PubMed:10580026
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/10580026","sourcedb":"PubMed","sourceid":"10580026","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10580026","text":"Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect.\nBACKGROUND: The cytosine deaminase gene of Escherichia coli converts the nontoxic compound 5-fluorocytosine into 5-fluorouracil (5-FU), thereby acting as a suicide gene when introduced into cancer cells, killing the cells when they are exposed to 5-fluorocytosine. We analyzed the efficacy of using cytosine deaminase-bearing cancer cells as an autologous tumor vaccine in a rat model that mimics liver metastasis from colon carcinoma.\nMETHODS: We introduced a plasmid vector containing the E. coli cytosine deaminase gene into a BDIX rat colon carcinoma cell line. Intrahepatic injection of the modified cells in syngeneic animals generates a single experimental liver \"suicide tumor.\" We then analyzed the effect of 5-fluorocytosine treatment in terms of regression of cytosine deaminase-expressing cells in vivo as well as protection against wild-type cancer cells.\nRESULTS: Treatment with 5-fluorocytosine induced regression of cytosine deaminase-expressing (CD+) tumors, with seven of 11 treated animals being tumor free at the end of 30 days and a statistically significant difference in tumor volumes between treated and control animals (two-sided P\u003c.0001). Intrahepatic injection of CD+ cells followed by 5-fluorocytosine treatment rendered the treated animals resistant to challenge with wild-type tumor cells, with no (zero of seven) treated animals developing wild-type tumors in contrast to all (four of four) control animals. Moreover, in animals with established wild-type liver tumors, injection of CD+ tumor cells followed by 5-fluorocytosine treatment produced a statistically significant increase in survival time (two-sided P\u003c.0001). In vivo immunodepletion and immunohistologic analysis of experimental tumors indicate that natural killer cells are the major immune component involved in this antitumor effect.\nCONCLUSIONS AND IMPLICATIONS: Taken together, these results suggest the potential use of suicide gene-modified tumor cells as therapeutic vaccines against liver metastasis from colon carcinoma.","tracks":[{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":304,"end":310},"obj":"HP_0002664"},{"id":"T2","span":{"begin":440,"end":446},"obj":"HP_0002664"},{"id":"T3","span":{"begin":470,"end":475},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":126,"end":549},"obj":"BACKGROUND"},{"id":"T2","span":{"begin":559,"end":982},"obj":"METHODS"},{"id":"T3","span":{"begin":992,"end":1944},"obj":"RESULTS"},{"id":"T4","span":{"begin":1975,"end":2138},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T4","pred":"source","obj":"PubMed_Structured_Abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubmedHPO","color":"#ecd493","default":true},{"id":"PubMed_Structured_Abstracts","color":"#ba93ec"}]}]}}