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)

Pursuit of endogenous functions for various members of the alcohol dehydrogenase (ADH) enzyme family has led to exploration of gene expression patterns. Herein, we have used transgenic mice to examine the mouse gene encoding class IV ADH (ADH4), an enzyme that is weakly effective as an ethanol dehydrogenase, but highly effective as a retinol dehydrogenase in vitro. ADH4 promoter and upstream regulatory sequences were fused to lacZ and stably introduced into mice so that embryonic expression of ADH4 could be easily monitored by examination of beta-galactosidase activity in situ. Several independent founder mice carrying ADH4-lacZ transgenes with either 2.7 or 9.0 kb of upstream regulatory sequences produced embryos in which expression was highly localized in the brain and craniofacial region at stages E8.5 to 9.5 during neurulation. Expression in the brain was limited to the ventral midbrain and its boundary with the hindbrain. At stage E8.5, ADH4-lacZ expression was noticed in several dispersed regions throughout the head, and by stage E9.5 it was evident that these regions corresponded to the otic vesicles and migrating neural crest cells, particularly the mesencephalic, trigeminal, facial, and olfactory neural crest. ADH4-lacZ expression in the trigeminal neural crest appeared as long fibers emanating from the midbrain/hindbrain boundary and extending to the first branchial arch following the tract of the trigeminal nerve. These findings support the hypothesis that ADH4 may normally function in retinoic acid synthesis needed for brain and neural crest development and that it participates in the mechanism of ethanol-induced brain and craniofacial birth defects.
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PMID:ADH4-lacZ transgenic mouse reveals alcohol dehydrogenase localization in embryonic midbrain/hindbrain, otic vesicles, and mesencephalic, trigeminal, facial, and olfactory neural crest. 980 48

Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS) radioiodine gene therapy in a mouse colon xenograft model. In vitro uptake of Tc-99m sestamibi was increased approximately two-fold in cells infected with an adenovirus vector that expressed MDR1 shRNA (Ad-shMDR1) and I-125 uptake was 25-fold higher in cells infected with an adenovirus vector that expressed human NIS (Ad-hNIS) as compared with control cells. As compared with doxorubicin or I-131 treatment alone, the combination of doxorubicin and I-131 resulted in enhanced cytotoxicity for both Ad-shMDR1- and Ad-hNIS-infected cells, but not for control cells. In vivo uptake of Tc-99m sestamibi and Tc-99m pertechnetate was twofold and 10-fold higher for Ad-shMDR1 and Ad-hNIS-infected tumors as compared with tumors infected with a control adenovirus construct that expressed beta-galactosidase (Ad-LacZ), respectively. In mice treated with either doxorubicin or I-131 alone, there was a slight delay in tumor growth as compared to mice treated with Ad-LacZ. However, combination therapy with doxorubicin and I-131 induced further significant inhibition of tumor growth as compared with mice treated with Ad-LacZ. We have shown successful therapeutic efficacy of combined MDR shRNA and hNIS radioiodine gene therapy using an adenoviral vector system in a mouse colon cancer model. Adenovirus-mediated cancer gene therapy using MDR1 shRNA and hNIS would be a useful tool for the treatment of cancer cells expressing multi-drug resistant genes.
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PMID:Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model. 2018 72