Figure 2
Figure 2. Evaluation of potential markers of drug effect in samples from this trial. (A) CD19+ cells (lanes 1 and 2) and CD3+ cells from 2 normal (Nl) persons were probed with antibodies to RasGRP1 and, as a loading control, histone H1. (B) Example of RasGRP1 blotting in 4 lymphoma samples. β-actin served as a loading control. Nonadjacent lanes from a single blot have been juxtaposed to assemble this panel. (C) Effect of tipifarnib on signaling and Bim expression in situ. Each blot is a separate patient with pre- and post-tipifarnib results. In patients 5 (MCL) and 11 (small lymphocytic lymphoma), circulating tumor cells were examined; in patients 3 and 6 (both large cell), paired lymph node samples were assayed. The HDJ-2 shift after treatment (patients 3 and 5) confirms tipifarnib-induced inhibition of FT. Effects on ERK phosphorylation were variable, with decreases in patients 5 and 6 but an increase in patient 3. Some or all Bim isoforms increased in patients 5, 6, and 11 with a smaller increase in patient 3. (D) Examples of pretreatment Bcl-2 levels.

Evaluation of potential markers of drug effect in samples from this trial. (A) CD19+ cells (lanes 1 and 2) and CD3+ cells from 2 normal (Nl) persons were probed with antibodies to RasGRP1 and, as a loading control, histone H1. (B) Example of RasGRP1 blotting in 4 lymphoma samples. β-actin served as a loading control. Nonadjacent lanes from a single blot have been juxtaposed to assemble this panel. (C) Effect of tipifarnib on signaling and Bim expression in situ. Each blot is a separate patient with pre- and post-tipifarnib results. In patients 5 (MCL) and 11 (small lymphocytic lymphoma), circulating tumor cells were examined; in patients 3 and 6 (both large cell), paired lymph node samples were assayed. The HDJ-2 shift after treatment (patients 3 and 5) confirms tipifarnib-induced inhibition of FT. Effects on ERK phosphorylation were variable, with decreases in patients 5 and 6 but an increase in patient 3. Some or all Bim isoforms increased in patients 5, 6, and 11 with a smaller increase in patient 3. (D) Examples of pretreatment Bcl-2 levels.

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