5-fluoro-2--deoxycytidine has been researched along with Breast-Neoplasms* in 3 studies
1 trial(s) available for 5-fluoro-2--deoxycytidine and Breast-Neoplasms
2 other study(ies) available for 5-fluoro-2--deoxycytidine and Breast-Neoplasms
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5-Iododeoxyuridine increases the efficacy of the radioimmunotherapy of human tumors growing in nude mice.
Recently, there has been much interest in the use of radionuclide conjugated monoclonal antibodies for the treatment of human malignancies. One way to potentially maximize the therapeutic effectiveness of radioimmunotherapy would be to sensitize tumor cells to the radiation dose delivered by the antibody. Since radioimmunotherapy can potentially treat disseminated disease, including micrometastasis, we chose to study a halogenated pyrimidine radiosensitizer, a class of compounds that affect nonhypoxic cells. 5-Iododeoxyuridine, administered with pyrimidine metabolism modulators, increased the therapeutic effectiveness of radioimmunotherapy, resulting in individual cures of human tumors growing in BALB/c nu/nu (nude) mice. 5-Iododeoxyuridine was administered with N-(phosphonacetyl)-L-aspartic acid and 5-fluoro-deoxycytidine plus tetrahydrouridine. This drug treatment was combined with radioimmunotherapy using 131I conjugated to a monoclonal antibody, Mc5. Mc5 binds to a mucin component of the human milk fat globule. This antigen is expressed on the surface of MX-1 cells, the transplantable human tumor used in this study. Tumor-bearing mice treated with both the drug protocol and 131I-Mc5 (540 microCi, 10 microCi/micrograms) showed a regression in average tumor volume. The average tumor volume was reduced below the initial size at treatment for 50 days; two of five cures were obtained. Neither cures nor regressions were observed with either the drug or antibody treatments alone. Our results indicate the potential for increasing the therapeutic effectiveness of radioimmunotherapy of human solid tumors with halogenated pyrimidines. Topics: Animals; Aspartic Acid; Breast Neoplasms; Deoxycytidine; Drug Therapy, Combination; Humans; Idoxuridine; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Phosphonoacetic Acid; Radiation-Sensitizing Agents; Radioimmunotherapy; Tetrahydrouridine; Transplantation, Heterologous | 1992 |
Incorporation of 5-fluorodeoxycytidine and metabolites into nucleic acids of human MCF-7 breast carcinoma cells.
Several mechanisms of action have been proposed for the antitumor agents, 5-fluorouracil (FUra) and 5-fluorodeoxyuridine (FdUrd), including their incorporation into both cellular RNA and DNA. Another fluorinated pyrimidine, 5-fluorodeoxycytidine (FdCyd), has been shown to be even more active than FdUrd against certain experimental tumors. Although FdCyd is deaminated to FdUrd, the precise mechanism of action of this agent has remained unclear. We have therefore monitored the incorporation of FdCyd and its metabolites into the nucleic acids of human MCF-7 breast carcinoma cells. The results demonstrate the internucleotide incorporation of FdCyd in MCF-7 DNA. The results also demonstrate that FUra residues are detectable in both MCF-7 DNA and RNA following treatment with FdCyd. Cytidine and deoxycytidylate deaminase inhibitors increased the extent of (FdCyd) DNA synthesis, but they had little if any effect on formation of (FUra) RNA. In contrast, deoxyuridine increased incorporation of FdCyd into DNA and blocked the formation of FUra RNA. Deoxyuridine also enhanced the cytotoxicity associated with FdCyd treatment. The present results further demonstrate that FdCyd inhibits postsynthetic methylation of MCF-7 DNA. These findings would suggest that FdCyd has multiple mechanisms of action and that incorporation of this agent into DNA distinguishes its effects from those of FUra and FdUrd. Topics: Azacitidine; Breast Neoplasms; Cell Line; Cell Survival; Decitabine; Deoxycytidine; Deoxyuridine; DNA, Neoplasm; Floxuridine; Humans; Methylation; RNA, Neoplasm; Tetrahydrouridine | 1986 |