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  • Digitale Medien  (3)
  • Mammary carcinoma  (3)
  • 1
    ISSN: 1432-1335
    Schlagwort(e): Antineoplastic efficacy ; Melphalan ; Diazoxide ; Insulin ; Mammary carcinoma ; Sprague-Dawley rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The anticancer activity of melphalan andN-(2-chloroethyl)-N-nitrosocarbamoyl-ω-lysine (CNC-ω-Lys), was compared in the autochthonous, methylnitrosourea-induced mammary carcinoma of the Sprague-Dawley rat. In addition, the influence on the therapeutic efficacy of the combination with diazoxide, causing a mild, reversible diabetes, and with insulin was investigated. The comparison of melphalan and CNC-ω-Lys clearly showed the superiority of melphalan. Both compounds displayed a significant tumour inhibition in their medium and the highest dosages in comparison to the untreated control. The combination with diazoxide resulted for almost all groups in an increased tumour inhibition. Only the lowest dose of CNC-ω-Lys + diazoxide did not reduce the tumour volume significantly versus the control group. The combination with insulin, however, resulted in a loss of tumour inhibition compared to the effect of the cytotoxic drug alone, although in these groups, too, a significant decrease of tumour volumes versus controls could be observed. Mortality was within tolerable limits (〈20%) through the treatment period for all experimental groups. Median lifespans were increased in all therapy groups, but no additional benefit could be observed in the combination treatment groups.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 116 (1990), S. 538-549 
    ISSN: 1432-1335
    Schlagwort(e): Androgen-linked alkylating agents ; Methylnitrosourea ; Mammary carcinoma ; Anticancer activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary This article gives a comprehensive survey on the anticancer activity of nitrosoureas linked to steroidal androgens in methylnitrosourea (MMU)-induced rat mammary carcinoma. cis-Androsterone, testosterone, 19-nortestosterone and 5-α-dihydrotestosterone were used as carrier hormones and were linked to various cytotoxic N-[N′-(2-chloroethyl)-N′-nitrosocarbamoyl] (CNC)-aminoacids and to N-(2-hydroxyethyl)-N′-(2-chloroethyl)-N′-nitrosourea hemisuccinate (HECNU-hemisuccinate). In the MNU-model used esters of dihydrotestosterone (DHT) invariably were more active and less toxic than those of testosterone, nortestosterone and cis-androsterone. Within the DHT esters of CNC-aminoacids those of CNC-glycine, CNC-methionine and CNC-alanine showed the highest antineoplastic activities and superiority compared with equimolar dosages of their unlinked mixtures. Additionally, CNC-alanine-DHT ester had the highest therapeutic ratio of all agents investigated. HECNU-hemisuccinate-DHT ester, on the other hand, achieved even higher antitumor activity at the optimal dose but had a narrower therapeutic ratio. No obvious correlation between antineoplastic efficacy and receptor binding affinity could be demonstrated, but, to be active, a conjugate apparently had to have some receptor binding affinity for both androgen and progesterone receptors. The results obtained indicate that linking antineoplastic agents to transport molecules with affinity to steroid receptors is a highly promising approach to obtain drugs with specific activity in steroid receptor containing tumors.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 116 (1990), S. 470-474 
    ISSN: 1432-1335
    Schlagwort(e): Vitamins A, E ; Semisynthetic fatty diet ; Methylnitrosourea ; Mammary carcinoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Prolonged supplementation of vitamins A and E (2500 IU and 11.3 IU/rat daily) in 10.3% and 21.6% fatty diets administered to methylnitrosourea-induced Sprague-Dawley rats caused alterations in plasma and liver levels of both vitamins as well as of the total lipids. Liver vitamin A levels increased steadily (more than four-fold) until termination of the experiment, whereas plasma vitamin A levels only showed a minor increase at the end of the study in comparison to rats fed a standard diet. Liver vitamin E levels initially showed no difference from those of rats treated with a standard diet, and were decreased at the end of the experiment, whereas the respective plasma levels were increased throughout the study, only showing a decrease relative to initial values at termination of the experiment. Plasma total lipids increased with age and following supplementation of the vitamins in the high-fat diet, whereas liver total lipids were influenced less by aging than by the fat and vitamin contents of the respective diets. The observed alterations were, however, not related to significant chemopreventive activity of the vitamins A and E contained in high-fat diets.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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