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  • 1
    ISSN: 1432-0843
    Keywords: Key Words AZT ; S-phase cytostasis ; cytotoxicity ; DNA histograms ; 5-FU ; MTX ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The mechanism of synergy between 3′-azido-3′-deoxythymidine (AZT) and anticancer agents was investigated with emphasis on cell-cycle events. Exposure of exponentially growing WiDr human colon carcinoma cells to AZT resulted in synchronization of cells in the S phase of the cell cycle. Following treatment with AZT at 50 or 200 μM, 62%±3% or 82%±4% of the cells were in the S phase as compared with 36%±2% in the control. Bromodeoxyuridine uptake studies revealed that the synchronized cells actively synthesized DNA. At concentrations of up to 200 μM, AZT produced a cytostatic rather than cytotoxic effect as indicated by viability and cell growth measurements. At 200 μM, AZT-induced synchronization was significant (P=〈0.001) after 12 h of drug exposure, reached a maximum at 24 h, and reversed to baseline levels by 72 h even in the continued presence of the drug. This indicates that AZT-induced cytostasis is a transient and reversible effect. The cell-cycle events seen with AZT in WiDr cells were also observed in eight of nine human tumor cell lines tested. Isobologram analysis of WiDr cells preexposed to AZT for 24 h and then exposed to either AZT-5-fluorouracil or AZT-methotrexate for a further 72 h revealed synergy between AZT and the anticancer agents, indicating that AZT-induced synchronization may have therapeutic benefits.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Keywords: AZT ; S-phase cytostasis ; cytotoxicity ; DNA histograms ; 5-FU ; MTX ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanism of synergy between 3′-azido-3′-deoxythymidine (AZT) and anticancer agents was inverstigated with emphasis on cell-cycle events. Exposure of exponentially growing WiDr human colon carcinoma cells to AZT resulted in synchronization of cells in the S phase of the cell cycle. Forllowing treatment with AZT at 50 or 200 μM, 62%±3% or 82%±4% of the cells were in the S phase as compared with 36%±2% in the control. Bromodeoxyuridine uptake studies revealed that the synchronized cells actively synthesized DNA. At concentrations of up to 200 μM, AZT produced a cytostatic rather than cytotoxic effect as indicated by viability and cell growth measurements. at 200 μM, AZT-induced synchronization was significant (P=〈0.001) after 12 h of drug exposure, reached a maximum at 24 h, and reversed to baseline levels by 72 h even in the continued presence of the drug. This indicates that AZT-induced cytostasis is a transient and reversible effect. The cell-cycle events seen with AZT in WiDr cells were also observed in eight of nine human tumor cell lines tested. Isobologram analysis of WiDr cells preexposed to AZT for 24 h and then exposed to either AZT-5-fluorouracil or AZT-methotrexate for a further 72 h revealed synergy between AZT and the anticancer agents, indicating that AZT-induced synchronization may have therapeutic benefits.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 5 (1985), S. 117-128 
    ISSN: 1573-7217
    Keywords: aneuploidy ; DNA index ; flow cytometry ; S-phase fraction ; thymidine-labelling index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prime importance of axillary node status in predicting recurrence and survival has been appreciated for a long time. More recently routine measurements of estrogen and progesterone receptors have added to our prognostic abilities. The next generation of prognostic markers to be used in the routine clinical setting will be measures of tumor aggressiveness which will prompt therapeutic decisions. The technique of flow cytometry can provide clinicians with two new important pieces of information. First, it gives a measurement of the percentage of cells in S phase of the DNA replicative cycle, in other words, how fast a tumor is growing. Second, it assesses the aneuploidy, or total amount of extra DNA in the tumor cell, which appears to correlate with malignant aggressive tumor behavior. In this teleconference, the panelists discuss the kinetic and background considerations leading up to flow cytometry measurements in tumor cells. They evaluate currently available correlations with patient outcome, and assess whether the technique is sufficiently mature for use in certain clinical circumstances in the near future.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: aneuploidy ; clinical relationships ; DNA index ; flow cytometry ; proliferative index ; steroid receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Flow cytometry (FC), estrogen receptor (ER), and progesterone receptor (PR) analyses were performed on 226 breast cancers. The presence of steroid receptors was inversely proportional to proliferative index and percent aneuploidy. Within the two ER (+ and −) groups, the presence of PR did not add significantly to the comparison. The mean proliferative index for the diploid tumors was 17.5±6.8 compared to 27.8±9.8 for aneuploid tumors (p〈.001). The degree of aneuploidy, or DNA index, was not related to cell cycle kinetics or steroid receptor status. In 163 tissues analyzed for percent tumor present, a correlation between the relative number of aneuploid cells and percent tumor in the histologic review was observed. A study of the diploid tumors indicated greater than 75% had at least 10% tumor cells by histologic review. Since with FC one can observe at least 10% aneuploid cells in a tumor sample, it is our opinion that the percent aneuploidy in this study is not artifactually low due to sampling error. There was no significant relationship between nodal status or number of positive nodes and proliferative index, aneuploidy, or steroid receptor status. Metastatic tumors had a higher mean proliferative index, but this was not statistically significant. There was a relationship between age and proliferative index but not between age and ploidy status. In a small group of patients there was a trend for proliferative index and percent aneuploidy to be higher in the poorly differentiated and larger tumors when compared to the well differentiated and smaller tumors.
    Type of Medium: Electronic Resource
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