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  • 1
    ISSN: 1432-0851
    Keywords: Key words Immunotherapy ; Monocytes/macrophages ; Interferon γ ; Endotoxin ; Lipopolysaccharides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cells of the monocyte/macrophage lineage have shown antitumor activity in vitro and in murine models after activation with interferon (IFN) γ. In vitro data suggest an additional effect on macrophage antitumor activity when IFNγ is combined with endotoxin (lipopolysaccharides; LPS). In this study we treated nine cancer patients with a total of 62 MAK infusion cycles with autologous macrophages given intravenously (i.v.) after in vitro activation with IFNγ and LPS. Low-grade fever (WHO I/II) was the commonest side-effect. Chills, nausea, and headache were noted when the number of transfused macrophages exceeded 2×108. One WHO IV toxicity occurred, consisting of hypotension after transfer of 3×108 cells, defining this dose as the maximum cell number tolerated. After pretreatment with ibuprofen, however, the maximum cell number could be increased without reaching dose-limiting toxicity. The highest number of cells reinfused was 15×108. Circulating interleukin(IL)-6 increased in a dose-dependent manner as did IL-1 receptor antagonist (IL-1RA) and IL-8. Tumor response consisted of one case of stable disease (12 weeks) in a patient with formerly progressing colorectal cancer and progressive diseases in eight patients. This study indicates that reinfusion of autologous LPS-activated macrophages upon pretreatment with ibuprofen is feasible and tolerated without major side-effects.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Human macrophage maturation ; Functional transferrin ; Binding sites ; High affinity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human blood monocytes (mo) when cultured in suspension on hydrophobic teflon membranes undergo terminal maturation to macrophages (MO). Together with the appearance of new lineage-restricted differentiation antigens, mature MO but not blood mo, express transferrin (TF) receptor molecules as detected by immunostaining methods. Here we report that radio- and fluorescein-labelled TF binds to a single class of high-affinity binding sites on MO but not on mo. As mo mature in vitro in the presence of human serum, their receptor numbers increase to about 106 per cell, showing an apparent Kd for Fe2TF of approximately 5 nM. These receptor numbers were comparable with our estimates for cultured K 562 human tumor cells, and about 20× greater than reported for human MO cultured in the presence of fetal calf serum. Our MO showed 58Fe uptake comparable with uptake by tumor cells and also exhibited TF-promoted uptakes of 61Ga. The possibility that MO might recycle stored iron through receptor-bound apoTF was not supported by experiments which showed that their Fe2TF receptors had much lower affinity for apoTF (Kd〉1μM) and which could not detect separate high-affinity receptors specific for apoTF. Expression of TF receptors was not substantially altered by treatment with human recombinant interferon-gamma.
    Type of Medium: Electronic Resource
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