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  • 1
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies on structure-activity relationships of anthracycline antitumor antibiotics have shown that removal of the methoxyl group at position 4 of the aglycone causes a marked increase in the potency of the compounds: 4-demethoxydaunorubicin and 4-demethoxyadriamycin had an antitumor effect similar to that of the parent compound at doses five to eight times lower, and they were active even when administered orally. This paper reports the effects of further substitutions at positions 1, 2, 3, and 4 of 4-demethoxy aglycone. The introduction of methyl groups at positions 2 and 3, or 1 and 4 resulted in decreased cytotoxicity and biological activity. The addition of a benzoyl ring at positions 2 and 3 decreased the activity further. 1,4-Dichloro-4-demethoxydaunorubicin and 2,3-dichloro-4-demethoxydaunorubicin were respectively as active and 2.5 times less active than was daunorubicin against HeLa cells in vitro while they were inactive against P388 and L1210 leukemias in vivo. 2,3-Dimethyl-4-demethoxyadriamycin showed an antitumor activity against mouse leukemias that was slightly higher than was that of adriamycin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: Malignant glioblastoma ; Cell line GBM ; Drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A cell line, GBM, was established from a human malignant glioblastoma and was characterized with particular reference to its response to conventional drugs. The GBM cell line exhibited a 73±7 h doubling time in monolayer cultures. Experssion of glial fibrillary acidic and S-100 proteins was observed. Karyotype analysis of GBM cells at early passages revealed the presence of two near-triploid clones (A and B) with multiple chromosome rearrangements; a 100% frequency for clone B was observed in the established cell line. GBM cells had tumorigenic properties, since the s.c. injection of cultured cells into nude mice gave rise to slowly growing tumors. The morphology of GBM cells was retained during in vitro and in vivo passages, as judged by light microscopy. GBM cells were relatively resistant to most conventional drugs; among the tested drugs, only taxol exhibited a marked cytotoxic effect comparable to that found in cells of a different tumor type. GBM cells were found positive for the epidermal growth factor receptor, HER2-neu and P-glycoprotein by flow cytometry of cells labelled with monoclonal antibodies. In spite of the expression of relatively high γ-glutamyltransferase activity, the intracellular glutathione level was comparable to that of other chemosensitive tumor cells. This glioblastoma cell line is a suitable model for the identification and preclinical studies of new agents and provides an additional system to explore the molecular basis of the intrinsic drug resistance of glioblastoma.
    Type of Medium: Electronic Resource
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