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  • 1
    Electronic Resource
    Electronic Resource
    Factors Affecting Topotecan Sensitivity in Human Leukemia Samples (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 803 (1996), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1996.tb26382.x
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of adding the topoisomerase I poison 7-ethyl-10-hydroxycamptothecin (SN-38) to 5-fluorouracil and folinic acid in HCT-8 cells: elevated dTTP pools and enhanced cytotoxicity (1998)
    Springer
    Cancer chemotherapy and pharmacology 42 (1998), S. 391-399 
    Details
    ISSN: 1432-0843
    Keywords: Key words Irinotecan ; Deoxynucleotide pools ; Thymidylate synthase ; Fluoropyrimidines ; Colon cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To determine the effect of combined treatment with 7-ethyl-10-hydroxycamptothecin (SN-38, the active metabolite of irinotecan) and 5-fluorouracil/folinic acid (5FU/FA) in vitro using HCT-8 human intestinal adenocarcinoma cells. Methods: Cell survival was examined using colony forming assays. Cell cycle distribution before and after treatment was assessed by flow microfluorimetry. Levels of thymidylate synthase (TS) and topoisomerase I (topo I) in untreated and treated cells were determined by immunoblotting. Changes in deoxynucleotide pools were examined by high-performance liquid chromatography. Results: Clonogenic assays revealed that colony formation was decreased by 50% after a 24-h exposure to 8 ± 2 nM SN-38 or 12 ± 3 μM 5FU, the latter being assayed in the presence of 2 μM FA. When treatment with 5FU/FA was followed by SN-38, the cytotoxicity was similar to that observed with 5FU/FA alone. In contrast, when HCT-8 cells were exposed to both agents simultaneously or to SN-38 followed by 5FU/FA, the cytotoxicity was greater than that of SN-38 or 5FU/FA treatment alone. Investigation of the mechanistic basis for this sequence dependence revealed that SN-38 treatment was associated with a dose- and time-dependent decrease in conversion of [5-3H]-2′-deoxyuridine to [3H]-H2O and thymidylate in intact cells. Immunoblotting failed to reveal any decrease in TS protein that could account for the decreased activity. High-performance liquid chromatography revealed that SN-38 treatment was associated with increased levels of the deoxynucleotide dTTP and decreased levels of dUTP. Flow microfluorimetry revealed that a 24-h treatment with 10 nM SN-38 resulted in accumulation of HCT-8 cells in late S and G2 phases of the cell cycle, with a further increase in the G2 fraction during the 24 h after SN-38 removal. Conclusions: These observations are consistent with a model in which SN-38 sequentially induces diminished DNA synthesis, elevated dTTP pools, inhibition of dUMP synthesis and enhanced toxicity of 5FU/FA. Accordingly, sequencing of irinotecan and 5FU/FA might be important in combining these agents into an effective treatment for colorectal cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050835
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  • 3
    Electronic Resource
    Electronic Resource
    Antiproliferative activity of 2-[N,N-bis-2-chloroethyl}-amino]-4-[2-sulfonato-ethylthio]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide cyclohexamine (ASIA Z 7557, INN mafosfamide) against human and murine tumor cells in vitro (1984)
    Springer
    Investigational new drugs 2 (1984), S. 155-159 
    Details
    ISSN: 1573-0646
    Keywords: oxazaphosphorine ; cyclophosphamide ; in vitro colony formation ; ASTA Z 7557
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The ability of ASTA Z 7557 to inhibit colony formation in vitro by 6 human tumor cell lines and 3 methylcholanthrene-induced murine fibrosarcomas was compared to that of cyclophosphamide, 4-hydroperoxy-cyclophosphamide, BCNU, cisplatin, mitomycin C, doxorubicin, and 5-fluorouracil, as a function of dose, and duration of exposure. All drugs except cyclophosphamide were active in a dose and time dependent manner against all cell lines. ASTA Z 7557 and 4-hydroperoxy-cyclophosphamide at equimolar concentrations had similar antiproliferative activities. The stabilities of ASTA Z 7557 and 4-hydroperoxy-cyclophosphamide as measured by cytotoxic activity remaining after incubation at various times at 37° in complete tissue culture medium containing 10% fetal calf serum were identical. At initial concentrations of 20 μM, cytotoxic activity of both compounds began to decline after two hours of incubation and all activity was lost after 24 hours of incubation. In vitro, ASTA Z 7557 produced, at least, additive cytotoxic activity with cisplatin, the combination of cisplatin plus doxorubicin, and human lymphoblastoid interferon.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00232345
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