Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion gene transfer (uracil phosphoribosyl transferase and herpes simplex virus thymidine kinase)

Citation
T. Shimizu et al., Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion gene transfer (uracil phosphoribosyl transferase and herpes simplex virus thymidine kinase), CANC GENE T, 8(7), 2001, pp. 512-521
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER GENE THERAPY
ISSN journal
0929-1903 → ACNP
Volume
8
Issue
7
Year of publication
2001
Pages
512 - 521
Database
ISI
SICI code
0929-1903(200107)8:7<512:EGSIEC>2.0.ZU;2-W
Abstract
Advanced esophageal cancers are highly malignant and frequently resistant t o 5-fluorouracil (5-FU). Escherichia coli uracil phosphoribosyltransferase (UP) is a pyrimidine salvage enzyme that alters 5-FU metabolism and sensiti vity. A recombinant adenovirus encoding the UP gene (AxCA.UP) has been appl ied in gastric cancer gene therapy to sensitize cancer cells to lower conce ntrations of 5-FU. We have generated a recombinant adenovirus (AxCA.UT) enc oding UP and herpes simplex virus thymidine kinase fusion protein (UT) to e xamine whether it would enhance the antitumor activity of AxCA.UP treatment . AxCA.UT treatment significantly enhanced the sensitivity of human esophag eal cancer cells to and significantly enhanced the growth inhibition effect s of UP gene therapy in vitro. Moreover, both 5-FU and ganciclovir showed b ystander effects on growth inhibition. In an in vivo study, the therapeutic outcome of AxCA.UT treatment significantly enhanced the antitumor activity of AxCA.UP treatment. These observations suggest that AxCA.UT may be usefu l in esophageal cancer gene therapy.