Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacokinetic properties and gene expression of naked plasmid DNA and its cationic liposome complexes after intratumoral injection were studied. Using Walker 256 tissue-isolated tumor perfusion system, we quantified the recovery of naked plasmid DNA and cationic liposome complexes in the tumor, leakage from the tumor surface and the venous outflow after intratumoral injection. Approximately 50% of naked plasmid DNA was eliminated from the tumor at 2 hr after injection, while more than 90% of plasmid DNA was retained in the tumor when complexed with cationic liposome. However, distribution of these complexes in the tumor was restricted only in the vicinity of the injection site. Furthermore, we have examined the expression of chloramphenicol acetyltransferase (CAT) DNA constructs (naked pCMV-CAT) and its cationic liposome (DC-chol) complexes after intratumoral injection into subcutaneous rat Walker 256 carcinosarcoma. Significant gene expression was observed in both cases, but localization of gene expressing cells in the tumor tissue was limited to the vicinity of the injection site. Thus the pharmacokinetic and gene expression studies have demonstrated that in vivo gene expression in the tumor can be achieved by direct injection of naked plasmid DNA. In addition, there is a possibility that restricted localization of naked DNA and its cationic liposome complexes in tumor inhibits gene expression.
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PMID:[Cancer gene therapy by direct intratumoral injection: gene expression and intratumoral pharmacokinetics of plasmid DNA]. 906 88

The pharmacokinetic properties and gene expression of naked plasmid DNA and its cationic liposome complexes were studied after direct intratumoral injection. Using a Walker 256 tissue-isolated tumor perfusion system, we quantified the recovery of naked plasmid DNA and cationic liposome complexes in the tumor, leakage from the tumor surface, and the venous outflow after intratumoral injection. Approximately 50% of naked plasmid DNA had been eliminated from the tumor 2 h after injection, whereas more than 90% of plasmid DNA was retained in the tumor when it was complexed with cationic liposomes. However, the distribution of these complexes in the tumor was restricted to the tissue surrounding the injection site. Pharmacokinetic analysis of the venous outflow profiles suggested that the rate-limiting process that determines the retention of plasmid DNA in the tumor is transferred from the injection site in the tumor tissue and that complexation with cationic liposomes may retard this process. Furthermore, we examined the gene expression of chloramphenicol acetyltransferase DNA constructs (naked pCMV-CAT) and the corresponding cationic liposome [3-beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol] complexes. A similar level of gene expression was observed in vivo after direct intratumoral injection of naked DNA and its cationic liposome complexes. In both cases, a great variation was observed between tumors, and localization of gene-transduced cells in the tumor tissue was limited to the area in the vicinity of the injection site. Thus, these pharmacokinetic and gene expression studies have demonstrated that cationic liposomes can enhance the retention of injected DNA in the tumor model, whereas cationic liposome complex does not necessarily improve gene expression because of its poor dissemination in this tumor. The present study also suggested that there is a need to control the behavior of the injected naked plasmid DNA and its cationic liposome complexes to ensure better distribution throughout the tumor.
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PMID:Intratumoral pharmacokinetics and in vivo gene expression of naked plasmid DNA and its cationic liposome complexes after direct gene transfer. 920 77