Objective To systematically evaluate the effectiveness of dasatinib in doses of 140 mg once daily and 70 mg twice daily for chronic myeloid leukemia (CML). Methods The randomized controlled trials (RCTs) were retrieved from Embase (1974 to November 2011), Pubmed (1966 to November 2011), The Cochrane Library (Issue 11, 2011), CBM (1979 to November 2011), VIP (1989 to November 2011), CNKI (1994 to November 2011), Wanfang Data (1997 to November 2011) and references listed in all articles. RCTs meeting inclusive criteria were included, the data were extracted, the quality was evaluated and cross-checked by two reviewers independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then meta-analyses were conducted using RevMan 5.1 software. Results A total of four studies involving two RCTs and 862 patients were included. Results of meta-analyses showed that when dasatinib was used in the long-term treatment of CML, no significant difference was found between 140 mg once daily and 70 mg twice daily in the complete hematologic response (RR=0.97, 95%CI 0.88 to 1.07, P=0.58), complete cytogenetic response (RR=0.94, 95%CI 0.80 to 1.11, P=0.47) and major cytogenetic response (RR=0.99, 95%CI 0.86 to 1.13, P=0.86). In the short-term treatment of CML, there were no significant differences in the complete hematologic response (RR=0.99, 95%CI 0.90 to 1.07, P=0.73), complete cytogenetic response (RR=0.99, 95%CI 0.78 to 1.26, P=0.95) and major cytogenetic response (RR=1.01, 95%CI 0.83 to 1.22, P=0.95). The subgroup analyses on the long-term treatment of CML in both chronic phase and advanced phase showed that there were no significant differences in the complete hematologic response, major cytogenetic response and complete cytogenetic response. Conclusion In the effectiveness of dasatinib for CML, the dose of 140 mg once daily is similar to the dose of 70 mg twice daily. Considering possible moderate selection bias existing in the methodological quality of the included studies which may affect the authenticity of outcomes, this conclusion should be further proved by conducting more high-quality, large-scale and double- blinded RCTs.
Objective To assess the clinical effectiveness and safety of fludarabine and cyclophosphamide (FC) combined with rituximab chemotherapy regimen (FCR regimen) for patients with chronic lymphoblastic leukemia (CLL). Methods The databases such as PubMed, The Cochrane Library, SpringerLink, CNKI, and CBM were searched from 2000 to 2011. The randomized controlled trials (RCTs) on FC regimen versus FCR regimen for CLL were retrieved. The methodological quality of the included studies was assessed according to the Cochrane Reviewer’s Handbook, and meta-analyses were performed using RevMan 5.0 software. Results Three RCTs involving 1 623 patients with CLL were included. The results of meta-analyses showed that significant differences were found in the progression-free survival (PSF)(Plt;0.001), overall response (OR=1.94, 95%CI 1.49 to 2.53, Plt;0.000 01), complete remission (OR=2.54, 95%CI 2.00 to 3.22, Plt;0.000 01), and grade III or IV neutropenia (OR=1.60, 95%CI 1.33 to 1.92, Plt;0.000 01); but no significant differences were found in the partial response (OR=0.74, 95%CI 0.35 to 1.55, P=0.43), grade III or IV thrombocytopenia (OR=0.97, 95%CI 0.74 to 1.27, P=0.83) and autoimmune hemolytic anemia (OR=0.86, 95%CI 0.59 to 1.27, P=0.45) between FCR and FC regimen. Conclusion The FCR regimen can improve the progression-free survival, overall response and complete remission. Meanwhile, it sometimes increases the incidence of Grade III or IV events, such as neutropenia, thrombocytopenia, autoimmune hemolytic anemia and nausea and vomiting.
This study aims to construct the recombinant lentivirus vector containing specific small interfering RNA (siRNA) targeting rat CREB binding protein(CBP)gene and to identify its function of inhibiting the expressions of acetylated histone in primarily cultured hippocampal neurons. Firstly, we constructed four kinds of recombinant lentivirus siCBP. And then we used them to infect the primarily cultured hippocampal neurons, and performed real-time PCR, western blot respectively to detect the expressions of CBP. Afterwards, the most effective lentivirus siCBP was used to infect the primarily cultured hippocampal neurons, and then the HAT activity and protein expressions of acetylated histone Ac-H3, Ac-H4 of the neurons were examined. By using PCR, endonuclease cutting and gene sequencing, we confirmed that the target genes were correctly cloned in lentivirus vector. Besides, CBP mRNA and protein expressions in neurons were found to be with varying degrees of decreases after infections of the four kinds of lentivirus siCBP. Furthermore, the representative and most effective lentivirus GR806 could effectively inhibit the HAT activity and the protein expressions of Ac-H3, Ac-H4 in neurons. It provides the experimental basis for the subsequent application of siCBP to clarify the effects and corresponding molecular mechanism of the CBP-dependent histone acetylation on learning and memory function in hippocampus.
