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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 109 (1985), S. 156-158 
    ISSN: 1432-1335
    Keywords: Experimental liver metastases ; Colon tumor ; 5-Fu ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The combined effect of 5-Fluorouracil (5-Fu) and partially purified rat interferon (RIFN) was assessed on experimental liver metastases of a transplantable colon tumor in rats. Treatment was given for 8 weeks and started 1 week after inoculation into the portal vein of 5×105 tumor cells. Administration of 105 units RIFN/kg/day for 7 days, in alternate weeks, had no effect on the number or size of liver metastases as judged by laparotomy on days 30 and 50, whereas treatment with 5-Fu at a dose of 15 mg/kg once a week had a moderate but significant inhibitory influence. The combined administration of RIFN and 5-Fu led to earlier development of liver metastases than in the control group. There was no difference in survival time between the control group and the RIFN-treated group; all animals died within 20 weeks after tumor cell injection. However, three of eight animals in the 5-Fu group and, surprisingly, four of ten animals in the RIFN+ 5-Fu group survived for more than 20 weeks and were found to be free of tumor when inspected after 175 days. The data indicate that 5-Fu, given either alone or combined with RIFN, is effective in about 40% of cases, and further suggest that RIFN has tumor-enhancing properties in those animals in which treatment with 5-Fu has no antitumor effect.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: Cyclosporin A ; Multidrug resistance ; P glycoprotein ; Chemosensitizing ; In vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Colon tumours are intrinsically resistant to chemotherapy and most of them express the multidrug transporter P glycoprotein (Pgp). Whether this Pgp expression determines their resistance to anticancer agents in patients is not known. We report here on the reversibility of intrinsic multidrug resistance in a syngeneic, solid tumour model. CC531 is a rat colon carcinoma that expresses Pgp, as was shown with the monoclonal antibody C-219. In vitro the sensitivity to doxorubicin, daunorubicin and colchicine was enhanced by the addition of the chemosensitizers verapamil and cyclosporin A (CsA), while the sensitivity to cisplatin was not enhanced. In a daunorubicin accumulation assay verapamil and CsA enhanced the daunorbicin content of CC531 cells. In vivo CsA was injected intramuscularly for 3 consecutive days at a dose of 20 mg kg−1 day−1. This resulted in whole-blood CsA levels above 2 μmol/l, while intratumoral CsA levels amounted to 3.6 μmol/kg. In a subrenal capsule assay the maximal tolerable dose of doxorubicin (4 mg/kg) significantly reduced tumour growth. Doxorubicin at 3 mg/kg was not effective, but in combination with CsA this dose was as effective as 4 mg/kg doxorubicin. These experiments show that adequate doses of the chemosensitizing drug CsA can be obtained in vivo, resulting in increased antitumoral activity of doxorubicin in vivo. The in vitro and in vivo data together suggest that the chemosensitization by CsA is mediated by Pgp. This finding may have implications for the application of CsA and CsA-like chemosensitizers in the clinical setting.
    Type of Medium: Electronic Resource
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