and neck cancer
Autore:
Li, DQ; Jiang, W; Bishop, JS; Ralston, R; OMalley, BW;
Indirizzi:
Johns Hopkins Univ, Baltimore, MD 21287 USA Johns Hopkins Univ Baltimore MD USA 21287 s Univ, Baltimore, MD 21287 USA Genemed Inc, The Woodlands, TX 77381 USA Genemed Inc The Woodlands TX USA77381 d Inc, The Woodlands, TX 77381 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 6, volume: 5, anno: 1999,
pagine: 1551 - 1556
SICI:
1078-0432(199906)5:6<1551:CSANI2>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYSTIC-FIBROSIS; KILLER-CELLS; IMMUNOTHERAPY; ADENOVIRUS; PROGRESS; DNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: O'Malley, BW Univ Maryland, Sch Med, 16 S Eutaw St,Suite 500, Baltimore, MD 21201 USA Univ Maryland 16 S Eutaw St,Suite 500 Baltimore MD USA 21201
Citazione:
D.Q. Li et al., "Combination surgery and nonviral interleukin 2 gene therapy for head and neck cancer", CLIN CANC R, 5(6), 1999, pp. 1551-1556

Abstract

We have developed a novel nonviral interleukin 2 (IL-2) gene therapy that demonstrates significant treatment-specific, antitumor efficacy in combination with subtotal surgical resection in a head and neck cancer murine model, Treatment of established head and neck tumors in immunocompetent mice wasperformed via direct injection with a cationic liposome composed of DOTMA and cholesterol formulation carrying DNA plasmid for human IL-2 ( hIL-2) gene expression, ELISA assays of tumor extracts 24 h after treatment of hIL-2gene therapy revealed increased local hIL-2 production as well as a formulation-specific secondary induction of murine IFN-gamma and IL-12. We hypothesize that the paracrine production of multiple cytokines after IL-2 singlegene transfer is important for generating a therapeutic effect, and that this strategy will be well tolerated and effective in combination with surgery for head and neck cancer, In animal experiments where surgery was performed in conjunction with an operative site injection of hIL-2 plasmid formulation, no pre-, intra-, or postoperative toxicity or compromise to wound healing was identified. In murine experiments combining partial surgical resection with the nonviral gene therapy, significant antitumor efficacy was demonstrated in the hIL-2 plasmid formulation group compared with empty plasmid formulation and lactose-injected controls. In a separate experiment using smaller tumor sizes, we also demonstrated that treatment outcomes were dependent on the technical aspect of the actual treatment injection as well as visualization with surgical access, The hIL-2 plasmid formulation gene therapy induces local expression of multiple cytokines, results in treatment-specific antitumor effects, and circumvents many of the concerns and toxicity encountered,vith viral gene transfer, These data support the need for continued preclinical investigation and the consideration of human clinical trials for combination nonviral hIL-2 gene therapy and surgery for head and neck cancer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 07:39:09