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GLI1 and SOX2 were overexpressed in HL60 cells as compared with pcDNA3.1 empty vector-transfected group. Growth curve demonstrated significant proliferative advantage of GLI1/SOX2-transfected cells. CCK8 assay indicated that GLI1/SOX2-overexpressed HL60 cells were more resistant to NCTD treatment.
NCTD attenuates HL60 proliferation via targeting the Hedgehog/SOX2 axis.
NCTD attenuates HL60 proliferation via targeting the Hedgehog/SOX2 axis.
To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML).
Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls.
The ratio of CD4
/CD8
T cells, the percentage of NK cells, the expression of perforin and Granzyme B of No of CD4
/CD8
T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.
The ITI regimen can raise the ratio of CD4+/CD8+ T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.
To investigate the antileukemia activity of phosphatidylinositol-3 kinase (PI3K) inhibitor ZSTK474 on human leukemia cell line U937.
MTT, soft agar assay, flow cytometric analysis and western blot were used to detect the effect of ZSTK474 on U937 cell proliferation, tumorigenicity, cell cycle, cell apoptosis and phosphorylation levels of the key factor of PI3K/AKT pathway. Chou-Talalay method was used to evaluate the combination of ZSTK474 with Cytarabine or Homoharringtonine.
PI3K inhibitor ZSTK474 could inhibit the proliferation and tumorigenicity of U937 cell, induce G
cell cycle arrest and promote cell apoptosis, and enhance intracellular ROS production and decrease MMP, downregulate Cyclin D1, p-Rb, BCL-2 and upregulate p27, caspase-9, caspase-3, PARP and BAX. Furthermore, the phosphorylation of PDK1, GSK-3β, AKT and mTOR could be downregulated by ZSTK474. The combination of ZSTK474 with Homoharringtonine was synergistic.
ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells.
ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells.
To analyze the relationship between the expression level of SQLE and the prognosis of patients with acute myeloid leukemia (AML) through large sample data.
The data of genome, transcriptome, gene chip expression, and clinical information were statistically analyzed in multiple cohorts of AML patients with large samples.
It was found that the expression level of SQLE gene in tumor cells of AML patients was significantly higher than that of healthy controls (P=0.001). In the three AML corhort, the SQLE high expression group showed a worse therapeutic outcome (OS, P=0.009, P=0.0001, P=0.006; EFS, P=0.005, P=0.001). The unvariate and multivariate survival prognosis analysis indicated that the high expression of SQLE suggests lower event-free survival rate (EFS, HR=1.551, P<0.05) and overall survival rate (OS, HR=1.484, P<0.05). selleck chemical At the same time, it was also found that among different risk subgroups, the expression of SQLE in high risk group was higher (P<0.001, P=0.01), while the patients with high SQLE expression, who received allogeneic HSCT, had longer overall survival time (P=0.006).
The up-regulation SQLE expression suggests a poor prognosis for the patients with AML.
The up-regulation SQLE expression suggests a poor prognosis for the patients with AML.
To investigate the correlation of receptor gene (P2X7, VDR and SLC19A1) polymorphisms with risk suffering from acute leukemia (AL) in Fujian area.
Ninety-three cases of newly diagnosed AL as AL group and 90 persons not suffered from hematologic and other tumors as control group were selected and used for comparative analysis of receptor gene polymorphisms and risk suffering from AL between case and control groups. The bone marrow and peripheral blood were collected, from which the DNA was extracted. The PCR-RFLP was used to detect 8 SNP sites (P2X7 rs208294, rs2230911, rs3751143; VDR rs2228570, rs7975232; SLC194A1 rs1051266, rs1131596, rs3788200) of receptor genes related with the environment response, and the genotypes analysis was used to the correlation of receptor gene polymorphisms with risk suffering from adult AL.
The unvariate logistic analysis showed that as compared with control group, P2X7 rs208294 T>C mutation and rs3751143 A>C mutation in codominant model, dominant model and over-dominant model were higher in case group, moreover the differences were statistically significant (P<0.01, P<0.05 and P<0.05, respectively), which suggested that they could reduce the risk suffering from AL. The recessive inheritance model showed that SLC1941 rs1131596 G>A mutation could increase the risk suffering from AL (P<0.05). The stepwise multivariate logistic regression analysis showed that there was still statistically significant difference in P2X7 rs208294 mutation between case group and control group (P<0.05), moreover, the heterozygous mutation (CT) could decrease the risk suffering from AL, showing the better protective effect, compared with homozygous mutation(CC).
The P2X7 rs208294 T>C mutation is one of protective factors against adult acute leukemia.
C mutation is one of protective factors against adult acute leukemia.
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