Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: KEGG:D03345 (
beta-Galactosidase
)
434
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Using our model to grow superficial human bladder cancer in the mouse bladder, we have found that the polyamide compound, Syn3, when injected intravesically for 1 hour at 1 mg/mL on two consecutive days, markedly increases rAd-beta-gal intravesical gene transfer and expression. This enhanced transgene expression was much greater than obtain by the use of 22% ethanol, which had previously been shown to increase intravesical adenoviral gene transfer, whereas little or no gene expression was seen with exposure to only rAd-beta-gal.
beta-Galactosidase
staining was seen in virtually every normal urothelial and superficial tumor cell present, including tumors that express little or no coxsackie-adenovirus receptors when Syn3 was present. High adenoviral-mediated gene transfer was also documented in the pig bladder using Syn3 in a similar protocol. Therefore, Syn3 may overcome the limitations of adequate intravesical adenoviral-mediated gene transfer and, when combined with an appropriate adenoviral-mediated gene, could offer an effective approach to the treatment of superficial bladder cancer and perhaps even genetically altered precursor lesions.
Cancer
Gene Ther 2002 Aug
PMID:Syn3 provides high levels of intravesical adenoviral-mediated gene transfer for gene therapy of genetically altered urothelium and superficial bladder cancer. 1213 30
The development of gene delivery systems for therapeutic use involves vectors (often retrovirus or adenovirus) which typically encode one target protein, but the use of internal ribosome entry sites (IRES) can confer the ability to express more than one protein from bi- or polycistronic mRNAs. IRES elements can display tissue-specific expression, so it is necessary to determine suitable IRES for specific clinical applicability. Blood vessel endothelial cells are important clinically since many different conditions involve neo-vascularisation (angiogenesis). We have demonstrated that the viral hepatitis C IRES element is a powerful mediator of protein synthesis in angiogenesis, such as found in solid tumours. Homologous recombination was used to introduce IRES-lacZ sequences into the Lmo2 gene, which is expressed in endothelial cells.
beta-Galactosidase
expression was determined during vascular remodelling in mouse embryos and in sprouting endothelium during growth of solid tumours, and showed that the hepatitis C IRES is used efficiently for protein synthesis in endothelial cells. This IRES element can provide the means to express two or more therapeutic genes in blood vessel endothelium in clinical conditions, such as
cancer
, which depend on angiogenesis.
...
PMID:The hepatitis C virus internal ribosome entry site facilitates efficient protein synthesis in blood vessel endothelium during tumour angiogenesis. 1268 81
beta-Galactosidase
(beta-gal) has been widely used as a transgene reporter enzyme, and several substrates are available for its in vitro detection. The ability to image beta-gal expression in living animals would further extend the use of this reporter. Here we show that DDAOG, a conjugate of beta-galactoside and 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) (DDAO), is not only a chromogenic beta-gal substrate but that the cleavage product has far-red fluorescence properties detectable by imaging. Importantly, the cleavage substrate shows a 50-nm red shift, enabling its specific detection in a background of intact probe, a highly desirable feature for in vivo imaging. Specifically, we show that beta-gal-expressing 9L gliomas are readily detectable by red fluorescence imaging in comparison with the native 9L gliomas. We furthermore show that herpes simplex virus amplicon-mediated LacZ gene transfer into tumors can be transiently and thus serially visualized over time. The results indicated that in vivo real-time detection of beta-gal activity is possible by fluorescence imaging technology.
Cancer
Res 2004 Mar 01
PMID:In vivo imaging of beta-galactosidase activity using far red fluorescent switch. 1499 12