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Autologous Bone Marrow Transplantation - Blog Science Connections

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Pharmacological Manipulation and Purging 181<br />

seen with vincristine alone (Fig 2) (22). These results suggest that the strategy<br />

of employing verapamil to circumvent resistance to vincristine, and possibly<br />

other drugs associated with the multiple-resistance phenotype, during in vitro<br />

purging can be attempted without significant risk to normal hematopoietic<br />

stem cells. Yalowich et al. (21), who also found that short exposures to<br />

verapamil did not enhance vincristine's toxicity against CFCJ-QM cells, reported<br />

enhanced toxicity of etoposide against CFCI-GM cells.<br />

Selective Protection of Normal Stem Cells<br />

We have previously shown that the cytotoxicity of nucleoside analogues<br />

depends on the presence of a functional nucleoside transporter in the<br />

COLONIES, % SURVIVED<br />

CFU-GM<br />

I 10 100<br />

VINCRISTINE, MM<br />

Figure 2. Effects of vincristine alone ('solid circles; and with 5 uM (open circles;, 10 uM<br />

(solid triangles;, and 20 uM (open squares; verapamil on CFU-GM, BFU-E, and CFU-<br />

GEMM colony formation (mean values of five to ten experiments). Differences in values<br />

for vincristine with and without verapamil are not statistically significant.

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