Fig. 5.
Fig. 5. Correlations between Pgp activity (measured by the effect of CsA on calcein-AM uptake) (y-axis, A and B) and the LC50 of DNR (x-axis, A) and the LC50 of etoposide (x-axis, B); between MRP1 activity (which was measured by the effect of probenecid on calcein-AM uptake) (y-axis, C and D) and the LC50 of DNR (x-axis, C) and the LC50 of etoposide (x-axis, D); and between the simultaneous activity of MRP1 and Pgp (which was quantified by the combined effect of probenecid and CsA on calcein-AM uptake) (y-axis, E and F) and the LC50 of DNR (x-axis, E) and the LC50 of etoposide (x-axis, F). When the combined effect of CsA/probenecid on calcein-AM uptake is analyzed, some cases had a fluorescence ratio which ranged from 0.59 to 1 (E and F). As for protein detection, this was probably caused by variations in cellular uptake of calcein-AM in the experiments. A similar variation in the opposite direction (1.41) can also represent some experimental variability. Therefore, we have used this threshold of positivity (1.41) for the simultaneous activity of Pgp and MRP1 (horizontal dotted line). With this cut-off, 52% of patients expressed combined activity of both MRP1 and Pgp.

Correlations between Pgp activity (measured by the effect of CsA on calcein-AM uptake) (y-axis, A and B) and the LC50 of DNR (x-axis, A) and the LC50 of etoposide (x-axis, B); between MRP1 activity (which was measured by the effect of probenecid on calcein-AM uptake) (y-axis, C and D) and the LC50 of DNR (x-axis, C) and the LC50 of etoposide (x-axis, D); and between the simultaneous activity of MRP1 and Pgp (which was quantified by the combined effect of probenecid and CsA on calcein-AM uptake) (y-axis, E and F) and the LC50 of DNR (x-axis, E) and the LC50 of etoposide (x-axis, F). When the combined effect of CsA/probenecid on calcein-AM uptake is analyzed, some cases had a fluorescence ratio which ranged from 0.59 to 1 (E and F). As for protein detection, this was probably caused by variations in cellular uptake of calcein-AM in the experiments. A similar variation in the opposite direction (1.41) can also represent some experimental variability. Therefore, we have used this threshold of positivity (1.41) for the simultaneous activity of Pgp and MRP1 (horizontal dotted line). With this cut-off, 52% of patients expressed combined activity of both MRP1 and Pgp.

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