Mice treated for 3 days with SCH66336 showed a large decrease in the number of isolated splenocytes, resulting in numbers equal to unma nipulated C57BL/6 mice. Tumor recipient mice that were treated with a vehicle control instead of SCH66336 actu ally showed a slight decrease in the number of spleno cytes, although this was not consistently seen in other Treatment of lymphoma bearing mice with SCH66336 experiments. During SCH66336 treatment both tumor recipient and untransplanted mice were adversely affected by the drug, as demonstrated by weight loss and lack of activity. Because of these effects, we were unable to extend the treatment at this dosage past 3 days. Flow cytometry analysis of lymphocytes from FTI treated mice Flow cytometry was used to more closely examine the effects of FTI treatment on the tumor cells and normal lymphocytes.

Dacomitinib In Figure 4A, cells from the lymph nodes, spleen, or thymus of wild type mice were fluorescently stained with antibodies to Thy1. 2 and B220 to identify T cells and B cells, respectively. Comparison of untreated mice to mice treated for 28 days with L 744,832 demonstrates that there were no significant differences in the relative numbers of B cells or T cells in the lymph nodes and spleen. It did not appear that prolonged FTI treatment had substantially affected the normal distribution of lymphocytes in these organs. Mice that received tumor transplants 28 days prior to analysis had a large increase in the number of B cells in all three lymphoid organs. The presence of the tumor cells was accompanied by a large increase in the size of the affected organs.

However, a small percentage of T cells remained and the total number of T cells in each organ did not decrease appreciably. Treatment of the tumor recipient mice with L 744,832 for either 28 days or for the last 7 days results in flow cytometry profiles that appeared much more similar to those from wild type mice. The relative numbers of B cells and T cells in the lymph nodes and spleen returned to nearly normal. Careful comparison of the plots does reveal subtle differ ences, such as the presence of a significant number of B cells with a lower amount of B220 in the peripheral lym phoid organs. A small, but significant, percentage of resid ual B220 Thy1 cells remained in the thymus, even after 28 days of treatment. This appears to be due to a decrease in the number of T cells in the thymus that accompanied L 744,832 treatment. The absolute number of T cells declined substantially in all of the lym phoid organs of tumor bearing mice that were treated with L 744,832.