Induction of apoptosis and down regulation of cell cycle proteins in mantle cell lymphoma by flavopiridol treatment.

Typical mantle cell lymphoma (MCL) is a distinct B-cell non-Hodgkin's lymphoma associated with over-expression of cyclin D1 related to translocation between the IgH and BCL-1 genes. Due to the important functional interaction between cyclin D1 and cyclin dependent kinases, cyclin dependent kinase inhibitors such as flavopiridol are under consideration for treatment of patients with MCL. The present study investigated the in vitro effects of flavopiridol on the MCL cell line (JeKo-1). Flavopiridol at a dose of 10nmol/L induced apoptosis by 6h of treatment as noted by flow cytometric analysis, morphologic examination and Western blotting. The cleavage of procaspase-3 and PARP and the decrease of flavopiridol-induced apoptosis by pan-caspase inhibition suggested that the caspase pathway serves an important role in the apoptotic process. Furthermore, MCL cells exposed to flavopiridol showed down regulation of key cell cycle proteins acting at the restriction point control between the G1 and S phases. The onset of flavopiridol-induced apoptosis also coincided with the down regulation of Mcl-1, anti-apoptotic protein. Collectively, our data indicates that flavopiridol may have significant therapeutic potential in the context of MCL.

The comparison of antibody response to influenza vaccination in continuous ambulatory peritoneal dialysis, hemodialysis and renal transplantation patients.

BACKGROUND: The immune system in renal transplant (Tx), Continuous Ambulatory Peritoneal Dialysis (CAPD) and hemodialysis (HD) patients have been suppressed and antibody response to vaccination is weaker than that of the normal population. Additionally immune response to vaccination also differs from each other in aforementioned three groups resulting from different levels immunosuppression. In the present study, detection of antibody response to influenza vaccine as an indicator of the level of immunity in Tx, CAPD and HD patients was aimed PATIENTS AND METHODS: Forty-eight patients (17 Tx, 16 CAPD and 15 HD) and 10 healthy adults, as a control group were enrolled into the study. Purified, split-virus, commercial trivalent influenza vaccine (VAXIGRIP--Pasteur Merieux Connaught, single dose of 0.5 ml into the deltoid muscle) containing 15 microg of each hemagglutinin of A/Johannesburg/82/96 (H1N1), A/Nachang/933/95 (H3N2) and B/Harbin/07/94 (B) strains were administered to all subjects. Serum samples were collected before and 1 month after vaccination to determine antibody titers. Hemagglutination-inhibition test (HI) was applied for determination of antibody response. The antibody response against each strain was measured separately. In addition to measurement of antibody response, increments in antibody titer (n-fold increase in titer), proportion of patients with protective antibody levels and seroconversion levels were taken into account. Wilcoxon paired 2 test and Mann-Whitney U test were applied for statistical analysis. p < 0.05 was accepted as significance level. RESULTS: Significant increases in antibody titers for all three antigens were observed in the study groups after vaccination (p = 0.001). However, the increase in titer of H3N2 was lower in Tx, CAPD and HD patients than that of the control group (1.0-2.0 vs 5.00) (p = 0.01). The proportion of protective antibody titers and seroconvertions were increased after vaccination in all subjects. Proportions of patients with protective antibody titers after vaccination were lower in Tx, CAPD and HD groups in comparison to control group. CONCLUSION: Although antibody titers in Tx, CAPD and HD patients presented significant increases after vaccination, the proportions of patients with protective antibody titers were lower in comparison to control group. Tx, CAPD and HD patients should be vaccinated every year to be able avoid potential morbidity and mortality of the influenza infection. Trial of high dose vaccination protocols may be useful to increase the proportion of patients with protective antibody levels.