Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region with a 5-year survival level of approximately 65%. To explore novel therapeutic strategies in the management of this disease, the potential of Ad5CMV-p53-mediated gene transfer to NPC cells was investigated in vitro. Two NPC cell lines, CNE-1 and CNE-2Z, were infected with either Ad5CMV-p53 or Ad5CMV-beta-galactosidase and evaluated for transduction efficiency and cytotoxicity. At a multiplicity of infection of 50 plaque-forming units (pfu)/cell, Ad5CMV-beta-galactosidase infection and beta-galactosidase expression were detected in almost 100% of treated NPC cells. High levels of recombinant p53 protein expression were also observed in the NPC cell lines when treated with Ad5CMV-p53 at 50 pfu/cell. Expression of recombinant p53 was dose and time dependent, with peak levels observed at 24 h. A marked increase in WAF1/CIP1 expression was also observed in NPC cells after Ad5CMV-p53 infection. Expression of bcl-2 and bax were minimally detectable at baseline; infection with Ad5CMV-p53 induced no changes in the protein levels in the NPC cells. Growth of NPC cells treated with Ad5CMV-p53 was observed to be significantly inhibited when determined by either the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or clonogenic assay. Infection with Ad5CMV-p53 at 25 pfu/cell resulted in survival levels of 0.35 and 11% in CNE-1 and CNE-2Z cells, respectively. Chromatin condensation and DNA fragmentation were also observed, demonstrating that these cells were undergoing apoptosis. However, when GM38 (normal human fibroblasts) were subjected to identical treatments, they demonstrated significantly lower infection efficiency and transgene expression and were resistant to Ad5CMV-p53-mediated cytotoxicity. These data demonstrate the efficacy of Ad5CMV-p53-mediated gene therapy in human NPC, thus warranting additional investigations of this therapeutic strategy.
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PMID:Cytotoxic effects of Ad5CMV-p53 expression in two human nasopharyngeal carcinoma cell lines. 981 13

The multi-stage cell model of the nasopharyngeal carcinoma development in vitro by Epstein-Barr virus transformation is beneficial for the elucidation of the mechanism of nasopharyngeal cancer. To observe the biological changes of primary human nasopharyngeal epithelial cells in early phase of immortalization, in this study, we have detected the morphological changes and the expression profile of senescence-associated beta-galactosidase (SA-beta-Gal) in primary culture. In addition, the expression of EB virus latent membrane protein 1 (LMP1) and the growth curve of primary cells were also detected. Our results showed a low percentage of cells infected with EB virus expressing SA-beta-Gal activity at the late primary culture. In morphology, the cells also formed multilayer foci, and the cell population doubling time was showed. These results demonstrated that the nasopharyngeal epithelial cells by EB virus infection have passed through the senescence and entered the early phase of immortalization. These cells have some of the transformed characteristics. Our results provided the data for further study on the mechanism of immortalization and the establishment of human nasopharyngeal epithelial cell line.
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PMID:[Observation of the biological characterizations of nasopharyngeal epithelial cells by EB virus infection in early phase of immortalization]. 1254

EBV-associated nasopharyngeal cancer (NPC) occurs with high frequency in China and is a major cause of morbidity and mortality. To explore the potential use of adenovirus-mediated tumor suppressor p53 gene therapy In NPC, we first examined the in vitro effects of p53 introduced into the NPC cell lines RPMI 2650, Fadu and Detroit 562. p21(WAF1/CIP1) induction by chemotherapy was used as a functional assay which revealed that RPMI 2650 expresses wild-type p53 whereas Fadu and Detroit 562 encode mutant p53. Infection with p53-expressing adenovirus (Ad-p53) induced apoptosis and inhibited cell growth in all three NPC cell lines, regardless of the endogenous p53 status. Adenovirus infectivity was greatest in RPMI 2650 cells, with 100% of the cells expressing beta-galactosidase following Ad-LacZ infection using an MOI of 100, as compared to 20-30% infectivity with the other NPC lines. Using RPMI 2650 cells injected into nude mice, we developed an animal model for nasopharyngeal cancer. Established tumors (0.6-0.8 cm) were injected with 5x10(9) PFU Ad-LacZ, Ad-p53 or PBS in a 100 mu l volume. We found evidence for in vivo expression of beta-galactosidase or p53 and p21 up to two weeks following Ad-LacZ or Ad-p53 virus injection respectively. Objective regression of tumor size was observed at two weeks in 4/6 Ad-p53-treated tumors, but not in Ad-LacZ or PBS-treated tumors. The results provide an animal model for human nasopharyngeal cancer, and indicate a potential use of p53 in its therapy in vivo.
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PMID:Adenovirus-mediated p53 gene therapy in nasopharyngeal cancer. 2152 3