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)

Tumor cells that express a fusion gene comprised of Escherichia coli cytosine deaminase (CD) and herpes simplex virus type 1 thymidine kinase (TK) sequences exhibit activation of and subsequent killing by the normally innocuous prodrugs 5-fluorocytosine and ganciclovir (Rogulski et al., Hum. Gene Ther., 8: 73-85, 1997). To target localized expression of this therapeutic gene, we have constructed a recombinant adenovirus containing the CD-TK fusion gene under the control of a human inducible heat shock protein 70 promotional sequence. Strong expression of the fusion gene product was induced by heating at 41 degrees C for 1 h. Expression levels obtained were dependent on the multiplicity of infection used and the incubation time after heat shock. Heat-induced expression of the CD-TK protein significantly reduced the survival of PC-3 cells in the presence of both 5-fluorocytosine and ganciclovir. These studies represent a novel form of gene therapy for the transduction and regulation of a double suicide gene in tumor cells and may provide a unique application for hyperthermia in cancer therapy.
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PMID:Adenoviral-mediated transfer of a heat-inducible double suicide gene into prostate carcinoma cells. 953 29

Prostate tumor cells (PC-3) were transduced with defective, recombinant adenovirus containing a fusion gene encoding the Escherichia coli cytosine deaminase and herpes simplex virus type-1 thymidine kinase under the control of a cytomegalovirus promoter. Expression levels of the fusion protein were dependent on the multiplicity of infection used and incubation time following infection. PC-3 cells expressing this protein were sensitized to killing by the normally innocuous prodrugs 5-fluorocytosine and ganciclovir. In addition, radiation-induced killing was enhanced in virally infected cells in the presence of the prodrugs.
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PMID:Adenoviral transduction of a cytosine deaminase/thymidine kinase fusion gene into prostate carcinoma cells enhances prodrug and radiation sensitivity. 1038 66

We have previously developed a recombinant adenovirus containing a fusion gene of Escherichia coli cytosine deaminase (CD) and herpes simplex virus type 1 thymidine kinase (HSV-1 TK) controlled by a cytomegalovirus (CMV) enhancer-promoter. This replication-incompetent adenovirus effectively transduced the CD-TK gene into human prostate adenocarcinoma DU-145 or PC-3 cells. Interestingly, heat shock at 41 degrees C for 4 hours elevated the level of CD-TK by approximately 5- to 20-fold at a multiplicity of infection (MOI) of 1. Heat-enhanced expression of CD-TK promoted cytotoxicity by 23-, 9-, or 47-fold in the presence of 50 microg/mL ganciclovir (GCV), 500 microg/mL 5-fluorocytosine (5-FC), or 50 microg/mL GCV+500 microg/mL 5-FC, respectively, at an MOI of 1. Moreover, there was an increase in radiosensitivity when adenovirus-infected cells were heated at 41 degrees C for 4 hours followed by irradiation in the presence of the prodrugs. Virus+heat+1 microg/mL GCV treatment increased radiosensitivity by a dose-modifying factor (DMF) of 2.2, whereas virus+heat+10 microg/mL 5-FC exposure resulted in a DMF of 2.3. Radiosensitization was clearly enhanced as a result of combined prodrug exposure (DMF=4.4). Our results suggest that the efficiency in expression of suicide genes from an adenoviral vector used for cytotoxic anticancer therapy could be improved by combining heat treatment with radiation therapy.
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PMID:Gene transfer into human prostate adenocarcinoma cells with an adenoviral vector: Hyperthermia enhances a double suicide gene expression, cytotoxicity and radiotoxicity. 1189 43