Restoration of daunomycin retention in multidrug-resistant P388 cells by submicromolar concentrations of SDZ PSC 833, a nonimmunosuppressive cyclosporin derivative

SDZ 280-446, a novel semi-synthetic cyclopeptolide: in vitro and in vivo circumvention of the P-glycoprotein-mediated tumour cell multidrug resistance

“…Definite shifts of the fluorescence profiles of the RMAtreated MDR-P388 cell populations were observed at low concentrations of all three RMAs. As already described for several other RMAs (Boesch et al, 1991b), these shifts were obtained at different concentrations and showed subtle differences for the different RMAs.…”

“…Intracellular fluorescence studies for DA U retention They were performed in parallel with studies on the activity of SDZ PSC 833 and of a variety of other RMAs to restore DAU retention in MDR-P388 cells (see [Boesch et al, 1991b] for methodological procedures). [Boesch et al, 1991b] for details).…”

“…[Boesch et al, 1991b] for details). In order to facilitate the comparison of the effects of the RMAs on the fluorescence levels of Par-P388 and MDR-P388 cells, the peak fluorescence levels (Y-axes) were plotted vs the RMA concentrations (X-axes) in the diagrams shown in this paper.…”

“…It is an order of magnitude more active than CsA to normalise the ACD-dependent growth inhibition of several MDR-tumour cell lines (Gaveriaux et al, 1991). In vitro, at sub-micromolar concentrations, this RMA is capable of restoring to normal levels the intracellular ACD retention of MDR-tumour cells (Boesch et al, 1991b). It is also active in vivo (Boesch et al, 1991c), being able to restore chemotherapeutic responses of MDRtumour cells whose degree of resistance is much higher than that known to occur in cancer patients.…”

Combined action of PSC 833 (Valspodar), a novel MDR reversing agent, with mitoxantrone, etoposide and cytarabine in poor-prognosis acute myeloid leukemia

“…[30][31][32][33][34][35][36][37][38][39] PSC 833 (Valspodar; Novartis Pharma Corporation, East Hanover, NJ, USA), a cyclosporine analog without immunosuppressive or nephrotoxic toxicity, is approximatively five-fold to 30-fold more potent than cyclosporine A (CsA) in vitro, and, unlike CsA, is a high-affinity noncompetitive inhibitor of P-gp. [40][41][42] A few studies investigating the use of PSC 833 in human malignancies have shown the improvement of clinical response in patients with AML, [30][31][32][33][34][35][36] as well as with other refractory malignancies. [37][38][39] Older and relapsed/refractory AML patients, however, are burdened by an unacceptable toxicity when treated with aggressive regimens, and schemes with low-toxic profile seem to be appropriate in these kinds of patients.…”