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Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.
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Objective To investigate the effects of uric acid (UA) and UA under oxidative stress on cultured human umbillical vein endothelial cells (HUVEC).Methocds HUVECs were incubated with different concentration UA (0,4,8,16 mg/dL),H2O2 (500 mmol/l) and UA+H2O2 (500 mmol/l) for 24,48 and 72 hours.Then we observed the morphology of HUVECs and evaluated the proliferation of HUVECs by MTT assay.NO and ET-1 in supernatant medium was detected by ELISA.Results For the viability of HUVECs,there was no statistically significant difference between 4 mg/dL UA group and control group after incubation for 24,48 and 72 hours (P＞0.05) and between UA groups(8 mg/dL and 12 mg/dL) and control group after incubation for 24,48 and 72 hours (P＞0.05).After incubation with 12 mg/dL of UA for 48 hours or 8 mg/dL of UA for 72 hours,the viability of HUVECs decreased significantly (P ＜0.05) The viability of HUVECs in H2O2 group decreased significantly (P＜0.05).The viability of HUVECs in UA+H2O2 groups after incubation for 24 h was significantly better than H2O2 group.There was no signifiant difference in the cell viability between (8 mg/dL or 12 mg/dL) UA+H2O2 group and H2O2 group.Compared with the control group,the NO levels were decreased and the ET-1 levels were increased in the supernatants of HUVECs in 12 mg/dL UA group for 72 hours (P＜0.05).Compared with H2O2 group,the NO levels were increased and the ET-1 levels were decreased in the supematants of HUVECs in (8 mg/dL or 12 mg/dL) UA +H2O2 groups for 24 hours (P＜0.05),while for (12 mg/dL) UA +H2O2 group for 72 hours,the results were just the contary.Conclusion The effects of UA on HUVECs are related with both concentration and action rime.Acutely increased UA may protect HUVECs form injury,while long action of UA may injure HUVECs,especially under oxidative stress.
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Objective To investigate the influences of imatinib on Survivin gene expression in bcr-abl-transformed leukemia cells.Methods Firstly,PCR and Western blot were carried out to detected Survivin expression with imatinib treatment in 32Dcl3 and 32D-bcr-abl cell lines.Then the luciferase reporter plasmids containing human Survivin promoter as well as its deletion and site-directed mutation were constructed to identify the essential responsive elements for suppressing Survivin promoter activity by imatinib.Chromatin immunoprecipitation was performed to confirm the binding of c-myc to Survivin promoter.10058-F4,a small molecule c-myc inhibitor,was used to disrupt c-myc activity and evaluate its anti-leukemic effect combined with imatinib.Results Both of mRNA and protein level of Survivin in bcr-abl-transformed cells were downregulated upon imatinib treatment.The decrease of Survivin expression was controlled at the transcriptional level through a mechanism in which imatinib repressed survivin promoter activity by disturbing the interaction between c-myc and E-box elements.Interruption of c-myc activity by 10058-F4 exerted an anti-leukemia effect with enhancing the sensibility of K562/G01 cells to imatinib.Conclusion Imatinib down-regulates Survivin expression through c-myc-mediated transcription and interference with c-myc might be a potential utility for treatment of imatinib resistant leukemia.
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Objective To discuss whether mild hyperuricemia can lead to kidney damage and the protection of decreased uric acid,through observing that hyperuricemia did damage to glomerulus endothelial function and cell proliferation of vascular smooth muscle in rats. Methods Fifty-four male SD rats were divided into four groups,the control group,model group (Oxonate),allopurinol group and Oxonate+allopurinol group.Rats were administered on a low sodium diet and their systolic blood pressure (SBP) were measured each 10 days.ELISA was used to detect rat plasma markers of endothelial function damage [nitric oxide (NO),type-1 plasminogen activator inhibitor (PAI-1),endothelin 1 (ET-1)] and cell proliferation of vascular smooth muscle[plateletderived growth factor (PDGF),cycloxygenase 2 (COX2),monocyte chemotactic protein-1 (MCP-1)],and the markers of inflammatory reaction[interleukin-18 (IL-18),tumor necrosis factor α(TNF-α)].PDGF and nitric oxide synthase (NOS) levels of rats were detected by immunohistochemical method.Renal tissue pathology of rats was observed. Results Compared to the control group,the plasmic concentration of COX2,ET-1,IL-18,PAI-1,PDGF,TNF-o,MCP-1 increased,and NO decreased significantly in rats of model group (all P＜0.05),expression of NOS significantly reduced and PDGF increased (all P＜0.05).Under light microscope,vascular wall thickening,intimal proliferation and lumen slight stricture without uric acid crystals in renal tissue were found in model group,which were obviously improved by using allopurinol. Conclusion Mild hyperuricemia can do damage to endothelial function of glomerulus and lead to vascular cell proliferation,which can be improved through decreasing uric acid.