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)

We previously investigated the role of basic fibroblast growth factor (bFGF) as a mediator of angiogenesis, tumorigenicity, and metastasis of transitional cell carcinoma (TCC) of the bladder. In the present study, we determined whether adenoviral-mediated antisense bFGF gene transfer therapy (Ad bFGF-AS) would inhibit TCCs growing in the subcutis of nude mice. In vitro, Ad bFGF-AS inhibited endothelial cell proliferation and enhanced apoptosis. The highly metastatic human TCC cell line 253J-BV(R) was implanted ectopically in the subcutis of athymic nude mice, and therapy was begun when the tumors reached a diameter between 5 and 7 mm. Intralesional therapy with Ad bFGF-AS decreased the in vivo expression of bFGF and matrix metalloproteinase type 9 mRNA and protein, and reduced microvessel density and enhanced endothelial cell apoptosis. Tumor growth was significantly inhibited by Ad bFGF-AS (mean, 58 mg) compared with controls [saline (mean, 562 mg), beta-galactosidase adenovirus (mean, 586 mg), and sense bFGF adenoviral therapy (Ad bFGF-S; mean, 3012 mg)]. These results suggest that Ad bFGF-AS therapy affects endothelial cells directly and tumor cells indirectly through down-regulation of bFGF and matrix metalloproteinase type 9, resulting in endothelial cell apoptosis and significant tumor growth inhibition. Furthermore, these studies confirm that bFGF expression is a valid target for the therapy of bladder cancer.
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PMID:Gene therapy of human bladder cancer with adenovirus-mediated antisense basic fibroblast growth factor. 1110 63

We previously demonstrated the importance of interleukin-8 (IL-8) as a mediator of angiogenesis, tumorigenicity, and metastasis of transitional cell carcinoma (TCC) of the bladder. In the present study, we evaluated the feasibility of adenoviral mediated antisense IL-8 gene transfer (Ad IL-8-AS) as therapy for established TCC. In vitro, Ad IL-8-AS inhibited endothelial cell proliferation and enhanced endothelial cell apoptosis. The highly metastatic human TCC cell line 253J B-V(R) was implanted into the subcutis of athymic nude mice, and intralesional therapy with Ad IL-8-AS commenced when the tumors reached a diameter between 5 and 7 mm. Tumor growth was significantly inhibited compared with therapy in controls (saline and beta-galactosidase adenovirus). Ad IL-8-AS therapy decreased the in vivo expression of IL-8 and matrix metalloproteinase type 9 (MMP-9), reduced microvessel density, and enhanced endothelial cell apoptosis. These results indicate that Ad IL-8-AS therapy targets both tumor cells and host endothelial cells resulting in endothelial cell apoptosis and significant inhibition of tumor growth.
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PMID:Adenoviral-mediated gene therapy of human bladder cancer with antisense interleukin-8. 1149 99

We determined whether the IFN-beta gene could suppress angiogenesis, tumor growth, and metastasis of human bladder transitional cell carcinoma. The highly tumorigenic and metastatic 253J B-V(R) human bladder transitional cell carcinoma (TCC) cell line (resistant to the antiproliferative effects of IFN-beta) was infected in vitro with adenoviral beta-galactosidase (Ad-LacZ), murine adenoviral IFN-beta (Ad-mIFN-beta), or human adenoviral IFN-beta (Ad-hIFN-beta) and implanted into the bladders of athymic nude mice. Ad-mIFN-beta and Ad-hIFN-beta were used because of the species specificity of IFN-beta. The transient production of mIFN-beta and hIFN-beta from the infected 253JB-V(R) tumor cells significantly inhibited tumorigenicity and spontaneous lymph node metastasis. Subsequently, the 253J B-V(R) cells were implanted into the subcutis of athymic nude mice, and established tumors were treated by direct intratumoral injection with Ad-mIFN-beta, Ad-hIFN-beta, Ad-LacZ, or PBS. By in situ hybridization (ISH) and immunohistochemical analysis (IHC), expression of hIFN-beta and mIFN-beta mRNA and protein within the tumors was demonstrated after Ad-hIFN-beta and Ad-mIFN-beta gene therapy, respectively. The therapy also induced necrosis in both the Ad-mIFN-beta- and Ad-hIFN-beta-treated tumors. IHC revealed decreased tumor cell proliferation and the sequestration of activated macrophages within the tumors after Ad-mIFN-beta therapy. In addition, the expression of the proangiogenic factors bFGF, and MMP-9 protein (by IHC) was significantly down-regulated by Ad-hIFN-beta gene therapy. Double-immunofluorescent IHC for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) and CD-31 demonstrated tumor and endothelial cell apoptosis in those tumors treated with Ad-hIFN-beta gene therapy. Tumor-induced angiogenesis, as determined by the microvessel density, was decreased in tumors treated with both Ad-mIFN-beta and Ad-hIFN-beta. These data suggest that the inhibition of tumorigenicity and the metastasis of the 253J B-V(R) cells after infection with Ad-IFN-beta is caused by the inhibition of angiogenesis and the activation of host effector cells.
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PMID:Inhibition of tumorigenicity and metastasis of human bladder cancer growing in athymic mice by interferon-beta gene therapy results partially from various antiangiogenic effects including endothelial cell apoptosis. 1194 41