Objective: The efficacy and the safety of bortezomib-based chemotherapy were characterized in mantle cell lymphoma (MCL) patients. Materials and Methods: The PubMed, Cochrane Library, Clinical Key, Science Direct, Oxford Journals, and China National Knowledge Internet databases were searched up to 1 May 2019. The selected trials needed to match the inclusion criteria and be carried out to evaluate quality appraisal and the synthesis of efficacy and safety. The enrolled MCL patients using bortezomib-based chemotherapy or chemotherapy alone needed to have been compared. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were combined to evaluate the efficacy while serious adverse events (SAEs) (grade III-IV peripheral neuropathy, neutropenia, and infection) were used to evaluate the safety. The heterogeneity of the results were analyzed simultaneously. Results: A total of 620 patients were enrolled across four studies in our meta-analysis, and the pooled results showed that the PFS [hazard ratio (HR)=0.66, 95% confidence interval (CI)=0.54-0.82; p=0.0001)] and OS (HR=0.73, 95% CI=0.55-0.96; p=0.03) of patients with bortezomib-based chemotherapy were better than those of patients with chemotherapy alone, unlike ORR (risk ratio=1.46, 95% CI=0.85-2.49; p=0.17), while SAEs were prominent in the combination group. Conclusion: MCL patients who are ineligible for transplant or high-dose chemotherapy could benefit from bortezomib-based chemotherapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bortezomib/administration & dosage , Clinical Trials as Topic , Humans , Lymphoma, Mantle-Cell/diagnosis , Lymphoma, Mantle-Cell/mortality , Prognosis , Proportional Hazards Models , Proteasome Inhibitors/administration & dosage , Treatment Outcome
Retinoic acid inducible gene I (RIGI) is upregulated during alltrans retinoic acid (ATRA)induced terminal granulocytic differentiation of NB4 acute promyelocytic leukemia (APL) cells. However, the function and mechanism of RIGI in NB4 cells remains to be fully elucidated. In the present study, lentivirusmediated RIGIknockdown was used to investigate the proliferation, cell cycle and apoptotic processes of ATRAinduced NB4 cells in vitro using an MTT assay and flow cytometry, respectively. The roles of RIGI and the AKTFOXO3A signaling pathway were investigated using western blot analysis. The results showed that the ATRAinduced expression of RIGI was specifically and effectively knocked down at the mRNA and protein levels by lentivirus mediated RIGI short hairpin RNA. In addition, silencing of RIGI reduced the ATRAinduced inhibition of NB4 cell proliferation, cell cycle arrest and apoptosis. Further investigations indicated that with ATRAinduced expression of RIGI, levels of phosphorylated (p)AKTThr308 and pForkhead Box (FOX) O3AThr32 were decreased, the expression levels of cell cycle arrest protein p27 and the apoptotic protein, tumor necrosis factorrelated apoptosisinducing ligand (TRAIL), directly transcribed by FOXO3A were increased. By contrast, following the knockdown of ATRAinduced expression of RIGI, the levels of pAKTThr308 and pFOXO3AThr32 were increased, and the protein expression levels of p27 and TRAIL were decreased. Taken together, these results showed that the knockdown of RIGI reduced the inhibition of cell proliferation, cell cycle arrest and apoptosis in the ATRAinduced NB4 cells via the AKTFOXO3A signaling pathway.
Apoptosis , Cell Cycle Checkpoints , Cell Proliferation , DEAD Box Protein 58/genetics , Leukemia, Promyelocytic, Acute/genetics , Signal Transduction , Cell Line, Tumor , DEAD Box Protein 58/metabolism , Forkhead Box Protein O3/metabolism , Gene Expression Regulation, Leukemic , Gene Knockdown Techniques , Humans , Lentivirus/genetics , Leukemia, Promyelocytic, Acute/chemically induced , Leukemia, Promyelocytic, Acute/metabolism , Leukemia, Promyelocytic, Acute/pathology , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Immunologic , Tretinoin/adverse effects