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  • 1
    Electronic Resource
    Electronic Resource
    Efficacy of suramin against human prostate carcinoma DU145 xenografts in nude mice (1999)
    Springer
    Cancer chemotherapy and pharmacology 43 (1999), S. 198-204 
    Details
    ISSN: 1432-0843
    Keywords: Key words Suramin ; Prostate cancer ; Nude mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Toward developing a model to study the mechanism of action of suramin against prostate cancer, we identified the effect of suramin on the growth of xenografts of the androgen-independent human prostate carcinoma DU145 cell line and our subline of suramin-resistant (SR) DU145 cells which are less responsive to suramin in vitro. Methods: Athymic nude mice bearing DU145 or SR DU145 xenografts were treated intraperitoneally (IP) once weekly with normal saline (vehicle control) or suramin in normal saline. For data analysis mice were grouped as follows: 0 mg/kg (controls), 〈210 mg/kg, 210 to 260 mg/kg, or gt;260 mg/kg suramin. Results: The growth of DU145 xenografts was slowed by treatment with 210 to 260 mg/kg suramin IP once weekly: differences in tumor volume for the 210 to 260 mg/kg group compared with the control group on days 29 and 57 showed growth inhibited by 43% and 55%, respectively. At the same time, growth of SR DU145 xenografts generally was not slowed by suramin treatment at any dose, but appeared to be enhanced to some degree by all doses of suramin during the typical slower initial growth phase of xenografts of this cell line: differences in tumor volume compared with control on day 29 showed growth enhanced by 100% to 342%. Mice treated with 210 to 260 mg/kg maintained nadir suramin plasma levels near our clinically relevant target of 1 × 10−4 M. Conclusions: Suramin, without concomitant corticosteroid therapy, was effective in slowing the growth of DU145 xenografts in nude mice at clinically relevant plasma suramin levels. The data showing efficacy for DU145 xenografts was supported by the lack of efficacy at the same time for xenografts of cells known to be less responsive to suramin in vitro, i.e. the SR DU145 cells, at similar doses and nadir plasma suramin levels. In discussions on the utility of suramin our data should be considered as support for continuing the study of suramin in the treatment of advanced, androgen-independent prostate cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050884
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of the polyamine analogues BE-4-4-4-4, BE-3-7-3, and BE-3-3-3 on the proliferation of three prostate cancer cell lines (1997)
    Springer
    Cancer chemotherapy and pharmacology 40 (1997), S. 172-179 
    Details
    ISSN: 1432-0843
    Keywords: Key words Polyamine  ;  Prostate carcinoma  ;  Nude mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Polyamines are biologic cations necessary for normal cell growth. Polyamine analogues have been shown to be effective inhibitors of tumor growth. We tested the effect of the polyamine analogues 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), N1,N11-bis(ethyl)norspermine (BE-3-3-3) and 1,15-bis(ethylamino)-4,12-diazapentadecane (BE-3-7-3) on the growth of the prostate cancer cell lines DU145, LNCaP and PC-3 in vitro. We also tested the effect of␣BE-4-4-4-4 on androgen-independent DU145 cells in␣vivo via a nude mouse xenograft model.Methods: In␣vitro, cell proliferation was measured using a DNA assay or a colony-formation assay. In vivo, mice were given saline or BE-4-4-4-4 3 mg/kg or 5 mg/kg intraperitoneally twice daily on days 7–10 and 14–17 (cycle 1), days 49–52 and 56–59 (cycle 2) and days 91–94 and 98–101 (cycle 3).Results: The proliferation of DU145, LNCaP and PC-3 prostate cancer cell lines was inhibited in a dose-dependent manner by BE-4-4-4-4. Intracellular putrescine, spermidine and spermine levels in all three cell lines declined after only 24 h exposure to BE-4-4-4-4 in vitro. Animals receiving BE-4-4-4-4 showed inhibition of tumor growth which continued throughout the experiment with 74% (3 mg/kg) and 81% (5 mg/kg) growth inhibition seen on day 101. No overt toxic reactions besides weight loss were observed in BE-4-4-4-4-treated animals. Tumor tissue from animals treated with BE-4-4-4-4 showed a dose-dependent decrease in spermidine and spermine levels but no decline in putrescine levels as compared with control. BE-4-4-4-4 levels were highest in tumors on day 63 with levels reaching 0.33 and 1.45 nmol/mg protein from animals treated at the 3 mg/kg and 5 mg/kg doses, respectively. Conclusion: These results show the polyamine analogues BE-4-4-4-4, BE-3-3-3 and BE-3-7-3 to be effective inhibitors of prostate cancer cell growth in vitro and BE-4-4-4-4 to be an effective inhibitor of DU145 cells in vivo with minimal toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050643
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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