The treatment is a completely Requests reference requests getting to achieve remission in AML is an anthracycline, principally Chlich daunorubicin, with a t Adjusted dose 45-60 mg/m2 K Rperoberfl Surface for 3 days, with cytarabine combined for 7 days . Or leasing several other drugs may need Estrogen Receptor Pathway during the induction phase of treatment or increasing dose cytarabine Ngerten overall survival. Recently, researchers assessed ECOG in the United States and a group of european European scientists take advantage of doubling the dose of daunorubicin may need during the induction phase in patients of different ages. Both studies report significant h More often in the Czech Republic’s box, no erh Increase early mortality, cure of h Dermatological or cardiac toxicity T. In the ECOG study, an increase of CR in the high dose group at l Ngerem OS was associated. In the european European study, improved OS in the high dose group only in younger patients and in the small subgroup of patients leukemiaAnthracyclines base observed Restrict Nkenden factors such as daunorubicin and idarubicin, DNA intercalators, DNA and RNA polymerases may inhibit k, Top 2 YEARS engined cause DNA strand cleavage to influence the activity t Top2 and cause apoptosis. We show that idarubicin-induced arrest of G2 / M cell cycle leuk Cells mix with a high Top2 and Top2 activated PP and MEK 1/2. Previous studies have shown that Top2 expression cell is cycledependent, wherein the h Chsten values in the G2 / M cell cycle. The observation of increased Hten PP MEK 1/2 levels in G2 / M arrested cells described in our previous work, the activation of cell cycle-dependent Independent Ras to ERK 1/2 signaling. These high PP idarubicin induced MEK 1/2 levels, the activity of t potentiate that idarubicin Ras ERK 1/2-Signalisierung been shown to stimulate DNA Top2 expression. In addition, k ERK can phosphorylate and activate two Top2. We used two different cell cycle dependent prenyltransferase inhibitors Independent ERK 1/2 activation to block, to investigate the influence of Ras on ERK 1/2 signaling on Top2 and Top2 expression / activity T and the effects idarubicininduced.
Average reported in vitro IC50 concentrations of FTI BMS 214662 for Ras Ras FTase using H and K were 1.3 nM and 8.4 nM and 1.9 to 2.3 m for GGTase I with KRAS protein as a substrate, which on a 250 000 times for the specificity of FTase t. In contrast, reported in vitro IC 50 concentrations of L medium CIO 778123 to FTase and GGTase I with K 2 Ras were 98 nM and 100 nM, indicating a specificity t of only 50 times for FTase. The cellular Re activity T lag of BMS 214662 in vivo in the range of average half-maximal inhibitory concentration for inhibition of the prenylation of 0.025 M to 2.5 M and the EC50 average L 778123 was reported in vivo of 92 nM to 6.3 M for HDJ 2 K and Ras, which is about where we go to is used. The Rolipram efficacy was evaluated by prenyltransferase inhibitor loss prenylated Ras proteins And the interruption of the Ras pathway downstream Rts shown. In our experiments, induced DPI and L 778123 214662 FTI BMS various biochemical and biological effects. Characterized, for example, only 778 123 L cytostatic HL60 cells, the induction of G1 arrest by reduced ERK 1/2-Signalisierung and Top2 expression. In contrast, BMS 214662 was highly cytotoxic to induce apoptosis. At EC50 concentrations, L 778 123 strong.