The use of cationic liposomes DC-CHOL/DOPE and DDAB/DOPE for direct transfer of Escherichia coli cytosine deaminase gene into growing melanoma tumors.

Abstract

An attempt was made to use simple cationic liposomes DC-Chol/DOPE and DDAB/DOPE (DC-Chol is 3 beta (N(N',N-dimethylaminoethane) carbamoyl) cholesterol, DDAB is dimethyldioctadecyl ammonium bromide and DOPE is dioleoylphosphatidylethanolamine) for transfer of Escherichia coli cytosine deaminase 'suicide' gene under the control of tissue-specific tyrosinase gene promoter directly into the murine melanoma B16(F10) tumor. Several repeated intratumoral injections of DNA-liposome complexes followed by intraperitoneal administrations of 5-fluorocytosine, which is converted to 5-fluorouracil, caused strong retardation of murine melanoma B16(F10) tumor growth and, in some cases, rejection of the pre-established tumor. The inhibition of tumor growth expressed as the increased survival of mice is better seen in the case of using DNA-DDAB/DOPE complexes as compared to DNA-DC-Chol/DOPE ones. It seems that the observed therapeutic effect appears to result from several factors: 5-fluorouracil generation by transfected cells, liposome toxicity (DDAB is more toxic than DC-Chol and hence more tumor cells are killed), increased transfection efficiency of surviving cancer cells (in this case DDAB is a better transfection agent than DC-Chol) and, finally, the bystander effect which causes destruction of cells untransfected with CD gene by easily diffusible 5-fluorouracil.

• Authors: S Szala, E Missol, A Sochanik, M Strozyk
• Journal: Gene therapy (Gene Ther) Vol. 3 Issue 11 Pg. 1026-31 (Nov 1996) ISSN: 0969-7128 [Print] England
• PMID: 9044744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Cations
• Drug Carriers
• Liposomes
• Phosphatidylethanolamines
• Quaternary Ammonium Compounds
• didodecyldimethylammonium
• 3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol
• 1,2-dielaidoylphosphatidylethanolamine
• Cholesterol
• Nucleoside Deaminases
• Cytosine Deaminase
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Cations
• Cholesterol (analogs & derivatives, chemistry)
• Cytosine Deaminase
• Drug Carriers
• Escherichia coli (enzymology)
• Fluorouracil (pharmacology)
• Gene Transfer Techniques
• Liposomes
• Melanoma (therapy)
• Mice
• Neoplasms, Experimental (therapy)
• Nucleoside Deaminases (genetics)
• Phosphatidylethanolamines (chemistry)
• Quaternary Ammonium Compounds (chemistry)