Library

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 29 (1992), S. 455-460 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ara-U-induced S-phase accumulation and the interaction between high concentrations of ara-U (HiCAU) and ara-C were investigated in L1210 leukemia cells in vitro. Treatment of exponentially growing L1210 murine leukemia cells with ara-U (200–1000 μm) for 48 h caused a dose-dependent accumulation of cells in the S-phase. The extent of this ara-U-induced S-phase accumulation correlated with ara-U incorporation into DNA and with increases of up to 172% and 464% in the specific activities of deoxycytidine kinase and thymidine kinase, respectively, over control values. Metabolism of 1 μm ara-C following the exposure of cells to ara-U (1mm) resulted in 4.5 pmol ara-C DNA/mg protein vs 2.1 pmol/mg protein in control cells. Although 48-h exposure of cells to 200 and 400 μm ara-U is not cytotoxic, it enhances the cytotoxicity of ara-C (10–100 μm) 4- to 10-fold. Ara-U-induced S-phase accumulation is inhibited by deoxypyrimidine nucleosides but not by pyrimidine or deoxypurine nucleosides. Some of the ara-U and ara-C concentrations used in this study are achievable in clinical practice, and ara-U/ara-C interactions may explain in part the unique therapeutic utility of high-dose ara-C.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Toxin molecules, such as Pseudomonas exotoxin A (PEA), kill a cell by inactivating the elongation factor-2 (EF-2) in the cytosol2'8, suggesting that mammalian cells can be genetically modified to produce and secrete targeted toxins by using a signal sequence to lead newly synthesized toxins into ...
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1573-7217
    Keywords: prognostic markers ; proteases ; protease inhibitors ; node negative
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prognostic factors are highly needed to divide node negative breast cancer patients into groups of low versus high risk of recurrence and death. In order to invade and spread, cancer cells must degrade extracellular matrix proteins. Accordingly, tumor levels of molecules involved in this degradation might be associated with patient outcome. Previous work has demonstrated that high levels of the aspartyl protease cathepsin D in breast cancer are associated with a poor prognosis and similar findings have been reported for molecules involved in the urokinase pathway of plasminogen activation. Interactions between different protease systems have been described and data suggest that several proteolytic enzymes may be operable at the same time in a tumor. In the present study we measured cathepsin D (n=162), uPA (n=116), uPAR (n=109) and PAI-1 (n=135) in tumor cytosols obtained from a population of node negative breast cancer patients. A significant correlation was found between levels of uPA, uPAR, and PAI-1. Levels of cathepsin D were directly related to levels of uPA and uPAR. With a median observation time of 4.81 years, univariate survival analyses showed that high levels of uPA and cathepsin D significantly predicted a shorter disease free survival, while only high levels of cathepsin D were able to significantly predict a shorter overall survival. Tumor levels of uPAR and PAI-1 gave mixed results depending on the cut-off point choosen. Interestingly, multivariate analysis demonstrated that PAI-1 and cathepsin D were independent significant prognostic indicators for disease-free survival while only cathepsin D was helpful in overall survival. The five year relapse rate of patients with low PAI-1 and low cathepsin D was 13% while patients who had greater than the median value for both of these molecules had a 5 year relapse rate of 40%. These data would indicate that at least two different protease systems are active in spread of node negative breast cancer and that measurement of these molecules may aid in the decisions to be made when offering adjuvant treatment to these patients.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA flow cytometry ; ploidy ; prognostic factors ; S-phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This is the consensus statement regarding the clinical utility of DNA cytometry in breast cancer from the DNA Cytometry Consensus Conference held in Prout's Neck, Maine, USA, on October 1–4, 1992. Guidelines for clinical DNA cytometry generated at that meeting also appear in this issue of Breast Cancer Research and Treatment.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...