Clinical Efficacy of L-Asparaginasum Combined with CHOP for Treating Patients with Extranodal Natural Killer/T Cell Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy of L-asparginasum, ASP) combined with CHOP for treating patients with extranodal natural killer/T-cell lymphoma.</p><p><b>METHODS</b>A total of 68 patients with extranodal natural killer/T-cell lymphoma in our hospital from August 2007 to May 2009 were enrolled in this study, out of them 34 patients received CHOP regimen (CHOP group) and other 34 patients received CHOP regimen combined with L-Asparaginasum (ASP+CHOP group). The clinical efficacy of both groups was analyzed and compared after treatment.</p><p><b>RESULTS</b>In CHOP group 16 patients achieved CR+PR, the total remission rate (TRR) was 47.06%; in ASP+CHOP group 24 patients achieved CR+PR, the TRR was 70.58%, and the TRR in ASP+CHOP group was higher than that in CHOP group, there was statistical significance between these 2 groups (X(2) = 3.886, P < 0.05). The time of PFS in CHOP group was 24.7 months, and the time of PFS in ASP+CHOP group was 47.5 months which was significantly longer than that in CHOP group, and there was statistical siguificance between these 2 groups (P < 0.05). The incidence of anemia with grade I-II and III-IV blood cell reduction in ASP+CHOP group was higher than that in CHOP group (P < 0.05). The incidence of fever with grade I-II and albumin decrease in ASP+CHOP group was higher than that in CHOP group (P < 0.05). The abnormality of coagulation function in ASP+CHOP group was higher than that in CHOP group (P < 0.05). The anaphylactic reaction was found in 6 cases. The increase of serum amylase was observed in 1 case of aggressive NK/T cell lymphoma, the acute pancreatitis occured in 1 case who was inproved after treatment, but this patients died due to rapid progression of disease caused by poor general condition and untolerance to chemotherapy. The incomplete intestinal obstruction was found in 3 patients who recovered after conservative treatment. The grade II serum creatinine was elevated in 2 cases of ASP+CHOP group and in 1 case of CHOP group who was inproved after symptomatic therapy.</p><p><b>CONCLUSION</b>L-Asparaginasum combined with CHOP for treating patients with extranodal natural killer/T-cell lymphoma is effective, and may be used in clinic.</p>

Sequestration of copper from beta-amyloid promotes selective lysis by cyclen-hybrid cleavage agents.

Decelerated degradation of beta-amyloid (Abeta) and its interaction with synaptic copper may be pathogenic in Alzheimer disease. Recently, Co(III)-cyclen tagged to an aromatic recognition motif was shown to degrade Abeta in vitro. Here, we report that apocyclen attached to selective Abeta recognition motifs (KLVFF or curcumin) can capture copper bound to Abeta and use the Cu(II) in place of Co(III) to become proteolytically active. The resultant complexes interfere with Abeta aggregation, degrade Abeta into fragments, preventing H2O2 formation and toxicity in neuronal cell culture. Because Abeta binds Cu in amyloid plaques, apocyclen-tagged targeting molecules may be a promising approach to the selective degradation of Abeta in Alzheimer disease. The principle of copper capture could generalize to other amyloidoses where copper is implicated.

Astragaloside IV inhibits spontaneous synaptic transmission and synchronized Ca2+ oscillations on hippocampal neurons.

AIM: To investigate the changes in the spontaneous neuronal excitability induced by astragaloside IV (AGS-IV) in the cultured hippocampal network. METHODS: Hippocampal neurons in culture for 9-11 d were used for this study. The spontaneous synaptic activities of these hippocampal neurons were examined by Ca2+ imaging and whole-cell patch-clamp techniques. In total, 40 mg/L AGS-IV dissolved in DMSO and 2 mL/L DMSO were applied to the neurons under a microscope while the experiments were taking place. RESULTS: AGS-IV inhibited the frequencies of synchronized spontaneous Ca2+ oscillations to 59.39%+/- 3.25%(mean+/-SEM), the spontaneous postsynaptic currents to 43.78%+/- 7.72%(mean+/-SEM), and the spontaneous excitatory postsynaptic currents to 49.25%+/- 7.06%(mean+/-SEM) of those of the control periods, respectively, at 16 min after the AGSIV applications. AGS-IV also decreased the peak values of the voltage-gated K+ and Na+ channel currents at that time point. CONCLUSION: These results indicate that AGS-IV suppresses the spontaneous neuronal excitabilities effectively. Such a modulation of neuronal activity could represent new evidence for AGS-IV as a neuroprotector.

MEK inhibitor PD98059 acutely inhibits synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks.

AIM: To investigate the changes in synchronized spontaneous Ca2+ oscillations induced by mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 at different concentrations in cultured hippocampal network. METHODS: Hippocampal neurons in culture for 1-2 weeks were used for this study. Spontaneous synaptic activities of these hippocampal neurons were examined by Ca2+ imaging using calcium-sensitive dye. MEK inhibitor PD98059 (10, 30, and 60 micromol/L) and SB202474 (10 and 60 micromol/L), a negative control for mitogen-activated protein kinase (MAPK) cascade study, were applied to the cells under the microscope while imaging was taking place. RESULTS: PD98059 at a lower concentration of 10 micromol/L had little effect on the Ca2+ oscillation. At the higher concentration of 30 micromol/L, 5 min after application of PD98059, the spike frequency was decreased to 25.38% +/-7.40% (mean+/-SEM, n=16, P<0.01 vs medium control) of that of the control period. At an even higher concentration of 60 micromol/L, 5 min after application of PD98059, the spike frequency was decreased to 14.53%+/-5.34% (mean+/-SEM, n=16, P< 0.01 vs medium control) of that of the control period. The spike amplitude underwent a corresponding decrease. However, the negative control SB202474 at concentrations of 10 and 60 micromol/L had little inhibition effect on the Ca2+ oscillation. CONCLUSION: These results indicate that PD98059 inhibits synchronized spontaneous Ca2+ oscillation through inhibition of MEK, which hints that the MAPK cascade is required to maintain synchronized spontaneous Ca2+ oscillation.