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Biomedical subjects

X F Hu

Publications and source records attributed to X F Hu.

28 records · Page 2Linked to original sources
PubMed1991

Circumvention of doxorubicin resistance in multi-drug resistant human leukaemia and lung cancer cells by the pure antioestrogen ICI 164384.

ICI 164384, a new steroidal antioestrogen, entirely devoid of oestrogenic activity, modulates doxorubicin resistance in vitro. At non-cytotoxic concentrations, ICI 164384 potentiated the cytotoxicity of doxorubicin in a dose-dependent manner in both the classical multi-drug resistant (MDR) human leukaemia cell lines CEM/VLB 100 and CEM/VLB 1000 and the human small cell lung cancer cell line H69 LX4. ICI 164384 had no effect on the two respective parental cell lines, CEM/CCRF and H69 P. None of these cell lines expressed the oestrogen receptor. In comparative studies at concentrations ranging from 1.25 to 10 mumols/l, ICI 164384 was significantly more effective (1.2-6-fold) than tamoxifen in reducing the IC50 of doxorubicin in the CEM/VLB 100 line. In resistant cells, ICI 164384 increased 3H-daunomycin accumulation in a dose-dependent manner and was significantly more effective than tamoxifen at concentrations ranging from 2.5 to 10 mumol/l. ICI 164384 reduced the efflux of daunomycin from resistant cells more effectively than tamoxifen. These studies suggest that ICI 164384 is an effective modulator of MDR.

Carcinoma, Small Cell↗
PubMed1990

Combined use of cyclosporin A and verapamil in modulating multidrug resistance in human leukemia cell lines.

This study describes the synergistic interaction of two biochemical modulators, cyclosporin A (CyA) and verapamil (Vp), in multidrug-resistant cells, the highly resistant and moderately resistant variants (CEM/VLB 1000 and CEM/VLB 100) of the parental drug-sensitive T-cell leukemia cell line CEM/CCRF. In the absence of either modulator, the 50% inhibitory concentration for Adriamycin in these cell lines was 270 +/- 10.6 (SD) micrograms/ml, 96 +/- 8.5 micrograms/ml, and 1.5 +/- 0.1 micrograms/ml, respectively. CyA and Vp dramatically reduced multidrug resistance in CEM/VLB 100 and CEM/VLB 1000 in a dose-dependent manner but had no effect on the sensitivity of the parental line to Adriamycin. At a CyA concentration of 8.3 mumol (10 micrograms/ml), the 50% inhibitory concentration of Adriamycin of CEM/VLB 1000 and CEM/VLB 100 fell to 5.9 +/- 0.9 micrograms/ml and 3.3 +/- 0.6 micrograms/ml, respectively. Similarly at a Vp concentration of 10 mumol the 50% inhibitory concentration of Adriamycin of CEM/VLB 1000 and CEM/VLB 100 fell to 23.7 +/- 3.7 micrograms/ml and 5.7 +/- 0.2 micrograms/ml, respectively. More importantly, CyA and Vp showed significant synergism when tested in combination in the moderately resistant line at concentrations normally seen after the clinical administration of these modulators. Synergy was also present when both drugs were tested in the highly resistant variant. These data indicate the need for in vivo studies, given the potential clinical importance of these observations.

Cyclosporins↗
PubMed1990

Effect of cyclosporin and verapamil on the cellular kinetics of daunorubicin.

Both cyclosporin and verapamil modulate the multidrug-resistant (MDR) phenotype in the classical MDR cell lines, CEM/VLB100 and CEM/VLB1000. Initial studies demonstrated a significant reduction in daunorubicin accumulation in the two resistant lines compared with the drug-sensitive parent line CEM/CCRF. Both cyclosporin and verapamil increased drug accumulation in the resistant lines. This effect was dose-dependent although a plateau occurred in CEM/VLB100 cells at concentrations of cyclosporin exceeding 4.2 mumol/l. Cyclosporin 4.2 mumol/l and verapamil 10 mumol/l significantly increased daunorubicin uptake and reduced drug efflux in the CEM/VLB100 and CEM/VLB1000 lines. At low clinical concentrations of cyclosporin (0.8-1.6 mumol/l and verapamil (1-2 mumol/l), there was a synergistic increase in drug accumulation in the two resistant cell lines (P less than 0.007). These data suggest that cyclosporin modulates the classical MDR phenotype by altering the cellular kinetics of daunorubicin. The in vitro synergistic action of cyclosporin and verapamil could be interesting clinically.

Cell Line↗