ASO treatment alone has no effect, it can sensitize myeloma cell lines to dexamethasone (Dex), whereas Bcl-x L ASO in combination with Dex still had no effect. As MM remains an incurable disease despite intensive chemotherapy, these results suggest that Mcl-1 antisense strategy rather than Bcl-2 antisense strategy could be of considerable importance in the treatment of MM. (Blood. 2002;100:194-199)
CD20 has been reinvestigated in 66 patients with multiple myeloma (MM). Twelve of the patients (18%) expressed CD20, including 5 of 50 patients at diagnosis presenting 100% CD20 ؉ cells. Seven (58%) of 12 CD20 ؉ patients with MM had a small mature plasma cell morphology as opposed to 4 (7%) of 54 with CD20 ؊ MM (P ؍ .0001). Of note, 10 (83%) of 12 patients with CD20 ؉ MM had t(11;14) as opposed to 5 of 54 (9%) CD20 ؊ patients (P < .001). All the patients with 100% CD20 ؉ cells presented with t(11;14) and 4 of 5 with a small mature plasma cell morphology. Thus, 66% of the patients with t(11;14) expressed CD20, whereas only 4% of the 51 patients lacking such translocation expressed CD20 (P < .0001). In conclusion, CD20 expression is associated with small mature plasma cell morphology and with
A series of compounds structurally related to staurosporine, rebeccamycin, and corresponding aglycones was synthesized, and their activities toward protein kinase C and topoisomerases I and II were tested together with their in vitro antitumor efficiency against murine B16 melanoma and P388 leukemia cells. Their antimicrobial activities were also examined against a Gram-negative bacterium (Escherichia coli), a yeast (Candida albicans), and three Gram-positive bacteria (Bacillus cereus, Streptomyces chartreusis, and Streptomyces griseus). To avoid side effects expected with protein kinase C inhibitors, we introduced substitution on the maleimide nitrogen and/or a sugar moiety linked to one of the indole nitrogens to obtain specific inhibitors of topoisomerase I with minimal activities on protein kinase C. As expected, these structures were inefficient on topoisomerase II, and some of them exhibited a strong activity against topoisomerase I. Generally, dechlorinated compounds were found to be more active than chlorinated analogues against both purified topoisomerase I and protein kinase C. On the other hand, opposite results were obtained in the cell antiproliferative assays. These results suggest lack of cell membrane permeability in the absence of the chlorine residue or cleavage of carbon-chlorine bonds inside the cell.
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