Bortezomib demonstrates encouraging efficacy in MCL in heavily pretreated individuals. Response was associated with a reduction in plasma TNF-alpha and in vitro sensitivity in a small number of patients.

M3G appears to be devoid of significant activity; in these circumstances and at these doses, it does not antagonize either the analgesic or respiratory depressant effects of M6G or morphine.

Bortezomib is a proteasome inhibitor with proven efficacy in multiple myeloma and non-Hodgkin's lymphoma. This study reports the effects of bortezomib in B-cell lymphoma cell lines with differing sensitivity to bortezomib to investigate factors that influence sensitivity. Bortezomib induced a time-and concentration-dependent reduction in cell viability in five lymphoma cell lines, with EC 50 values ranging from 6 nmol/L (DHL-7 cells) to 25 nmol/L (DHL-4 cells) after 72 h. Bortezomib cytotoxicity was independent of p53 function, as all cell lines exhibited mutations by sequence analysis. The difference in sensitivity was not explained by proteasome or nuclear factor-KB (NF-KB) inhibition as these were similar in the most and least sensitive cells. NF-KB inhibition was less marked than that of a specific NF-KB inhibitor, Bay 11-7082. Cell cycle analysis showed a marked G 2 -arrested population in the least sensitive DHL-4 line only, an effect that was not present with