Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.1 (cytosine deaminase)
 747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Efficient negative selection systems are increasingly needed for numerous applications in plant biology. In recent years various counter-selectable genes have been tested in six dicotyledonous species, whereas there are no data available for the use of negative selection markers in monocotyledonous species. In this study, we compared the applicability and reliability of two different conditional negative selection systems in transgenic barley. The bacterial codA gene encoding cytosine deaminase, which converts the non-toxic 5-fluorocytosine (5-FC) into the toxic 5-fluorouracil (5-FU), was used for in vitro selection of germinating seedlings. Development of codA-expressing seedlings was strongly inhibited by germinating the seeds in the presence of 5-FC. For selecting plants in the greenhouse, a bacterial cytochrome P450 mono-oxygenase gene, the product of which catalyses the dealkylation of a sulfonylurea compound, R7402, into its cytotoxic metabolite, was used. T1 plants expressing the selectable marker gene showed striking morphological differences from the non-transgenic plants. In experiments with both negative selectable markers, the presence or absence of the transgene, as predicted from the physiological appearance of the plants under selection, was confirmed by PCR analysis. We demonstrate that both marker genes provide tight negative selection; however, the use of the P450 gene is more amenable to large-scale screening under greenhouse or field conditions.
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PMID:Negative selection systems for transgenic barley (Hordeum vulgare L.): comparison of bacterial codA- and cytochrome P450 gene-mediated selection. 1057 57

Gene therapy of cancer offers the possibility of a targeted treatment that destroys tumors and metastases, but not normal tissues. In gene-directed enzyme prodrug therapy (GDEPT), or suicide gene therapy, the gene encoding an enzyme is delivered to tumor cells, followed by administration of a prodrug, which is converted locally to a cytotoxin by the enzyme. The producer cells as well as surrounding bystanders are subsequently killed. Promising results have meant that suicide gene therapy has reached multicenter phase III clinical trials. This review will discuss the development, efficiency, mode of action and pharmacokinetics of seven GDEPT systems in vitro and in vivo. We will review the latest data of those systems in clinical trials (herpes simplex virus thymidine kinase/gancyclovir, bacterial cytosine deaminase/5-fluorocytosine, bacterial nitroreductase/CB1954 and cytochrome P450/cyclophosphamide), as well as the development of more recent and experimental systems which are not yet in clinical trials (P450 reductase/tirapazamine, carboxypeptidase/CMDA, horseradish peroxidase/indole-3-acetic acid or paracetamol and others).
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PMID:From bench to bedside for gene-directed enzyme prodrug therapy of cancer. 1574 71

Gene therapy provides a potentially powerful approach for cancer treatment. One strategy is based on direct transfer of a suicide gene, which encodes enzymes that can activate a prodrug within tumor cells and thereby render the tumor cells sensitive to agents that are otherwise nontoxic to the cell. For example, introduction of the herpes simplex virus thymidine kinase gene (HSV-tk) or the bacterial cytosine deaminase (CD) gene, which respectively render mammalian cells sensitive to the otherwise nontoxic antiviral agent ganciclovir (1,2) and to the antifungal drug 5-fluorocytosine (3,4). Another novel prodrug activation system is the activation of conventional anticancer prodrug cyclo-phosphamide and ifosphamide by intratumor expression of mammalian cyto-chrome P450, such as rat 2B1 or human 2B6 to further sensitize cancer cells (5,6). Whereas gene therapy may provide a new therapeutic approach, clinical efficacy will require gene delivery systems, which possess both high gene-transduction efficiency and target-cell specificity.
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PMID:Adenovirus-mediated targeted gene therapy for breast cancer and for purging hematopoietic stem-cell sources. 2139 Aug 17