miR-181b-5p promotes cell proliferation and induces apoptosis in human acute myeloid leukemia by targeting PAX9 / 细胞与分子免疫学杂志

Objective To investigate the effects of miR-181b-5p on cells proliferation and apoptosis in acute myeloid leukemia (AML) by targeting paired box 9 (PAX9). Methods The relationship between expression level of PAX9 and prognosis in AML patients was analyzed by gene expression profiling interactive analysis (GEPIA) database and The Cancer Genome Atlas (TCGA) database. Kasumi-1 and AML5 cells were transfected with empty vector (Vector group) or PAX9 (PAX9 group). The proliferation activity was detected by CCK-8 assay, and cells cycle and apoptosis were detected by flow cytometry. Expressions of cyclin-dependent kinase 2 (CDK2), cyclin B1 (CCNB1), B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (BAX) were detected by Western blot analysis. The targeted microRNA (miRNA) by PAX9 was predicted by bioinformatics analysis, and the targeted effect was verified by luciferase reporter assay. The level of PAX9 mRNA was detected by real-time quantitative PCR, and expression of PAX9 protein was detected by Western blot analysis. Kasumi-1 and AML5 cells were transfected with miR-NC (miR-NC group) or miR-181b-5p (miR-181b-5p group). The cells were further transfected with PAX9 (miR-181b-5p combined with PAX9 group) in miR-181b-5p group. The proliferation, cycle and apoptosis of cells were detected by the above methods.Results GEPIA and TCGA databases showed that the expression of PAX9 was down-regulated in AML patients, which was correlated with poor prognosis. In Kasumi-1 and AML5 cells, compared with Vector group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were decreased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were increased in PAX9 group. It was confirmed by double luciferase reporter assay that PAX9 was the target gene of miR-181b-5p. Compared with miR-NC group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were increased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were decreased in miR-181b-5p group. Compared with miR-181b-5p group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were decreased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were increased in miR-181b-5p combined with PAX9 group. Conclusion The miR-181b-5p can promote the proliferation of AML cells and delay apoptosis by inhibiting PAX9.

Effect of XELOX regimens plus combination of endostar and thalidamide as first?line treatment for advanced colorectal cancer / 中国综合临床

Objective To investigate the efficacy and safety of two antiangiogenic drugs (recombinant human endostatin endostar and thalidomide ) combined with capecitabine and oxaliplatin (XELOX) regimens in the treatment of advanced colorectal cancer.Methods From January 2015 to May 2018,40 patients of advanced metastatic colorectal cancer with organ metastasis and non?resectable were selected from the first people′s hospital of Hefei and Anhui Provincial Hospital, and they were randomly divided into treatment and control group, with 20 cases in each group.The treatment group received intravenous infusion (IV) of endostar for continuous 7 days (day 1～7) combined with oral administration of thalidomide for continuous 14 days (day 1～14) plus XELOX regimens after the fifth dose of endostar (day 6～19),and the control group was treated with XELOX regimen (day6～19).Results The objective response rate (ORR) was 50%(10／20) and 20%(4／20) respectively (χ2＝3.956,P＜0.05),the disease control rate (DCR) was 85%( 17／20) and 70%(14／20) respectively ( χ2＝1.290,P＞0.05),and the median progression free survival (mPFS) was 6.8 in both groups.There was no significant difference in Karnofsky performance score ( KPS) and incidence of adverse reactions between the two groups before and after treatment (P＞0.05).Conclusion Combination of endostar and thalidamide plus XELOX regimen as first?line treatment have better antitumor activity and are well?tolerated in patients with advanced colorectal cancer.

Application of pegylated recombinant human granulocyte colony-stimulating factor to prevent chemotherapy-induced neutropenia in patients with lymphoma: a prospective, multicenter, open-label clinical trial / 中华血液学杂志

Objective@#To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma.@*Methods@#This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed.@*Results@#①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) .@*Conclusion@#During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

The Effect of Combination Use of 1,25(OH)_2D_3 and Celecoxib on Growth and Apoptosis in Breast Cancer Cell Line Hs578T / 医学研究杂志

Objective To study the effect of combined 1,25-dihydroxyvitamin D31,25(OH)2D3 and celecoxib on growth, call cycle and apoptosis in breast cancer cell line Hs578T.Methods We compared cell numbers by using MTT method , analyzed cell cycle percentage and apoptosis with flow cytometric.Results Both with 1,25(OH)2D3 and celecoxib could inhibite tumov growth,induc apoptosis in a dose-time-dependent manner. comparing with 1,25(OH)2D3 alone,combination wse of the two drugs had a additive effect but was inferior to cececoxib alone. The combination use of 10-8mol/L1,25(OH)2D3 and celecoxib group is more effective than the combination use of 10-7mol/L1,25(OH)2D3 and celecoxib group. Conclusion 1,25(OH)2D3 and celecoxib could be a new drug for the prevention and treatment of breast cancer.

Relationships between induction of apoptosis by Taxol in Hela cells and apoptosis-related proteins / 中国药理学通报

Aim To investigate the effects of taxol on apoptosis in Hela cell and the mechanism of apoptosis. The apoptotic cells were detected by TUNEL, HE, eletronic micrpscopy and flow cytometry method. The expressions and activity of apoptosis associated proteins such as PCNA and caspase-3 were examined using S-P and enzyme histochemistric method.The results followed as: HeLa cells exposed to Taxol undergo cell death, presenting morphological and biochemical characteristics typical of apoptosis and the apoptotic cells increased with time and concentration. In contrast to untreated Hela cells, which express low PCNA, Ones treated with Taxol expressed high amounts of PCNA. Conclusion Taxol may induced apoptosis in Hela cell. The apoptosis induced by taxol is related to the increase of PCNA protein and activity of caspase-3.