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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0001418,
umls-concept:C0017262,
umls-concept:C0017337,
umls-concept:C0025260,
umls-concept:C0038661,
umls-concept:C0056997,
umls-concept:C0086035,
umls-concept:C0242724,
umls-concept:C0439662,
umls-concept:C0591833,
umls-concept:C1167395,
umls-concept:C1171362,
umls-concept:C1515670,
umls-concept:C1546857
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pubmed:issue |
10
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pubmed:dateCreated |
1995-5-31
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pubmed:abstractText |
The nonmammalian cytosine deaminase (CD) enzyme converts the nontoxic prodrug 5-fluorocytosine (5-FC) to the toxic metabolite 5-fluorouracil. Parental cells of a mammary adenocarcinoma (TSA-pc) of BALB/c mice were transfected with the CD gene (TSA-CD), and the ability of 5-FC to hamper their growth was evaluated. A quantity amounting to 0.5 mg of 5-FC/0.3 ml of medium inhibits the proliferation of TSA-CD cells, but not that of TSA-pc, nor that of TSA-pc transfected with neomycin-resistance gene only (TSA-neo). In BALB/c mice, 800 mg 5-FC/kg of body weight injected daily i.p. for 30 days causes total regression of incipient (1-day-old), and established (3- and 7-day-old) TSA-CD tumors, and of 3-day-old experimental lung metastases, but does not impair TSA-pc nor TSA-neo cell growth. Because in CD8+ T lymphocyte- and granulocyte-depleted mice 5-FC no longer impairs TSA-CD growth, immune mechanisms appear to play an important role in this regression. Following, regression, all mice are resistant to subsequent s.c. or i.v. lethal challenges with TSA-pc. The induction of this immune memory is dependent on CD4+ lymphocytes, whereas its effector phase depends on both CD4+ and CD8+ lymphocytes. The memory elicited in tumor-bearing mice by the 5-FC-dependent regression of TSA-CD tumors cures a significant number of mice with 4-day-old TSA-pc metastases, but does not impair the growth of 4-day-old solid s.c. tumors. The reliability of this regression and the subsequent establishment of an efficient immune memory against poorly immunogenic TSA-pc offer the prospect that CD-transduced tumor cells and 5-FC can be used as components of a live antitumor vaccine.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
154
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5302-12
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7730633-Adenocarcinoma,
pubmed-meshheading:7730633-Animals,
pubmed-meshheading:7730633-Combined Modality Therapy,
pubmed-meshheading:7730633-Cytosine Deaminase,
pubmed-meshheading:7730633-Female,
pubmed-meshheading:7730633-Flucytosine,
pubmed-meshheading:7730633-Gene Therapy,
pubmed-meshheading:7730633-Immunologic Memory,
pubmed-meshheading:7730633-Mice,
pubmed-meshheading:7730633-Mice, Inbred BALB C,
pubmed-meshheading:7730633-Neoplasm Transplantation,
pubmed-meshheading:7730633-Nucleoside Deaminases,
pubmed-meshheading:7730633-Transfection,
pubmed-meshheading:7730633-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
5-Fluorocytosine-induced eradication of murine adenocarcinomas engineered to express the cytosine deaminase suicide gene requires host immune competence and leaves an efficient memory.
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pubmed:affiliation |
Department of Clinical and Biological Sciences, University of Turin, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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