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Titolo:
Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer
Autore:
Coukos, G; Makrigiannakis, A; Kang, EH; Caparelli, D; Benjamin, I; Kaiser, LR; Rubin, SC; Albelda, SM; Molnar-Kimber, KL;
Indirizzi:
Univ Penn, Med Ctr, Dept Surg, Thorac Oncol Lab, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Oncol Lab, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Philadelphia, Univ Penn Philadelphia PA USA 19104 col, Div Gynecol Oncol, Philadelphia, UnivAPenn, Med Ctr, Dept Obstet & Gynecol, Div Reprod Biol, Philadelphia, P Univ Penn Philadelphia PA USA 19104 col, Div Reprod Biol, Philadelphia, P Univ4Penn, Med Ctr, Dept Med, Div Pulm Med Crit Care, Philadelphia, PA 1910 Univ Penn Philadelphia PA USA 19104 Med Crit Care, Philadelphia, PA 1910
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 6, volume: 5, anno: 1999,
pagine: 1523 - 1537
SICI:
1078-0432(199906)5:6<1523:UOCCTD>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN BRAIN-TUMORS; VIVO GENE-THERAPY; I CLINICAL-TRIAL; PHASE-I; GLYCOPROTEIN-E; MALIGNANT MESOTHELIOMA; MOUSE MODEL; TYPE-1; ADENOVIRUS; CARCINOMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Molnar-Kimber, KL UnivamiltonMed Ctr, Dept Surg, Thorac Oncol Lab, 351 Stemmler Hall,36th & H Univ Penn 351 Stemmler Hall,36th & Hamilton Walk Philadelphia PA USA 19104
Citazione:
G. Coukos et al., "Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer", CLIN CANC R, 5(6), 1999, pp. 1523-1537

Abstract

Epithelial ovarian cancer (EOC) remains localized within the peritoneal cavity in a large number of patients, lending itself to i.p. approaches of therapy. In the present study, we investigated the effect of replication-selective herpes simplex virus-1 (HSV-1) used as an oncolytic agent against EOCand the use of human teratocarcinoma PA-1 as carrier cells for i.p. therapy. HSV-1716, a replication-competent attenuated strain lacking ICP34.5, caused a direct dose-dependent oncolytic effect on EOC cells in vitro. A single i.p. administration of 5 x 10(6) plaque-forming units resulted in a significant reduction of tumor volume and tumor spread and an increase in survival in a mouse xenograft model. PA-1 cells supported HSV replication in vitro and bound preferentially to human ovarian carcinoma surfaces compared with mesothelial surfaces in vitro and in vivo. In comparison with the administration of HSV-1716 alone, irradiated PA-1 cells, infected at two multiplicities of infection with HSV-1716 and injected i.p. at 5 x 10(6) cells/animal, led to a significant tumor reduction in the two models tested and the significant prolongation of mean survival in one model. Histological evaluation revealed extensive necrosis in tumor areas infected by HSV-1716. Immunohistochemistry against HSV-1 revealed areas of viral infection within tumor nodules, which persisted for several weeks after treatment, Administration of HSV-infected PA-1 carrier cells resulted in larger areas of tumor infected by the virus. Our results indicate that replication-competent attenuatedHSV-1 exerts a potent oncolytic effect on EOC, which may be further enhanced by the utilization of a delivery system with carrier cells, based on amplification of the viral load and possibly on preferential binding of carrier cells to tumor surfaces.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 10:24:52