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Titolo:
AN HSVTK-MEDIATED LOCAL AND DISTANT ANTITUMOR BYSTANDER EFFECT IN TUMORS OF HEAD AND NECK ORIGIN IN ATHYMIC MICE
Autore:
BI WL; KIM YG; FELICIANO ES; PAVELIC L; WILSON KM; PAVELIC ZP; STAMBROOK PJ;
Indirizzi:
UNIV CINCINNATI,COLL MED,DEPT CELL BIOL NEUROBIOL & ANAT CINCINNATI OH 45267 UNIV CINCINNATI,COLL MED,DEPT CELL BIOL NEUROBIOL & ANAT CINCINNATI OH 45267 UNIV CINCINNATI,COLL MED,DEPT OTOLARYNGOL CINCINNATI OH 45267
Titolo Testata:
Cancer gene therapy
fascicolo: 4, volume: 4, anno: 1997,
pagine: 246 - 252
SICI:
0929-1903(1997)4:4<246:AHLADA>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXPERIMENTAL BRAIN-TUMORS; GENE-THERAPY; TRANSDUCTION; REGRESSION; CELLS;
Keywords:
HEAD AND NECK TUMORS; GENE THERAPY; GANCICLOVIR; HERPES THYMIDINE KINASE; THERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
21
Recensione:
Indirizzi per estratti:
Citazione:
W.L. Bi et al., "AN HSVTK-MEDIATED LOCAL AND DISTANT ANTITUMOR BYSTANDER EFFECT IN TUMORS OF HEAD AND NECK ORIGIN IN ATHYMIC MICE", Cancer gene therapy, 4(4), 1997, pp. 246-252

Abstract

The ''bystander effect,'' produced by ganciclovir-mediated killing ofcells transduced with a herpes simplex virus thymidine kinase (HSVtk)gene, defines the cooperative killing of non-HSVtk-transduced cells. In vitro, a major contributor to this phenomenon is metabolic cooperation involving transfer of cytotoxic small molecules between cells via gap junctions. In this study, the bystander effect was assessed in vivo using cells of oral squamous cell carcinoma origin. Mixtures of HSVtk(+) and HSVtk(-) tumor cells were implanted subcutaneously in the left flank of nude mice, and naive HSVtk(-) cells were implanted subcutaneously in the right Flank. When tumors attained a size of 0.5 to 1 cm,the animals were treated with ganciclovir on a daily basis. The rumors comprised of mixed cells in the left flank resolved, consistent witha predicted bystander effect. The naive tumors in the right flank either resolved or became cytostatic showing little further growth compared to controls. Similar results were obtained when naive tumors were grown in both flanks and the tumor in the left flank received intratumoral injection of HSVtk retroviral producer cells or PA317 (HSVtk(+)) packaging cells, but not parental NIH 3T3 cells. Concomitant treatment with dexamethasone impaired the antitumor effect on the contralateral side. When these experiments were performed in SCID-Beige mice, there was a reduced antitumor effect on the ipsilateral flank and no antitumor response in the contralateral flank. Together with histology of regressing tumors, which showed an infiltration of lymphoid cells, these results are suggestive of an immune-related antitumor response that could account for the distant bystander effect.

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Documento generato il 05/04/20 alle ore 06:48:57