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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 45 (2000), S. 502-508 
    ISSN: 1432-0843
    Keywords: Key words Malignant mesothelioma ; Chemotherapy ; Gemcitabine ; Irinotecan ; Interleukin-6
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The benefits of chemotherapy can be assessed in terms of tumour shrinkage, prolongation of life or simply palliation of symptoms. In the study reported here, in vitro correlates of these parameters were sought as a rational guide to the choice of newer agents in the clinic. Methods: The cytotoxicity and effects on IL-6 production of ten chemotherapy agents representing four different classes of drugs were tested against a panel of five mesothelioma cell lines. Results: The mesothelioma cells were more sensitive to the action of irinotecan (and its active metabolite SN38) and gemcitabine than the control cell lines. Gemcitabine and to a lesser extent irinotecan inhibited the secretion of the proinflammatory cytokine IL-6 at concentrations of each drug that produced only small decreases in cell viability. This effect was not seen in cells treated with docetaxel or vindesine. Higher doses of gemcitabine and irinotecan caused a surge in IL-6 release and this was not due to release of intracellular stores of IL-6 through lysis of the cells. Conclusions: These results suggest that irinotecan and gemcitabine are not only more likely to be active against mesothelioma than other new chemotherapy agents but may also produce a palliative effect in nonresponders to these agents by decreasing the secretion of IL-6.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7365
    Keywords: Ethanol ; GLUT1 ; GLUT3 ; Glucose ; Cerebral Metabolism ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the normal adult brain, glucose provides 90% of the energy requirements as well as substrate for nucleic acid and lipid synthesis. In the present study, effects of ethanol on glucose transporters (GLUT) and glucose utilization were examined in rat brain. Male Sprague-Dawley rats weighing 250-300 gms were given either ethanol 3 gm/kg BW or saline IP 4 hrs prior to the animal sacrifice and removal of the cerebral cortical tissue. The cortical plasma membranes analyzed by cytochalasin B binding assay showed a decrease in GLUT number but not in GLUT affinity in the ethanol treated rats as compared to the control rats. The estimated Ro values were 70 ± 8.9 Vs 91 ± 8.9 pmoles/mg protein (p 〈 0.05 N=4) and the estimated Kd values were 0.37 ± 0.03 and 0.28 ± 0.05 μM (p: NS) in ethanol and control experiments respectively. Immunoblots of purified cerebral plasma membranes and low density microsomal fraction showed 17% and 71% decrease for GLUT1 and 54% and 21% (p〈0.05 or less; n=6) for GLUT3 respectively in ethanol treated rats than in control animals. Immunofluoresence studies also showed reduction of GLUT1 immunoreactively in choroid plexus and cortical microvessels of ethanol treated rats as compared to control rats. The effect of ethanol on regional cerebral metabolic rates for glucose (CMRGle) was studied using [6-14C] glucose and showed statistically insignificant decrease in brain glucose utilization. These data suggest that ethanol invivo decrease GLUT number and protein content in rat cerebral cortex
    Type of Medium: Electronic Resource
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