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Titolo:
The evaluation of adenoviral p53-mediated bystander effect in gene therapyof cancer
Autore:
Rizk, NP; Chang, MY; El Kouri, C; Seth, P; Kaiser, LR; Albelda, SM; Amin, KM;
Indirizzi:
Univ Penn Hlth Syst, Thorac Oncol Res Lab, Dept Surg, Div Pulm & Crit Care, Philadelphia, PA 19104 USA Univ Penn Hlth Syst Philadelphia PA USA 19104 Philadelphia, PA 19104 USA Univ Penn Hlth Syst, Dept Med, Philadelphia, PA 19104 USA Univ Penn Hlth Syst Philadelphia PA USA 19104 Philadelphia, PA 19104 USA NCI, Med Branch, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892NCI, Med Branch, NIH, Bethesda, MD 20892 USA
Titolo Testata:
CANCER GENE THERAPY
fascicolo: 4, volume: 6, anno: 1999,
pagine: 291 - 301
SICI:
0929-1903(199907/08)6:4<291:TEOAPB>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
WILD-TYPE P53; TUMOR-SUPPRESSOR GENE; HUMAN-MALIGNANT MESOTHELIOMA; LUNG-CANCER; IN-VIVO; RECOMBINANT ADENOVIRUS; GLIOBLASTOMA CELLS; EXPRESSION; GROWTH; HEAD;
Keywords:
p53; gene therapy; bystander effect; adenovirus; cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Amin, KM Hosp Univ Penn, Dept Surg, Thorac Oncol Res Lab, 810 Maloney Bldg,3600 Spruce St, Philadelphia, PA 19104 USA Hosp Univ Penn 810 Maloney Bldg,3600 Spruce St Philadelphia PA USA 19104
Citazione:
N.P. Rizk et al., "The evaluation of adenoviral p53-mediated bystander effect in gene therapyof cancer", CANC GENE T, 6(4), 1999, pp. 291-301

Abstract

Because many tumors have mutated p53, one potential strategy proposed for cancer gene therapy is the introduction of the wild-type p53 gene into tumor cells. One puzzling aspect of this approach is that currently available gene transfer protocols result in a small percentage of tumor cells being transduced in vivo, thus implicating a "bystander effect" to achieve therapeutic efficacy. Because bystander effects in the context of p53-mediated genetherapy have not been well characterized, Lye evaluated the role of in vitro and in vivo bystander effects of adenovirally delivered p53 (AdWTp53), Using human tumor cell lines that did not express p53 protein but were infectible with adenovirus and showed sensitivity to p53-mediated apoptosis, we were unable to demonstrate an AdWTp53-mediated in vitro bystander effect, despite seeing strong bystander effects when cells were infected with an adenovirus containing the suicide gene herpes simplex virus thymidine kinase and treated with ganciclovir. In contrast, in vivo flank mixing studies using one of these cell lines showed a weak but significant p53-mediated bystander effect (a 40% inhibition of tumor growth). This bystander effect translated into a small survival advantage in an established intraperitoneal tumor model when tumor burden was low at the lime of viral instillation. The survival advantage was lost, however, when tumor burden was increased. This study indicates that treatment of human tumors using AdWTp53 may be possible; however, because of the weak bystander effect in vivo, effective treatment will likely require a large percentage of tumor cells to be transduced.

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Documento generato il 27/09/20 alle ore 12:24:28